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Neural implants that deliver multi-site electrical stimulation to the nervous systems are no longer the last resort but routine treatment options for various neurological disorders. Multi-site electrical stimulation is also widely used to study nervous system function and neural circuit transformations. These technologies increasingly demand dynamic electrical stimulation and closed-loop feedback control for real-time assessment of neural function, which is technically challenging since stimulus-evoked artifacts overwhelm the small neural signals of interest. We report a novel and versatile artifact removal method that can be applied in a variety of settings, from single- to multi-site stimulation and recording and for current waveforms of arbitrary shape and size. The method capitalizes on linear electrical coupling between stimulating currents and recording artifacts, which allows us to estimate a multi-channel linear Wiener filter to predict and subsequently remove artifacts via subtraction. We confirm and verify the linearity assumption and demonstrate feasibility in a variety of recording modalities, including in vitro sciatic nerve stimulation, bilateral cochlear implant stimulation, and multi-channel stimulation and recording between the auditory midbrain and cortex. We demonstrate a vast enhancement in the recording quality with a typical artifact reduction of 25-40 dB. The method is efficient and can be scaled to arbitrary number of stimulus and recording sites, making it ideal for applications in large-scale arrays, closed-loop implants, and high-resolution multi-channel brain-machine interfaces.The spinocerebellar ataxias (SCAs) are a heterogeneous group of neurodegenerative diseases that share convergent disease features. A common symptom of these diseases is development of ataxia, involving impaired balance and motor coordination, usually stemming from cerebellar dysfunction and neurodegeneration. For most spinocerebellar ataxias, pathology can be attributed to an underlying gene mutation and the impaired function of the encoded protein through loss or gain-of-function effects. Strikingly, despite vast heterogeneity in the structure and function of disease-causing genes across the SCAs and the cellular processes affected, the downstream effects have considerable overlap, including alterations in cerebellar circuitry. Interestingly, aberrant function and degeneration of Purkinje cells, the major output neuronal population present within the cerebellum, precedes abnormalities in other neuronal populations within many SCAs, suggesting that Purkinje cells have increased vulnerability to cellular perturbations. Factors that are known to contribute to perturbed Purkinje cell function in spinocerebellar ataxias include altered gene expression resulting in altered expression or functionality of proteins and channels that modulate membrane potential, downstream impairments in intracellular calcium homeostasis and changes in glutamatergic input received from synapsing climbing or parallel fibers. This review will explore this enhanced vulnerability and the aberrant cerebellar circuitry linked with it in many forms of SCA. It is critical to understand why Purkinje cells are vulnerable to such insults and what overlapping pathogenic mechanisms are occurring across multiple SCAs, despite different underlying genetic mutations. Enhanced understanding of disease mechanisms will facilitate the development of treatments to prevent or slow progression of the underlying neurodegenerative processes, cerebellar atrophy and ataxic symptoms.Transcutaneous auricular vagus nerve stimulation (taVNS) has gained growing interest as a non-invasive and non-pharmacologic treatment option in various neurological and psychiatric disorders. Animal experiments and clinical trials confirm that taVNS at the auricular concha region has beneficial effects on depression. However, stimulation frequencies are selected empirically, and there is no evidence showing that any frequency is superior to the others. This study explores antidepressant-like effects of three frequencies of taVNS on rats subjected to chronic unpredictable mild stress (CUMS). Sprague-Dawley rats were randomly divided into five groups, i.e., the control, CUMS, 5 Hz-taVNS, 20 Hz-taVNS, and 100 Hz-taVNS groups. The three different frequencies were administered during the 30-min taVNS procedure once a day for 28 consecutive days. Rats exposed to CUMS showed signs of depression-like behaviors, including reduction in sucrose preference and increased immobility time in forced swimming and open field tests as well as significant dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis as detected by plasma corticosterone and adrenocorticotropic hormone concentration. The 28 days' taVNS sessions with three frequencies elicited quite different consequences. Although 20 Hz taVNS significantly reversed the depression-like behaviors and downregulated the hyperactivity of the HPA axis, neither 5 nor 100 Hz showed any antidepressant-like effect on CUMS-induced rat behavior. Based on these results, we propose that, out of the three frequencies for taVNS intervention on depression, 20 Hz may be the optimized frequency to have a better modulation effect on HPA axis function by activating the auricular vagus nerve.Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most frequent cause of familial Parkinson's disease (PD). Several genetic manipulations of the LRRK2 gene have been developed in animal models such as rodents, Drosophila, Caenorhabditis elegans, and zebrafish. see more These models can help us further understand the biological function and derive potential pathological mechanisms for LRRK2. Here we discuss common phenotypic themes found in LRRK2-associated PD animal models, highlight several issues that should be addressed in future models, and discuss emerging areas to guide their future development.Background Chronic pain is a significant global health issue. For most individuals with chronic pain, biomedical treatments do not provide adequate relief. Given the evidence that neurophysiological abnormalities are associated with pain, it is reasonable to consider treatments that target these factors, such as neurofeedback (NF). The primary objectives of this review were to summarize the current state of knowledge regarding (1) the different types of NF and NF protocols that have been evaluated for pain management; (2) the evidence supporting each NF type and protocol; (3) if targeted brain activity changes occur with NF training; and (4) if such brain activity change is associated with improvements on treatment outcomes. Methods Inclusion criteria were intentionally broad to encompass every empirical study using NF in relation to pain. We considered all kinds of NF, including both electroencephalogram- (EEG-) and functional magnetic resonance imagining- (fMRI-) based. We searched the following databases from inception through September 2019 Pubmed, Ovid, Embase, Web of Science, PsycINFO.
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