Low-frequency stimulation of corpus callosum suppresses epileptiform activity in the cortex through γ-aminobutyric acid type B receptor and slow afterhyperpolarization-mediated reduction in tissue excitability.

Objective: Deep brain stimulation, particularly low-frequency stimulation (LFS) targeting fiber tracts, has emerged as a potential therapy for drug-resistant epilepsy (DRE) and for generalized epilepsy, both of which pose significant treatment challenges. LFS diffusely suppresses seizures in the cortex when applied to fiber tracts like the corpus callosum (CC). Nevertheless, the specific processes responsible for suppressing epileptic activity in the cortex induced by LFS remain unclear.

Neural recordings can differentiate between spontaneously metastasizing melanomas and melanomas with low metastatic potential.

Multiple studies report that melanomas are innervated tumors with sensory and sympathetic fibers where these neural fibers play crucial functional roles in tumor growth and metastasis with branch specificity. Yet there is no study which reports the direct neural recording and its pattern during in-vivo progression of the cancer. We performed daily neural recordings from male and female mice bearing orthotopic metastasizing- melanomas and melanomas with low metastatic poential, derived from B16-F10 and B16-F1 cells, respectively.

Selective chronic recording in small nerve fascicles of sciatic nerve with carbon nanotube yarns in rats.

. The primary challenge faced in the field of neural rehabilitation engineering is the limited advancement in nerve interface technology, which currently fails to match the mechanical properties of small-diameter nerve fascicles. Novel developments are necessary to enable long-term, chronic recording from a multitude of small fascicles, allowing for the recovery of motor intent and sensory signals.

Spatial and amplitude dynamics of neurostimulation: Insights from the acute intrahippocampal kainate seizure mouse model.

Objective: Neurostimulation is an emerging treatment for patients with drug-resistant epilepsy, which is used to suppress, prevent, and terminate seizure activity. Unfortunately, after implantation and despite best clinical practice, most patients continue to have persistent seizures even after years of empirical optimization. The objective of this study is to determine optimal spatial and amplitude properties of neurostimulation in inhibiting epileptiform activity in an acute hippocampal seizure model.

Mechanisms of Neurostimulation for Epilepsy.

This review discusses the use of neurostimulation therapies for epilepsy treatment, including vagal nerve stimulation, responsive neurostimulation, and deep brain stimulation. Different therapeutic strategies and their underlying mechanisms are explored, with a focus on optimizing parameters for seizure reduction. The review also highlights the paradigm shift toward a more diverse and multimodal approach to deep brain neuromodulation.

Spatial and Amplitude Dynamics of Neurostimulation: Insights from the Acute Intrahippocampal Kainate Seizure Mouse Model.

Objective: Neurostimulation is an emerging treatment for patients with medically refractory epilepsy, which is used to suppress, prevent, and terminate seizure activity. Unfortunately, after implantation and despite best clinical practice, most patients continue to have persistent seizures even after years of empirical optimization. The objective of this study is to determine optimal spatial and amplitude properties of neurostimulation in inhibiting epileptiform activity in an acute hippocampal seizure model.

Subthreshold Oscillating Waves in Neural Tissue Propagate by Volume Conduction and Generate Interference.

Subthreshold neural oscillations have been observed in several brain regions and can influence the timing of neural spikes. However, the spatial extent and function of these spontaneous oscillations remain unclear. To study the mechanisms underlying these oscillations, we use optogenetic stimulation to generate oscillating waves in the longitudinal hippocampal slice expressing optopatch proteins.

Theta waves, neural spikes and seizures can propagate by ephaptic coupling in vivo.

Electric field coupling has been shown to be responsible for non-synaptic neural activity propagation in hippocampal slices and cortical slices. Epileptiform and slow-wave sleep activity can propagate by electric field coupling without using synaptic connections at speeds of ~0.1 m/s in vitro.

Low-frequency stimulation of a fiber tract in bilateral temporal lobe epilepsy.

Objective: Pharmacoresistant bilateral mesial temporal lobe epilepsy often implies poor resective surgical candidacy. Low-frequency stimulation of a fiber tract connected to bilateral hippocampi, the fornicodorsocommissural tract, has been shown to be safe and efficacious in reducing seizures in a previous short-term study. Here, we report a single-blinded, within-subject control, long-term deep-brain stimulation trial of low-frequency stimulation of the fornicodorsocommissural tract in bilateral mesial temporal lobe epilepsy.

Pulse-frequency-dependent resonance in a population of pyramidal neuron models.

Stochastic resonance is known as a phenomenon whereby information transmission of weak signal or subthreshold stimuli can be enhanced by additive random noise with a suitable intensity. Another phenomenon induced by applying deterministic pulsatile electric stimuli with a pulse frequency, commonly used for deep brain stimulation (DBS), was also shown to improve signal-to-noise ratio in neuron models. The objective of this study was to test the hypothesis that pulsatile high-frequency stimulation could improve the detection of both sub- and suprathreshold synaptic stimuli by tuning the frequency of the stimulation in a population of pyramidal neuron models.

Decoding Vagus-Nerve Activity with Carbon Nanotube Sensors in Freely Moving Rodents.

The vagus nerve is the largest autonomic nerve and a major target of stimulation therapies for a wide variety of chronic diseases. However, chronic recording from the vagus nerve has been limited, leading to significant gaps in our understanding of vagus nerve function and therapeutic mechanisms. In this study, we use a carbon nanotube yarn (CNTY) biosensor to chronically record from the vagus nerves of freely moving rats for over 40 continuous hours.

Delta oscillation underlies the interictal spike changes after repeated transcranial direct current stimulation in a rat model of chronic seizures.

Background: Transcranial direct current stimulation (tDCS) provides a noninvasive polarity-specific constant current to treat epilepsy, through a mechanism possibly involving excitability modulation and neural oscillation.

Objective: To determine whether EEG oscillations underlie the interictal spike changes after tDCS in rats with chronic spontaneous seizures.

Methods: Rats with kainic acid-induced spontaneous seizures were subjected to cathodal tDCS or sham stimulation for 5 consecutive days.

Neural recruitment by ephaptic coupling in epilepsy.

Objective: One of the challenges in treating patients with drug-resistant epilepsy is that the mechanisms of seizures are unknown. Most current interventions are based on the assumption that epileptic activity recruits neurons and progresses by synaptic transmission. However, several experimental studies have shown that neural activity in rodent hippocampi can propagate independently of synaptic transmission.

Model-based analysis of implanted hypoglossal nerve stimulation for the treatment of obstructive sleep apnea.

Study Objectives: Individuals with obstructive sleep apnea (OSA), characterized by frequent sleep disruptions from tongue muscle relaxation and airway blockage, are known to benefit from on-demand electrical stimulation of the hypoglossal nerve. Hypoglossal nerve stimulation (HNS) therapy, which activates the protrusor muscles of the tongue during inspiration, has been established in multiple clinical studies as safe and effective, but the mechanistic understanding for why some stimulation parameters work better than others has not been thoroughly investigated.

Methods: In this study, we developed a detailed biophysical model that can predict the spatial recruitment of hypoglossal nerve fascicles and axons within these fascicles during stimulation through nerve cuff electrodes.

Direct measurement of vagal tone in rats does not show correlation to HRV.

The vagus nerve is the largest autonomic nerve, innervating nearly every organ in the body. "Vagal tone" is a clinical measure believed to indicate overall levels of vagal activity, but is measured indirectly through the heart rate variability (HRV). Abnormal HRV has been associated with many severe conditions such as diabetes, heart failure, and hypertension.

Chronic neural activity recorded within breast tumors.

Nerve fibers are known to reside within malignant tumors and the greater the neuronal density the worse prognosis for the patient. Recent discoveries using tumor bearing animal models have eluded to the autonomic nervous system having a direct effect on tumor growth and metastasis. We report the first direct and chronic in vivo measurements of neural activity within tumors.

Transcranial direct current stimulation alleviates seizure severity in kainic acid-induced status epilepticus rats.

Status epilepticus (SE) is a state of prolonged and repeated seizures that can lead to permanent brain damage or life-threatening conditions. Transcranial direct current stimulation (tDCS) non-invasively provides a polarity-specific electric current to modulate brain excitability. Little is known about the therapeutic potential of tDCS in SE.

Comparison of fiber tract low frequency stimulation to focal and ANT stimulation in an acute rat model of focal cortical seizures.

Background: Current implementations of direct brain stimulation for epilepsy in patients involve high-frequency (HFS) electrical current and targeting of grey matter. Studies have shown that low-frequency (LFS) fiber-tract stimulation may also prove effective. To compare the efficacy of high-frequency grey matter stimulation to the low-frequency fiber tract stimulation technique a well-controlled set of experiments using a single animal model of epilepsy is needed.

Sonic Hedgehog is expressed by hilar mossy cells and regulates cellular survival and neurogenesis in the adult hippocampus.

Sonic hedgehog (Shh) is a multifunctional signaling protein governing pattern formation, proliferation and cell survival during embryogenesis. In the adult brain, Shh has neurotrophic function and is implicated in hippocampal neurogenesis but the cellular source of Shh in the hippocampus remains ill defined. Here, we utilize a gene expression tracer allele of Shh (Shh-nlacZ) which allowed the identification of a subpopulation of hilar neurons known as mossy cells (MCs) as a prominent and dynamic source of Shh within the dentate gyrus.

Self-propagating, non-synaptic epileptiform activity recruits neurons by endogenous electric fields.

It is well documented that synapses play a significant role in the transmission of information between neurons. However, in the absence of synaptic transmission, neural activity has been observed to continue to propagate. Previous studies have shown that propagation of epileptiform activity takes place in the absence of synaptic transmission and gap junctions and is outside the range of ionic diffusion and axonal conduction.

Corpus callosum low-frequency stimulation suppresses seizures in an acute rat model of focal cortical seizures.

Objective: Low-frequency fiber-tract stimulation has been shown to be effective in treating mesial temporal lobe epilepsies through activation of the hippocampal commissure in rodents and human patients. The corpus callosum is a major pathway connecting the two hemispheres of the brain; however, few experiments have documented corpus callosum stimulation. The objective is to determine the efficacy of corpus callosum stimulation at low frequencies to suppress cortical seizures.

Slow periodic activity in the longitudinal hippocampal slice can self-propagate non-synaptically by a mechanism consistent with ephaptic coupling.

Key Points: Slow periodic activity can propagate with speeds around 0.1 m s and be modulated by weak electric fields. Slow periodic activity in the longitudinal hippocampal slice can propagate without chemical synaptic transmission or gap junctions, but can generate electric fields which in turn activate neighbouring cells.

Recovering Motor Activation with Chronic Peripheral Nerve Computer Interface.

Interfaces with the peripheral nerve provide the ability to extract motor activation and restore sensation to amputee patients. The ability to chronically extract motor activations from the peripheral nervous system remains an unsolved problem. In this study, chronic recordings with the Flat Interface Nerve Electrode (FINE) are employed to recover the activation levels of innervated muscles.

Slow moving neural source in the epileptic hippocampus can mimic progression of human seizures.

Fast and slow neural waves have been observed to propagate in the human brain during seizures. Yet the nature of these waves is difficult to study in a surgical setting. Here, we report an observation of two different traveling waves propagating in the in-vitro epileptic hippocampus at speeds similar to those in the human brain.