High-frequency Stimulation Research Articles

Analysis of lumbar dorsal spinal potentials evoked by electrical stimulation of the colon and their changes induced by high-frequency stimulation or ischemia in rats

The clinical-related input and processing of intestinal afferents to the spinal cord is not well known. This study aims to develop an electrophysiological experimental animal model to study spinal cord afferents from the colon during clinical-related conditions such as hyperexcitability or ischemia. Spinal cord evoked potentials (SCEP) were elicited by colonic stimulation in ten male adult Sprague-Dawley rats anesthetized with thiobarbital, 60 mg kg-1 i.p. After laminectomy (T11 to L5), a tungsten electrode (500 μm; <50Ω) was placed in the spinal dorsum to record SCEP induced by bipolar electrical stimulation of colon mucosa (basal 30 V; 1 ms) at low (0.2 Hz; 10 min) or high (5 Hz; 5 min) frequency. In 3 experiments, after the basal recording, a respiratory arrest was induced by D-tubocurarine to evaluate the ischemia effects. The SCEPs were stable and reliable (n=310), displaying a N1 wave (delay: 3.9±0.1 ms; amplitude 7.78±0.39 μV) and P1 wave (delay 9.96±0.14 ms; amplitude 2.97±0.21 μV). Colonic high-frequency stimulation induced an amplitude increase in both +11% (N1) and +23.7% (P1) (p<0.001). The ischemia induced a linear decay of both wave amplitudes more intense for the P1 wave. sensitive. These results denote the intense colonic input to the lumbar dorsal spinal cord, the presence of spinal sensory potentiation mechanisms induced by colonic high frequency stimulation, and the high oxygen dependency of the neuronal networks involved in the N1 and P1 wave generation. This experimental model could contribute to the study of visceral pain and inflammation, allowing the electrophysiological evaluation of experimental treatment response in experimental colon disease models.

Evaluation of post-tetanic motor evoked potential as an augmentation technique under partial neuromuscular blockade during craniotomy

ObjectiveIn craniotomies requiring motor evoked potential (MEP) monitoring, avoiding neuromuscular blockade (NMB) is preferable, but its complete avoidance poses risks of unexpected movement. This retrospective study investigates the application of a post-tetanic MEP augmentation technique to enhance baseline recording of transcranial stimulation MEP (Tc-MEP) under partial NMB during craniotomy. MethodsTwenty-six patients were included. The level of partial NMB was maintained at a train-of-four ratio of approximately 40 %. Monophasic constant-current stimulation was applied on the craniotomy side with + 20 % of the threshold intensity. Post-tetanic Tc-MEP, involving tetanic stimulation of the median nerve 1 s before transcranial stimulation, was performed on patients who failed to record using conventional baseline recording. ResultsThe post-tetanic Tc-MEP technique successfully improved the success rate of baseline recording from 61.5 % to 100 %. Application of post-tetanic Tc-MEP significantly increased amplitudes in both the upper (p = 0.04) and lower limbs (p < 0.01) compared to before post-tetanic Tc-MEP. No patients had unexpected movements. ConclusionsThis study indicates that post-tetanic Tc-MEP enhanced the success rate of baseline recording during craniotomy under partial NMB. SignificanceThe combination of partial NMB and post-tetanic Tc-MEP could be a useful regimen for craniotomy with MEP monitoring, addressing both safety concerns and successful baseline recording.

High-Frequency versus Conventional Spinal Cord Stimulation in Patients with Failed-Back Surgery Syndrome

High-Frequency versus Conventional Spinal Cord Stimulation in Patients with Failed-Back Surgery Syndrome

Comparative analysis of the efficacy of domestic and imported sugammadex for reversal of rocuronium-induced deep neuromuscular block in adult patients

Objective: To evaluate the efficacy of domestic and imported sugammadex for reversal of rocuronium-induced deep neuromuscular block (NMB) in adult patients. Methods: The clinical data of adult patients who scheduled for elective surgery with general anesthesia that required muscle relaxants in Peking University First Hospital from June 2023 to June 2024 were prospectively included. The patients were devided into domestic group and imported group according to random number table method. Anesthetized patients received rocuronium for intubation and muscle relaxation, and anesthesia was maintained with propofol, sevoflurane, and remifentanil. The effect of neuromuscular block was monitored. During deep muscle relaxation (with a single stimulation muscle twitch count of 1-2 after tetanic stimulation), domestic and imported sugammadex 4 mg/kg was given, respectively. The primary outcome was the recovery time from sugammadex injection to return of the train-of-four ratio (TOFr) to 0.9, with a non-inferiority margin of 1 minute (the range of non-inferiority boundary value is ±1 minute). The secondary outcome included the ratios of TOFr to 0.9 at different times and adverse effects. Results: A total of 70 patients were included, including 35 patients in the domestic group (13 males and 22 females), aged (46.9±12.7) years, and 35 patients in the imported group (13 males and 22 females), aged (45.7±11.5) years. There was no statistically significant difference in demographic characteristics, surgical time, anesthesia time, total rocuronium dose, and extubation time between two groups. All patients recovered to a TOFr of 0.9 within 5 minutes. Reversal time was 1.8 (1.3, 2.6) minutes in the domestic sugammadex group and 2.0 (1.7, 2.9) minutes in the imported sugammadex group respectively. The difference in reversal times between two groups was -0.40 minutes (95%CI:-0.75 to -0.02, P=0.039), which was within the range of non-inferiority threshold. Within 5 minutes of administration of antagonists, the incidence of bradycardia was 14% (5/35 and 5/35) in both domestic and imported groups. The incidence of skin allergy in patients transported to the post-anesthesia recovery room (PACU) was 3% (3/35) and 0 in both groups, respectively, with no statistical significance (all P>0.05). There were no serious drug-related adverse events in both groups. Conclusion: The effect of domestic sugammadex is not inferior to imported sugammadex in reversal of deep rocuronium-induced neuromuscular block in adult patients, and the incidence of postoperative adverse events is not increased.

Influence of remifentanil on the pharmacokinetics and pharmacodynamics of remimazolam in healthy volunteers

Background: Synergistic effects between opioids and remimazolam on bispectral index (BIS) and modified observer’s assessment of alertness and/or sedation (MOAAS) score were previously described. This study aimed to characterize the influence of remifentanil on the sedative properties of remimazolam as measured by MOAAS, BIS, tolerance to laryngoscopy or tetanic stimulation (TOL or TOTS) and to determine target concentrations that maximize MOAAS 2/3. Methods: A three-period, cross-over, dose-ranging clinical trial was performed in 24 healthy volunteers. In all periods, remimazolam was administered using a step-up and step-down TCI protocol (50 – 2000 ng/mL). Stable remifentanil target concentrations of 0.5 ng/mL and 0.1 to 4.0 ng/mL were maintained in periods 2 and 3, respectively. Remifentanil, remimazolam and CNS7054 (metabolite) concentrations and, MOAAS, BIS, TOL and TOTS were collected in each step of the TCI protocol. Data were analyzed using non-linear mixed-effects models, where p≤0.01 was considered significant. Results: Remifentanil reduced the apparent clearance of CNS7054 with a half-maximum inhibition at 8.0 ng/mL (95% CI 5.5 to 13.4 ng/mL). A pharmacodynamic interaction was detected on all endpoints. Simulations indicate that the probability of observing a MOAAS 2/3 is highest at remimazolam target concentration of 275, 250 or 200 ng/mL combined with 0, 0.1, or 0.5 ng/mL remifentanil resulting in probabilities of 45%, 45% and 44%, respectively. Additionally, simulations indicate that the highest probability of observing TOTS and TOL was 93.3% and 85.5%, respectively, at the highest studied target concentrations. Conclusions: A pharmacokinetic and pharmacodynamic drug-drug interaction between remimazolam and remifentanil was quantified in this clinical trial. Appropriate target concentrations for MOAAS and BIS could be estimated, but, for TOL and TOTS, the trial design did not allow to fully characterize the exposure-response relationship.

Cortical HFS-induced neo-Hebbian local plasticity enhances efferent output signal and strengthens afferent input connectivity.

High-frequency stimulation (HFS)-induced long-term potentiation (LTP) is generally regarded as a homosynaptic Hebbian-type LTP, where synaptic changes are thought to occur at the synapses that project from the stimulation site and terminate onto the neurons at the recording site. In this study, we first investigated HFS-induced LTP on urethane-anesthetized rats and found that cortical HFS enhances neural responses at the recording site through the strengthening of local connectivity with nearby neurons at the stimulation site, rather than through synaptic strengthening at the recording site. This enhanced local connectivity at the stimulation site leads to increased output propagation, resulting in signal potentiation at the recording site. Additionally, we discovered that HFS can also non-specifically strengthen distant afferent synapses at the HFS site, thereby expanding its impact beyond local neural connections. This form of plasticity exhibits a neo-Hebbian characteristic as it exclusively manifests in the presence of cholecystokinin (CCK) release, induced by HFS. The cortical HFS-induced local LTP was further supported by a behavioral task, providing additional evidence. Our results unveil a previously overlooked mechanism underlying cortical plasticity: synaptic plasticity is more likely to occur around the soma site of strongly activated cortical neurons, rather than solely at their projection terminals.Significance Statement This manuscript reveals that cortical HFS triggers the local release of CCK, a crucial neuromodulator for cortical plasticity, which is released at the HFS site from other cortical efferents rather than in a homosynaptic manner. Therefore, cortical HFS influences long-range cortical efferents through changes at the HFS location, not at the projection terminals. Additionally, the HFS-triggered locally released CCK strengthens long-range afferent synapses to the HFS site. This evidence suggests that a CCK-dependent neo-Hebbian mechanism underlies cortical plasticity.

25-Hydroxycholesterol modulates synaptic vesicle endocytosis at the mouse neuromuscular junction.

Many synaptic vesicles undergo exocytosis in motor nerve terminals during neuromuscular communication. Endocytosis then recovers the synaptic vesicle pool and presynaptic membrane area. The kinetics of endocytosis may shape neuromuscular transmission, determining its long-term reliability. Here, using fluorescent dyes, the time course of endocytosis induced by intense activity of the phrenic nerve was studied at the mouse diaphragm neuromuscular junction. It was found that a significant portion of endocytic events occurs after the end of tetanic stimulation. Pitstop 2, clathrin inhibitor, and more profoundly dynole 34-2, dynamin antagonist, suppressed endocytic FM1-43 dye uptake both during and after tetanus. Furthermore, synaptic vesicles formed in the presence of the endocytic blockers released FM-dye during subsequent evoked exocytosis at a lower rate. 25-Hydroxycholesterol (25HC) is an oxysterol, ubiquitously synthetized from excessive cholesterol. In addition, its production greatly increases by activated macrophages. 25HC accelerated FM-dye endocytosis and its sequential evoked exocytosis, and dynole (but not pitstop) prevented 25HC-mediated enhancement of endocytic FM-dye uptake. The positive effects of 25HC were interfered with chelation of cytosolic Ca2+ with a slow Ca2+ buffer EGTA-AM, Ca2+ antagonist TMB8, and sphingomyelin-hydrolyzing enzyme. In contrast to amphiphilic FM1-43 dye capture, 25HC reduced uptake of hydrophilic high molecular weight markers (labeled dextrans and toxin), which utilize bulk endocytosis to enter into nerve terminals. Thus, synaptic vesicle endocytosis had a relatively slow kinetics following the tetanic activity and can be accelerated by 25HC. The positive effect of 25HC on endocytosis engages a dynamin-dependent pathway, interconnected with cytoplasmic Ca2+ and sphingomyelin integrity.

High-frequency epidural electrical stimulation reduces spasticity and facilitates walking recovery in patients with spinal cord injury.

Spinal cord injury (SCI) causes severe motor and sensory deficits, and there are currently no approved treatments for recovery. Nearly 70% of patients with SCI experience pathological muscle cocontraction and spasticity, accompanied by clinical signs such as patellar hyperreflexia and ankle clonus. The integration of epidural electrical stimulation (EES) of the spinal cord with rehabilitation has substantial potential to improve recovery of motor functions; however, abnormal muscle cocontraction and spasticity may limit the benefit of these interventions and hinder the effectiveness of EES in promoting functional movements. High-frequency excitation block introduced in peripheral nerve stimulation could reduce abnormal activity and lead to more physiological activation patterns. Here, we evaluated the application of high-frequency EES (HF-EES) in alleviating undesired muscular cocontraction and spasticity in two patients with motor incomplete SCI implanted with a commercial 32-channel EES paddle commonly used for pain therapy. To design custom HF-EES protocols, we first mapped the muscles targeted by different EES configurations. Our results showed that HF-EES substantially reduced patellar reflex in one participant and eliminated both patellar reflex and ankle clonus in the other participant. By combining HF-EES and low-frequency EES (LF-EES) to enhance functional movements with intensive rehabilitation, we observed notable improvements in lower limb kinematics, muscle strength, and clinical lower limb motor assessments over the trial period. This study suggests that HF-EES could be an important supplementary tool in SCI treatment, emphasizing the importance of personalized rehabilitation approaches and advanced tools to optimize EES treatments and offering hope for individuals with SCI-related motor deficits.

Ex vivo electrophysiological evaluation of peripheral nerve functioning following exposition of adult mice to the organophosphorus pesticide chlormephos.

The organophosphorus pesticide chlormephos was tested for its potential peripheral neurotoxicity by analyzing the diphasic compound action potential (CAP) of sciatic nerves isolated from adult mice chronically exposed to a sub-lethal dose of this pesticide, compared with control age-matched animals being only exposed to the vehicle. No significant modification was detected between chlormephos-exposed and control groups in their nerve responsiveness to stimulus. Furthermore, similar values of CAP kinetic variables were obtained from the two mouse groups. Finally, no abnormality concerning CAP refractory periods and responsiveness to high frequency stimulation (nerve fatigue) was exhibited by chlormephos-treated mice, when compared with control animals. These results complicate the screening for the potential neurotoxicity of organophosphates since they support the contention that the peripheral neuropathy induced by chronical exposition to sub-lethal doses of chlormephos is species dependents does not necessary correlate well with the clinical signs observed at the central nervous system level.

Behavioural and electrophysiological features of WAG/Rij rats with different forms of genetic epilepsy

WAG/Rij rats are widely used as a genetic model of absence epilepsy. Approximately 15–50% rats of the strain are susceptible to audiogenic seizures. WAG/Rij rats demonstrate depressive-like behavior. After preliminary sound provocation an increased level of anxiety was found in audiogenic susceptible WAG/Rij subgroup. Electrophysiological and behavioral studies suggest the involvement of the dopaminergic system in both absence and audiogenic epilepsy. An increased binding density to dopamine receptors was found in the dorsal striatum subregions in audiogenic prone rats compared to non-audiogenic. The study aims were (1) to determine whether behavioral changes in WAG/Rij rats were genetically determined or induced by prior sound stimulation; (2) how regions of the dorsal striatum with different density of dopamine receptors in subpopulations of WAG/Rij rats are involved in the absence epilepsy control. The study was conducted using two rat groups: WAG/Rij-nonAGS (absence epilepsy) and WAG/Rij-AGS (mixed epilepsy). The study was performed using tests: “Elevated plus maze”, “Forced swimming” and “Three chamber sociability test”. High-frequency deep brain stimulation was performed for evaluation of dorsal striatum involvement in the absence seizure control. After experiments animals were tested for the susceptibility to audiogenic seizures. It demonstrated that the increased level of anxiety in WAG/Rij-AGS rats is genetically determined, while depressive-like behavior in WAG/Rij rats is not dependent on a predisposition to audiogenic seizures. Deviations in social behavior were observed in WAG/Rij-AGS rats. Stimulation of the dorsal striatum indicates differences in the control of absence and mixed forms of epilepsy in the

Differential effects of Phosphodiesterase 4A5 on cAMP-dependent forms of long-term potentiation.

cAMP signalling is critical for memory consolidation and certain forms of long-term potentiation (LTP). Phosphodiesterases (PDEs), enzymes that degrade the second messengers cAMP and cGMP, are highly conserved during evolution and represent a unique set of drug targets, given the involvement of these enzymes in several pathophysiological states including brain disorders. The PDE4 family of cAMP-selective PDEs exert regulatory roles in memory and synaptic plasticity, but the specific roles of distinct PDE4 isoforms in these processes are poorly understood. Building on our previous work demonstrating that spatial and contextual memory deficits were caused by expressing selectively the long isoform of the PDE4A subfamily, PDE4A5, in hippocampal excitatory neurons, we now investigate the effects of PDE4A isoforms on different cAMP-dependent forms of LTP. We found that PDE4A5 impairs long-lasting LTP induced by theta burst stimulation (TBS) while sparing long-lasting LTP induced by spaced four-train stimulation (4 × 100Hz). This effect requires the unique N-terminus of PDE4A5 and is specific to this long isoform. Targeted overexpression of PDE4A5 in area CA1 is sufficient to impair TBS-LTP, suggesting that cAMP levels in the postsynaptic neuron are critical for TBS-LTP. Our results shed light on the inherent differences among the PDE4A subfamily isoforms, emphasizing the importance of the long isoforms, which have a unique N-terminal region. Advancing our understanding of the function of specific PDE isoforms will pave the way for developing isoform-selective approaches to treat the cognitive deficits that are debilitating aspects of psychiatric, neurodevelopmental and neurodegenerative disorders. KEY POINTS: Hippocampal overexpression of PDE4A5, but not PDE4A1 or the N-terminus-truncated PDE4A5 (PDE4A5Δ4), selectively impairs long-term potentiation (LTP) induced by theta burst stimulation (TBS-LTP). Expression of PDE4A5 in area CA1 is sufficient to cause deficits in TBS-LTP. Hippocampal overexpression of the PDE4A isoforms PDE4A1 and PDE4A5 does not impair LTP induced by repeated tetanic stimulation at the CA3-CA1 synapses. These results suggest that PDE4A5, through its N-terminus, regulates cAMP pools that are critical for memory consolidation and expression of specific forms of long-lasting synaptic plasticity at CA3-CA1 synapses.

Superior semicircular canal dehiscence isolation by transmastoid two-point canal plugging with preservation of the vestibulo-ocular reflex.

This article describes the surgical treatment of superior semicircular canal dehiscence syndrome (SCDS) by isolating the dehiscence using transmastoid two-point canal plugging while preserving the high-frequency vestibulo-ocular reflex (VOR) of the affected semicircular canal. The superior semicircular canal is opened via atransmastoid approach anterior (as far from the ampulla as possible) and posterior to the dehiscence and then plugged with connective tissue and bone dust. In two clinical exemplary cases, vestibular testing showed that the VOR measured by video head impulse (vHIT) test was preserved (patient1: gain preoperative 0.7, long-term postoperative 0.75; patient2: gain preoperative 0.64, long-term postoperative 0.79; reduction of corrective saccades in each case) with asimultaneous reduction in pathologically increased amplitudes of vestibular evoked myogenic potentials (VEMPs) and asignificant improvement in clinical symptoms with almost complete freedom from symptoms. One possible explanation for preservation of the high-frequency VOR of the superior semicircular canal would be the deformability of the endolymphatic space described at high stimulation frequencies, which can lead to endolymph movements in the area of the ampulla with deflection of the cupula despite blockage of the semicircular canal.

The role of action depolymerization in the changes of inhibitory control during long-term potentiation of excitatory transmission in the rat hippocampus

The plasticity of inhibitory resposes during CA3-CA1 long-term potentiation (LTP) in the rat hippocampal slices was studied by the method of paired-pulse stimulation. Coefficients of inhibition were estimated by the differences between IPSP dependent and independent paired-pulse plasticity. In the experimental group high frequency stimulation of Schaffer collaterals was delivered under jasplakinolide exposure, this inhibitor of actin depolymerization is used also as activator of actin polymerization. It was shown that the feature of LTP development after induction with blockade of actin depolymerization include altered modification profile of inhibition, specifically involved in resposes to paired-pulse stimulation. Initial enhancement of inhibition depended on the value before tetanization. Therefore this factor may be responsible for between-group differences and it was taken into account in the evaluation of specific for posttetanic depolymerization changes. In result, this phase is related to disinhibition disorder during LTP consolidation and maintenance. It may be assumed that coordinating role of actin cytoskeleton is essential for balanced modifications of excitatory and inhibitory transmission during long-term plasticity.

Effects of chronic empathic stress on synaptic efficacy, as well as short-term and long-term plasticity at the Schaffer collateral/commissural- CA1 synapses in the dorsal hippocampus of rats.

Empathy, the ability to comprehend and share others' emotional states, impacts brain functions. This invivo electrophysiological study explored the influence of chronic empathic stress on synaptic efficacy, as well as short-term and long-term plasticity at the Schaffer collateral/Commissural - CA1 synapses in the dorsal hippocampus of rats, in situations of social equality and inequality. Forty-eight male rats were randomized into six groups: control, pseudo-observer, pseudo-demonstrator, observer, demonstrator, and co-demonstrator(Co, Pse-Ob, Pse-De, Ob, De, Co-De) groups. Stress induction(2h/day, 21 days) was performed in situations of equality and inequality. Serum corticosterone levels, slope, amplitude, and area under the curve(AUC) of field excitatory postsynaptic potentials(fEPSPs) were assessed in the hippocampal CA1 area using input-output(I/O) functions, paired-pulse(PP) responses with different interpulse intervals(IPIs), and long-term potentiation (LTP) after high-frequency stimulation (HFS). The fEPSP slope, amplitude, and AUC significantly decreased in all stress groups, especially in the De and Pse-De groups. These parameters were significantly increased in the Co-De and Ob groups compared to theDe group. Notably, the corticosterone levels strongly confirmed the electrophysiological findings. Chronic empathic stress could disrupt synaptic efficacy and plasticity in the CA1 area. Empathic stress, involving the presence of cagemates in situations of social equality and inequality, can modify long-term plasticity and serum corticosterone levels in demonstrators and co-demonstrators. Under empathic stress related to situations of inequality, freely moving observers may influence the demonstrators' stress experience. Therefore, the presence of a conspecific in the social inequality conditions had significant suppressive effects on long-term plasticity, while conversely, under equality conditions, long-term plasticity was favorably improved through social buffering.

Superior semicircular canal dehiscence isolation by transmastoid two-point canal plugging with preservation of the vestibulo-ocular reflex. German version

This article describes the surgical treatment of superior semicircular canal dehiscence syndrome (SCDS) by isolating the dehiscence using transmastoid two-point canal plugging while preserving the high-frequency vestibulo-ocular reflex (VOR) of the affected semicircular canal. The superior semicircular canal is opened via atransmastoid approach anterior (as far from the ampulla as possible) and posterior to the dehiscence and then plugged with connective tissue and bone dust. In two clinical exemplary cases, vestibular testing showed that the VOR measured by video head impulse (vHIT) test was preserved (patient1: gain preoperative 0.7, long-term postoperative 0.75; patient2: gain preoperative 0.64, long-term postoperative 0.79; reduction of corrective saccades in each case) with asimultaneous reduction in pathologically increased amplitudes of vestibular evoked myogenic potentials (VEMPs) and asignificant improvement in clinical symptoms with almost complete freedom from symptoms. One possible explanation for preservation of the high-frequency VOR of the superior semicircular canal would be the deformability of the endolymphatic space described at high stimulation frequencies, which can lead to endolymph movements in the area of the ampulla with deflection of the cupula despite blockage of the semicircular canal.

Stability of sputtered iridium oxide neural microelectrodes under kilohertz frequency pulsed stimulation

Objective. Kilohertz (kHz) frequency stimulation has gained attention as a neuromodulation therapy in spinal cord and in peripheral nerve block applications, mainly for treating chronic pain. Yet, few studies have investigated the effects of high-frequency stimulation on the performance of the electrode materials. In this work, we assess the electrochemical characteristics and stability of sputtered iridium oxide film (SIROF) microelectrodes under kHz frequency pulsed electrical stimulation.Approach. SIROF microelectrodes were subjected to 1.5-10 kHz pulsing at charge densities of 250-1000μC cm-2(25-100 nC phase-1), under monopolar and bipolar configurations, in buffered saline solution. The electrochemical behavior as well as the long-term stability of the pulsed electrodes was evaluated by voltage transient, cyclic voltammetry, and electrochemical impedance spectroscopy measurements.Main results. Electrode polarization was more pronounced at higher stimulation frequencies in both monopolar and bipolar configurations. Bipolar stimulation resulted in an overall higher level of polarization than monopolar stimulation with the same parameters. In all tested pulsing conditions, except one, the maximum cathodal and anodal potential excursions stayed within the water window of iridium oxide (-0.6-0.8 V vs Ag|AgCl). Additionally, these SIROF microelectrodes showed little or no changes in the electrochemical performance under continuous current pulsing at frequencies up to 10 kHz for more than 109pulses.Significance. Our results suggest that 10 000μm2SIROF microelectrodes can deliver high-frequency neural stimulation up to 10 kHz in buffered saline at charge densities between 250 and 1000μC cm-2(25-100 nC phase-1).

Deep brain stimulation of Hippocampus in Treatment-resistant Schizophrenia (DBS-HITS): protocol for a crossover randomized controlled trial

BackgroundVentral hippocampus (vHipp) in schizophrenia is in a state of hyperactivity and hypermetabolism, where the glutamate/gamma-aminobutyric acid (GABA) imbalance leads to downstream dopamine hyperactivity in the midbrain-limbic system. High-frequency deep brain stimulation (DBS) can disrupt the abnormal synchronization of functional circuits and modulate local brain networks.MethodsThe DBS-HITS study is a crossover randomized controlled trial. DBS will be applied to bilateral vHipp in six patients. They will be randomly assigned to receive 3-month high-frequency active stimulation and then 3-month sham stimulation, or vice versa. After 6-month crossover trial phase, all participants will undergo personalized active stimulation. Researchers will assess clinical symptoms and neurocognition, collect EEG and PET-CT data during planned follow-ups. Adverse event will be researcher-assessed or participant self-reported throughout the trial.DiscussionTo our knowledge, the DBS-HITS study is the first hippocampal DBS randomized controlled trial for schizophrenia. The goal of the DBS-HITS study is to assess the efficacy and safety of hippocampal DBS in treatment-resistant schizophrenia (TRS) and to investigate its impact on hippocampal activity and glutamate/GABA metabolism. The study is expected to deepen our understanding of the effects and side-effects of neuromodulation in TRS to facilitate individualized DBS treatment.Trial registrationNCT05694000 in ClinicalTrial.gov, registered on January 23, 2023.

Repetitive Transcranial Magnetic Stimulation: Is it an Effective Treatment for Cancer Pain?

Cancer is a major public health issue, with an estimated 20 million new cases and 9.7 million cancer-related deaths worldwide in 2022. Approximately 44.5% of patients experience cancer pain, significantly impacting their quality of life and causing physical and psychological burdens. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive neuromodulation technique, shows potential in managing cancer pain. This review summarizes current research on rTMS for cancer pain, focusing on pain directly caused by tumors, pain from cancer treatments, postoperative pain, and cancer-related symptoms. Additionally, rTMS shows promise in improving cancer-related fatigue, anxiety, depression, and cognitive dysfunction, which can indirectly reduce cancer pain. The analgesic mechanisms of rTMS include inhibiting nociceptive signal transmission in the spinal cord, modulating hemodynamic changes in brain regions, and promoting endogenous opioid release. High-frequency stimulation of the primary motor cortex (M1) has shown significant analgesic effects, improving patients' emotional and cognitive functions and overall quality of life. rTMS has a favorable safety profile, with most studies reporting no severe adverse events. In conclusion, rTMS holds substantial potential for cancer pain management, offering a non-invasive and multifaceted therapeutic approach. Continued research and clinical application are expected to establish rTMS as an essential component of comprehensive cancer pain treatment strategies, significantly enhancing the overall well-being of patients with cancer.

Opposite effects of low and high frequency deep brain stimulation of lateral hypothalamus on arousal and temperature in a monkey pilot study

Deep brain stimulation is a well-established treatment for improving motor symptoms in Parkinson’s disease. However, persistent non-motor symptoms, such as excessive daytime sleepiness, remain a significant challenge and necessitate further investigation. In this study, we conducted repeated measurements of daytime sleepiness using a modified multiple sleep latency test in a healthy monkey (macaca fascicularis), which was later rendered parkinsonian through MPTP administration. Deep brain stimulation targeting the lateral hypothalamic area revealed frequency-dependent modulation of both sleepiness level and core body temperature. High-frequency stimulation (80 Hz) increased sleepiness in the healthy state, while low-frequency stimulation (20 Hz) promoted wakefulness in the parkinsonian state. These findings suggest a promising therapeutic approach for addressing sleep/wake disturbances, not only in Parkinson’s disease but also in other severe sleep disorders.

Does Post-Tetanic Transcranial Stimulation Augment the Wave Amplitudes of Spinal Cord Evoked Potential (Tc-SCEP)?

Prospective within-subjects study. Although motor-evoked potential (MEP) amplitude can reportedly be increased by tetanic stimulation of the peripheral nerves before transcranial electrical stimulation (TES), no reports have described on whether tetanic transcranial stimulation augments the wave amplitudes of spinal cord-evoked potentials (Tc-SCEP). The primary purpose of this study was to investigate whether tetanic stimulation induces waveform amplification of Tc-SCEP. The secondary purpose was to elucidate the mechanism of the amplification effect of tetanic stimulation. We recruited 20 patients who underwent cervical or thoracic spine surgeries. We compared the compound muscle active potentials (CMAPs) of Tc-MEP and Tc-SCEP before and after tetanic stimulation of the median or tibial nerve. Although the CMAP wave amplitudes of the abductor pollicis brevis (APB) and abductor hallucis (AH) showed significant enlargement on Tc-MEP following tetanic stimulation of the median and tibial nerves, an augmentation effect regarding Tc-SCEP (203μV [without tetanic stimulation], 212μV [tetanic stimulation of the median nerve], and 208μV [tetanic stimulation of tibial nerve]) could not be demonstrated. Although MEP amplitudes can be enlarged by tetanic stimulation of the peripheral nerves, the amplification mechanism may not involve the lateral corticospinal tract from the brain stem to the anterior horn.