Magnetically coupled percutaneous connector for chronic electrical peripheral nerve stimulation and recording in awake rats

IEEE Trans Biomed Eng. 2024 Aug 2;PP. doi: 10.1109/TBME.2024.3436649. Online ahead of print.

ABSTRACT

A fast-growing field of neuroscience and medicine is the treatment of disease via electrical stimulation of the peripheral nervous system. Peripheral nerve stimulation delivers stimulation to nerves of the periphery where the target nerve can and is often located deep within the abdomen. Long-term preclinical animal models that demonstrate the safety and/or efficacy of electrical stimulation have predominantly used a skull mount to connect to neural interfaces. When targeting nerves of the extremities and abdomen, this mount location is less favourable due to its distance to the implant causing complications in surgery and to the longevity of the device in vivo.

OBJECTIVE: Here we aimed to develop and validate a chronic magnetic percutaneous connector designed for placement on the dorsal-lumbar aspect of the spine of awake, freely moving rats.

METHODS: A pedestal and external connector was developed, bench tested to assess for continuity, durability and disconnection forces, and validated in awake rats chronically implanted with an abdominal vagus nerve electrode array. The implanted pedestal and external connector were designed with custom PCBs, spring-loaded pins, magnets and biocompatible 3D printed housing.

RESULTS: The magnetic coupling mechanism allowed disconnection with minimal force, was highly reliable in maintaining electrical connection in awake rats and allowed recording of electrically evoked compound action potentials after chronic implantation.

CONCLUSION: In conclusion, this percutaneous connector is a useful research tool for peripheral nerve stimulation studies.

SIGNIFICANCE: The connector described will allow investigation into the safety and efficacy of emerging neuromodulation therapies for the treatment of disease.

PMID:39093683 | DOI:10.1109/TBME.2024.3436649

Transcutaneous auricular vagus nerve stimulation can modulate fronto-parietal brain networks

Front Neurosci. 2024 Jul 18;18:1368754. doi: 10.3389/fnins.2024.1368754. eCollection 2024.

ABSTRACT

OBJECTIVE: Recent studies have shown that transcutaneous vagal nerve stimulation (tVNS) holds promise as a treatment for neurological or psychiatric disease through the ability to modulate neural activity in some brain regions without an invasive procedure. The objective of this study was to identify the neural correlates underlying the effects of tVNS.

METHODS: Twenty right-handed healthy subjects with normal hearing participated in this study. An auricle-applied tVNS device (Soricle, Neurive Co., Ltd., Gyeongsangnam-do, Republic of Korea) was used to administer tVNS stimulation. A session consisted of 14 blocks, including 7 blocks of tVNS stimulation or sham stimulation and 7 blocks of rest, and lasted approximately 7 min (1 block = 30 s). Functional magnetic resonance imaging (fMRI) was performed during the stimulation.

RESULTS: No activated regions were observed in the fMRI scans following both sham stimulation and tVNS after the first session. After the second session, tVNS activated two clusters of brain regions in the right frontal gyrus. A comparison of the activated regions after the second session of each stimulation revealed that the fMRI following tVNS exhibited four surviving clusters. Additionally, four clusters were activated in the overall stimulated area during both the first and second sessions. When comparing the fMRI results after each type of stimulation, the fMRI following tVNS showed four surviving clusters compared to the fMRI after sham stimulation.

CONCLUSION: tVNS could stimulate some brain regions, including the fronto-parietal network. Stimulating these regions for treating neurological or psychiatric disease might require applying tVNS for at least 3.5 min.

PMID:39091347 | PMC:PMC11292796 | DOI:10.3389/fnins.2024.1368754

Non-invasive brain stimulation for post-COVID-19 conditions: a systematic review

Am J Med. 2024 Jul 30:S0002-9343(24)00468-6. doi: 10.1016/j.amjmed.2024.07.007. Online ahead of print.

ABSTRACT

Alongside the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic, the number of patients with persistent symptoms following acute infection with SARS-CoV-2 is of concern. It is estimated that at least 65 million people worldwide meet criteria for what the World Health Organization (WHO) defines as “post-COVID-19 condition” – a multisystem disease comprising a wide range of symptoms. Effective treatments are lacking. In the present review, we aim to summarize the current evidence for the effectiveness of non-invasive or minimally invasive brain stimulation techniques in reducing symptoms of post-COVID-19. A total of nineteen studies were identified, one using transcutaneous vagus nerve stimulation (tVNS), another using transorbital alternating current stimulation (toACS), six studies on transcranial magnetic stimulation (TMS) and eleven studies on transcranial direct current stimulation (tDCS) for the treatment of post-COVID-19 symptoms. Existing studies report first promising results, illustrating improvement in clinical outcome parameters. Yet, the mechanistic understanding of post-COVID-19 and how brain stimulation techniques may be benefitial are limited. Directions for future research in the field are discussed.

PMID:39089436 | DOI:10.1016/j.amjmed.2024.07.007

Asymptomatic Purely Intracranial Vagal Schwannoma: Clinical Case Report and Literature Review

Turk Neurosurg. 2024 Mar 13. doi: 10.5137/1019-5149.JTN.46250-24.2. Online ahead of print.

ABSTRACT

Background：Vagus nerve schwannoma is an infrequently occurring schwannoma, in which a distinct subtype exists wherein the tumor is confined to the cerebellomedullary cistern without invading the jugular foramen. This unique tumor is called purely intracranial vagal schwannoma. Clinical Presentation：In this report, we present a case of purely intracranial vagal schwannoma in its asymptomatic early phase, incidentally discovered during surgery performed on a patient with hemifacial spasm. Because of the small size of the tumor, we definitively recognized that it originated from the second rootlet on the caudal side. The tumor was totally resected uneventfully and a favorable prognosis was achieved. Furthermore, we conducted a comprehensive literature review to summarize the classification, origin, and surgical complications associated with this rare tumor type. Conclusions：To the best of our knowledge, this is the first case report of an asymptomatic purely intracranial vagal schwannoma. Based on our literature review, we propose that: 1) the origin of tumor is related to the time of onset of symptoms, 2) nearly all purely intracranial vagal schwannomas can be entirely resected and favorable prognosis can be achieved, and 3) surgeons should be aware of potential cardiovascular complications during surgical procedures.

PMID:39087301 | DOI:10.5137/1019-5149.JTN.46250-24.2

H-coil repetitive transcranial magnetic stimulation does not improve executive function in patients with chronic peripheral neuropathic pain: a randomized sham-controlled crossover study

Front Psychiatry. 2024 Jul 17;15:1401008. doi: 10.3389/fpsyt.2024.1401008. eCollection 2024.

ABSTRACT

INTRODUCTION: Deep rTMS is an increasingly popular noninvasive brain stimulation technique which has shown promise for treating cognitive impairments. However, few studies have investigated the cognitive effects it could exert in patients with chronic peripheral neuropathic pain. Therefore, we aimed to assess the effects of deep rTMS on executive functioning in patients with peripheral neuropathic pain, in a randomized, double-blind crossover trial.

METHODS: In total, 17 patients were randomly assigned to receive both active and sham deep H-coil rTMS targeting the primary motor cortex. Each treatment period consisted of five daily rTMS sessions. Selected tests of executive functioning from the CANTAB test battery (paired associates learning, stop signal task, spatial working memory and multitasking test) were performed at baseline, and at 1 week and 3 weeks follow-ups.

RESULTS: We did not find any significant interactions between time and treatment for the measures of executive functioning for the patient group, or for patients with reduced cognition compared to normative means.

CONCLUSION: High-frequency deep H-coil rTMS targeting the hand area of the primary motor cortex and delivered over 5 consecutive days did not improve executive functioning in patients with chronic peripheral neuropathic pain.

CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/, identifier NCT05488808.

PMID:39086728 | PMC:PMC11288963 | DOI:10.3389/fpsyt.2024.1401008

The combined effect of transcutaneous electrical nerve stimulation and transcutaneous auricular vagus nerve stimulation on pressure and heat pain thresholds in pain-free subjects: a randomized cross-over trial

Trials. 2024 Jul 31;25(1):516. doi: 10.1186/s13063-024-08352-x.

ABSTRACT

BACKGROUND: Transcutaneous electrical nerve stimulation (TENS) is a non-invasive modality that utilizes electrical currents to modulate pain in populations with acute and chronic pain. TENS has been demonstrated to produce hypoalgesic effects in postoperative pain, fibromyalgia, knee osteoarthritis, and healthy subjects. Transcutaneous auricular vagus nerve stimulation (TaVNS) is a non-invasive modality that modulates the vagus nerve by stimulating its auricular branches. The effects of the combination of TENS and TaVNS on producing an analgesic response have not been studied. Considering that TENS and TaVNS both stimulate similar analgesic pathways but through different means of activation, we can hypothesize that a combination of both methods can produce a more pronounced analgesic response. Therefore, the objective of this study is to assess the hypoalgesic effect of a combination of TENS and TaVNS in pain-free subjects.

METHODS/DESIGN: The study will be a simple crossover design conducted at the University of Hartford. Subjects will be recruited from the University of Hartford population via oral communication, digital flyers, and posters on campus. Thirty participants will undergo two sessions in a crossover manner with one week in between. During one session, the participants will receive TENS with active TaVNS and the other session will be a placebo procedure (TENS with placebo TaVNS). The order of these sessions will be randomized. Importantly, the pressure pain threshold (PPT) and heat pain threshold (HPT) assessors will be blinded to the treatment category. For active TaVNS, a frequency of 25 Hz will be applied with a pulse duration of 200 µs. For placebo TaVNS, the intensity will be increased to a sensory level and then decreased to 0 mA. High-frequency TENS of 100 Hz will be applied in both sessions, with a pulse duration of 200 µsec, asymmetrical biphasic square waveform, and intensity of maximal tolerance without pain. TENS and TaVNS will be turned on for 30 min after a baseline measurement of outcomes. TENS and TaVNS will then be turned off, but the electrodes will remain on until completion of post-treatment assessment. Pressure pain threshold, heat pain threshold, blood pressure, oxygen saturation, and heart rate will be tested 4 times: Once pre-intervention, once during intervention, once immediately after the intervention, and once 15 min post-intervention. Statistical analysis of the data obtained will consider a significance level of p < 0.05.

DISCUSSION: This study will provide evidence concerning the combined effects of TENS and TaVNS on pain threshold in pain-free participants. Based on the outcomes, a greater understanding of how TENS and TaVNS, when used in conjunction, can modulate pain pathways.

TRIAL REGISTRATION: ClinicalTrials.gov NCT06361381. Registered on 09 April 2024.

PMID:39085951 | PMC:PMC11290061 | DOI:10.1186/s13063-024-08352-x

Diagnostic accuracy and confounders of vagus nerve ultrasound in amyotrophic lateral sclerosis-a single-center case series and pooled individual patient data meta-analysis

J Neurol. 2024 Jul 31. doi: 10.1007/s00415-024-12601-z. Online ahead of print.

ABSTRACT

BACKGROUND: Several single-center studies proposed utility of vagus nerve (VN) ultrasound for detecting disease severity, autonomic dysfunction, and bulbar phenotype in amyotrophic lateral sclerosis (ALS). However, the resulting body of literature shows opposing results, leaving considerable uncertainty on the clinical benefits of VN ultrasound in ALS.

METHODS: Relevant studies were identified up to 04/2024 and individual patient data (IPD) obtained from the respective authors were pooled with a so far unpublished cohort (from Munich). An IPD meta-analysis of 109 patients with probable or definite ALS (El Escorial criteria) and available VN cross-sectional area (CSA) was performed, with age, sex, ALS Functional Rating Scale-revised (ALSFRS-R), disease duration, and bulbar phenotype as independent variables.

RESULTS: Mean age was 65 years (± 12) and 47% of patients (± 12) had bulbar ALS. Mean ALSFRS-R was 38 (± 7), and mean duration was 18 months (± 18). VN atrophy was highly prevalent [left: 67% (± 5), mean CSA 1.6mm2 (± 0.6); right: 78% (± 21), mean CSA 1.8 mm2 (± 0.7)]. VN CSA correlated with disease duration (mean slope: left – 0.01; right – 0.01), but not with ALSFRS-R (mean slope: left 0.004; mean slope: right – 0.002). Test accuracy for phenotyping bulbar vs. non-bulbar ALS was poor (summary receiver operating characteristic area under the curve: left 0.496; right 0.572).

CONCLUSION: VN atrophy in ALS is highly prevalent and correlates with disease duration, but not with ALSFRS-R. VN CSA is insufficient to differentiate bulbar from non-bulbar ALS phenotypes. Further studies are warranted to analyze the link between VN atrophy, autonomic impairment, and survival in ALS.

PMID:39085618 | DOI:10.1007/s00415-024-12601-z

Pharmacologic, Surgical, and Device-Based Cardiac Neuromodulation

Card Electrophysiol Clin. 2024 Sep;16(3):315-324. doi: 10.1016/j.ccep.2023.12.002. Epub 2024 Jan 9.

ABSTRACT

The cardiac autonomic nervous system plays a key role in maintaining normal cardiac physiology, and once disrupted, it worsens the cardiac disease states. Neuromodulation therapies have been emerging as new treatment options, and various techniques have been introduced to mitigate autonomic nervous imbalances to help cardiac patients with their disease conditions and symptoms. In this review article, we discuss various neuromodulation techniques used in clinical settings to treat cardiac diseases.

PMID:39084724 | DOI:10.1016/j.ccep.2023.12.002