Diabetes Technol Ther. 2024 Oct 24. doi: 10.1089/dia.2024.0175. Online ahead of print.

ABSTRACT

Objective: Autonomic neuropathy is associated with dysglycemia that is difficult to control. We investigated if transcutaneous vagus nerve stimulation (tVNS) could improve glycemic levels. Methods: We randomized 145 individuals with type 1 diabetes (T1D) (n = 70) or type 2 diabetes (T2D) (n = 75) and diabetic autonomic neuropathy (DAN) to self-administered treatment with active cervical tVNS (n = 68) or sham (n = 77) for 1 week (4 daily stimulations) and 8 weeks (2 daily stimulations), separated by a wash-out period of at least 2 weeks. Continuous glucose monitoring (CGM) indices were measured for 104 participants starting 5 days prior to intervention periods, during the 1-week period, and at end of the 8-week period. Primary outcomes were between-group differences in changes in coefficient of variation (CV) and in time in range (TIR 3.9-10 mmol/L). Secondary outcomes were other metrics of CGM and HbA1c. Results: For the 1-week period, median [interquartile range] changes of CV from baseline to follow-up were -1.1 [-4.3;2.0] % in active and -1.5 [-4.4;2.5] % in sham, with no significance between groups (P = 0.54). For TIR, the corresponding changes were 2.4 [-2.1;7.4] % in active and 5.1 [-2.6;8.8] in sham group (P = 0.84). For the 8-week treatment period, changes in CV and TIR between groups were also nonsignificant. However, in the subgroup analysis, persons with T1D receiving active tVNS for 8 weeks had a significant reduction in CV compared with the T1D group receiving sham stimulation (estimated treatment effect: -11.6 [95% confidence interval -20.2;-2.0] %, P = 0.009). None of the changes in secondary outcomes between treatment groups were significantly different. Conclusions: Overall, no significant changes were observed in CGM metrics between treatment arms, while individuals with T1D and DAN decreased their CV after 8 weeks of tVNS treatment.

PMID:39446990 | DOI:10.1089/dia.2024.0175

Front Physiol. 2024 Oct 9;15:1452490. doi: 10.3389/fphys.2024.1452490. eCollection 2024.

ABSTRACT

OBJECTIVE: This systematic review aims to comprehensively analyze the efficacy and underlying mechanisms of vagus nerve stimulation (VNS) in enhancing cognitive functions and its therapeutic potential for various cognitive impairments. The review focuses on the impact of VNS on emotional processing, executive functions, learning, memory, and its clinical applications in conditions such as epilepsy, depression, Alzheimer’s disease, and other neurological disorders.

METHODS: A systematic search of electronic databases (PubMed, Scopus, Web of Science) was conducted using the keywords “vagus nerve stimulation,” “cognitive enhancement,” “emotional processing,” “executive function,” “learning and memory,” “epilepsy,” “depression,” “Alzheimer’s disease,” “neurological disorders,” “attention-deficit/hyperactivity disorder,” “sleep disorders,” and “long COVID.” The inclusion criteria encompassed controlled trials, longitudinal studies, and meta-analyses published in English between 2000 and July 2024.

RESULTS: A comprehensive review of 100 articles highlighted the cognitive effects of Vagus Nerve Stimulation (VNS). Studies show that VNS, especially through transcutaneous auricular VNS (taVNS), enhances emotional recognition, particularly for facial expressions, and improves selective attention under high cognitive demands. Additionally, VNS enhances learning and memory, including associative memory and spatial working memory tasks. In clinical applications, VNS exhibits promising benefits for improving cognitive functions in treatment-resistant epilepsy, depression, and Alzheimer’s disease.

CONCLUSION: VNS represents a promising therapeutic approach for enhancing cognitive function across diverse patient populations. The reviewed evidence highlights its efficacy in modulating cognitive domains in healthy individuals and improving cognition in neurological conditions. However, the comparative effectiveness of different VNS modalities and the differential effects of online versus offline VNS on cognitive psychology require further investigation. Future research should focus on optimizing VNS protocols and elucidating specific cognitive domains that benefit most from VNS interventions. This ongoing exploration is essential for maximizing the therapeutic potential of VNS in clinical practice.

PMID:39444752 | PMC:PMC11496278 | DOI:10.3389/fphys.2024.1452490

ACS Pharmacol Transl Sci. 2024 Sep 9;7(10):3071-3085. doi: 10.1021/acsptsci.4c00270. eCollection 2024 Oct 11.

ABSTRACT

It is widely said that a healthy intestinal environment plays an essential role in better mental condition. One known dietary nutrient that maintains the intestinal environment is dietary fiber. A recent study showed that maintaining the intestinal environment with dietary fiber alleviated symptoms of psychiatric disorders in animals. However, such effects have only been reported with soluble fiber, which is highly fermentable and promotes short-chain fatty acid (SCFA) production, and not with insoluble fiber. Therefore, we aimed to verify whether insoluble fiber, such as cellulose, can alter emotion via changes in the gut. We divided mice into two groups and fed either a standard diet (SD, which contains both insoluble and soluble dietary fibers) or a cellulose-rich diet (CRD, which contains cellulose alone as the dietary fibers). We found that CRD-fed mice display increased anxiety-like behavior. CRD-fed animals also showed decreased intestinal SCFA levels along with increased intestinal permeability, dysmotility, and hypersensitivity. This behavioral and physiological effect of CRD has been completely abolished in vagotomized mice, indicating the direct link between intestinal environment exacerbation to the emotion through the gut-brain axis. Additionally, we found that amygdalar dopamine signaling has been modified in CRD-fed animals, and the opioid antagonist abolished this dopaminergic modification as well as CRD-induced anxiety. Altogether, our findings indicate that consumption of cellulose alone as the dietary fiber may evoke intestinal abnormalities, which fire the vagus nerve, then the opioidergic system, and amygdalar dopamine upregulation, resulting in the enhancement of anxiety.

PMID:39416961 | PMC:PMC11475280 | DOI:10.1021/acsptsci.4c00270

Front Psychiatry. 2024 Oct 2;15:1376140. doi: 10.3389/fpsyt.2024.1376140. eCollection 2024.

ABSTRACT

Anxiety is an increasingly prevalent mental disorder, causing widespread hardship and interfering with society’s economic progression. Standard treatments include various talk therapies with poor prognoses or drug interventions with complex side effects, both introducing unnecessary burdens to patients. To remedy this, non-invasive ultrasound stimulation to the vagus nerve is a novel, low-cost treatment that is showing promise. Although vagus nerve stimulation is already approved for epilepsy and other conditions, it requires regular maintenance. In contrast, studies using non-invasive ultrasound stimulation have shown preliminary positive results in affecting vagal activity with minimal drawbacks. This review covers a variety of studies investigating the effects of ultrasound stimulation on the vagus nerve. With rising levels of anxiety with each generation, there is a pressing need for more innovative and diverse treatments with fewer costs and more benefits.

PMID:39415887 | PMC:PMC11480057 | DOI:10.3389/fpsyt.2024.1376140

Sci Rep. 2024 Oct 17;14(1):24391. doi: 10.1038/s41598-024-72179-4.

ABSTRACT

The efficacy of transcutaneous auricular vagus nerve stimulation (taVNS) as a non-invasive method to modulate physiological markers of noradrenergic activity of the Locus Coeruleus (LC), such as pupil dilation, is increasingly more discussed. However, taVNS studies show high heterogeneity of stimulation effects. Therefore, a taVNS setup was established here to test different frequencies (10 Hz and 25 Hz) and intensities (3 mA and 5 mA) during phasic stimulation (3 s) with time-synchronous recording of pupil dilation in younger adults. Specifically, phasic real taVNS and higher intensity led to increased pupil dilation, which is consistent with phasic invasive VNS studies in animals. The results also suggest that the influence of intensity on pupil dilation may be stronger than that of frequency. However, there was an attenuation of taVNS-induced pupil dilation when differences in perception of sensations were considered. Specifically, pupil dilation during phasic stimulation increased with perceived stimulation intensity. The extent to which the effect of taVNS induces pupil dilation and the involvement of sensory perception in the stimulation process are discussed here and require more extensive research. Additionally, it is crucial to strive for comparable stimulation sensations during systematic parameter testing in order to investigate possible effects of phasic taVNS on pupil dilation in more detail.

PMID:39420188 | PMC:PMC11487125 | DOI:10.1038/s41598-024-72179-4

Neurol Res Pract. 2024 Oct 17;6(1):47. doi: 10.1186/s42466-024-00346-z.

ABSTRACT

BACKGROUND/ AIM: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting upper and lower motor neurons, causing progressive atrophy of muscles, hypertonia, and paralysis. This study aimed to evaluate the current evidence and effectiveness of ultrasound in investigating nerve cross-sectional area (CSA) of peripheral nerves, vagus and cervical roots in those with ALS compared with healthy controls and to pool the CSA measurements.

METHODS: A systematic search was conducted on Cochrane, Clarivate Web of Science, PubMed, Scopus, and Embase for the mesh terms nerve, ultrasonography, and amyotrophic lateral sclerosis. A quality assessment was performed using the New-Ottawa scale. In addition, a double-arm meta-analysis using Review Manager 5 software version 5.4 was performed.

RESULTS: From the seventeen studies included in this review, the overall mean difference showed that individuals with ALS had a significantly smaller CSA in comparison to healthy controls for median, ulnar, C6 root, and phrenic nerves. However, no significant difference in the CSA was found in radial, vagal, sural, and tibial nerves.

DISCUSSION: This study confirmed results of some of the included studies regards the anatomic sites, where nerve atrophy in ALS could be detected to potentially support the diagnosis of ALS. However, we recommend further large, prospective studies to assess the diagnostic value of these anatomical sites for the diagnosis of ALS.

CONCLUSIONS: Our findings confirmed specific anatomic sites to differentiate ALS patients from healthy controls through ultrasound. However, these findings cannot be used to confirm the ALS diagnosis, but rather assist in differentiating it from other diagnoses.

TRIAL REGISTRATION: Retrospectively registered on July 30th 2024 in PROSPERO (PROSPERO (york.ac.uk)) with ID574702.

PMID:39415277 | PMC:PMC11484457 | DOI:10.1186/s42466-024-00346-z

Epilepsia. 2024 Oct 16. doi: 10.1111/epi.18153. Online ahead of print.

ABSTRACT

Vagus nerve stimulation (VNS) is an established therapy for drug-resistant epilepsy. However, there is a lack of reliable predictors of VNS response in clinical use. The identification of factors predictive of VNS response is important for patient selection and stratification as well as tailored stimulation programming. We conducted a narrative review of the existing literature on prognostic markers for VNS response using clinical, demographic, biochemical, and modality-specific information such as from electroencephalography (EEG), magnetoencephalography, and magnetic resonance imaging (MRI). No individual marker demonstrated sufficient predictive power for individual patients, although several have been suggested, with some promising initial findings. Combining markers from underresearched modalities such as T1-weighted MRI morphometrics and EEG may provide better strategies for treatment optimization.

PMID:39412361 | DOI:10.1111/epi.18153

Dev Cell. 2024 Oct 15:S1534-5807(24)00542-2. doi: 10.1016/j.devcel.2024.09.016. Online ahead of print.

ABSTRACT

Vagal nerve stimulation has emerged as a promising modality for treating a wide range of chronic conditions, including metabolic disorders. However, the cellular and molecular pathways driving these clinical benefits remain largely obscure. Here, we demonstrate that fibroblast growth factor 3 (Fgf3) mRNA is upregulated in the mouse vagal ganglia under acute metabolic stress. Systemic and vagal sensory overexpression of Fgf3 enhanced glucose-stimulated insulin secretion (GSIS), improved glucose excursion, and increased energy expenditure and physical activity. Fgf3-elicited insulinotropic and glucose-lowering responses were recapitulated when overexpression of Fgf3 was restricted to the pancreas-projecting vagal sensory neurons. Genetic ablation of Fgf3 in pancreatic vagal afferents exacerbated high-fat diet-induced glucose intolerance and blunted GSIS. Finally, electrostimulation of the vagal afferents enhanced GSIS and glucose clearance independently of efferent outputs. Collectively, we demonstrate a direct role for the vagal afferent signaling in GSIS and identify Fgf3 as a vagal sensory-derived metabolic factor that controls pancreatic β-cell activity.

PMID:39413782 | DOI:10.1016/j.devcel.2024.09.016

Res Dev Disabil. 2024 Oct 13;154:104855. doi: 10.1016/j.ridd.2024.104855. Online ahead of print.

ABSTRACT

BACKGROUND: Prader-Willi Syndrome (PWS) is a genetic neurodevelopmental disorder marked by disruptions in circadian rhythms and autonomic nervous system (ANS) activity, hyperphagia, and episodes of emotional outbursts. Previous trials suggest that both invasive and non-invasive vagus nerve stimulation (VNS) can reduce emotional outbursts in PWS, potentially through its effects on vagal activity.

AIM: This case series investigated the effects of transcutaneous auricular VNS (taVNS) on cardiac markers of circadian vagal activity, specifically heart rate variability (HRV) and heart rate (HR), and their potential links to improvements in emotional outbursts.

METHODS: Five individuals with PWS (mean age: 26.9 years; 3 males, 2 females) received four hours of daily taVNS for 12 months, followed by one month of two-hour daily sessions. Outcome measures included daily recording of emotional outbursts and every three months 24-h HRV and HR recordings. Mixed cosinor models were applied to analyze changes in circadian rhythms of HRV and HR. A linear mixed model was used to assess the predictive value of cardiac vagal activity on emotional outbursts.

RESULTS: Circadian amplitudes of HRV and HR were significantly higher at the end of the treatment compared to baseline (all p’s < .01). There was a significant increase in the rhythm-adjusted mean of HRV (p < .01), while the rhythm-adjusted HR mean significantly decreased, both indicating increased cardiac vagal activity. Higher rhythm-adjusted mean HRV predicted a lower number of emotional outbursts.

CONCLUSION: The results suggest that taVNS may be effective by targeting ANS activity in individuals with PWS, contributing to improvements in behavioral regulation.

PMID:39405838 | DOI:10.1016/j.ridd.2024.104855

J Neuropsychiatry Clin Neurosci. 2024 Fall;36(4):278-282. doi: 10.1176/appi.neuropsych.20240118.

NO ABSTRACT

PMID:39402936 | DOI:10.1176/appi.neuropsych.20240118