Stimulation Period Research Articles

Transcranial alternating current stimulation modulates cortical processing of somatosensory information in a frequency- and time-specific manner

Neural oscillations can be modulated by non-invasive brain stimulation techniques, including transcranial alternating current stimulation (tACS). However, direct evidence of tACS effects at the cortical level in humans is still limited. In a tACS-electroencephalography co-registration setup, we investigated the ability of tACS to modulate cortical somatosensory information processing as assessed by somatosensory-evoked potentials (SEPs). To better elucidate the neural substrates of possible tACS effects we also recorded peripheral and spinal SEPs components, high-frequency oscillations (HFOs), and long-latency reflexes (LLRs). Finally, we studied whether changes were limited to the stimulation period or persisted thereafter. SEPs, HFOs, and LLRs were recorded during tACS applied at individual mu and beta frequencies and at the theta frequency over the primary somatosensory cortex (S1). Sham-tACS was used as a control condition. In a separate experiment, we assessed the time course of mu-tACS effects by recording SEPs before (T0), during (T1), and 1 min (T2) and 10 min (T3) after stimulation. Mu-tACS increased the amplitude of the N20 component of SEPs compared to both sham and theta-tACS. No differences were found between sham, beta-, and theta-tACS conditions. Also, peripheral and spinal SEPs, P25, HFOs, and LLRs did not change during tACS. Finally, mu-tACS-induced modulation of N20 amplitude specifically occurred during stimulation (T1) and vanished afterwards (i.e., at T2 and T3). Our findings suggest that TACS applied at the individual mu frequency is able to modulate early somatosensory information processing at the S1 level and the effect is limited to the stimulation period.

Ovarian response to follicle-stimulating hormone in women with polycystic ovary syndrome is diminished compared to ovulatory controls.

The mechanisms underlying ovarian dysfunction in polycystic ovary syndrome (PCOS) have not been definitively established. Our objective was to perform a detailed examination of ovarian responses to recombinant follicle-stimulating hormone (rFSH) in women with PCOS and controls. This prospective, crossover, dose-response study included three rFSH stimulation periods. Each stimulation period involved three consecutive, daily, subcutaneous injections of rFSH administered at a single dose. Low, medium and high rFSH doses were weight-adjusted, corresponding to 0.5, 1.1 and 2.2 IU/kg/d, respectively. Stimulation periods occurred in randomized order and were separated by 8-week washouts. Thirty participants (8 PCOS and 22 controls) were studied. PCOS was defined by oligomenorrhea and clinical or biochemical androgen excess, excluding other aetiologies of ovulatory dysfunction. Blood samples were obtained for hormone measurements before and 24 h after each rFSH injection. Participants with PCOS had significantly greater body mass index, antral follicle count and circulating testosterone, anti-mullerian hormone (AMH)and luteinizing hormone concentrations compared with controls participants. Baseline estradiol (E2) concentrations were similar in both groups. At the lowest dose of rFSH, PCOS participants did not demonstrate E2 increments, whereas a significant increase occurred in controls. rFSH-induced E2 production per follicle was significantly reduced in PCOS participants compared with controls at all rFSH doses. Increasing T and decreasing AMH concentrations were associated with augmented E2 production per follicle. Women with PCOS exhibited diminished initial E2 responses to rFSH compared with controls. These findings suggest that the mechanism of anovulation in PCOS may involve altered ovarian response to gonadotropins.

Fostering Functional Occupation and Mobility in People with Intellectual Disability and Visual Impairment Through Technology-Aided Support

ObjectivesThe study assessed a smartphone-based technology system, which was designed to support functional occupation and mobility in people with severe to profound intellectual disability and visual impairment.MethodsThe technology system provided (a) verbal orientation cues to guide the participants to a desk with two containers (and two groups of 10 objects that were to be transported to two different destinations), (b) verbal instructions to take the objects (one at a time), (c) verbal orientation cues to reach the destinations where the objects taken had to be transported, (d) instructions to put away the objects at the destinations, and (e) praise and brief periods of preferred stimulation. Seven participants were involved in the study, which was carried out according to a nonconcurrent multiple baseline across participants design.ResultsDuring the baseline (when the technology system was not available), the participants produced few or no correct responses (i.e., failed to collect, transport, and deposit objects at the right destinations). During the intervention phase (i.e., with the support of the technology system), their mean frequency of correct responses per session was between close to 19 and close to 20 (out of a maximum possible of 20) and their mean session duration varied between about 16 and 29 min.ConclusionsThe data suggest that the technology system used in this study may be a viable resource to support activity and mobility in people with intellectual and visual disabilities.

Characterization of bilateral, pudendal nerve-evoked, urethral rhabdosphincter contractions in anesthetized cats

Pudendal (PUD) efferent activity contracts urethral rhabdosphincters to resist urine leakage. This study evaluates the potential for PUD nerve stimulation to provide benefit for urinary incontinence. Acute responses of the urethral rhabdosphincter to modulation of current amplitude, pulse duration (PD), and frequency of stimulation were examined. Urethral pressure was measured using a microtip catheter in chloralose-anesthetized, male cats with or without acute spinalization at T10. Stimulation was applied from an external pulse generator coupled to cuff electrodes placed around left and right PUD nerves in the ischiorectal fossa, central to its branching. Bladder pressure clamp techniques were used for testing effects of stimulation on time and rate of leakage during PUD stimulation. Single pulses (0.1 ms) produced single transient increases in urethral pressure that peaked at 50 ms and diminished to 50% of peak at 90 ms. Threshold current was 88 ± 30μA with maximal responses occurring with 50% increases in current. Peak pressures increased with increasing PDs between 40–180μs. Summation, tetany, peak pressures, and fatigue of responses to increasing stimulation frequencies during 2 min periods of stimulation are described. Stimulation under pressures that are typical during bladder filling or during bladder contractions (30–40 cm H2O) prevented leakage up to an hour in some animals, increased the median time to leak from 0.3 min to 56.0 min, and decreased the median rate of leakage from 1.44 ml/min to 0.04 ml/min when leakage did occur in less than hour. During rapid elevations in bladder pressure to simulate a Valsalva-like bladder pressure (120 cm H2O), PUD stimulation increased the median time to leak from 9 s to 93 s and decreased the median rate of leakage from 5.5 ml/min to 3.4 ml/min. These results support future studies of bilateral PUD stimulation in a clinically-relevant, animal model of urinary incontinence.

60-Day PNS Treatment May Improve Identification of Delayed Responders and Delayed Non-Responders to Neurostimulation for Pain Relief.

ObjectiveConventional neurostimulation typically involves a brief (eg, ≤10-day) trial to assess presumed effectiveness prior to permanent implantation. Low trial conversion rates and high explant rates due to inadequate pain relief highlight the need for improved patient identification strategies. The development of a 60-day percutaneous peripheral nerve stimulation (PNS) system enables evaluation of outcomes following an extended temporary treatment period of up to 60 days, that may obviate or validate the need for permanent implant. The present study provides the first real-world evidence regarding patient response throughout a 60-day PNS treatment period.MethodsAnonymized data listings were compiled from patients who underwent implantation of temporary percutaneous leads and opted-in to provide real-world data to the device manufacturer during routine interactions with device representatives throughout the 60-day treatment.ResultsOverall, 30% (222/747) of patients were early responders (≥50% pain relief throughout treatment). Another 31% (231/747) of patients initially presented as non-responders but surpassed 50% pain relief by the end of treatment. Conversely, 32% (239/747) of patients were non-responders throughout treatment. An additional 7% (55/747) of patients initially presented as responders but fell below 50% relief by the end of the treatment period.ConclusionAn extended, 60-day PNS treatment may help identify delayed responders, providing the opportunity for sustained relief and improving access to effective PNS treatment. Compared to a conventionally short trial of ≤10 days, a longer 60-day PNS treatment may also help reduce explant rates by identifying delayed non-responders unlikely to benefit long-term. These scenarios support the importance of an extended 60-day temporary PNS stimulation period to help inform stepwise treatment strategies that may optimize outcomes and cost-effectiveness.

Seasonal dynamic of cholecalciferol (D3) and anti-Muellerian hormone (AMH) with impact on ovarian response and IVF/ICSI

ObjectiveRecent studies revealed intriguing associations between cholecalciferol (D3) and reproductive functions. Seasonal changes of D3 concentrations are well known; however, they are not always considered in the context of reproductive functions. In this study, we analyzed D3 serum concentration in IVF/ICSI patients with respect to seasonal 3-month quartiles and anti-Muellerian hormone (AMH) referring to the impact on Assisted Reproductive Technologies (ART) outcome.Materials and research methodsWe studied 469 female patients, presenting between 2012 and 2018 for ART treatment in our fertility center. D3 as well as the AMH serum concentrations were measured at the beginning of the follicle stimulation (days 3–5 of menstrual cycles). Results were evaluated with respect to seasonal quartiles and outcome of the ART cycles.ResultsD3 concentrations showed significant fluctuations within annual quartiles with a pronounced peak in August–October and a minimum in February–April (26.0 vs. 20.5 mg/dl; p < 0.0001). Similar seasonal dynamics were found for AMH (2.98 vs. 1.78 ng/ml; p = 0.010) and these were associated with significantly shorter stimulation periods during August–October (11.29 vs. 12.12 days; p = 0.042), higher number of fertilized oocytes between August and October (6.23 vs. 4.97; p = 0.05) along with a trend towards higher numbers of cumulus–oocyte complexes. However, no such differences were found for the numbers of MII oocytes or pregnancy rates.ConclusionOur data indicate seasonal 3-month quartile variations of AMH concentrations and characteristics of ART, such as days of ovarian stimulation and number of fertilized oocytes. Highest AMH concentrations were found between August and October and this quartile was associated with highest D3 concentrations.

Long-term prophylactic efficacy of transcranial direct current stimulation in chronic migraine. A randomised, patient-assessor blinded, sham-controlled trial

ObjectiveTo assess the prophylactic effect of anodal tDCS of the left motor cortex in patients with resistant chronic migraine (CM) and its long-term maintenance. MethodsIn a patient-assessor blinded, sham-controlled trial, 36 patients were randomized to receive anodal tDCS (active group, n = 18) or sham tDCS (sham group, n = 18). The studied population was characterized by a previous failure of at least 3 classes of preventive drugs and a mean duration of migraine history of 26 years. The tDCS procedure consisted of an induction phase of 5 consecutive daily sessions (week 1) followed by a maintenance phase of 1 weekly session during the next 4 weeks and two bimonthly sessions in the next month, for a total of 11 sessions during 2 months. Anodal tDCS was delivered at 2 mA intensity for 20 min over the left motor cortex. The primary endpoint was the reduction in the monthly number of migraine attacks from baseline to each period of follow-up (months 1, 2, 3, 5) between the active and sham groups. ResultsThe monthly number of migraine attacks expressed as the percentage of reduction from baseline was significantly reduced in the active versus the sham group, from the end of first month (−21% ± 22 vs. −2% ±25, p = 0.019) to the end of follow-up (3-month post-treatment) (−32% ± 33 vs. −6% ±39, p = 0.011). At this time, the rate of responders, defined as a reduction of the monthly number of migraine attacks ≥30% from baseline, was significantly higher in the active group than in the sham group (50% vs. 14%, p = 0.043). ConclusionOur results show a marked prophylactic effect of anodal tDCS of the left motor cortex in resistant CM extending several months after the stimulation period, and suggest that this neuromodulatory approach may be part of the prophylactic alternatives available for CM.

Prediction, assessment, and management of suboptimal GnRH agonist trigger: a systematic review.

This systematic review aimed to identify baseline patient demographic and controlled ovarian stimulation characteristics associated with a suboptimal response to GnRHa triggering, and available options for prevention and management of suboptimal response. PubMed, Google Scholar, Medline, and the Cochrane Library were searched for keywords related to GnRHa triggering, and peer-reviewed articles from January 2000 to September 2021 included. Thirty-seven studies were included in the review. A suboptimal response to GnRHa triggering was more likely following long-term or recent oral contraceptive use and with a low or high body mass index. Low basal serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol serum levels were correlated with suboptimal oocyte yield, as was a low serum LH level on the day of triggering. A prolonged stimulation period and increased gonadotropin requirements were correlated with suboptimal response to triggering. Post-trigger LH < 15 IU/L best correlated with an increased risk for empty follicle syndrome and a lower oocyte retrieval rate. Retriggering with hCG may be considered in patients with suboptimal response according to post-trigger LH, as in cases of failed aspiration. Pre-treatment assessment of patient characteristics, with pre- and post-triggering assessment of clinical and endocrine cycle characteristics, may identify cases at risk for suboptimal response to GnRHa triggering and optimize its utilization.

Early Transcutaneous Tibial Nerve Stimulation Acutely Improves Lower Urinary Tract Function in Spinal Cord Injured Rats.

Despite the fact that a majority of patients with an injury to the spinal cord develop lower urinary tract dysfunction, only few treatment options are available currently once the dysfunction arises. Tibial nerve stimulation has been used in pilot clinical trials, with some promising results. Hence, we investigated whether the early application of transcutaneous tibial nerve stimulation in the animal model of spinal cord injured rats can prevent the development of detrusor overactivity and/or detrusor-sphincter-dyssynergia. Rats were implanted with a bladder catheter and external urethral sphincter electromyography electrodes. A dorsal over-hemisection, resulting in an incomplete spinal cord injury at the T8/9 spinal level, induced immediate bladder paralysis. One week later, the animals received daily tibial nerve or sham stimulation for 15 days. Effects of stimulation on the lower urinary tract function were assessed by urodynamic investigation. Measurements showed improvements of several key parameters of lower urinary tract function—in particular, non-voiding bladder contractions and intravesical pressure—immediately after the completion of the stimulation period in the stimulated animals. These differences extinguished one week later, however. In the dorsal horn of the lumbosacral spinal cord, a small significant increase of the density of C-fiber afferents layers I-II was found in the stimulated animals at four weeks after spinal cord injury. Tibial nerve stimulation applied acutely after spinal cord injury in rats had an immediate beneficial effect on lower urinary tract dysfunction; however, the effect was transitory and did not last over time. To achieve more sustainable, longer lasting effects, further studies are needed looking into different stimulation protocols using optimized stimulation parameters, timing, and treatment schedules.

Simultaneous detection of metabolite concentration changes, water BOLD signal and pH changes during visual stimulation in the human brain at 9.4T

This study presents a method to directly link metabolite concentration changes and BOLD response in the human brain during visual stimulation by measuring the water and metabolite signals simultaneously. Therefore, the metabolite-cycling (MC) non-water suppressed semiLASER localization technique was optimized for functional 1H MRS in the human brain at 9.4 T. Data of 13 volunteers were acquired during a 26:40 min visual stimulation block-design paradigm. Activation-induced BOLD signal was observed in the MC water signal as well as in the NAA-CH3 and tCr-CH3 singlets. During stimulation, glutamate concentration increased 2.3 ± 2.0% to a new steady-state, while a continuous increase over the whole stimulation period could be observed in lactate with a mean increase of 35.6 ± 23.1%. These increases of Lac and Glu during brain activation confirm previous findings reported in literature. A positive correlation of the MC water BOLD signal with glutamate and lactate concentration changes was found. In addition, a pH decrease calculated from a change in the ratio of PCr to Cr was observed during brain activation, particularly at the onset of the stimulation.

Oxygen supplementation to limit hypoxia-induced muscle atrophy in C2C12 myotubes: comparison with amino acid supplement and electrical stimulation

In skeletal muscle, chronic oxygen depletion induces a disturbance leading to muscle atrophy. Mechanical stress (physical exercise) and nutritional supplement therapy are commonly used against loss of muscle mass and undernutrition in hypoxia, while oxygenation therapy is preferentially used to counteract muscle fatigue and exercise intolerance. However, the impact of oxygenation on skeletal muscle cells remains poorly understood, in particular on signalling pathways regulating protein balance. Thus, we investigated the effects of each separated treatment (mechanical stress, nutritional supplementation and oxygenation therapy) on intracellular pathways involved in protein synthesis and degradation that are imbalanced in skeletal muscle cells atrophy resulting from hypoxia. Myotubes under hypoxia were treated by electrical stimulation, amino acids supplement or oxygenation period. Signalling pathways involved in protein synthesis (PI3K-Akt-mTOR) and degradation (FoxO1 and FoxO3a) were investigated, so as autophagy, ubiquitin-proteasome system and myotube morphology. Electrical stimulation and oxygenation treatment resulted in higher myotube diameter, myogenic fusion index and myotubes density until 48h post-treatment compared to untreated hypoxic myotubes. Both treatments also induced inhibition of FoxO3a and decreased activity of ubiquitin-proteasome system; however, their impact on protein synthesis pathway was specific for each one. Indeed, electrical stimulation impacted upstream proteins to mTOR (i.e., Akt) while oxygenation treatment activated downstream targets of mTOR (i.e., 4E-BP1 and P70S6K). In contrast, amino acid supplementation had very few effects on myotube morphology nor on protein homeostasis. This study demonstrated that electrical stimulation or oxygenation period are two effective treatments to fight against hypoxia-induced muscle atrophy, acting through different molecular adaptations.

Doppler shift during overdrive pacing of spiral waves. Prediction of the annihilation site

Spiral waves of electrical excitation can occur in the heart in cases of dangerous arrhythmias. Low-voltage cardioversion is a treatment method that aims to induce drift and annihilation of the spiral waves. Drift of wave sources causes Doppler shift but it has not been studied for the waves that are interacting with plane wave trains in excitable media. In our numerical research, we made 2D and 3D solitary spiral waves drift by external pacing and studied the Doppler shift using detectors at the tissue boundary. We examined spiral waves with a circular core and meandering waves and tried various external stimulation periods. We observed that the period of the source in the direction of the drift decreased, which could be described quite precisely in 2D by the classical Doppler shift formula. Moreover, the boundary annihilation site of the spiral can be accurately predicted as the location where the minimal period at the boundary is measured.

Dopamine firing plays a dual role in coding reward prediction errors and signaling motivation in a working memory task

Little is known about how dopamine (DA) neuron firing rates behave in cognitively demanding decision-making tasks. Here, we investigated midbrain DA activity in monkeys performing a discrimination task in which the animal had to use working memory (WM) to report which of two sequentially applied vibrotactile stimuli had the higher frequency. We found that perception was altered by an internal bias, likely generated by deterioration of the representation of the first frequency during the WM period. This bias greatly controlled the DA phasic response during the two stimulation periods, confirming that DA reward prediction errors reflected stimulus perception. In contrast, tonic dopamine activity during WM was not affected by the bias and did not encode the stored frequency. More interestingly, both delay-period activity and phasic responses before the second stimulus negatively correlated with reaction times of the animals after the trial start cue and thus represented motivated behavior on a trial-by-trial basis. During WM, this motivation signal underwent a ramp-like increase. At the same time, motivation positively correlated with accuracy, especially in difficult trials, probably by decreasing the effect of the bias. Overall, our results indicate that DA activity, in addition to encoding reward prediction errors, could at the same time be involved in motivation and WM. In particular, the ramping activity during the delay period suggests a possible DA role in stabilizing sustained cortical activity, hypothetically by increasing the gain communicated to prefrontal neurons in a motivation-dependent way.

Low-Frequency rTMS over Contralesional M1 Increases Ipsilesional Cortical Excitability and Motor Function with Decreased Interhemispheric Asymmetry in Subacute Stroke: A Randomized Controlled Study

Objective To determine the long-term effects of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) over the contralesional M1 preceding motor task practice on the interhemispheric asymmetry of the cortical excitability and the functional recovery in subacute stroke patients with mild to moderate arm paresis. Methods Twenty-four subacute stroke patients were randomly allocated to either the experimental or control group. The experimental group underwent rTMS over the contralesional M1 (1 Hz), immediately followed by 30 minutes of motor task practice (10 sessions within 2 weeks). The controls received sham rTMS and the same task practice. Following the 2-week intervention period, the task practice was continued twice weekly for another 10 weeks in both groups. Outcomes were evaluated at baseline (T0), at the end of the 2-week stimulation period (T1), and at 12-week follow-up (T2). Results The MEP (paretic hand) and interhemispheric asymmetry, Fugl-Meyer motor assessment, Action Research Arm Test, and box and block test scores improved more in the experimental group than controls at T1 (p < 0.05). The beneficial effects were largely maintained at T2. Conclusion LF-rTMS over the contralesional M1 preceding motor task practice was effective in enhancing the ipsilesional cortical excitability and upper limb function with reducing interhemispheric asymmetry in subacute stroke patients with mild to moderate arm paresis. Significance. Adding LF-rTMS prior to motor task practice may reduce interhemispheric asymmetry of cortical excitabilities and promote upper limb function recovery in subacute stroke with mild to moderate arm paresis.

Effect of Biphasic kHz Field Stimulation on CA1 Pyramidal Neurons in Slices

Electrical stimulation in the kilohertz-frequency range has been successfully used for treatment of various neurological disorders. Nevertheless, the mechanisms underlying this stimulation are poorly understood. To study the effect of kilohertz-frequency electric fields on neuronal membrane biophysics we developed a reliable experimental method to measure responses of single neurons to kilohertz field stimulation in brain slice preparations. In the submerged brain slice pyramidal neurons of the CA1 subfield were recorded in the whole-cell configuration before, during and after stimulation with a biphasic charge balanced electric field at 2kHz, 5kHz or 10 kHz. The slice was placed in a 1 mm gap between two parallel 2 mm long platinum-iridium 0.1 mm diameter wire electrodes. Whole-cell recordings lasted for an hour or longer. Typically, a few 5-10 min long sessions of kHz-field stimulation (kHz-FS) with various frequency/amplitude combinations were applied to assess the type of neuronal response and possible changes of its membrane characteristics. It was found that kHz-field stimulation at all frequencies elicited reproducible excitatory neuronal responses lasting throughout stimulation period, but not after cessation of kHz-FS. During kHz-FS the rheobase usually decreased. In addition, spontaneous firing might be initiated in some silent neurons or became more intense in previously spontaneously active neurons. Response thresholds were in the range of 0.5-2 mA and were higher at higher frequencies. Blockade of glutamatergic synaptic transmission did not alter the magnitude of responses. Inhibitory synaptic input was not changed by kilohertz field stimulation. We conclude that kHz-frequency current applied in brain tissue has an excitatory effect on pyramidal neurons during stimulation. This effect is more prominent and occurs at a lower stimulus intensity at a frequency of 2kHz as compared to 5kHz and 10kHz.

Wheat Lysin-Motif-Containing Proteins Characterization and Gene Expression Patterns under Abiotic and Biotic Stress

Lysin motif (LysM)-containing proteins (LYPs) are important pattern recognition receptors in plants. However, the evolutionary history and characteristics of LYP genes remain largely unclear in wheat. In this study, 62 LYPs were identified at genome wide in wheat. Based on phylogenetic and domain analysis, wheat LYPs were classified into 6 subgroups (group LysMe, LysMn, LYP, LYK, LysMFbox). Syntenic analysis showed the evolution of LYP genes in wheat. RNA-seq data showed that 22 genes were not expressed at any tissue or stress stimulation period. Some LYP and LYK genes were tissue- or stage- specific. The majority of TaLYK5s, TaLYK6s, TaLYP2s and TaLysMns genes were induced under chitin, flg22 and fungal treatment. qRT-PCR analysis showed that 4 genes were upregulated during Puccinia triticina infection with a peak at 18 h post inoculation. Our findings suggested that wheat LYPs may have specific roles in response to fungal infection and provided insights into the function and characteristics of wheat LYP genes.

Impact of adaptive gastric electrical stimulation on weight, food intake, and food intake rate in dogs.

Gastric electrical stimulation (GES) has been studied for decades as a promising treatment for obesity. Stimulation pulses with fixed amplitude and pulse width are usually applied, but these have limitations with regard to overcoming habituation to GES and inter-subject variation. This study aims to analyze the efficacy of an adaptive GES protocol for reducing food intake and maintaining lean weight in dogs. Six beagle dogs were implanted with a remotely programmable gastric stimulator. An adaptive protocol was designed to increase the stimulation energy proportionally to the excess of food consumption, with respect to the dogs' maintenance energy requirements. After surgery and habituation to experimental conditions, the dogs went through both a control and a stimulation period of 4weeks each, in a randomized order. The stimulation parameters were adapted daily. Body weight, food intake, food intake rate, and postprandial cutaneous electrogastrograms (EGG) were recorded to assess the effect of adaptive GES. Adaptive GES decreased food intake and food intake rate (p<0.05) resulting in weight maintenance. In the absence of GES, the dogs gained weight (p<0.05). Postprandial EGG dominant frequency was accelerated by GES (p<0.05). The strategy of adapting the stimulation energy was effective in causing significant mid-term changes. Adaptive GES is effective for reducing food intake and maintaining lean weight. The proposed adaptive strategy may offer benefits to counter habituation and adapt to inter-subject variation in clinical use of GES for obesity.

Five weeks of intermittent transcutaneous vagus nerve stimulation shape neural networks: a machine learning approach

Invasive and transcutaneous vagus nerve stimulation [(t)-VNS] have been used to treat epilepsy, depression and migraine and has also shown effects on metabolism and body weight. To what extent this treatment shapes neural networks and how such network changes might be related to treatment effects is currently unclear. Using a pre-post mixed study design, we applied either a tVNS or sham stimulation (5 h/week) in 34 overweight male participants in the context of a study designed to assess effects of tVNS on body weight and metabolic and cognitive parameters resting state (rs) fMRI was measured about 12 h after the last stimulation period. Support vector machine (SVM) classification was applied to fractional amplitude low-frequency fluctuations (fALFF) on established rs-networks. All classification results were controlled for random effects and overfitting. Finally, we calculated multiple regressions between the classification results and reported food craving. We found a classification accuracy (CA) of 79 % in a subset of four brainstem regions suggesting that tVNS leads to lasting changes in brain networks. Five of eight salience network regions yielded 76,5 % CA. Our study shows tVNS’ post-stimulation effects on fALFF in the salience rs-network. More detailed investigations of this effect and their relationship with food intake seem reasonable for future studies.

Local accumbens in vivo imaging during deep brain stimulation reveals a strategy-dependent amelioration of hedonic feeding

Impulsive overeating is a common, disabling feature of eating disorders. Both continuous deep brain stimulation (DBS) and responsive DBS, which limits current delivery to pathological brain states, have emerged as potential therapies. We used invivo fiber photometry in wild-type, Drd1-cre, and A2a-cre mice to 1) assay subtype-specific medium spiny neuron (MSN) activity of the nucleus accumbens (NAc) during hedonic feeding of high-fat food, and 2) examine DBS strategy-specific effects on NAc activity. D1, but not D2, NAc GCaMP activity increased immediately prior to high-fat food approach. Responsive DBS triggered a GCaMP surge throughout the stimulation period and durably reduced high-fat intake. However, with continuous DBS, this surge decayed, and high-fat intake reemerged. Our results argue for a stimulation strategy-dependent modulation of D1 MSNs with a more sustained decrease in consumption with responsive DBS. This study illustrates the important role invivo imaging can play in understanding effects of such novel therapies.

Targeting the motor cortex to restore walking after incomplete spinal cord injury.

Targeting the motor cortex to restore walking after incomplete spinal cord injury.