Intermittent Stimulation Research Articles

Effects of analysis window on 40-Hz auditory steady-state responses in cochlear implant users

Auditory steady-state responses (ASSRs) are phase-locked responses of the auditory system to the envelope of a stimulus. These responses can be used as an objective proxy to assess temporal envelope processing and its related functional outcomes such as hearing thresholds and speech perception, in normal-hearing listeners, in persons with hearing impairment, as well as in cochlear-implant (CI) users. While ASSRs are traditionally measured using a continuous stimulation paradigm, an alternative is the intermittent stimulation paradigm, whereby stimuli are presented with silence intervals in between. This paradigm could be more useful in a clinical setting as it allows for other neural responses to be analysed concurrently. One clinical use case of the intermittent paradigm is to objectively program CIs during an automatic fitting session whereby electrically evoked ASSRs (eASSRs) as well as other evoked potentials are used to predict behavioural thresholds. However, there is no consensus yet about the optimal analysis parameters for an intermittent paradigm in order to detect and measure eASSRs reliably. In this study, we used the intermittent paradigm to evoke eASSRs in adult CI users and investigated whether the early response buildup affects the response measurement outcomes. To this end, we varied the starting timepoint and length of the analysis window within which the responses were analysed. We used the amplitude, signal-to-noise ratio (SNR), phase, and pairwise phase consistency (PPC) to characterize the responses. Moreover, we set out to find the optimal stimulus duration for efficient and reliable eASSR measurements. These analyses were performed at two stimulation levels, i.e., 100% and 50% of the dynamic range of each participant. Results revealed that inclusion of the first 300 ms in the analysis window leads to overestimation of response amplitude and underestimation of response phase. Additionally, the response SNR and PPC were not affected by the inclusion of the first 300 ms in the analysis window. However, the latter two metrics were highly dependent on the stimulus duration which complicates comparisons across studies. Finally, the optimal stimulus duration for quick and reliable characterization of eASSRs was found to be around 800 ms for the stimulation level of 100% DR. These findings suggest that inclusion of the early onset period of eASSR recordings negatively influences the response measurement outcomes and that efficient and reliable eASSR measurements are possible using stimuli of around 800 ms long. This will pave the path for the development of a clinically feasible eASSR measurement in CI users.

GelMA-glycol chitosan hydrogels for cartilage regeneration: The role of uniaxial mechanical stimulation in enhancing mechanical, adhesive, and biochemical properties.

Untreated osteochondral defects are a leading cause of osteoarthritis, a condition that places a heavy burden on both patients and orthopedic surgeons. Although tissue engineering has shown promise for creating mechanically similar cartilage-like constructs, their integration with cartilage remains elusive. Therefore, a formulation of biodegradable, biocompatible biomaterial with sufficient mechanical and adhesive properties for cartilage repair is required. To accomplish this, we prepared biocompatible, photo-curable, mechanically robust, and highly adhesive GelMA-glycol chitosan (GelMA-GC) hydrogels. GelMA-GC hydrogels had a modulus of 283 kPa and provided a biocompatible environment (>70% viability of embedded chondrocytes) in long-term culture within a bovine cartilage ring. The adhesive strength of bovine chondrocyte-laden GelMA-GC hydrogel to bovine cartilage increased from 38 to 52 kPa over four weeks of culture. Moreover, intermittent uniaxial mechanical stimulation enhanced the adhesive strength to ∼60 kPa, indicating that the cartilage-hydrogel integration could remain secure and functional under dynamic loading conditions. Furthermore, gene expression data and immunofluorescence staining revealed the capacity of chondrocytes in GelMA-GC hydrogel to synthesize chondrogenic markers (COL2A1 and ACAN), suggesting the potential for tissue regeneration. The promising in vitro results of this work motivate further exploration of the potential of photo-curable GelMA-GC bioadhesive hydrogels for cartilage repair and regeneration.

Student Competition (Technology Innovation) ID 1985239

Background Deep vein thrombosis (DVT) is a blood clot that forms in the deep veins and is the third most common cardiovascular disease today. One of the causes of DVT is venous stasis. Current methods of DVT prevention include anticoagulants and mechanical prophylaxis. Anticoagulant use is contraindicated in individuals with bleeding risks and mechanical interventions are often cumbersome and uncomfortable. Objective The overall goal of this project is to investigate a novel method for DVT prevention, termed intermittent electrical stimulation (IES). The current study investigated the effects of IES on healthy typical as well as post-stroke persons. Method Of the 32 participants, 22 were healthy subjects from Edmonton, and 10 were inpatient post-stroke subjects at the Glenrose Rehabilitation Hospital, Edmonton. A two-channel stimulator was used to administer IES through electrodes placed on the posterior and anterior sides of the leg and was applied in increasing stimulation amplitudes to the gastrocnemius muscle and the resulting plantar flexion force and changes in popliteal and femoral venous velocities were recorded for each stimulation respectively using B-mode ultrasound. Results IES-induced contractions produced significant increases in venous flow compared to baseline. Small contractions induced by comfortable levels of stimulation in typical and in post-stroke persons were sufficient to increase flow in the popliteal and femoral veins. Conclusion The results indicate that IES can sufficiently increase venous flow to prevent venous stasis and is comfortable for end users. Incorporation of IES into a clinical device could provide a feasible and effective alternative for DVT prophylaxis.

Intermittent and Mild Cold Stimulation Maintains Immune Function Stability through Increasing the Levels of Intestinal Barrier Genes of Broilers.

In order to improve the adaptability of broilers to low-temperature environments and their ability to resist acute cold stress (ACS), 240 one-day-old broilers were selected and randomly divided into three groups. The control treatment (CC) group was raised at the conventional feeding temperature from 1-43 days (d), the cold stimulation treatment (CS) group was kept at 3 °C below the temperature of CC at 1 d intervals for 3 and 6 h from 15 to 35 d, namely, CS3 and CS6, respectively. Then, all broilers were kept at 20 °C from 36 to 43 d. ACS was then carried out at 44 d, and the ambient temperature was dropped to 10 °C for 6 h. The study investigated the production performance, as well as levels of intestinal barrier genes (including Claudin-1, E-cadherin, Occludin, ZO-1, ZO-2 and Mucin2), secretory IgA in duodenum and jejunum, and immunoglobulins (IgA and IgG) in serum. The results showed that IMCS could increase the daily weight gain and decrease the feed conversion ratio. During IMCS, the expression levels of intestinal barrier genes were up-regulated and the content of secretory IgA was increased. When IMCS ceased for one week, the level of immunoglobulins in serum stabilized, and the expression levels of Occludin, ZO-2 and Mucin2 still maintained high levels. After ACS, broilers that received IMCS training maintained high levels of intestinal barrier genes and secretory IgA.

Sub-second timing irregularities in a simple motor task in autism spectrum disorder: Preliminary effects of intermittent light stimulation.

Several authors have contributed extensively to the neurocognitive understanding of timing. In Autism Spectrum Disorder (ASD) on the contrary, internal timing and its functioning is not well understood. In this study, we have adapted a simple finger-tapping motor task, with a timing component, as we aim at understanding whether the processing of time is preserved in this population. We have tested a group of people on the autism spectrum without intellectual disabilities and a control sample recruited from the general population, matched for age, sex, schooling and general cognitive abilities on this task with a learning and testing phase. In the testing phase, we have added two exploratory conditions where participants were exposed to intermittent light stimulation of 4 and 8 Hz. Results show that both in the learning and testing phase, besides troubles in the motor component encountered by the people on the spectrum, their timing component performance was also problematic. This reveals to be especially true for time intervals below the 1 s range, as hypothesized, whereas performance in longer intervals is clearly preserved. It was also observed that the exposure to intermittent light stimulation specifically overcomes the difficulties observed in the autistic group, at the timing components at this millisecond time range. The observed timing difficulties in this group seem to be restricted to the system responsible for the processing of time intervals in the milliseconds range, which helps accommodate disparate findings in the literature.

Deep brain stimulation of the anterior nucleus of the thalamus increases slow wave activity in NREM sleep.

Previous studies suggest that intermittent deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) affects physiological sleep architecture. Here, we investigated the impact of continuous ANT-DBS on sleep in epilepsy patients in a multicenter cross-over study in ten patients. We assessed sleep stage distribution, delta power, delta energy, and total sleep time (TST) in standardized 10/20 polysomnography (PSG) investigations before and 12 months after DBS lead implantation. In contrast to previous studies, we found no disruption of sleep architecture or alterations of sleep stage distribution under active ANT-DBS (P = 0.76). On the contrary, we observed more consolidated and deeper slow wave sleep (SWS) under continuous high frequency DBS as compared to baseline sleep prior to DBS lead implantation. In particular, biomarkers of deep sleep (delta power and delta energy) showed a significant increase post-DBS as compared to baseline (36.67 ± 13.68 μV2 and 799.86 ± 407.56 μV2 *s, P < 0.001). Furthermore, the observed increase in delta power was related to the location of the active stimulation contact within the ANT: we found higher delta power and higher delta energy in patients with active stimulation in more superior contacts as compared to inferior ANT stimulation. We also observed significantly less nocturnal EEG discharges in DBS ON condition. In conclusion, our findings suggest that continuous ANT-DBS in the most cranial part of the target region leads to more consolidated SWS. From a clinical perspective, these findings suggest that patients with sleep disruption under cyclic ANT-DBS could benefit from an adaptation of stimulation parameters to more superior contacts and continuous mode stimulation.

Protection against Microglia Senescence by the Dietary Supplement Dekosilhue® in BV2 Cells: A New Perspective for Obesity and Related Complications

Growing evidence indicates chronic low-grade systemic inflammation as a major pathophysiological mechanism of obesity. Systemic inflammation provokes an immune response in the brain through the activation of microglia that results in the development of neuroinflammation, cellular senescence, and occurrence of neurological dysfunction. In the efforts to identify an innovative intervention with potential efficacy on obesity and associated complications, our aim was to study the capability of the dietary supplement Dekosilhue® (DKS), successfully used for improving the control of body weight, to attenuate microglia senescent phenotype. Microglia senescence was induced by intermittent stimulation of BV2 cells with LPS 500 ng/mL every 72 h for 4 h/day, over a period of 10 days. DKS (100 µg/mL) treatment reduced ß-galactosidase activity and expression, the formation of senescence-associated heterochromatin foci to control levels, and increased cell viability of senescent BV2 (2 folds of control). DSK reduced the expression of Nuclear Factor-kB (NF-kB) (20% lower than control), a key molecule involved in the acquisition of the senescence-associated secretory phenotype (SASP). DKS promoted a neuroprotective effect by increasing the cell viability of SH-SY5Y neuronal cells exposed to the senescent BV2 conditioned medium to values of non-senescent cells. In conclusion, DKS attenuated the senescent microglia phenotype, showing senotherapeutic activity that might be further investigated as adjunctive intervention for obesity and obesity-related neurological disturbances.

Intermittent activation of large diameter phrenic afferents induces phrenic motor plasticity

We recently showed that in anesthetized rats, 30 minutes of electrical stimulation applied to the diaphragm muscle induces phrenic afferent dependent plasticity characterized by a long-lasting increase in diaphragm electromyography amplitude. Our previous data also indicate that large diameter phrenic afferents may be most effective at eliciting plasticity. Here we directly test the hypothesis that intermittent activation of large diameter phrenic afferents induces phrenic motor plasticity. In urethane anesthetized and mechanically ventilated male Sprague-Dawley rats, we isolated the left and right phrenic nerves. We applied inspiratory-triggered electrical stimulation (biphasic; 40Hz; 160mA) to one phrenic nerve in a sustained (n= 5, 25 minutes) or intermittent (n=5; 5 X 5-minute episodes) pattern, and recorded contralateral motor output before, during, and for 60 minutes after stimulation. We used a narrow pulse width (0.1ms) to preferentially activate large diameter afferents. At 60 minutes, rats receiving sustained stimulation showed no difference in contralateral phrenic motor amplitude compared to time controls not receiving stimulation (n=5; P=0.1320). In contrast, rats receiving intermittent stimulation had an increase at 60 minutes compared to time controls (P=0.0005) and sustained stimulation (P=0.0024). This suggests that intermittent, but not sustained, phrenic nerve stimulation induces contralateral phrenic motor plasticity. To test the hypothesis that phrenic afferents are necessary for intermittent induced plasticity, separate animals received either a left, C3-C6 dorsal rhizotomy (n=3) or laminectomy (n=4) prior to intermittent stimulation. Laminectomy controls expressed a long-lasting increase in contralateral phrenic motor amplitude compared to time controls (n=5) at 60 minutes after stimulation (P=0.0112). Animals receiving a dorsal rhizotomy were not different than time controls at 60 minutes (P=0.4058), indicating phrenic afferents are necessary for the induction of plasticity. These data show for the first time that intermittent activation of large diameter phrenic afferents induces phrenic motor plasticity. A detailed understanding of afferent mediated plasticity will be beneficial in the development of therapeutic techniques utilizing electrical stimulation of the diaphragm muscle (i.e., diaphragm pacing). This work was supported by funding from the National Institute of Health, grant numbers: R00 HL143207-01 (KAS). The authors declare no competing financial interests. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

β-Arrestin 2 knockout prevents bone loss in response to continuous parathyroid hormone stimulation in male and female mice

ABSTRACT Background β-Arrestin 2 (β-arr2) binds activated parathyroid hormone (PTH) receptors stimulating internalization. PTH stimulates both anabolic and catabolic effect on bone depending on the way it is administered. Intermittent PTH stimulation increases trabecular bone formation in mice, but this is decreased in mice lacking β-arr 2, suggesting a role for β-arr 2 in the anabolic effects of PTH. The role of β-arr 2 in the catabolic effects of continuous PTH (cPTH) treatment is not known. Objective To assess the effects of cPTH administration on bone in mice lacking β-arr 2 compared to wild-type (WT). Methods Groups of male and female WT or β-arr2 knockout (KO) mice were administered either PTH or phosphate-buffered saline by osmotic pumps for 2 weeks. Following treatment, serum calcium and phosphate levels were measured, bone structure and mineral density were measured by microcomputed tomography, and bone cells measured by static and dynamic histomorphometry. Results β-arr2 KO had no effects on skeletal development in mice of either sex. PTH treatment caused hypercalcemia and hypophosphatemia and decreased trabecular and cortical bone only in male WT mice. β-arr2 KO in male mice completely abrogated the effects of PTH on bone, while in female β-arr2 KO mice, PTH treatment increased trabecular bone with no effects on cortical bone. Conclusions These results demonstrate a profound sex effect on skeletal responses to cPTH treatment, suggesting a protective effect of estrogen on bone loss. β-arr2 plays a role in restraining the anabolic effects of PTH in both male and female mice.

3. Adjunctive D-Cycloserine With Intermittent Theta-Burst Transcranial Magnetic Stimulation Improves Suicidal Ideation and Implicit Suicide Risk in Major Depressive Disorder

3. Adjunctive D-Cycloserine With Intermittent Theta-Burst Transcranial Magnetic Stimulation Improves Suicidal Ideation and Implicit Suicide Risk in Major Depressive Disorder

Photosensitive occipital lobe epilepsy: Delineation of an under-recognized reflex epilepsy syndrome according to the new ILAE criteria and long-term follow-up.

Photosensitive occipital lobe epilepsy (POLE) should be suspected in patients with occipital lobe seizures triggered by photic stimuli, who have normal motor-mental development and brain imaging. We aimed to examine the clinical, electrophysiological, and prognostic features of POLE, which is a rare and under-investigated syndrome. Archives from two tertiary epilepsy centers were retrospectively scanned and patients with normal neurological examination and cranial imaging were identified with POLE if they had: (1) seizures consistently triggered by photic stimuli; (2) non-motor seizures with visual symptoms; and (3) photosensitivity documented on EEG. The clinical and electrophysiological features and prognostic factors were evaluated for patients who had follow-up ≥5 years. We identified 29 patients diagnosed with POLE with a mean age of 20.1± 7.6 years. In one-third of the patients, POLE syndrome overlapped with genetic generalized epilepsy (GGE). The overlap group had higher rates of febrile seizure history and self-induction; when compared to pure POLE patients, their EEGs showed more frequent interictal generalized epileptic discharges and posterior multiple spikes during intermittent photic stimulation. During long-term follow-up, the remission rate for POLE was 80%, but EEG photosensitivity persisted in three quarters of patients despite clinical remission, and more than half had relapsed after clinical remission. This first long-term follow-up study, utilizing newly suggested criteria of the International League Against Epilepsy, showed that POLE syndrome shows a notable overlap with GGE but also has distinctive features. POLE has a good prognosis; however, relapses are common, and photosensitivity persists as an EEG finding in the majority of patients.

Chronic basal forebrain activation improves spatial memory, boosts neurotrophin receptor expression, and lowers BACE1 and Aβ42 levels in the cerebral cortex in mice.

The etiology of Alzheimer's dementia has been hypothesized in terms of basal forebrain cholinergic decline, and in terms of reflecting beta-amyloid neuropathology. To study these different biological elements, we activated the basal forebrain in 5xFAD Alzheimer's model mice and littermates. Mice received 5 months of 1 h per day intermittent stimulation of the basal forebrain, which includes cholinergic projections to the cortical mantle. Then, mice were behaviorally tested followed by tissue analysis. The 5xFAD mice performed worse in water-maze testing than littermates. Stimulated groups learned the water maze better than unstimulated groups. Stimulated groups had 2-3-fold increases in frontal cortex immunoblot measures of the neurotrophin receptors for nerve growth factor and brain-derived neurotrophic factor, and a more than 50% decrease in the expression of amyloid cleavage enzyme BACE1. Stimulation also led to lower Aβ42 in 5xFAD mice. These data support a causal relationship between basal forebrain activation and both neurotrophin activation and reduced Aβ42 generation and accumulation. The observation that basal forebrain activation suppresses Aβ42 accumulation, combined with the known high-affinity antagonism of nicotinic receptors by Aβ42, documents bidirectional antagonism between acetylcholine and Aβ42.

Electroclinical characteristics of photosensitive epilepsy: A retrospective study of 31 Chinese children and literature review.

The objective of this study was to better understand the clinical features of photosensitive epilepsy (PSE) in Chinese children. Thirty-one children with PSE were screened out of 398 children with epilepsy who were consecutively diagnosed by the video-electroencephalogram (VEEG) monitoring method and by using an intermittent photic stimulation (IPS) test. Their EEGs and clinical features were retrospectively analyzed, and their treatment outcomes were followed up. PSE accounted for 7.79% (31/398) of children with epilepsy during the observation period in our single epilepsy center. The male to female ratio of PSE was 1:3.43, and the average seizure onset age was 7.8 ± 3.28 years. The highest range of frequency sensitivity of the IPS test for the induction of EEG epileptic discharge or electroclinical seizures was within 10-20 Hz. Electroclinical seizures were induced in 41.94% (13/31) of PSE patients by using the IPS test, while EEG discharge without clinical seizures was induced in 58.06% (18/31) of PSE patients. Among all PSE patients, an IPS-positive reaction in the eye-closure state was induced in 83.87% of patients, and this rate was significantly higher than that in the eye-opened state (41.94%) or eye-closed state (35.48%). (Eye-closure IPS stimulation means: make the subjects close their eyes at the beginning of each stimulation, open their eyes at the end of the stimulation, and close their eyes again at the beginning of the next stimulation, and so on. While Eye-closed IPS stimulation means the stimulation is started after 5 s of eye closure, and the subjects are kept closed throughout the whole process.) The common and effective drugs used for single or combined therapy in PSE children were valproic acid and levetiracetam. This study provides some useful information about electroclinical characteristics in a cohort of 31 PSE children. It may be beneficial for pediatric neurologists in terms of paying more attention to PSE and correctly dealing with it.

Lower-limb resistance training reduces exertional dyspnea and intrinsic neuromuscular fatigability in individuals with chronic obstructive pulmonary disease.

Skeletal muscle atrophy, dysfunction, and fatigue are important complications of chronic obstructive pulmonary disease (COPD). Greater reliance on glycolytic metabolism and increased type III/IV muscle afferent activity increase ventilatory drive, promote ventilatory constraint, amplify exertional dyspnea, and limit exercise tolerance. To investigate whether muscular adaptation with resistance training (RT) could improve exertional dyspnea, exercise tolerance, and intrinsic neuromuscular fatigability in individuals with COPD (n = 14, FEV1 = 62 ± 21% predicted), we performed a proof-of-concept single-arm efficacy study utilizing 4 wk of individualized lower-limb RT (3 times/wk). At baseline, dyspnea (Borg scale), ventilatory parameters, lung volumes (inspiratory capacity maneuvers), and exercise time were measured during a constant-load test (CLT) at 75% maximal workload to symptom limitation. On a separate day, fatigability was assessed using 3 min of intermittent stimulation of the quadriceps (initial output of ∼25% maximal voluntary force). Following RT, the CLT and fatigue protocols were repeated. Compared with baseline, isotime dyspnea was reduced (5.9 ± 2.4 vs. 4.5 ± 2.4 Borg units, P = 0.02) and exercise time increased (437 ± 405 s vs. 606 ± 447 s, P < 0.01) following RT. Isotime tidal volume increased (P = 0.01), whereas end-expiratory lung volumes (P = 0.02) and heart rate (P = 0.03) decreased. Quadriceps force, relative to initial force, was higher at the end of the stimulation protocol posttraining (53.2 ± 9.1 vs. 46.8 ± 11.9%, P = 0.04). This study provides evidence that 4 wk of RT attenuates exertional dyspnea and improves exercise tolerance in individuals with COPD, which in part, is likely due to delayed ventilatory constraint and reduced intrinsic fatigability. A pulmonary rehabilitation program beginning with individualized lower-limb RT may help mitigate dyspnea before performing aerobic training in individuals with COPD.NEW & NOTEWORTHY This study presents the novel finding that 4-wk resistance training (RT) focused specifically on the lower limbs can reduce exertional dyspnea during constant-load cycling, improve exercise tolerance, and reduce intrinsic fatigability of the quadriceps in individuals with COPD.

The patent foramen ovale may alter migraine brain activity: A pilot study of electroencephalography spectrum and functional connectivity analysis.

A link has been shown between patent foramen ovale (PFO) and migraine, particularly migraine with aura. However, it is unknown if PFO might cause migraine by altering cortical excitability and neural network, which may lower the threshold of cortical spreading depression (CSD). This study aims to compare the spectrum power and functional connectivity of the alpha and beta bands of electroencephalography (EEG) across migraine patients with and without PFO. Thirty-five migraine patients with PFO (PFO +), 35 migraine patients without PFO (PFO -) and 20 PFO patients without migraine (control) were enrolled in this cross-sectional analysis. 19-channel EEG was recorded for all patients under resting state and intermittent photic stimulation. Power spectrum density (PSD) and phase lag index (PLI) of alpha and beta bands were then calculated and compared between the three groups. During photic stimulation, the beta band PSD at the occipital area was substantially higher in PFO + migraine patients compared to PFO-migraine patients (p < 0.05, Bonferroni corrected). Subgroup analysis showed that both migraine with and without aura patients with PFO had increased PSD in the alpha and beta bands at the occipital region during photic stimulation (p < 0.05, Bonferroni corrected). Meanwhile, the beta band PLI during photic stimulation was significantly elevated (adjusted p = 0.008, utilizing the network-based statistic technique) in PFO + group compared to PFO-group. Furthermore, although failed to pass the correction, the beta band power in the occipital area during photic stimulation at 20 Hz on O1 (R = 0.392, p = 0.024) and O2 channel (R = 0.348, p = 0.047) was prone to positively correlated with MIDAS score, and during photic stimulation at 12 Hz on O2 channel (R = 0.396, p = 0.022) and 20 Hz (R = 0.365, p = 0.037) on O1 channel was prone to positively correlated to HIT-6 score in PFO+ migraineurs, whereas no similar correlation was found in the PFO-group patients. The outcomes of this investigation suggested that PFO may change the cortical excitability in the occipital lobe of both migraineurs with and without aura. Meanwhile, the beta band PSD on the occipital area during photic stimulation might be an objective measure of severity in migraineurs with PFO.

Continuous vagus nerve stimulation exerts beneficial effects on rats with experimentally induced Parkinson's disease: Evidence suggesting involvement of a vagal afferent pathway

BackgroundVagus nerve stimulation (VNS) exerts neuroprotective and anti-inflammatory effects in preclinical models of central nervous system disorders, including Parkinson's disease (PD). VNS setting applied for experimental models is limited into single-time or intermittent short-duration stimulation. We developed a VNS device which could deliver continuous stimulation for rats. To date, the effects of vagal afferent- or efferent-selective stimulation on PD using continuous electrical stimulation remains to be determined. ObjectiveTo investigate the effects of continuous and selective stimulation of vagal afferent or efferent fiber on Parkinsonian rats. MethodsRats were divided into 5 group: intact VNS, afferent VNS (left VNS in the presence of left caudal vagotomy), efferent VNS (left VNS in the presence of left rostral vagotomy), sham, vagotomy. Rats underwent the implantation of cuff-electrode on left vagus nerve and 6-hydroxydopamine administration into the left striatum simultaneously. Electrical stimulation was delivered just after 6-OHDA administration and continued for 14 days. In afferent VNS and efferent VNS group, the vagus nerve was dissected at distal or proximal portion of cuff-electrode to imitate the selective stimulation of afferent or efferent vagal fiber respectively. ResultsIntact VNS and afferent VNS reduced the behavioral impairments in cylinder test and methamphetamine-induced rotation test, which were accompanied by reduced inflammatory glial cells in substantia nigra with the increased density of the rate limiting enzyme in locus coeruleus. In contrast, efferent VNS did not exert any therapeutic effects. ConclusionContinuous VNS promoted neuroprotective and anti-inflammatory effect in experimental PD, highlighting the crucial role of the afferent vagal pathway in mediating these therapeutic outcomes.

Abnormal brain function in photophobic patients with dry eye disease: An fMRI study

Background and objectivesPhotophobia, a frequent and disabling symptom observed in various neurological conditions and eye diseases, is thought to involve maladaptive brain functioning. We assessed this hypothesis, using functional magnetic resonance imaging (fMRI) in photophobic patients with minimal-to-severe dry eye disease (DED), as compared to healthy controls. MethodsThis prospective, monocentric, comparative, cohort study included eleven photophobic DED patients compared to eight controls. Photophobic patients had a complete evaluation of DED to exclude any other cause of photophobia. All participants were scanned with fMRI under intermittent light stimulation with a LED lamp (27s. ON, 27 s. OFF), and cerebral activations were studied with univariate contrasts between the ON and OFF conditions, and with functional connectivity methods. ResultsFirstly, stimulation activated the occipital cortex more strongly in patients than in controls. Moreover, stimulation deactivated the superior temporal cortex in patients less than in controls. Secondly, functional connectivity analysis showed that light stimulation induced lesser decoupling between the occipital cortex and the salience and visual networks in patients than in controls. DiscussionThe current data shows that DED patients with photophobia have maladaptive brain anomalies. There is hyperactivity in the cortical visual system, associated with abnormal functional interactions, both within the visual cortex, and between visual areas and salience control mechanisms. Such anomalies show similarities with other conditions such as tinnitus, hyperacusis, and neuropathic pain. Those findings support novel neurally oriented methods for the care of patients with photophobia.

Data Augmentation Effects on Highly Imbalanced EEG Datasets for Automatic Detection of Photoparoxysmal Responses.

Photosensitivity is a neurological disorder in which a person's brain produces epileptic discharges, known as Photoparoxysmal Responses (PPRs), when it receives certain visual stimuli. The current standardized diagnosis process used in hospitals consists of submitting the subject to the Intermittent Photic Stimulation process and attempting to trigger these phenomena. The brain activity is measured by an Electroencephalogram (EEG), and the clinical specialists manually look for the PPRs that were provoked during the session. Due to the nature of this disorder, long EEG recordings may contain very few PPR segments, meaning that a highly imbalanced dataset is available. To tackle this problem, this research focused on applying Data Augmentation (DA) to create synthetic PPR segments from the real ones, improving the balance of the dataset and, thus, the global performance of the Machine Learning techniques applied for automatic PPR detection. K-Nearest Neighbors and a One-Hidden-Dense-Layer Neural Network were employed to evaluate the performance of this DA stage. The results showed that DA is able to improve the models, making them more robust and more able to generalize. A comparison with the results obtained from a previous experiment also showed a performance improvement of around 20% for the Accuracy and Specificity measurements without Sensitivity suffering any losses. This project is currently being carried out with subjects at Burgos University Hospital, Spain.

The seizures that wake up with the patient: The effect of sleep deprivation and short sleep on epilepsy with eyelid myoclonia

ObjectiveIn this study, our aim was to demonstrate the effect of sleep deprivation, short sleep, and awakening on photoparoxysmal responses (PPR) and eyelid myoclonia (EM) in patients with Epilepsy with Eyelid Myoclonia (E-EM). MethodsE-EM patients with at least 1 year of follow-up in our clinic were included in the study. Video EEG(v-EEG) analyses were divided into three periods of wakefulness, sleep, and awakening. The PPR and onset of EMs were investigated. Results32 patients met the study criteria, of which 56.3% (n = 18) were male. The mean age at disease onset was 7.7 ± 4.1 years. The mean age at EEG recording was 12.4 ± 4.0 years. EM was observed only on awakening in 78.1% of patients (n = 22), of which it was seen only during intermittent photic stimulation (IPS) in 43.7% (n = 14). Eye closure (EC) sensitivity was detected in all patients. The proportion of patients with a PPR was significantly higher on awakening than before sleep (p = 0.01). ConclusionsThis study showed that EM is most prominent and sometimes can only be detected in the awakening period in E-EM. In order to detect E-EM, v-EEG recordings including both pre-sleep and post-sleep wakefulness periods should be recorded, with intermittent photic stimulation performed in both periods.

Visual opsins: Physiological alteration promoted by led light

Rods are the most sensitive cells to light present in the retina, being therefore responsible for dim light vision. Light photons captured by the retina stimulate rhodopsin, promoting phototransduction mechanisms that end up sending the information to the brain. However, overexposure to light and continuous receptor stimulation may promote retinal damage. Thus, artificial light might have harmful effects on the retina, most particularly in rods. Light‐emitting diodes (LEDs) are nowadays the most used devices, and therefore their potential damage to the visual system should be evaluated and considered as a potential environmental factor in retinal degeneration. Particularly in Wistar rats, tonic receptors stimulation under constant light exposure (LL) produces retinal remodeling, inducing classical photoreceptors death and a re-location of non-classical opsins.This work aims to show the effects of LED devices on rat retinas under intermittent stimulation. Wistar rats were exposed to white LED under 12:12 light/dark cycles for seven days (LD) to finally analyze the number of photoreceptors nuclei, electroretinograms (ERGs) activity, and glial activation. Our findings demonstrate that animals exposed to LED devices, even when they have intermittent periods of rest in darkness, present early retinal injury after seven days, compared with animals maintained in housing conditions (LDR) or darkness (DD). Altogether, these results suggest that extended LD conditions might induce retinal damage as constant light exposure (LL) does.