Single Stimulation Research Articles

Abstract TP111: Multielectrode Network Stimulation (ME-NETS) with tDCS modulates connectivity between brain regions as demonstrated by concurrent tDCS and rs-fMRI – implications for facilitating stroke recovery

Non-invasive transcranial direct current stimulation (tDCS) can modulate activity of targeted brain regions. Whether tDCS can reliably and repeatedly modulate intrinsic connectivity of entire brain networks is unclear. We used concurrent tDCS-MRI to investigate the effect of high dose anodal tDCS (4mA) on resting state connectivity between cortical regions within the Arcuate Fasciculus (AF) network, which spans the temporal, parietal, and frontal lobes and is connected via a structural backbone, the Arcuate Fasciculus (AF) white matter tract. The Arcuate Fasciculus Network plays an important role in the auditory-motor feedforward and feedback control of vocalizations and speech-language functions. The degree of injury to the Acuate Fasciculus Network on the dominant hemisphere is related to speech motor/language impairment after stroke. A rudimentary AF-network typically exists on the non-dominant hemisphere that might be enhanced and fostered to show plastic changes after stroke. We tested this approach with non-invasive high dose electrical stimulation. Effects of high-dose tDCS (4mA) delivered via a single electrode placed over one of the AF nodes (single electrode stimulation, SE-S) was compared to the same dose split between multiple electrodes placed over AF-network nodes (multielectrode network stimulation, ME-NETS). While both SE-S and ME-NETS significantly modulated connectivity between AF network nodes (increasing connectivity during stimulation epochs), ME-NETS had a significantly larger and more reliable effect than SE-S. Moreover, comparison with a control network, the Inferior Longitudinal Fasciculus (ILF) network on the same hemisphere targeted by tDCS suggested that the effect of ME-NETS on connectivity was specific to the targeted AF-network. This finding was further supported by the results of a seed-to-voxel analysis wherein we found ME-NETS primarily modulated connectivity between AF-network nodes, meaning cortical regions such as the Inferior Frontal Gyrus, the Supramarginal Gyrus, and the posterior superior temporal gyrus, which constitute the nodal regions of the AF network. Finally, an exploratory analysis looking at dynamic connectivity using sliding window correlation found strong and immediate modulation of connectivity during three stimulation epochs intermingled with no-stimulation epochs within the same imaging session suggesting that the intrinsic connectivity between these regions can reliably and repeatedly be modulated.

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

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

Associative brain-computer interface training increases wrist extensor corticospinal excitability in patients with subacute stroke.

In a recently developed associative rehabilitative brain-computer interface (BCI) system, electroencephalography (EEG) is used to identify the most active phase of the motor cortex during attempted movement and deliver precisely timed peripheral stimulation during training. This approach has been demonstrated to facilitate corticospinal excitability and functional recovery in patients with lower limb weakness following stroke. The current study expands those findings by investigating changes in corticospinal excitability following the associative BCI intervention in patients with post stroke with upper limb weakness. In a randomized controlled trial, 24 patients with subacute stroke, subdivided into an intervention group and a "sham" control group, performed 30 wrist extensions. The intervention comprised 30 pairings of single peripheral nerve stimulation at the motor threshold, timed so that the generated afferent volley arrived at the motor cortex during the peak negativity of the movement-related cortical potential (MRCP), which was identified with EEG. The sham group underwent the same intervention, though the intensity of the nerve stimulation was below the perception threshold. Immediately after training, patients in the associative group exhibited significantly larger amplitudes of muscular-evoked potentials, compared with pretraining measurements in response to transcranial magnetic stimulation. These changes persisted for at least 30 min and were not observed in the sham group. We demonstrate that motor-evoked potential amplitudes increased significantly following paired associative BCI training targeting upper limb muscles in patients with subacute stroke, which is in line with results from lower limb studies.NEW & NOTEWORTHY We have demonstrated that a single training session with an associative brain-computer interface increased corticospinal excitability in patients suffering from upper limb weakness following stroke. This is the first time such an effect is described in the upper limb, which paves the way for effect augmentation of existing upper limb rehabilitation protocols.

Single High-Frequency Repetitive Transcranial Magnetic Stimulation and Intermittent Theta Pulse Stimulation Promote Working Memory Behavior in Participants: An Event-Related Potential Study

ObjectiveRepetitive transcranial magnetic stimulation (rTMS) to the left dorsolateral prefrontal cortex (L-DLPFC) has an improving effect in cognitive function, but it is still not clear in what specific cognitive domains. We here combined a single session of TMS (HF-rTMS/iTBS) with electroencephalography (EEG) to clarify the effects of magnetic stimulation techniques on executive function, working memory, and visuospatial attention in healthy participants, and to investigate the underlying neurophysiological mechanisms. MethodsFifty-one healthy participants were randomly assigned to three stimulation groups (HF-rTMS, iTBS, and sham groups). Classical psychological paradigms (task-switching, 2-back with visual Oddball) and event-related potentials (ERPs) were performed to compare the behavioral indices of each paradigm before and after the two stimulations, as well as the changes in the ERP components. ResultsAnalysis of behavioral indicators showed that reaction times in the 2-back paradigm were faster after HF-rTMS and iTBS than after sham stimulation. However, no statistically significant differences were observed in the behavioral changes in the task-switching and visual Oddball paradigms. ERP analysis showed that N2 amplitude in the frontal and central regions of the participants increased during the 2-back paradigm following HF-rTMS and iTBS; however, no statistically significant differences were observed between the ERP components of the task-switching and visual Oddball paradigms. ConclusionSingle sessions of HF-rTMS and iTBS on the L-DLPFC specifically enhanced working memory performance, with no significant effects on executive function and visuospatial attention. Both true stimulations elicited more negative N2 in the frontal and central channels during the 2-back paradigm, suggesting increased recruitment of cognitive resources from these brain areas. Although iTBS and HF-rTMS improved working memory behavior, iTBS’s shorter stimulation time suggests it may have greater potential for clinical applications in terms of time-benefit costs.

Guilu Erxian Jiao remodels dendritic spine morphology through activation of the hippocampal TRPC6-CaMKIV-CREB signaling pathway and suppresses fear memory generalization in rats with post-traumatic stress disorder.

Guilu Erxian Jiao (GLEXJ) is a renowned traditional Chinese herbal formula used to tonify the kidney. It is employed to treat psychiatric disorders, and alleviate memory impairment, cognitive dysfunction, and behavioral disorders. Modern pharmacological studies have demonstrated GLEXJ's ability to significantly inhibit the fear response in post-traumatic stress disorder (PTSD) and facilitate the extinction of fear memory. However, the underlying pharmacological mechanisms remain elusive. Fear memory generalization, a fundamental characteristic of PTSD, remains poorly understood, and optimal pharmacological treatments are lacking. This study aimed to investigate GLEXJ's inhibitory effects on fear memory generalization in PTSD rats and elucidate its underlying mechanisms. PTSD rats were induced using the single prolonged stress and electrical stimulation (SPS&S) protocol and treated with GLEXJ or paroxetine (PRX). Fear memory generalization was assessed using a contextual fear memory test. Hippocampal dendritic spine morphology was analyzed using Golgi-Cox staining. The chemical composition of GLEXJ was determined using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Network pharmacology was employed to predict GLEXJ's therapeutic mechanism in PTSD treatment. Western blotting and immunofluorescence were used to measure indicators of the transient receptor potential channel 6 (TRPC6)-mediated calcium/calmodulin-dependent protein kinase IV-cAMP response element-binding protein (CaMKIV-CREB) signaling pathway. In vitro, TRPC6 was suppressed in rat adrenal pheochromocytoma (PC12) cells using lentiviral vectors, and phalloidin staining was employed to examine changes in Fibros actin (F-actin), elucidating the mechanistic effects of GLEXJ-containing serum. GLEXJ significantly mitigated fear memory generalization in PTSD rats, even with repeated stress exposure. It also alleviated abnormal hippocampal dendritic spine morphology. Network pharmacology analysis confirmed that GLEXJ was closely related to the Ca2+ signaling pathway in PTSD treatment. PTSD rats exhibited disrupted TRPC6-mediated CaMKIV-CREB signaling and impaired synaptic plasticity. GLEXJ upregulated TRPC6 expression, reactivated the CaMKIV-CREB pathway, and promoted synaptic remodeling. In vitro studies confirmed that TRPC6 suppression reduced F-actin levels while GLEXJ-containing serum increased TRPC6 expression and F-actin content. GLEXJ activates CaMKIV-CREB signaling by upregulating TRPC6 in the hippocampus of PTSD rats, leading to the positive modulation of dendritic spine morphology and synaptic remodeling. This mechanism contributes to the attenuation of fear memory generalization. Given the limitations of current PTSD treatments, these findings offer potential avenues for developing more effective therapeutic strategies.

Morphofunctional assessment of muscles of the lower leg and foot after autoneuroplasty of resection defect of tibial portion of the sciatic nerve and single intraoperative electrical neurostimulation in adult rats

INTRODUCTION: There are no data in the literature on the effect of a single intraoperative electrical stimulation (IES) on the condition of the muscles of the lower leg and foot in the long-term period after autoplasty of the sciatic nerve in adult rats. AIM: To study morphofunctional characteristics of muscles of the lower leg and foot after autoneuroplasty of a resection defect of the tibial portion of the sciatic nerve and a single IES in adult rats. MATERIALS AND METHODS: The experiment was performed on 30 Wistar rats who underwent autoneuroplasty (AN) after resection of the tibial portion of the sciatic nerve. Fourteen rats underwent a 40-munite IES session (AN + IES series). In 16 rats IES was not conducted (AN series). At 4 and 6 months after the operation, the tibial nerve function index (TFI) was calculated by analyzing rats’ paw traces on a walking track. At the same time, light microscopy and histomorphometry of paraffin and epoxy sections of gastrocnemius and plantar interosseous muscles were performed. A conventional control was muscles of intact limbs. RESULTS: Atrophy and endomysial fibrosis were less expressed in the gastrocnemius of the AN + IES series in comparison with AN series, the effect was mediated by enhancement of vascularization. In plantar interosseous muscles at 4 months after the operation, the volume density of blood vessels in the AN + IES series was 7.35 (5.49; 8.69), which was greater than in the AN series — 3.43 (2.02; 5.59), р = 0.0196. Diameters of muscle fibers and volume density of endomysium were comparable. At 6 months after the operation, endomysial fibrosis progressed in both series, but in the AN + IES series, myopathically altered muscle fibers were less common. After 6-month observation, TFI increased (-47.95) in the AN + IES series and became higher (p = 0.0339) than in the AN series, in which TFI became even lower (-93.64) than it was after 4 months (-81.95) of the experiment. CONCLUSION: A single IES permits to reduce the denervation alterations in the gastrocnemius and plantar interosseous muscles conditioned by damage to the nerve and maturation, and also to improve the tibial nerve function index in the long term after autoneuroplasty.

How to use clinical neurophysiology in functional neurological disorders (FND)?

I have reviewed the utility of clinical neurophysiological examinations in recently highlighted functional neurological disorders (FND) focusing mainly on functional movement disorders (FMD). There are many neurophysiological methods useful for diagnosis of FMD. I will hereafter summarize a few of them in the following part. Surface EMG: This is one of minimally required examinations for clinical analysis of movement disorders. It plays roles in the exclusion of organic disorders and showing positive findings to support FND, especially for functional tremor. The power spectral analysis of surface EMG clearly proves a few useful findings, such as entrainment, distraction and others. Somatosensory evoked potential (SEP): Giant SEP is critical because it proves organic disorders with hyperexcitability of the sensory cortex. Single pulse transcranial magnetic stimulation (TMS): Normal motor evoked potential (MEP) showing intact corticospinal tracts is a positive finding for functional paresis patients. It is also useful to exclude the corticospinal tracts organic dysfunction. Jerk-locked back averaging (JLA), bereitschaftspotential (BP), event related desynchronization (ERD): These are sometimes used for functional disorders, but their clinical validity remains to be determined.

Synaptic acetylcholine induces sharp wave ripples in the basolateral amygdala through nicotinic receptors.

While the basolateral amygdala (BLA) is critical in the consolidation of emotional memories, mechanisms underlying memory consolidation in this region are not well understood. In the hippocampus, memory consolidation depends upon network signatures termed sharp wave ripples (SWR). These SWRs largely occur during states of awake rest or slow wave sleep and are inversely correlated with cholinergic tone. While high frequency cholinergic stimulation can inhibit SWRs through muscarinic acetylcholine receptors, it is unclear how nicotinic acetylcholine receptors or different cholinergic firing patterns may influence SWR generation. SWRs are also present in BLA in vivo. Interestingly, the BLA receives extremely dense cholinergic inputs, yet the relationship between acetylcholine (ACh) and BLA SWRs is unexplored. Here, using brain slice electrophysiology in male and female mice, we show that brief stimulation of ACh inputs to BLA reliably induces SWRs that resemble those that occur in the BLA in vivo. Repeated ACh-SWRs are induced with single pulse stimulation at low, but not higher frequencies. ACh-SWRs are driven by nicotinic receptors which recruit different classes of local interneurons and trigger glutamate release from external inputs. In total, our findings establish a previously undefined mechanism for SWR induction in the brain. They also challenge the previous notion of neuromodulators as purely modulatory agents gating these events but instead reveal these systems can directly instruct SWR induction with temporal precision. Further, these results intriguingly suggest a new role for the nicotinic system in emotional memory consolidation.

Resting state EEG Abnormalities and their Relationship with TMS‐EEG induced Cortical Excitability in Alzheimer's Dementia

AbstractBackgroundPrevious literature has identified slowing of resting state electroencephalography (EEG) rhythm and abnormal cortical excitation in Alzheimer’s Dementia (AD). However, the relationship between these two divergent functional abnormalities and cognitive symptoms of AD are not well understood.MethodResting state EEG signal was recorded in participants with AD and HCs for 5 minutes with eyes closed. Relative resting state EEG power was measured for the five frequency bands. Participants underwent a single pulse transcranial magnetic stimulation (TMS) combined with EEG. Cortical evoked activity (CEA) was assessed using TMS‐evoked potential (TEP) rectified area under the curve (AUC) from 25 to 80 ms post‐TMS stimulus, and the TEPs peak amplitudes were calculated by taking the maximal peak in the following time windows: 25 – 35 ms (P30), 40 – 50 ms (N45), and 55 – 65 ms (P60).ResultCompared to 32 HC (18 females; mean ± SD age: 69.3 ± 7.9 years), 52 participants with AD (32 females; 74.2 ± 8.5 years) had higher relative theta power than HCs (t(66.6) = 5.34, p<0.001). AD participants also had a significantly lower alpha power (t(76) = ‐3.03, p=0.003) and beta power (t(76) = ‐2.51, p=0.014) than HCs. Controlling for sex, age and years of education, AD participants showed a positive association between theta power and CEA (rpartial=0.573, p=0.008); and an inverse association between alpha power and CEA (rpartial=‐0.471, p=0.036). Theta power in AD participants showed a positive association with P60 (rpartial=‐0.637, p=0.003) and an inverse association with N45 (rpartial=‐0.512, p=0.025), while alpha power was inversely associated with P60 (rpartial=‐0.531, p=0.016).ConclusionThis study showed a positive association between resting state EEG slowing and increased cortical excitability in AD, indicating a possible shared mechanistic pathway between these abnormalities.

Muscle twitch thresholds depending on the direction of current stimulation

Abstract Acoustic or visual warning signals for workers in hazardous situations might fail under loud and/or lowvisibility work situations. A warning system that uses electrocutaneous stimulation can overcome this problem. This study aimed to compare vertical, diagonal, and horizontal current stimulation directions at the upper arm to select the one with the lowest amount of muscle twitching. Fourteen electrodes were attached in two rows to the upper right arm of 15 participants. The stimulation was conducted with bi-phasic rectangular pulses of 150 μs and amplitudes of up to 25 mA. Muscle twitch thresholds have been determined and a circumferential stimulation signal was presented as warning pattern for the three current stimulation directions and evaluated regarding alertness, discomfort, and urgency. For single stimulation pulses, muscle twitches occurred slightly less often at the horizontal stimulation direction compared to the other two and muscle twitch thresholds showed no systematic differences. For the warning patterns, no considerable differences were found regarding the evaluation of alertness, discomfort, and urgency and no differences were found for muscle twitching. In conclusion, all orientations seem suitable for warning pattern presentation and none of the directions has a clear advantage in reducing muscle twitch.

The impact of Duostim protocol on pregnancy outcomes in infertile patients: A meta-analysis comparing single and double conventional stimulation cycles.

The DuoStim protocol has been proposed as an alternative to conventional single and double stimulation cycles in the treatment of infertility. However, its efficacy in improving pregnancy outcomes remains uncertain. To systematically evaluate the impact of the DuoStim protocol on pregnancy outcomes in infertile patients by comparing it with single and double conventional stimulation cycles. An online systematic search was conducted using PubMed, Cochrane Library, and EMBASE databases, covering the period from their inception to March 2024. Randomized controlled trials (RCTs) comparing the DuoStim protocol with single and double conventional stimulation cycles in infertile patients were identified. Data were extracted by two independent investigators who screened the literature and assessed the quality of the studies. Meta-analysis was performed using RevMan 5.4 software. A total of six RCTs involving 414 infertile patients were included. The DuoStim protocol significantly increased the total number of oocytes compared to single and double conventional stimulation (MD = - 1.47; 95% CI, - 2.12 to - 0.82; P < 0.00001). There were no statistically significant differences in the number of MII oocytes, total embryos, pregnancy rate, and live birth rate. Subgroup Analysis: compared to single stimulation, the DuoStim protocol significantly increased the number of MII oocytes (MD = 1.71; 95% CI, 0.77 to 2.66; P = 0.0004) and total embryos (MD = 1.34; 95% CI, 0.61 to 2.08; P = 0.0003). There were no significant differences in pregnancy rate and live birth rate. Secondary outcomes showed the effect of the DuoStim protocol in patients undergoing preimplantation genetic testing for aneuploidies (PGT-A). The time to obtain euploid blastocysts was significantly reduced in the DuoStim group compared to the control group (23.3 ± 2.8days vs. 44.1 ± 2.0days; P < 0.001). The DuoStim protocol shows a significant advantage in increasing the total number of oocytes, MII oocytes, and embryos compared to single stimulation. However, it does not significantly improve pregnancy and live birth rates. The protocol also shortens the time to obtain euploid blastocysts in patients undergoing PGT-A, indicating potential benefits for specific patient groups. Further research is needed to confirm these findings and evaluate long-term outcomes. Thus, the quality of evidence should be considered moderate, warranting cautious interpretation of the results.

Effects of yeast on inflammatory responses in yellow-feathered broilers induced by single and multiple lipopolysaccharide stimulation

Effects of yeast on inflammatory responses in yellow-feathered broilers induced by single and multiple lipopolysaccharide stimulation

Stimulation-Evoked Resonant Neural Activity in the Subthalamic Nucleus Is Modulated by Sleep.

Deep brain stimulation is a treatment for advanced Parkinson's disease and currently tuned to target motor symptoms during daytime. Parkinson's disease is associated with multiple nocturnal symptoms such as akinesia, insomnia, and sleep fragmentation, which may require adjustments of stimulation during sleep for best treatment outcome. There is a need for a robust biomarker to guide stimulation titration across sleep stages. This study aimed to investigate whether evoked resonant neural activity (ERNA) is modulated by sleep. We recorded local field potentials from the subthalamic nucleus of four Parkinson's patients with externalized electrodes while applying single stimulation pulses to investigate the effect of sleep on ERNA. We found that ERNA features change with wakefulness and sleep stages and are correlated with canonical frequency bands and heart rate. Given that ERNA modulates with sleep, it could be used as a robust marker for automatic stimulation titration during sleep. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The Effect of the Optogenetic Stimulation of Astrocytes on Neural Network Activity in an In Vitro Model of Alzheimer's Disease.

Optogenetics is a combination of optical and genetic technologies used to activate or, conversely, inhibit specific cells in living tissues. The possibilities of using optogenetics approaches for the treatment of epilepsy, Parkinson's and Alzheimer's disease (AD) are being actively researched. In recent years, it has become clear that one of the most important players in the development of AD is astrocytes. Astrocytes affect amyloid clearance, participate in the development of neuroinflammation, and regulate the functioning of neural networks. We used an adeno-associated virus carrying the glial fibrillary acidic protein (GFAP) promoter driving the optogenetic channelrhodopsin-2 (ChR2) gene to transduce astrocytes in primary mouse hippocampal cultures. We recorded the bioelectrical activity of neural networks from day 14 to day 21 of cultivation using multielectrode arrays. A single optogenetic stimulation of astrocytes at 14 day of cultivation (DIV14) did not cause significant changes in neural network bioelectrical activity. Chronic optogenetic stimulation from DIV14 to DIV21 exerts a stimulatory effect on the bioelectrical activity of primary hippocampal cultures (the proportion of spikes included in network bursts significantly increased since DIV19). Moreover, chronic optogenetic stimulation over seven days partially preserved the activity and functional architecture of neuronal network in amyloidosis modeling. These results suggest that the selective optogenetic activation of astrocytes may represent a promising novel therapeutic strategy for combating AD.

Intracranial EEG-Based Directed Functional Connectivity in Alpha to Gamma Frequency Range Reflects Local Circuits of the Human Mesiotemporal Network

To date, it is largely unknown how frequency range of neural oscillations measured with EEG is related to functional connectivity. To address this question, we investigated frequency-dependent directed functional connectivity among the structures of mesial and anterior temporal network including amygdala, hippocampus, temporal pole and parahippocampal gyrus in the living human brain. Intracranial EEG recording was obtained from 19 consecutive epilepsy patients with normal anterior mesial temporal MR imaging undergoing intracranial presurgical epilepsy diagnostics with multiple depth electrodes. We assessed intratemporal bidirectional functional connectivity using several causality measures such as Granger causality (GC), directed transfer function (DTF) and partial directed coherence (PDC) in a frequency-specific way. In order to verify the obtained results, we compared the spontaneous functional networks with intratemporal effective connectivity evaluated by means of SPES (single pulse electrical stimulation) method. The overlap with the evoked network was found for the functional connectivity assessed by the GC method, most prominent in the higher frequency bands (alpha, beta and low gamma), yet vanishing in the lower frequencies. Functional connectivity assessed by means of DTF and PCD obtained a similar directionality pattern with the exception of connectivity between hippocampus and parahippocampal gyrus which showed opposite directionality of predominant information flow. Whereas previous connectivity studies reported significant divergence between spontaneous and evoked networks, our data show the role of frequency bands for the consistency of functional and evoked intratemporal directed connectivity. This has implications for the suitability of functional connectivity methods in characterizing local brain circuits.

Proper reference selection and re-referencing to mitigate bias in single pulse electrical stimulation data.

Single pulse electrical stimulation experiments produce pulse-evoked potentials used to infer brain connectivity. The choice of recording reference for intracranial electrodes remains non-standardized and can significantly impact data interpretation. When the reference electrode is affected by stimulation or evoked brain activity, it can contaminate the pulse-evoked potentials recorded at all other electrodes and influence interpretation of findings. We highlight this specific issue in intracranial EEG datasets from two subjects recorded at separate institutions. We present several intuitive metrics to detect the presence of reference contamination and offer practical guidance on different mitigation strategies. Either switching the reference electrode or re-referencing to an adjusted common average effectively mitigated the reference contamination issue, as evidenced by increased variability in pulse-evoked potentials across the brain. Overall, we demonstrate the importance of clear quality checks and preprocessing steps that should be performed before analysis of single pulse electrical stimulation data.

Optogenetic Stimulation Recruits Cortical Neurons in a Morphology-Dependent Manner.

Single-photon optogenetics enables precise, cell-type-specific modulation of neuronal circuits, making it a crucial tool in neuroscience. Its miniaturization in the form of fully implantable wide-field stimulator arrays enables long-term interrogation of cortical circuits and bears promise for brain-machine interfaces for sensory and motor function restoration. However, achieving selective activation of functional cortical representations poses a challenge, as studies show that targeted optogenetic stimulation results in activity spread beyond one functional domain. While recurrent network mechanisms contribute to activity spread, here we demonstrate with detailed simulations of isolated pyramidal neurons from cats of unknown sex that already neuron morphology causes a complex spread of optogenetic activity at the scale of one cortical column. Since the shape of a neuron impacts its optogenetic response, we find that a single stimulator at the cortical surface recruits a complex spatial distribution of neurons that can be inhomogeneous and vary with stimulation intensity and neuronal morphology across layers. We explore strategies to enhance stimulation precision, finding that optimizing stimulator optics may offer more significant improvements than the preferentially somatic expression of the opsin through genetic targeting. Our results indicate that, with the right optical setup, single-photon optogenetics can precisely activate isolated neurons at the scale of functional cortical domains spanning several hundred micrometers.

Tinnitus Suppression with Electrical Stimulation at the Most Basal Contact of the Cochlear Implant Electrode as a Model for Round Window Stimulation.

The objective of this research was to test whether efficient tinnitus suppression could be achieved by electrical stimulation of the single most basal electrode contact of a cochlear implant. This approach simulates the effects of electrical stimulation using a round-window electrode. The study was performed in 10 adult cochlear implant patients showing complete or almost complete tinnitus suppression during electrical stimulation with their standard fitting-MAP. In all patients, tinnitus appeared again when the implant was switched off. Five Nucleus implant (1 CI532, 4 CI24RE CA) users and 5 Mi12xx series with FLEX28 electrodes with at least 6 months of CI experience were included. Two types of stimulation were presented at the most basal CI contact: a constant pulse train and a modulated pulse train. The variation in pulse rates was low rate (100-300 pps) and high (≥900 pps), and the current level ranged from the C-level to less than the T-level for both stimulation types. The effect of acute electrical stimulation at the most basal electrode contact was compared to the effect obtained with multichannel stimulation with the patient's current fitting MAP. Electrical stimulation was paused between tests with different stimulation types until tinnitus returned to baseline intensity. Patients reported Visual Analog Scale (VAS) scores for tinnitus loudness and intrusiveness during normal CI use and for each single contact stimulation type. Eight participants perceived complete suppression with one or more stimulation patterns. In 2 patients, suppression was less efficient than full-band CI stimulation. Louder stimuli are generally perceived as annoying and less effective in reducing tinnitus. In FLEX28 patients, it was also possible to obtain full tinnitus suppression with current amplitudes under the thresholds for auditory perception (this was not tested in patients with the Nucleus device). In 8 of the 10 included patients, we were able to obtain complete or almost complete tinnitus suppression with electrical stimulation at only 1 most basal electrode contact. Therefore, round-window stimulation with a single electrode may be a potential treatment for tinnitus in patients with significant residual hearing. The long-term effects of this therapy should be confirmed in future studies.

Evaluation of bone-conducted oVEMPs using frontal medial and mastoid stimulations

AimsTo determine the optimal stimulation intensity for frontal stimulation with a modified slit lamp holder and to compare the reliability and symmetry of bone-conducted ocular vestibular evoked myogenic potentials (oVEMPs) using two stimulation sites: frontal medial and mastoid. MethodsThis observational study included 33 healthy volunteers (15 women, 18 men; mean age 24.5years) at the University Hospital of Lausanne. Participants underwent otoneurological assessments, and those with normal results were included. Bone-conducted oVEMPs were recorded using a Brüel and Kjaer mini-shaker type 4810. A modified slit lamp holder was used for frontal stimulation to ensure consistent application pressure, freeing the examiner's hands. Mastoid stimulation was performed manually. ResultsThe best reproducibility of oVEMP recordings was observed at 70dB nHL. Frontal stimulation demonstrated lower dispersion of data and lower asymmetry ratios of latencies (up to 7%) and amplitudes (up to 50%) compared to mastoid stimulation (up to 40% for latencies). Single stimulations at both frontal and mastoid sites were sufficient to obtain reliable measurements of both utricles. ConclusionFrontal stimulation at 70dB nHL using a modified slit lamp holder is recommended for bone-conducted oVEMP recordings due to its superior reproducibility, comfort, and reliability. This study establishes a new standard for optimal stimulation intensity and supports the use of frontal stimulation in clinical practice.

P1.03D.09 Single Cell RNA Sequencing and Functional Monocyte Stimulation Reveals Phenotypic Predispositions to Developing Lung Cancer in Never Smokers

P1.03D.09 Single Cell RNA Sequencing and Functional Monocyte Stimulation Reveals Phenotypic Predispositions to Developing Lung Cancer in Never Smokers