Stimulation Strategies Research Articles

Abstract 18867: A Novel Light-Sensitive Ex-Vivo Rat Atrial Anatomical Model for Studying Atrial Arrhythmias and Cardioversion

Introduction: Atrial arrhythmias, including atrial fibrillation (AF), contribute to significant morbidity and mortality. However, the lack of suitable tissue models in small animals hampers our understanding of the underlying mechanisms. Optogenetic actuators offer precise and reversible stimulation with high spatiotemporal resolution, presenting a unique opportunity to investigate atrial arrhythmias. Hypothesis: Our aim was to develop a light-sensitive ex-vivo anatomical model in rats for studying atrial arrhythmias and to utilize this model for optimizing optogenetic stimulation and cardioversion strategies. Methods: We injected purified AAV particles containing the transgenic light-sensitive channel (CoChR) into 5-day-old Wistar rats, followed by an 8-10 week period for atrial growth. The atria were then isolated, flattened, and affixed to a custom-made silicon plate. Superfusion with oxygenated Tyrode's solution and loading with Di-4-ANBDQBS allowed for high-resolution optical mapping. Atrial arrhythmias were induced through targeted tachypacing combined with carbamylcholine treatment. Additionally, we compared different optical and pharmacological treatment strategies to evaluate their efficacy in modulating atrial arrhythmias. Results: Immunostaining confirmed atrial expression of CoChR. Optical mapping revealed a functional syncytium with sinus node activation and propagation throughout the atria. Pacing at increasing frequencies resulted in a relatively flattened action potential duration restitution curve. Successful induction of reentrant arrhythmias was achieved. Additionally, we demonstrated the feasibility of optogenetic actuators for atrial pacing, modulation of spontaneous activity, and optical termination of arrhythmias. Conclusions: The developed optogenetic superfused atria model provides a valuable platform for studying atrial electrophysiology and modeling reentrant arrhythmias. Furthermore, it enables the optimization of optogenetic stimulation and cardioversion strategies. This integrated approach enhances our understanding of atrial arrhythmias and holds promise for the development of novel therapeutic interventions.

Signal processing and stimulation potential within the ascending auditory pathway: a review.

The human auditory system encodes sound with a high degree of temporal and spectral resolution. When hearing fails, existing neuroprosthetics such as cochlear implants may partially restore hearing through stimulation of auditory neurons at the level of the cochlea, though not without limitations inherent to electrical stimulation. Novel approaches to hearing restoration, such as optogenetics, offer the potential of improved performance. We review signal processing in the ascending auditory pathway and the current state of conventional and emerging neural stimulation strategies at various levels of the auditory system.

Novel perturbation mechanism underlying the network fragility evolution

Studies have shown that fragility is an effective marker for seizures and seizure onset zone (SOZ). Through analysis and simulation of a probabilistic neural network under different inputs, the regularization mechanism of external input perturbations on the fragility is explored. It is theoretically found that the fragility of a perturbed node within seizure network is inversely associated with the received perturbation input, while the fragility of the other unperturbed nodes always oppositely changes with this perturbed node. By terming the node with high fragility as the fragile node (FN), it is interestingly shown that the FN would evolve to the node with the smallest input. Then, the network fragility is further investigated. Results show that the non-uniform perturbation inputs can more easily impact the network fragility. In addition, noise-induced variations of network connection can degrade the network fragility to some extent. Finally, the real data from a patient with epilepsy have verified the universality of the above obtained findings. These results may provide possible insights into stimulation strategies for seizure control in clinic.

A neuroimaging-based precision medicine framework for depression

BackgroundSymptom-based diagnostic criteria of depression leads to notorious heterogeneity and subjectivity. MethodsThe study was conducted in two stages at two sites: development of a neuroimaging-based subtyping and precise repetitive transcranial magnetic stimulation (rTMS) strategy for depression at Center 1 and its clinical application at Center 2. Center 1 identified depression subtypes and subtype-specific rTMS targets based on amplitude of low frequency fluctuation (ALFF) in a cohort of 238 major depressive disorder patients and 66 healthy controls (HC). Subtypes were identified using a Gaussian Mixture Model, and subtype-specific rTMS targets were selected based on dominant brain regions prominently differentiating depression subtypes from HC. Subsequently, one classifier was employed and 72 hospitalized, depressed youths at Center 2 received two-week precise rTMS. MRI and clinical assessments were obtained at baseline, midpoint, and treatment completion for evaluation. ResultsTwo neuroimaging subtypes of depression, archetypal and atypical depression, were identified based on distinct frontal-posterior functional imbalance patterns as measured by ALFF. The dorsomedial prefrontal cortex was identified as the rTMS target for archetypal depression, and the occipital cortex for atypical depression. Following precise rTMS, ALFF alterations were normalized in both archetypal and atypical depressed youths, corresponding with symptom response of 90.00% in archetypal depression and 70.73% in atypical depression. ConclusionsA precision medicine framework for depression was developed based on objective neurobiomarkers and implemented with promising results, actualizing a subtyping-treatment-evaluation closed loop in depression. Future randomized controlled trials are warranted.

Transcranial static magnetic stimulation reduces seizures in a mouse model of Dravet syndrome

Dravet syndrome is a rare form of severe genetic epilepsy characterized by recurrent and long-lasting seizures. It appears around the first year of life, with a quick evolution toward an increase in the frequency of the seizures, accompanied by a delay in motor and cognitive development, and does not respond well to antiepileptic medication. Most patients carry a mutation in the gene SCN1A encoding the α subunit of the voltage-gated sodium channel Nav1.1, resulting in hyperexcitability of neural circuits and seizure onset. In this work, we applied transcranial static magnetic stimulation (tSMS), a non-invasive, safe, easy-to-use and affordable neuromodulatory tool that reduces neural excitability in a mouse model of Dravet syndrome. We demonstrate that tSMS dramatically reduced the number of crises. Furthermore, crises recorded in the presence of the tSMS were shorter and less intense than in the sham condition. Since tSMS has demonstrated its efficacy at reducing cortical excitability in humans without showing unwanted side effects, in an attempt to anticipate a possible use of tSMS for Dravet Syndrome patients, we performed a numerical simulation in which the magnetic field generated by the magnet was modeled to estimate the magnetic field intensity reached in the cerebral cortex, which could help to design stimulation strategies in these patients. Our results provide a proof of concept for nonpharmacological treatment of Dravet syndrome, which opens the door to the design of new protocols for treatment.

Responsive deep brain stimulation guided by ventral striatal electrophysiology of obsession durably ameliorates compulsion

Treatment-resistant obsessive-compulsive disorder (OCD) occurs in approximately one-third of OCD patients. Obsessions may fluctuate over time but often occur or worsen in the presence of internal (emotional state and thoughts) and external (visual and tactile) triggering stimuli. Obsessive thoughts and related compulsive urges fluctuate (are episodic) and so may respond well to a time-locked brain stimulation strategy sensitive and responsive to these symptom fluctuations. Early evidence suggests that neural activity can be captured from ventral striatal regions implicated in OCD to guide such a closed-loop approach. Here, we report on a first-in-human application of responsive deep brain stimulation (rDBS) of the ventral striatum for a treatment-refractory OCD individual who also had comorbid epilepsy. Self-reported obsessive symptoms and provoked OCD-related distress correlated with ventral striatal electrophysiology. rDBS detected the time-domain area-based feature from invasive electroencephalography low-frequency oscillatory power fluctuations that triggered bursts of stimulation to ameliorate OCD symptoms in a closed-loop fashion. rDBS provided rapid, robust, and durable improvement in obsessions and compulsions. These results provide proof of concept for a personalized, physiologically guided DBS strategy for OCD.

Random-start ovarian stimulation in an oocyte donation programme: a large, single-centre, experience

Research questionDo live birth rates differ between recipients matched with donors using conventional ovarian stimulation compared with those using random-start protocols? DesignRetrospective analysis of 891 ovarian stimulations in egg donors (January–December 2018) and clinical outcomes in matched recipients (n = 935). Donors commenced ovarian stimulation on day 1–3 of the menstrual cycle (n = 223) or in the mid/late-follicular (n = 388) or luteal phase (n = 280) under a conventional antagonist protocol. Live birth rate of matched recipients was the main outcome. ResultsDuration of stimulation and total gonadotrophin dose were comparable between conventional versus random-start groups. The number of collected eggs were similar (17.6 ± 8.8 versus 17.2 ± 8.5, P = 0.6, respectively). Sub-group analysis showed that stimulation length (10.2 ± 1.8 versus 9.8 ± 1.7 versus 10.4 ± 1.7, P < 0.001) and gonadotrophin consumption (2041.5 ± 645.3 versus 2003.2 ± 647.3 versus 2158.2 ± 685.7 IU, P = 0.01) differed significantly between the conventional, mid/late follicular and luteal phase groups, respectively. In matched recipients receiving fresh oocytes and undergoing fresh embryo transfer, the biochemical pregnancy (63.8% and 63.3%; P = 0.9), clinical pregnancy (54.6% and 56.1%; P = 0.8) and live birth rates (47.7% and 46.6%; P = 0.7) per embryo-transfer were similar between conventional versus random groups. Similar results were obtained in recipients receiving vitrified eggs. Euploidy rate was also comparable. ConclusionsNo notable variations were found in clinical outcomes using oocytes obtained from random-start protocols and those proceeding from conventional ovarian stimulation in oocyte donation treatments. Luteal-phase stimulation seems to require longer stimulation and higher FSH consumption. Random-start stimulation strategy does not impair the potential of the oocyte yield or clinical outcomes in oocyte donation cycles.

A comparison of binaural cues transmitted by clinically available cochlear-implant stimulation strategies

Cochlear implants (Cis) effectively restore speech understanding in quiet for many recipients. However, bilateral CI listeners continue to perform poorer than acoustic-hearing listeners on spatial-hearing tasks (e.g., speech understanding in noise and sound localization). One explanation is that current clinically available stimulation strategies and unsynchronized sound processors degrade the fidelity of binaural cues. However, no conclusive comparison of the binaural cues transmitted by different stimulation strategies has been made. Therefore, this study compared binaural cues transmitted by two clinically available cochlear implant stimulation strategies. Two unsynchronized Cochlear Ltd. Nucleus 6 sound processors were placed on a binaural mannequin centered in a horizontal ring of loudspeakers in an anechoic chamber. Acoustic stimuli were presented from the loudspeakers and the resulting electrical pulse trains were recorded for both a peak-picking stimulation strategy and constantly stimulating strategy. Envelope interaural time differences and interaural level differences were extracted from the recordings and compared between stimulation strategies. Compared to the constantly stimulating strategy, results show that the peak-picking strategy led to more variable and less monotonic binaural cues, which could constrain sound-localization abilities. These findings argue for the bilateral synchronization of CIs in multiple domains, including electrode selection in peak-picking stimulation strategies and pulse timing.

Numerical simulation of hydraulic fracture extension patterns at the interface of coal-measure composite rock mass with Cohesive Zone Model

This study presents the development of a numerical computational model for hydraulic fracturing of coal-measure rock mass. The model is based on the B-K hybrid fracture energy criterion and is implemented using the extended finite element method (XFEM) and cohesive zone model (CZM) in the ABAQUS software. The study took into account the elastic-plastic damage properties of the coal-measure rock mass, as well as the combined effects of tensile and shear damage during the start and expansion of hydraulic fractures. The expansion trajectories and fracture morphology of hydraulic fractures at the interface of coal-measure rock mass under different lithological combinations (lithological strength differences) and ground stress conditions are revealed, and the main controlling factors affecting the expansion across the bedding are clarified. The study provides valuable insights into the management of hydraulic fracturing in the challenging context of hard roof coal mines, the stimulation of coal-measure gas co-production reservoirs, and the development of effective fracturing stimulation strategies for shale oil reservoirs interlayered with thin sandstone, and it can promote the development of industrial production technology for coal-measure gas and shale oil and gas resources, and is beneficial to increase the proportion of clean energy in China's energy consumption structure, and thus promoting a further reduction in the carbon emissions from energy consumption.

An extraocular electrical stimulation approach to slow down the progression of retinal degeneration in an animal model

Retinal diseases such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD) are characterized by unrelenting neuronal death. However, electrical stimulation has been shown to induce neuroprotective changes in the retina capable of slowing down the progression of retinal blindness. In this work, a multi-scale computational model and modeling platform were used to design electrical stimulation strategies to better target the bipolar cells (BCs), that along with photoreceptors are affected at the early stage of retinal degenerative diseases. Our computational findings revealed that biphasic stimulus pulses of long pulse duration could decrease the activation threshold of BCs, and the differential stimulus threshold between ganglion cells (RGCs) and BCs, offering the potential of targeting the BCs during the early phase of degeneration. In vivo experiments were performed to evaluate the electrode placement and parameters found to target bipolar cells and evaluate the safety and efficacy of the treatment. Results indicate that the proposed transcorneal Electrical Stimulation (TES) strategy can attenuate retinal degeneration in a Royal College of Surgeon (RCS) rodent model, offering the potential to translate this work to clinical practice.

Risk factors and management strategies of inadvertent facial nerve stimulation in cochlear implant recipients: A systematic review.

To systematically review the prevalence and risk factors of inadvertent facial nerve stimulation (FNS) after cochlear implant (CI) surgery. And to report the different management strategies used for reducing and resolving FNS. Web of Science, Scopus, PubMed, Cochrane Library, and Virtual Health Library (VHL) of the World Health Organization (WHO). A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) on studies that reported FNS as a complication after CI. A comprehensive electronic search strategy was used to identify the relevant articles. We extracted the data on the prevalence of FNS after CI activation, the reported grades, and the management strategies. The number of associated electrodes; cause of deafness; co-anomalies; and duration of hearing loss and their relationships with FNS were also studied. Twenty-one relevant articles were included in this review. The prevalence of FNS among the CI populations was 5.29% (175/3306 patients). Among those whose ages were reported, 58.3% (95/163) were adults, and 41.7% (68/163) were pediatrics. Modifying the different fitting parameters was the most used strategy, as it successfully resolved FNS in 85.5% of the patients (142/166). The second commonly used management strategy was surgical intervention (reimplantation or explantation), which was reported in seven studies for 23 patients. FNS after CI activation could be controlled and resolved with many advances that range from readjusting the fitting parameters to surgical intervention. However, further studies are required to validate the efficacy of each management strategy and its impact on patients' performance. Our findings demonstrate that CI recipients with FNS could still benefit from the CI devices and their FNS could be controlled.

Diya – A universal light illumination platform for multiwell plate cultures

Recent progress in protein engineering has established optogenetics as one of the leading external non-invasive stimulation strategies, with many optogenetic tools being designed for invivo operation. Characterization and optimization of these tools require a high-throughput and versatile light delivery system targeting micro-titer culture volumes. Here, we present a universal light illumination platform- Diya, compatible with a wide range of cell culture plates and dishes. Diya hosts specially designed features ensuring active thermal management, homogeneous illumination, and minimal light bleedthrough. It offers light induction programming via a user-friendly custom-designed GUI. Through extensive characterization experiments with multiple optogenetic tools in diverse model organisms (bacteria, yeast, and human cell lines), we show that Diya maintains viable conditions for cell cultures undergoing light induction. Finally, we demonstrate an optogenetic strategy for invivo biomolecular controller operation. With a custom-designed antithetic integral feedback circuit, we exhibit robust perfect adaptation and light-controlled set-point variation using Diya.

Generation of direct current electrical fields as regenerative therapy for spinal cord injury: A review.

Electrical stimulation (ES) shows promise as a therapy to promote recovery and regeneration after spinal cord injury. ES therapy establishes beneficial electric fields (EFs) and has been investigated in numerous studies, which date back nearly a century. In this review, we discuss the various engineering approaches available to generate regenerative EFs through direct current electrical stimulation and very low frequency electrical stimulation. We highlight the electrode-tissue interface, which is important for the appropriate choice of electrode material and stimulator circuitry. We discuss how to best estimate and control the generated field, which is an important measure for comparability of studies. Finally, we assess the methods used in these studies to measure functional recovery after the injury and treatment. This work reviews studies in the field of ES therapy with the goal of supporting decisions regarding best stimulation strategy and recovery assessment for future work.

Invited Session I: Vision restoration: Deep learning-based stimulus optimization for prosthetic vision.

Visual neuroprostheses are emerging as a promising technology to restore a rudimentary form of vision to people living with incurable blindness. However, phosphenes elicited by current devices often appear artificial and distorted. Although current computational models can predict the neural or perceptual response to an electrical stimulus, an optimal stimulation strategy needs to solve the inverse problem: what is the required stimulus to produce a desired response? Here we frame this as an end-to-end optimization problem, where a deep neural network encoder is trained to invert a psychophysically validated phosphene model that predicts phosphene appearance as a function of stimulus amplitude, frequency, and pulse duration. As a proof of concept, we show that our strategy can produce high-fidelity, patient-specific stimuli representing handwritten digits and segmented images of everyday objects that drastically outperform conventional encoding strategies by relying on smaller stimulus amplitudes at the expense of higher frequencies and longer pulse durations. Overall, this work is an important first step towards improving visual outcomes in visual prosthesis users across a wide range of stimuli.

Motor development in premature infants: Study protocol for an interdisciplinary hospital-home intervention.

Deviations occur in the neuropsychomotor development of premature infants; early interventions minimize delay motor. This study aimed to determine the effect of an interdisciplinary hospital-home intervention addressing motor development adaptation in premature infants in Colombia in comparison with traditional interventions. This study was based on a parallel design, with two groups, namely, experimental and control. The experimental group, hospital-home intervention (HHI) performed in two settings (i.e., hospital neonatal care units and homes), and the control group, traditional intervention, (TI) performed in institutions for premature infants. The sample will be composed of 130 randomly-allocated infants, 65 in the experimental group (HHI) and 65 in the control group (TI) of moderate to late preterm infants (gestational age between 34 and 37 weeks), weighing more than or equal to 1.800 g, who are hemodynamically stable and reside in the cities of Tunja and Bogotá-Colombia recruited between 2021 and 2022. For the pre- and post-intervention assessments, the TIMPSI and the CapDMP are the instruments used to assess motor development and the degree of parents' or caregivers' knowledge about motor development. The HHI is composed of 10 intervention strategies based on stimulation of motor development, performed twice a day for 10 min for two months, in combination with calls to a mobile device, using software (Baby Motor Skills) and an instant messaging system (WhatsApp). This hospital-home intervention program proposes an approach focused on the motor development of premature infants, based on sensory and motor stimulation strategies, in addition to follow-up performed at home with the use of a mobile application that improves the motor development of premature infants. Register Clinical Trial: NCT04563364. The HHI provides the opportunity to determine whether the individualized four-week from admission to follow up at home with parent training will improve the motor skills of premature infants.

Population Pharmacokinetic Analysis of Follicle-Stimulating Hormone During Ovarian Stimulation: Relation with Weight, Prolactin and Gene Polymorphism in THADA and ADIPOQ.

Personalisation strategies of ovarian stimulation for in vitro fertilisation (IVF)/ intracytoplasmic sperm injection (ICSI) treatments using exogenous follicle-stimulating hormone (FSH) have been extensively studied over the past 20 years. This research aimed to develop a FSH population pharmacokinetic (PPK) model taking into account the contribution of gene polymorphisms in Chinese reproductive-age women. Data from 173 patients undergoing GnRH agonist down-regulation long protocols of IVF/ICSI treatment were collected. PPK analysis was subsequently conducted using the nonlinear mixed-effect model (NONMEM) software. Several covariates, including 18 single nucleotide polymorphisms, demographic factors and biological characteristics, were evaluated. The final PPK model was extensively validated using bootstrapping and normalised prediction error distribution, as well as external validation on an independent group of 35 patients. FSH PPK was accurately described by a one-compartment model with first-order absorption. The typical population value of apparent clearance was estimated to be 0.81 L/h [relative standard errors (RSE) 5.3%] with an inter-individual variability (IIV) of 16.0%. The typical apparent distribution volume was 8.36 L (RSE 9.7%, 59.7% IIV), and the absorption rate constant was estimated to be 0.0444 h-1 (RSE 9.1%). Body weight, basal prolactin concentration and the gene ADIPOQ (rs1501299) showed a significant covariate effect on the FSH clearance rate and exposure concentration. Genotypes of THADA (rs12478601) significantly influenced the distribution volume. Simulation results indicated that patients with the TT genotype of THADA (rs12478601) required a longer time to reach steady state and had less fluctuation in FSH levels. Model evaluations showed that the final model accurately and precisely described the observed data and demonstrated effective prediction performance. PPK models of FSH have been developed, which could potentially be used for FSH dosage individualisation in the clinical setting. This study has been registered with the Chinese Clinical Trials Registry (ChiCTR2100049142).

Multi-objective optimization via evolutionary algorithm (MOVEA) for high-definition transcranial electrical stimulation of the human brain

Designing a transcranial electrical stimulation (tES) strategy requires considering multiple objectives, such as intensity in the target area, focality, stimulation depth, and avoidance zone. These objectives are often mutually exclusive. In this paper, we propose a general framework, called multi-objective optimization via evolutionary algorithm (MOVEA), which solves the non-convex optimization problem in designing tES strategies without a predefined direction. MOVEA enables simultaneous optimization of multiple targets through Pareto optimization, generating a Pareto front after a single run without manual weight adjustment and allowing easy expansion to more targets. This Pareto front consists of optimal solutions that meet various requirements while respecting trade-off relationships between conflicting objectives such as intensity and focality. MOVEA is versatile and suitable for both transcranial alternating current stimulation (tACS) and transcranial temporal interference stimulation (tTIS) based on high definition (HD) and two-pair systems. We comprehensively compared tACS and tTIS in terms of intensity, focality, and steerability for targets at different depths. Our findings reveal that tTIS enhances focality by reducing activated volume outside the target by 60%. HD-tTIS and HD-tDCS can achieve equivalent maximum intensities, surpassing those of two-pair tTIS, such as 0.51 V/m under HD-tACS/HD-tTIS and 0.42 V/m under two-pair tTIS for the motor area as a target. Analysis of variance in eight subjects highlights individual differences in both optimal stimulation policies and outcomes for tACS and tTIS, emphasizing the need for personalized stimulation protocols. These findings provide guidance for designing appropriate stimulation strategies for tACS and tTIS. MOVEA facilitates the optimization of tES based on specific objectives and constraints, advancing tTIS and tACS-based neuromodulation in understanding the causal relationship between brain regions and cognitive functions and treating diseases. The code for MOVEA is available at https://github.com/ncclabsustech/MOVEA.

Suppression of beta oscillations by delayed feedback in a cortex-basal ganglia-thalamus-pedunculopontine nucleus neural loop model.

Excessive neural synchronization of neural populations in the beta (β) frequency range (12-35 Hz) is intimately related to the symptoms of hypokinesia in Parkinson's disease (PD). Studies have shown that delayed feedback stimulation strategies can interrupt excessive neural synchronization and effectively alleviate symptoms associated with PD dyskinesia. Work on optimizing delayed feedback algorithms continues to progress, yet it remains challenging to further improve the inhibitory effect with reduced energy expenditure. Therefore, we first established a neural mass model of the cortex-basal ganglia-thalamus-pedunculopontine nucleus (CBGTh-PPN) closed-loop system, which can reflect the internal properties of cortical and basal ganglia neurons and their intrinsic connections with thalamic and pedunculopontine nucleus neurons. Second, the inhibitory effects of three delayed feedback schemes based on the external globus pallidum (GPe) on β oscillations were investigated separately and compared with those based on the subthalamic nucleus (STN) only. Our results show that all four delayed feedback schemes achieve effective suppression of pathological β oscillations when using the linear delayed feedback algorithm. The comparison revealed that the three GPe-based delayed feedback stimulation strategies were able to have a greater range of oscillation suppression with reduced energy consumption, thus improving control performance effectively, suggesting that they may be more effective for the relief of Parkinson's motor symptoms in practical applications.

Transspinal Focused Ultrasound Suppresses Spinal Reflexes in Healthy Rats

ObjectivesLow-intensity, focused ultrasound (FUS) is an emerging noninvasive neuromodulation approach, with improved spatial and temporal resolution and penetration depth compared to other noninvasive electrical stimulation strategies. FUS has been used to modulate circuits in the brain and the peripheral nervous system, however, its potential to modulate spinal circuits is unclear. In this study, we assessed the effect of trans-spinal FUS (tsFUS) on spinal reflexes in healthy rats. Materials and MethodstsFUS targeting different spinal segments was delivered for 1 minute, under anesthesia. Monosynaptic H-reflex of the sciatic nerve, polysynaptic flexor reflex of the sural nerve, and withdrawal reflex tested with a hot plate were measured before, during, and after tsFUS. ResultstsFUS reversibly suppresses the H-reflex in a spinal segment-, acoustic pressure- and pulse-repetition frequency (PRF)-dependent manner. tsFUS with high PRF augments the degree of homosynaptic depression of the H-reflex observed with paired stimuli. It suppresses the windup of components of the flexor reflex associated with slower, C-afferent, but not faster, A- afferent fibers. Finally, it increases the latency of the withdrawal reflex. tsFUS does not elicit neuronal loss in the spinal cord. ConclusionsOur study provides evidence that tsFUS reversibly suppresses spinal reflexes and suggests that tsFUS could be a safe and effective strategy for spinal cord neuromodulation in disorders associated with hyperreflexia, including spasticity after spinal cord injury and painful syndromes.

Intelligibility of speech in Parkinson's disease relies on anatomically segregated subthalamic beta oscillations

BackgroundSpeech impairment is commonly reported in Parkinson's disease and is not consistently improved by available therapies – including deep brain stimulation of the subthalamic nucleus (STN-DBS), which can worsen communication performance in some patients. Improving the outcome of STN-DBS on speech is difficult due to our incomplete understanding of the contribution of the STN to fluent speaking. ObjectiveTo assess the relationship between subthalamic neural activity and speech production and intelligibility. MethodsWe investigated bilateral STN local field potentials (LFPs) in nine parkinsonian patients chronically implanted with DBS during overt reading. LFP spectral features were correlated with clinical scores and measures of speech intelligibility. ResultsOvert reading was associated with increased beta-low ([1220) Hz) power in the left STN, whereas speech intelligibility correlated positively with beta-high ([2030) Hz) power in the right STN. ConclusionWe identified separate contributions from frequency and brain lateralization of the STN in the execution of an overt reading motor task and its intelligibility. This subcortical organization could be exploited for new adaptive stimulation strategies capable of identifying the occurrence of speaking behavior and facilitating its functional execution.