Side Of Stimulation Research Articles

Association of medullary reticular formation ventral part with spasticity in mice suffering from photothrombotic stroke

Strokes cause spasticity via stretch reflex hyperexcitability in the spinal cord, and spastic paralysis due to involuntary muscle contraction in the hands and fingers can severely restrict skilled hand movements. However, the underlying neurological mechanisms remain unknown. Using a mouse model of spasticity after stroke, we demonstrate changes in neuronal activity with and without electrostimulation of the afferent nerve to induce the stretch reflex, measured using quantitative activation-induced manganese-enhanced magnetic resonance imaging. Neuronal activity increased within the ventral medullary reticular formation (MdV) in the contralesional brainstem during the acute post-stroke phase, and this increase was characterised by activation of circuits involved in spasticity. Interestingly, ascending electrostimulation inhibited the MdV activity on the stimulation side in normal conditions.Moreover, immunohistochemical staining showed that, in the acute phase, the density of GluA1, one of the α-amino-3 hydroxy‑5 methyl -4 isoxazolepropionic acid receptor (AMPAR) subunits, at the synapses of MdV neurons was significantly increased. In addition, the GluA1/GluA2 ratio in these receptors was altered at 2 weeks post-stroke, confirming homeostatic plasticity as the underlying mechanisms of spasticity. These results provide new insights into the relationship between impaired skilled movements and spasticity at the acute post-stroke phase.

An interpretative phenomenological analysis of eating behaviors and mealtimes experiences of young people with Tourette syndrome

ABSTRACT Little is known about how young people with Tourette Syndrome (TS) perceive their own eating behaviors and subsequent effects on their mealtimes. Six adolescents aged 12–14 years with a self-reported clinical diagnosis of TS took part in semi-structured interviews. Interpretative Phenomenological Analysis of the transcribed interviews revealed central experiences of mealtime challenges in relation to their tics. Tics were described as creating functional mealtime challenges, often interrupting their ability to eat, drink and be seated. While sensory-based food preferences were noted, including the need for food to be plated a certain way, these preferences were not viewed as being problematic. Adolescents taking Aripiprazole reported dissatisfaction with the appetite stimulating side effects and subsequent weight gain. Eating out-of-home was found to be especially challenging, with some of the young people reporting feeling self-conscious and stigmatized when eating out-of-home, including at friends’ houses. There is a need for clinical guidance around eating and mealtimes, to meet the specific need of young people with TS and their families. Support from clinicians could entail monitoring changes in eating patterns resulting from tics and/or from side effects of medication, as well as in helping young people to manage any discomfort associated with eating out.

Beyond the buzz: the fatal consequences of caffeine overconsumption.

Caffeine is a naturally occurring stimulant present in dozens of plant species including Coffea arabica and Camellia sinensis, from which we obtain coffee and tea, respectively. It is one of the world's most widely consumed psychoactive substances frequently used to increase alertness, elevate mood, and ward off fatigue. In traditional preparations, caffeine is generally well-tolerated by the consumer. However, complications can arise with the addition of caffeine to products like energy drinks, medications, and supplements. Furthermore, with pure caffeine accessible online, a consumer may unknowingly or inadvertently consume caffeine in dangerous amounts. Symptoms of caffeine toxicity include classic central nervous system stimulation side effects, such as agitation, insomnia, gastrointestinal distress, tachycardia, seizures, and death in extreme cases. To evaluate concentrations of toxicological significance, caffeine cases were assessed at a large reference laboratory (NMS Labs). From 2019 to 2023, 406 blood cases underwent confirmation testing via LC-MS-MS; the mean and median caffeine concentrations were 35 and 4.8 µg/mL, respectively. While most caffeine-containing cases indicate traditional use in the general population with concentrations <25 µg/mL (62%, N = 254), 10% (N = 42) of the cases were >100 µg/mL, indicating levels which may contribute to a fatal outcome. To gain insight into the significance of caffeine in determining the cause and manner of death, cases with various manners of death are presented. Despite being one of the most common toxicological findings in medicolegal death investigations, caffeine is often overlooked. Screening results should undergo scrutiny, and confirmation testing should be considered in cases where caffeine intoxication is prominently featured in the case history or scene investigation.

Sound-Evoked Neural Activity in Normal-Hearing Tinnitus: Effects of Frequency and Stimulated Ear Side.

Tinnitus is a common phantom auditory percept believed to be related to plastic changes in the brain due to hearing loss. However, tinnitus can also occur in the absence of any clinical hearing loss. In this case, since there is no hearing loss, the mechanisms that drive plastic changes remain largely enigmatic. Previous studies showed subtle differences in sound-evoked brain activity associated with tinnitus in subjects with tinnitus and otherwise normal hearing, but the results are not consistent across studies. Here, we aimed to investigate these differences using monaural rather than binaural stimuli. Sound-evoked responses were measured using functional magnetic resonance imaging (MRI) in participants with and without tinnitus. All participants had clinically normal audiograms. The stimuli were pure tones with frequencies between 353 and 8000 Hz, presented monaurally. A Principal Component Analysis (PCA) of the response in the auditory cortex revealed no difference in tonotopic organization, which confirmed earlier studies. A GLM analysis showed hyperactivity in the lateral areas of the bilateral auditory cortex. Consistent with the tonotopic map, this hyperactivity mainly occurred in response to low stimulus frequencies. This may be related to hyperacusis. Furthermore, there was an interaction between stimulation side and tinnitus in the parahippocampus. This may reflect an interference between tinnitus and spatial orientation.

The dark side of random-start ovarian stimulation: ovarian hyperstimulation syndrome due to inadvertent pregnancy

Research QuestionCan inadvertent pregnancies go unnoticed when initiating random-start ovarian stimulation (RSOS) despite monitoring? DesignCase series at the university-based tertiary-care fertility clinic. ResultsBetween June 2022 and December 2023, two cases of undetected early pregnancy at the onset of random-start ovarian stimulation were identified, both leading to severe ovarian hyperstimulation syndrome (OHSS) with hospitalization. ConclusionRSOS protocols add flexibility in fertility clinics when there is no intention of a fresh embryo transfer but may be associated with insidious risk of OHSS. We advocate for comprehensive consultation and serial monitoring of human chorionic gonadotropin (hCG) during stimulation while cautioning against overreliance on baseline hormone levels when initiating RSOS. If the benefits of RSOS seem limited, healthcare providers should consider delaying the stimulation to avert health, but also medicolegal, and financial complications.

Heart rate variability as a preictal marker for determining the laterality of seizure onset zone in frontal lobe epilepsy.

Determining the laterality of the seizure onset zone is challenging in frontal lobe epilepsy (FLE) due to the rapid propagation of epileptic discharges to the contralateral hemisphere. There is hemispheric lateralization of autonomic control, and heart rate is modulated by interactions between the sympathetic and parasympathetic nervous systems. Based on this notion, the laterality of seizure foci in FLE might be determined using heart rate variability (HRV) parameters. We explored preictal markers for differentiating the laterality of seizure foci in FLE using HRV parameters. Twelve patients with FLE (6 right FLE and 6 left FLE) were included in the analyzes. A total of 551 (460 left FLE and 91 right FLE) 1-min epoch electrocardiography data were used for HRV analysis. We found that most HRV parameters differed between the left and right FLE groups. Among the machine learning algorithms applied in this study, the light gradient boosting machine was the most accurate, with an AUC value of 0.983 and a classification accuracy of 0.961. Our findings suggest that HRV parameter-based laterality determination models can be convenient and effective tools in clinical settings. Considering that heart rate can be easily measured in real time with a wearable device, our proposed method can be applied to a closed-loop device as a real-time monitoring tool for determining the side of stimulation.

480 Effect of Chronic DBS on Ventral Capsule Ventral Striatum-Specific Circadian Rhythm in Refractory Obsessive-Compulsive Disorder

INTRODUCTION: Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) improves symptoms in ∼66% of patients with treatment-resistant obsessive-compulsive disorder (OCD). However, a common adverse effect of VC/VS DBS is hypomania, marked by decreased need for sleep and increased risk-taking behaviors. Modern DBS devices have enabled 24-hour collection of neural data, allowing for tracking of circadian rhythms reflected by VC/VS local field potentials (LFPs). METHODS: We implanted six patients with treatment-resistant OCD with a DBS device configured for constant VC/VS stimulation and recording. Spectral power in the 9 ± 2.5 Hz band was estimated onboard the device every 10 minutes for a median of 249 days (range 77-608). We assessed the rhythmicity of power in this spectral band by fitting 7-day retrospective rolling windows of per-day normalized LFP power to cosine functions using least-squared regression. Output metrics included acrophase (time of peak activity), amplitude, and fit significance. We quantified trends in acrophase over time using Pearson correlation. RESULTS: All six patients demonstrated consistent 24-hour cyclic LFP activity bilaterally. Two of the six had diurnal peaks which shifted significantly earlier across the study period. The remaining four patients had nocturnal peaks, all shifting significantly later over time. Notably, a patient in the latter group experienced three days of hypomania after DBS initiation associated with circadian disruptions even after clinical symptom resolution. Only after clinical DBS adjustment 2 weeks later did circadian rhythm rapidly return to pre-hypomanic levels. CONCLUSIONS: Study patients demonstrated evolving circadian VC/VS LFP activity across the course of DBS therapy, usually independent of cyclic whole-brain activity (i.e. sleep). Conversely, disruptions to these circadian patterns, as observed here during hypomania, may serve as biomarkers of region-specific stimulation side effects.

Benefits of subthalamic nucleus deep brain stimulation on visually-guided saccades depend on stimulation side and classic paradigm in Parkinson’s disease

ObjectiveWe aimed to gain further insight into previously reported beneficial effects of subthalamic nucleus deep brain stimulation (STN-DBS) on visually-guided saccades by examining the effects of unilateral compared to bilateral stimulation, paradigm, and target eccentricity on saccades in individuals with Parkinson’s disease (PD). MethodsEleven participants with PD and STN-DBS completed the visually-guided saccade paradigms with OFF, RIGHT, LEFT, and BOTH stimulation. Rightward saccade performance was evaluated for three paradigms and two target eccentricities. ResultsFirst, we found that BOTH and LEFT increased gain, peak velocity, and duration compared to OFF stimulation. Second, we found that BOTH and LEFT stimulation decreased latency during the gap and step paradigms but had no effect on latency during the overlap paradigm. Third, we found that RIGHT was not different compared to OFF at benefiting rightward saccade performance. ConclusionsLeft unilateral and bilateral stimulation both improve the motor outcomes of rightward visually-guided saccades. Additionally, both improve latency, a cognitive-motor outcome, but only in paradigms when attention does not require disengagement from a present stimulus. SignificanceSTN-DBS primarily benefits motor and cognitive-motor aspects of visually-guided saccades related to reflexive attentional shifting, with the latter only evident when the fixation-related attentional system is not engaged.

Transcutaneous auricular vagus nerve stimulation alters cough sensitivity depending on stimulation parameters: potential implications for aspiration risk.

Transcutaneous auricular vagus nerve stimulation (taVNS) is considered a safe and promising tool for limb rehabilitation after stroke, but its effect on cough has never been studied. It is known that the ear and larynx share vagal afferent pathways, suggesting that stimulating the ear with taVNS might have effects on cough sensitivity. The specific stimulation parameters used can influence outcomes. To investigate the effect of various stimulation parameters on change in cough sensitivity, compared to the reference parameter of 25 Hz stimulation at the left concha (most commonly-used parameter for stroke rehabilitation). Design, setting, and participants: Randomized, single-blind, active-controlled, eight-period cross-over design conducted March to August 2022 at a New Zealand research laboratory with 16 healthy participants. All participants underwent eight stimulation conditions which varied by stimulation side (right ear, left ear), zone (ear canal, concha), and frequency (25 Hz, 80 Hz). Main outcome measures: Change in natural and suppressed cough threshold (from baseline to after 10 min of stimulation) assessed using a citric acid cough reflex test. When compared to the reference parameter of 25 Hz stimulation at the left concha, there was a reduction in natural cough threshold of -0.16 mol/L for 80 Hz stimulation at the left canal (p = 0.004), indicating increased sensitivity. For the outcome measure of suppressed cough threshold, there was no significant effect of any of the stimulation conditions compared to the active reference. Since stroke patients often have cough hyposensitivity with resulting high risk of silent aspiration, using 80 Hz taVNS at the left canal may be a better choice for future stroke rehabilitation studies than the commonly used 25 Hz taVNS at the left concha. Treatment parameters should be manipulated in future sham-controlled trials to maximize any potential treatment effect of taVNS in modulating cough sensitivity. ACTRN12623000128695.

Improved Side-Effect Stimulation Thresholds and Postoperative Transient Confusion With Asleep, Image-Guided Deep Brain Stimulation.

Asleep, image-guided deep brain stimulation (DBS) is a modern alternative to awake, microelectrode recording (MER) guidance. Studies demonstrate comparable efficacy and complications between techniques, although some report lower stimulation thresholds for side effects with image guidance. In addition, few studies directly compare the risk of postoperative transient confusion (pTC) across techniques. The purpose of this study was to compare clinical efficacy, stimulation thresholds for side effects, and rates of pTC with MER-guided DBS vs intraoperative 3D-fluoroscopy (i3D-F) guidance in Parkinson's disease and essential tremor. Consecutive patients from 2006 to 2021 were identified from the departmental database and grouped as having either MER-guided DBS or i3D-F-guided DBS insertion. Directional leads were used once commercially available. Changes in Unified Parkinson's Disease Rating Scale (UPDRS)-III scores, levodopa equivalent daily dose, Fahn-Tolosa-Marin scores, and stimulation thresholds were assessed, as were rates of complications including pTC. MER guidance was used to implant 487 electrodes (18 globus pallidus interna, GPi; 171 subthalamic nucleus; 76 ventrointermediate thalamus, VIM) in 265 patients. i3D-F guidance was used in 167 electrodes (19 GPi; 25 subthalamic nucleus; 41 VIM) in 85 patients. There were no significant differences in Unified Parkinson's Disease Rating III Scale, levodopa equivalent daily dose, or Fahn-Tolosa-Marin between groups. Stimulation thresholds for side effects were higher with i3D-F guidance in the subthalamic nucleus (MER, 2.80 mA ± 0.98; i3D-F, 3.46 mA ± 0.92; P = .002) and VIM (MER, 2.81 mA ± 1.00; i3D-F, 3.19 mA ± 1.03; P = .0018). Less pTC with i3D-F guidance (MER, 7.5%; i3D-F, 1.2%; P = .034) was also found. Although clinical efficacy between MER-guided and i3D-F-guided DBS was comparable, thresholds for stimulation side effects were higher with i3D-F guidance and the rate of pTC was lower. This suggests that image-guided DBS may affect long-term side effects and pose a decreased risk of pTC.

Skull Vibration-Induced Nystagmus in Superior Semicircular Canal Dehiscence: A New Insight into Vestibular Exploration-A Review.

The third window syndrome, often associated with the Tullio phenomenon, is currently most often observed in patients with a superior semicircular-canal dehiscence (SCD) but is not specific to this pathology. Clinical and vestibular tests suggestive of this pathology are not always concomitantly observed and have been recently complemented by the skull-vibration-induced nystagmus test, which constitutes a bone-conducted Tullio phenomenon (BCTP). The aim of this work was to collect from the literature the insights given by this bedside test performed with bone-conducted stimulations in SCD. The PRISMA guidelines were used, and 10 publications were included and analyzed. Skull vibration-induced nystagmus (SVIN), as observed in 55 to 100% of SCD patients, usually signals SCD with greater sensitivity than the air-conducted Tullio phenomenon (ACTP) or the Hennebert sign. The SVIN direction when the test is performed on the vertex location at 100 Hz is most often ipsilaterally beating in 82% of cases for the horizontal and torsional components and down-beating for the vertical component. Vertex stimulations are more efficient than mastoid stimulations at 100 Hz but are equivalent at higher frequencies. SVIN efficiency may depend on stimulus location, order, and duration. In SCD, SVIN frequency sensitivity is extended toward high frequencies, with around 400 Hz being optimal. SVIN direction may depend in 25% on stimulus frequency and in 50% on stimulus location. Mastoid stimulations show frequently diverging results following the side of stimulation. An after-nystagmus observed in 25% of cases can be interpreted in light of recent physiological data showing two modes of activation: (1) cycle-by-cycle phase-locked activation of action potentials in SCC afferents with irregular resting discharge; (2) cupula deflection by fluid streaming caused by the travelling waves of fluid displacement initiated by sound or vibration at the point of the dehiscence. The SVIN direction and intensity may result from these two mechanisms' competition. This instability explains the SVIN variability following stimulus location and frequency observed in some patients but also discrepancies between investigators. SVIN is a recent useful insight among other bedside examination tests for the diagnosis of SCD in clinical practice.

Changes in myelinated nerve fibers induced by pulsed electrical stimulation: A microstructural perspective on the causes of electrical stimulation side effects

Electrical brain stimulation technology is widely used in the clinic to treat brain neurological disorders. However, during treatment, patients may experience side effects such as pain, poor limb coordination, and skin rash. Previous reports have focused on the brilliant chapter on electrical brain stimulation technology and have not paid attention to patients' suffering caused by side effects during treatment. In this study, electrodes were arranged on the medulla oblongata. Pulsed electric fields of different frequencies were used to perform electrical stimulation to study the impact of electric fields on myelinated nerve fibers and reveal the possible microstructural origin of side effects. Transmission electron microscopy was used to analyze and quantify the changes in microstructure. The results illustrated that myelinated nerve fibers underwent atrophy under pulsed electric fields, with the mildest degree of atrophy under high-frequency (400 Hz) electric fields. Myelin sheaths experienced plate separation under pulsed electric fields, and a distinct laminar structure appeared. The microstructure changes may be related to the side effects of clinical electrical stimulation. This study can provide pathological possibilities for exploring the causes of the side effects of electrical stimulation and supply guidance for selecting electrical parameters for clinical electrical stimulation therapy from a distinctive perspective.

Selective Activation of Subthalamic Nucleus Output Quantitatively Scales Movements.

The subthalamic nucleus (STN) is a common target for deep brain stimulation (DBS) treatments of Parkinsonian motor symptoms. According to the dominant model, the STN output can suppress movement by enhancing inhibitory basal ganglia (BG) output via the indirect pathway, and disrupting STN output using DBS can restore movement in Parkinson's patients. But the mechanisms underlying STN DBS remain poorly understood, as previous studies usually relied on electrical stimulation, which cannot selectively target STN output neurons. Here, we selectively stimulated STN projection neurons using optogenetics and quantified behavior in male and female mice using 3D motion capture. STN stimulation resulted in movements with short latencies (10-15 ms). A single pulse of light was sufficient to generate movement, and there was a highly linear relationship between stimulation frequency and kinematic measures. Unilateral stimulation caused movement in the ipsiversive direction (toward the side of stimulation) and quantitatively determined head yaw and head roll, while stimulation of either STN raises the head (pitch). Bilateral stimulation does not cause turning but raised the head twice as high as unilateral stimulation of either STN. Optogenetic stimulation increased the firing rate of STN neurons in a frequency-dependent manner, and the increased firing is responsible for stimulation-induced movements. Finally, stimulation of the STN's projection to the brainstem mesencephalic locomotor region was sufficient to reproduce the behavioral effects of STN stimulation. These results question the common assumption that the STN suppresses movement, and instead suggest that STN output can precisely specify action parameters via direct projections to the brainstem.SIGNIFICANCE STATEMENT Our results question the common assumption that the subthalamic nucleus (STN) suppresses movement, and instead suggest that STN output can precisely specify action parameters via direct projections to the brainstem.

Pathways and parameters of sacral neuromodulation in rats.

The stimulation paradigm for sacral neuromodulation has remained largely unchanged since its inception. We sought to determine, in rats, whether stimulation-induced increases in bladder capacity correlated with the proportion of sensory pudendal (PudS) neurons at each stimulated location (L6, S1). If supported, this finding could guide the choice of stimulation side (left/right) and level (S2, S3, S4) in humans. Unexpectedly, we observed that acute stimulation at clinically relevant (low) amplitudes [1-1.5 × motor threshold (Tm)], did not increase bladder capacity, regardless of stimulus location (L6 or S1). More importantly for the ability to test our hypothesis, there was little anatomic variation, and S1 infrequently contributed nerve fibers to the PudS nerve. During mapping studies we noticed that large increases in PudS nerve activation occurred at amplitudes exceeding 2Tm. Thus, additional cystometric studies were conducted, this time with stimulation of the L6-S1 trunk, to examine further the relationship between stimulation amplitude and cystometric parameters. Stimulation at 1Tm to 6Tm evoked increases in bladder capacity and decreases in voiding efficiency that mirrored those produced by PudS nerve stimulation. Many animal studies involving electrical stimulation of nerves of the lower urinary tract use stimulation amplitudes that exceed those used clinically (∼1Tm). Our results confirm that high amplitudes generate immediate changes in cystometric parameters; however, the relationship to low-amplitude chronic stimulation in humans remains unclear. Additional studies are needed to understand changes that occur with chronic stimulation, how these changes relate to therapeutic outcomes, and the contribution of specific nerve fibers to these changes.NEW & NOTEWORTHY Acute low-amplitude electrical stimulation of sacral nerve (sacral neuromodulation) did not increase bladder capacity in anesthetized CD, obese-prone, or obese-resistant rats. Increasing stimulation amplitude correlated with increases in bladder capacity and pudendal sensory nerve recruitment. It is unclear how the high-amplitude acute stimulation that is commonly used in animal experiments to generate immediate effects compares mechanistically to the chronic low-amplitude stimulation used clinically.

Models of the player’s interactions with strings

In the context of physically inspired models for the synthesis, the development of accurate models for the interaction of the player with the instrument plays a fundamental role. Depending on the musical instrument, the palette of possible interactions is generally very broad and includes the coupling of body parts, mechanical objects, and/or devices with various components of the instrument. In this work, we focus on models of the interaction of the player with strings, which include elastoplastic models of the fingers, dynamic models of the bow, the plectrum and the friction of objects such as bottle necks. We consider interactions both at the stimulation side (e.g., plucking or bowing) and at the fingerboard side, where collisions and/or imperfect pressures introduce nonlinear effects. Other possible interactions in less conventional play modes such as those based on rotating motors and electromagnetic stimulation are taken into account in this work. The proposed models do not depend on the specific implementation of the physical model in, e.g., Finite-Difference Time-Domain (FDTD)-based or waveguide-based schemes. While the former class of implementations may produce more accurate results, the latter allows for simplifications and lower computational costs provided that stability can be guaranteed.

Hybrid Deep Brain Stimulation for Parkinson’s Disease and Dystonia Improves Side Effects, Maintaining Clinical Benefit

Introduction: Deep brain stimulation (DBS) in movement disorders does not always achieve optimal symptomatic control. Most common issues involve suboptimal electrode positioning and target stimulation and troublesome side effects limiting the therapeutic window. Recently approved implantable pulse generators (IPG) allow for pulse widths lower than 60 μs, increasing the therapeutic window, and current steering. These new constant-current IPG (CC-IPG), in addition to these characteristics, have rechargeable, thus longer duration, batteries. This work aims to describe a tertiary center’s experience with replacing a constant-voltage stimulation non-rechargeable implantable pulse generator (CV-IPG), at the end of its battery’s lifespan, with a CC-IPG, with more options in pulse duration changes and multiplesource current steering. Methods: A retrospective review of the clinical records of patients submitted to DBS who had their CV-IPG replaced with CC-IPG was performed, documenting reason for preference, stimulation parameters, clinical benefit pre and post-replacement and side effects. Results: Six patients who fulfilled the criteria were identified, four with Parkinson’s disease (PD) and two with dystonia. The reasons for preference were: stimulation side effects (2), suboptimal benefit (1), long battery duration (3). Side effects were improved by using a 30 μs pulse in two patients. Current steering allowed the shortening of OFF periods in 1 PD patient. One patient with dystonia had initial decrease in clinical benefit but recovered after amplitude correction according to impedance. The other two patients remained stable post-replacement. Conclusion: Replacement of CV-IPG with CC-IPG proved feasible and safe, with non-inferior clinical benefit, additionally providing pulse lowering and current steering strategies for solving suboptimal results with DBS.

Three-dimensional gait analysis of the effect of directional steering on gait in patients with Parkinson's disease

IntroductionDeep Brain Stimulation (DBS) is an option to treat advanced Parkinson's Disease (PD), but can cause gait disturbance due to stimulation side efffects. This study aims to evaluate the objective effect of directional current steering by DBS on gait performance in PD, utilizing a three-dimensional gait analysis system. MethodsEleven patients diagnosed with PD and were implanted with directional lead were recruited. The direction of the pyramidal tract (identified by the directional mode screening) was set as 0°. Patients performed the six-meter-walk test and the time up-and-go (TUG) test while an analysis system recorded gait parameters utilizing a three-dimensional motion capture camera. The gait parameters were measured for the baseline, the directional steering at eight angles (0°, 45°, 90°, 135°, 180°, 225°, 270°, and 315°), and the conventional ring mode with 1, 2, and 3 mA. Pulse width and frequency were fixed. Placebo stimulation (0 mA) was used for a control. ResultsEleven patients completed the study. No significant difference were observed between gait parameters during the directional, baseline, placebo, or ring modes during the six-meter-walk test (p > 0.05). During the TUG test, stride length was significantly different between 0° and other directions (p < 0.001), but no significant differences were observed for the other gait parameters. Stride width was non-significantly narrower in the direction of 0°. ConclusionControlling stimulation using directional steering may improve gait in patients with PD, while avoiding pyramidal side effects.

Neurotechnology for Pain.

Neurotechnologies for treating pain rely on electrical stimulation of the central or peripheral nervous system to disrupt or block pain signaling and have been commercialized to treat a variety of pain conditions. While their adoption is accelerating, neurotechnologies are still frequently viewed as a last resort, after many other treatment options have been explored. We review the pain conditions commonly treated with electrical stimulation, as well as the specific neurotechnologies used for treating those conditions. We identify barriers to adoption, including a limited understanding of mechanisms of action, inconsistent efficacy across patients, and challenges related to selectivity of stimulation and off-target side effects. We describe design improvements that have recently been implemented, as well as some cutting-edge technologies that may address the limitations of existing neurotechnologies. Addressing these challenges will accelerate adoption and change neurotechnologies from last-line to first-line treatments for people living with chronic pain.

Orientation selective stimulation with tetrahedral electrodes of the rat infralimbic cortex to indirectly target the amygdala.

Deep brain stimulation (DBS) is a rapidly developing therapeutic intervention with constantly expanding neurological and psychiatric indications. A major challenge for the approach is the precise targeting and limitation of the effect on the desired neural pathways. We have introduced a new approach, orientation selective stimulation (OSS) that allows free rotation of the induced electric field on a plane when using a probe with three parallel electrodes forming an equilateral triangle at the tip. Here, we expand the technique by introducing a tetrahedral stimulation probe that enables adjustment of the primary electric field direction freely at any angle in a 3D space around the stimulating probe. OSS in 3D will enable better targeting of the electric field according to the local brain anatomy. We tested its utility in a rat model of DBS for treatment-resistant depression. The stimulation directed to the subgenual anterior cingulate cortex (sgACC) has yielded dramatic improvement in individual patients suffering from therapy resistant depression, but no consistent benefit in larger series. This failure has been ascribed to the challenging anatomy of sgACC with several crossing neural tracts and individual differences in the local anatomy. We stimulated infralimbic cortex (IL), the rat analog of sgACC, and recorded local electrical responses in amygdala (AMG) that is monosynaptically connected to IL and plays a central role in emotional states. We further traced AMG-IL connections using a viral vector and tractography using diffusion magnetic resonance imaging (MRI). Finally, we mimicked the clinical situation by delivering sustained 130 Hz stimulation at IL at the most effective field orientation and followed changes in resting-state functional connectivity with IL using functional MRI. To help interpretation of responses in functional connectivity, we stimulated only the left IL, which we did not expect to evoke measurable changes in the rat behavior. The AMG evoked responses depended systematically on the IL stimulation field orientation and yielded the maximum response in near vertical field orientation in accordance with tractography. Sustained 130 Hz stimulation at a field orientation yielding the strongest AMG evoked responses increased functional connectivity between IL and AMG on the stimulation side. These findings suggest that OSS in 3D provides a new approach to optimize the DBS for every individual patient with a single stimulation probe implantation.

Effects of unilateral neck muscle vibration on standing postural orientation and spatial perception in healthy subjects based on stimulus duration and simultaneous stimulation of trunk muscles.

Neck muscle vibration (NMV) influences proprioceptive sensations and modulates standing postural orientation and spatial perception. However, the effects of NMV in healthy participants would vary based on the influence of stimulus duration and combination with trunk muscle vibration. Therefore, this study with a cross-over design clarified these effects. Twenty-four healthy participants (mean age, 25.7±3.7 years) were enrolled. To assess standing postural orientation, standing center-of-pressure (COP) measurements were recorded on a COP platform, starting with closed eyes and then with open eyes. The mean mediolateral (ML) and anteroposterior (AP) position [mm] of COP and other parameters were calculated. To assess spatial perception, subjective straight ahead (SSA) measurements were recorded, wherein participants were instructed to point and project the position of the manubrium of sternum on the touch panel using their right index finger with their eyes closed. Measurements were taken before and after four conditions: no vibration (control), left NMV for 30 s, left NMV for 10 min, and left NMV and left lumbar back vibration for 10 min. Vibratory stimulation was performed with the eyes closed at 80 Hz. The measurements under the four conditions were conducted with random cross-over and 5-min resting period between the conditions. COP and SSA values were subtracted before and after each condition for standardized variation and compared. NMV combined with trunk muscle vibration for 10 min resulted in significant deviations of the ML-COP toward the stimulation side and AP-COP toward the anterior side compared to the control condition with closed eyes. SSA showed no significant differences. These findings suggest that NMV-induced nervous system modulation would be amplified by proprioceptive sensory input to trunk muscles. Therefore, this method could provide a new option for clinical trials on postural orientation using NMV. SSA based on proprioceptive sensation may not be biased without visual illusions.