Minimum Stimulus Research Articles

Minimal Stimulus Strategy in Benign Paroxysmal Positional Vertigo: Its Application in a Resource Limited Setting.

Benign paroxysmal positional vertigo (BPPV) is the most common cause for vertigo. It is diagnosed by the characteristic nystagmus induced by provocative positional tests. During these positional tests the patient experiences spinning vertigo and neurovegetative symptoms such as nausea and vomiting. This can cause severe discomfort to the patient during treatment and in some cases reduced compliance. Minimal stimulation strategy reduced the episodes of induced vertigo, nausea and vomiting thereby making the treatment maneuvers more tolerable. This study aims to evaluate the utility of minimum stimulus strategy for managing BPPV in a resource limited center. The present study also evaluated the utility of 3rd step vertigo as an alternative marker for recovery nystagmus in predicting the efficacy of Epley's maneuver in treating posterior canal BPPV. All patients diagnosed with canalolithiasis of posterior semicircular canal (pc-BPPV), horizontal semicircular canal (hc-BPPV), anterior semicircular canal (ac-BPPV) and multiple semicircular canal (mc-BPPV) were included in the study. The side on which the maximum symptoms were experienced was asked to the patients and noted. The first positional test done in all patients was the Dix-Hallpike maneuver and minimum stimulation strategy was used for treating BPPV. Appropriate canalolith repositioning maneuvers (CRM) were used to treat BPPV. Positional maneuvers were repeated after the CRM in the same sitting and the treatment was considered successful if nystagmus had disappeared on repeat positional tests. The presence of 3rd step vertigo during Epley's maneuver was documented. A total of 71 patients were enrolled in the study. Patients correctly identified the side of BPPV in 76.31% of cases. 3rd step vertigo was able to predict a successful Epley's maneuver in pc-BPPV with a sensitivity and specificity of 41.67% and 60% respectively. Incidence of 3rd step vertigo was seen in 41.37% of patients with pc-BPPV and in 90.9% of patients with mc-BPPV. Minimal stimulation strategy is useful in reducing the discomfort experienced by the patients with BPPV during treatment and thereby improve the compliance to treatment maneuvers. Patients were able to identify the correct side of BPPV in 76.31% of cases. Third step vertigo could predict successful Epley's reposition maneuver with a sensitivity of 41.67% and specificity of 60% in our cohort. However, more studies with larger sample size are required to ascertain its role as an alternative marker for 'recovery nystagmus'.

To determine the value of iMAX, a new electrodiagnostic method, and its application in the evaluation of peripheral motor nerve excitability

Objective: To test the new method of iMAX (the minimum stimulus current that elicits the maximum compound muscle action potential amplitude) electrodiagnosis, verify the feasibility of this method in evaluating the excitability of peripheral motor axons, and preliminarily explore the clinical application value. Methods: This study was a cross-sectional study. A total of 50 healthy subjects were recruited from the outpatient department of Peking University Third Hospital from June 2022 to March 2023, including 25 males and 25 females, aged 25-68 (48±8) years. Eleven patients with Charcot-Marie-Pain-1A (CMT1A), 7 males and 4 females, aged 19-55 (41±13) years and 21 patients with diabetic peripheral neuropathy (DPN), 10 males and 11 females, aged 28-79 (53±16) years were enrolled in this study. iMAX of bilateral median nerves, ulnar nerves and peroneal nerves were detected in all patients. Repeatable motor responses with minimum motor threshold and amplitude of at least 0.1 mV and the minimum stimulus current intensity, at which the maximum compound muscle action potential amplitude is elicited, were measured respectively [1 mA increment is called (iUP) and, 0.1 mA adjustment is called (iMAX)].Comparison of the parameters: the parameters of threshold, iUP and iMAX were compared among different age groups, genders and sides, body mass index(BMI) values and detection time , as well as between CMT1A patients, DPN patients and healthy subjects. Results: In healthy subjects, the threshold, iUP value and iMAX value were (1.8±0.7) mA, (4.4±1.2) mA, and (4.2±1.3) mA respectively; ulnar nerve (3.1±1.6) mA, (6.8±3.2) mA, (6.4±3.2) mA; peroneal nerve (3.7±2.0) mA, (7.8±2.8) mA, (7.4±2.9) mA. There were statistically significant differences in threshold, iUP value and iMAX value among different age groups (all P<0.001).With the increase of age, there was a trend of increasing threshold, iUP, and iMAX values in different nerves, and the differences are statistically significant (all P<0.001). There were no significant differences in gender, side and detection time threshold, iUP value and iMAX value (all P>0.05). The parameters of healthy subjects with high BMI value were higher than those of healthy subjects with low BMI value(all P<0.05). Compared with the healthy subjects, the parameters of 11 CMT1A patients were significantly increased (all P<0.05), and the parameters of 21 DPN patients were slightly increased (P<0.05). Conclusion: The new iMAX method reflects the excitability of motor axons and early axonal dysfunction, which is an important supplement to the traditional nerve conduction, and can be used to monitor motor axon excitability disorders.

Normal behavioral discrimination of envelope statistics in budgerigars with kainate-induced cochlear synaptopathy

Cochlear synaptopathy is a common pathology in humans associated with aging and potentially sound overexposure. Synaptopathy is widely expected to cause “hidden hearing loss,” including difficulty perceiving speech in noise, but support for this hypothesis is controversial. Here in budgerigars (Melopsittacus undulatus), we evaluated the impact of long-term cochlear synaptopathy on behavioral discrimination of Gaussian noise (GN) and low-noise noise (LNN) signals processed to have a flatter envelope. Stimuli had center frequencies of 1–3kHz, 100-Hz bandwidth, and were presented at sensation levels (SLs) from 10 to 30dB. We reasoned that narrowband, low-SL stimuli of this type should minimize spread of excitation across auditory-nerve fibers, and hence might reveal synaptopathy-related defects if they exist. Cochlear synaptopathy was induced without hair-cell injury using kainic acid (KA). Behavioral threshold tracking experiments characterized the minimum stimulus duration above which animals could reliably discriminate between LNN and GN. Budgerigar thresholds for LNN-GN discrimination ranged from 40 to 60ms at 30dB SL, were similar across frequencies, and increased for lower SLs. Notably, animals with long-term 39–77% estimated synaptopathy performed similarly to controls, requiring on average a ∼7.5% shorter stimulus duration (-0.7±1.0dB; mean difference ±SE) for LNN-GN discrimination. Decision-variable correlation analyses of detailed behavioral response patterns showed that individual animals relied on envelope cues to discriminate LNN and GN, with lesser roles of FM and energy cues; no difference was found between KA-exposed and control groups. These results suggest that long-term cochlear synaptopathy does not impair discrimination of low-level signals with different envelope statistics.

Epidural combined optical and electrical stimulation induces high-specificity activation of target muscles in spinal cord injured rats.

Epidural electrical stimulation (EES) has been shown to improve motor dysfunction after spinal cord injury (SCI) by activating residual locomotor neural networks. However, the stimulation current often spreads excessively, leading to activation of non-target muscles and reducing the accuracy of stimulation regulation. Near-infrared nerve stimulation (nINS) was combined with EES to explore its regulatory effect on lower limb muscle activity in spinal-cord-transected rats. In this study, stimulation electrodes were implanted into the rats' L3-L6 spinal cord segment with T8 cord transected. Firstly, a series of EES parameters (0.2-0.6 mA and 20-60 Hz) were tested to determine those that specifically regulate the tibialis anterior (TA) and medial gastrocnemius (MG). Subsequently, to determine the effect of combined optical and electrical stimulation, near-infrared laser with a wavelength of 808 nm was used to irradiate the L3-L6 spinal cord segment while EES was performed. The amplitude of electromyography (EMG), the specific activation intensity of the target muscle, and the minimum stimulus current intensity to induce joint movement (motor threshold) under a series of optical stimulation parameters (power: 0.0-2.0 W; pulse width: 0-10 ms) were investigated and analyzed. EES stimulation with 40 Hz at the L3 and L6 spinal cord segments specifically activated TA and MG, respectively. High stimulation intensity (>2 × motor threshold) activated non-target muscles, while low stimulation frequency (<20 Hz) produced intermittent contraction. Compared to electrical stimulation alone (0.577 ± 0.081 mV), the combined stimulation strategy could induce stronger EMG amplitude of MG (1.426 ± 0.365 mV) after spinal cord injury (p < 0.01). The combined application of nINS effectively decreased the EES-induced motor threshold of MG (from 0.237 ± 0.001 mA to 0.166 ± 0.028 mA, p < 0.001). Additionally, the pulse width (PW) of nINS had a slight impact on the regulation of muscle activity. The EMG amplitude of MG only increased by ~70% (from 3.978 ± 0.240 mV to 6.753 ± 0.263 mV) when the PW increased by 10-fold (from 1 to 10 ms). The study demonstrates the feasibility of epidural combined electrical and optical stimulation for highly specific regulation of muscle activity after SCI, and provides a new strategy for improving motor dysfunction caused by SCI.

Studies of multisensory integration in sound localization and updating of auditory spatial attention during head motion

In daily life, our heads are in continual motion, but much of our knowledge of spatial hearing is based on experimental paradigms in which this behavior is discouraged or prevented. Head motion can benefit spatial hearing though the creation of dynamic acoustical cues, but also creates challenges such as the need to update head-centered spatial representations or the locus of spatial auditory attention. To utilize acoustic information generated by, or to compensate for, head movements, the auditory system must integrate self-motion information provided by other sensory systems. This presentation will review and contextualize a series of studies from the author's laboratory focused on the psychophysics of dynamic sound localization and the weighting of sensory information from vestibular, proprioceptive, and visual modalities in dynamic localization and maintenance of spatially selective auditory attention during head rotation. Notable findings include a velocity-independent ∼100-ms minimum stimulus duration for disambiguation of front/rear location in dynamic localization and the apparent dominance of vestibular information in the interpretation of dynamic localization cues and in attentional updating. The approach taken provides a step towards understanding the effects of naturalistic behavior on spatial hearing while maintaining significant experimental control and repeatability of stimuli and head movements.

Magnetic stimulation of the sciatic nerve using an implantable high-inductance coil with low-intensity current

Objective. Magnetic stimulation using implantable devices may offer a promising alternative to other stimulation methods such as transcranial magnetic stimulation (TMS) or electric stimulation using implantable devices. This alternative may increase the selectivity of stimulation compared to TMS, and eliminate the need to expose tissue to metals in the body, as is required in electric stimulation using implantable devices. However, previous studies of magnetic stimulation of the sciatic nerve used large coils, with a diameter of several tens of mm, and a current intensity in the order of kA. Approach. Since such large coils and high current intensity are not suitable for implantable devices, we investigated the feasibility of using a smaller implantable coil and lower current to elicit neuronal responses. A coil with a diameter of 3 mm and an inductance of 1 mH was used as the implantable stimulator. Main results. Before in vivo experiments, we used 3D computational models to estimate the minimum stimulus intensity required to elicit neuronal responses, resulting in a threshold current above 3.5 A. In in vivo experiments, we observed successful nerve stimulation via compound muscle action potentials elicited in hind-limb muscles when the applied current was above 3.8 A, a significantly reduced current than that used in conventional magnetic stimulation. Significance. We report the feasibility of magnetic stimulation using an implantable millimeter-sized coil and low current of a few amperes to elicit neural responses in peripheral nerves. The proposed method is expected to be an alternative to TMS, with the merit of improved selectivity in stimulation, and to electrical stimulation based on implantable devices, with the merit of avoiding the exposure of conducting metals to neural tissues.

Measurement of individual color space using a luminous vector field.

This study is intended to measure the geometry of the observer's color space when viewing a computer screen and to define individual variations from these data. A CIE photometric standard observer assumes that the eye's spectral efficiency function is constant, and photometry measurements correspond to vectors with fixed directions. By definition, the standard observer decomposes color space into planar surfaces of constant luminance. Using heterochromatic photometry with a minimum motion stimulus, we systematically measure the direction of luminous vectors for many observers and many color points. During the measurement process, the background and stimulus modulation averages are fixed to the given points to ensure that the observer is in a fixed adaptation mode. Our measurements result in a vector field or set of vectors (x,v), where x is the point's color space position, and v is the observer's luminosity vector. To estimate surfaces from vector fields, two mathematical hypotheses were used: (1)that surfaces are quadratic or, equivalently, that the vector field model is affine, and (2)that the metric of surfaces is proportional to a visual origin. Across 24 observers, we found that vector fields are convergent and the corresponding surfaces are hyperbolic. The equation of the surface in the display's color space coordinate system, and in particular the axis of symmetry, varied systematically from individual to individual. A hyperbolic geometry is compatible with studies that emphasize a modification of the photometric vector with changing adaptations.

Assessing the arrhythmogenic risk of engineered heart tissue patches through in silico application on infarcted ventricle models

BackgroundPost myocardial infarction (MI) ventricles contain fibrotic tissue and may have disrupted electrical properties, both of which predispose to an increased risk of life-threatening arrhythmias. Application of epicardial patches obtained from human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are a potential long-term therapy to treat heart failure resulting from post MI remodelling. However, whether the introduction of these patches is anti- or pro-arrhythmic has not been studied. MethodsWe studied arrhythmic risk using in silico engineered heart tissue (EHT) patch engraftment on human post-MI ventricular models. Two patient models were studied, including one with a large dense scar and one with an apparent channel of preserved viability bordered on both sides by scar. In each heart model a virtual EHT patch was introduced as a layer of viable tissue overlying the scarred area, with hiPSC-CMs electrophysiological properties. The incidence of re-entrant and sustained activation in simulations with and without EHT patches was assessed and the arrhythmia inducibility compared in the context of different EHT patch properties (conduction velocity (CV) and action potential duration (APD)). The impact of the EHT patch on the likelihood of focal ectopic impulse propagation was estimated by assessing the minimum stimulus strength and duration required to generate a propagating impulse in the scar border zone (BZ) with and without patch. ResultsWe uncovered two main mechanisms by which ventricular tachycardia (VT) risk could be either augmented or attenuated by the interaction of the patch with the tissue. In the case of isthmus-related VT, our simulations predict that EHT patches can prevent the induction of VT when the, generally longer, hiPSC-CMs APD is reduced towards more physiological values. In the case of large dense scar, we found that, an EHT patch with CV similar to the host myocardium does not promote VT, while EHT patches with lower CV increase the risk of VT, by promoting both non-sustained and sustained re-entry. Finally, our simulations indicate that electrically coupled EHT patches reduce the likelihood of propagation of focal ectopic impulses. ConclusionsThe introduction of EHT patches as a treatment for heart failure has the potential to augment or attenuate the risk of ventricular arrhythmias, and variations in the anatomic configuration of the substrate, the functional properties of the BZ and the electrophysiologic properties of the patch itself will determine the overall impact. Planning for delivery of this therapy will need to consider the possible impact on arrhythmia.

Clinical Practice Guidelines for the Therapeutic Use of Repetitive Transcranial Magnetic Stimulation in Neuropsychiatric Disorders.

Clinical Practice Guidelines for the Therapeutic Use of Repetitive Transcranial Magnetic Stimulation in Neuropsychiatric Disorders.

WNK3 kinase maintains neuronal excitability by reducing inwardly rectifying K+ conductance in layer V pyramidal neurons of mouse medial prefrontal cortex.

The with-no-lysine (WNK) family of serine-threonine kinases and its downstream kinases of STE20/SPS1-related proline/alanine-rich kinase (SPAK) and oxidative stress-responsive kinase-1 (OSR1) may regulate intracellular Cl− homeostasis through phosphorylation of cation-Cl− co-transporters. WNK3 is expressed in fetal and postnatal brains, and its expression level increases during development. Its roles in neurons, however, remain uncertain. Using WNK3 knockout (KO) mice, we investigated the role of WNK3 in the regulation of the intracellular Cl− concentration ([Cl−]i) and the excitability of layer V pyramidal neurons in the medial prefrontal cortex (mPFC). Gramicidin-perforated patch-clamp recordings in neurons from acute slice preparation at the postnatal day 21 indicated a significantly depolarized reversal potential for GABAA receptor-mediated currents by 6 mV, corresponding to the higher [Cl−]i level by ~4 mM in KO mice than in wild-type littermates. However, phosphorylation levels of SPAK and OSR1 and those of neuronal Na+-K+-2Cl− co-transporter NKCC1 and K+-Cl− co-transporter KCC2 did not significantly differ between KO and wild-type mice. Meanwhile, the resting membrane potential of neurons was more hyperpolarized by 7 mV, and the minimum stimulus current necessary for firing induction was increased in KO mice. These were due to an increased inwardly rectifying K+ (IRK) conductance, mediated by classical inwardly rectifying (Kir) channels, in KO neurons. The introduction of an active form of WNK3 into the recording neurons reversed these changes. The potential role of KCC2 function in the observed changes of KO neurons was investigated by applying a selective KCC2 activator, CLP290. This reversed the enhanced IRK conductance in KO neurons, indicating that both WNK3 and KCC2 are intimately linked in the regulation of resting K+ conductance. Evaluation of synaptic properties revealed that the frequency of miniature excitatory postsynaptic currents (mEPSCs) was reduced, whereas that of inhibitory currents (mIPSCs) was slightly increased in KO neurons. Together, the impact of these developmental changes on the membrane and synaptic properties was manifested as behavioral deficits in pre-pulse inhibition, a measure of sensorimotor gating involving multiple brain regions including the mPFC, in KO mice. Thus, the basal function of WNK3 would be the maintenance and/or development of both intrinsic and synaptic excitabilities.

Prediction of blood pressure change during surgical incision under opioid analgesia using sympathetic response evoking threshold

Opioid inhibition of nociceptive stimuli varies in individuals and is difficult to titrate. We have reported the vascular stiffness value (K) as a standard monitor to quantify sympathetic response with high accuracy. On the contrary, among individuals, a considerable variation in the rate of change in K for constant pain has been observed. In this study, we proposed a new index, the minimum stimulus intensity value that evoked the response on K (MECK: Minimum Evoked Current of K), and evaluated its accuracy in predicting sympathetic response to nociceptive stimuli under constant opioid administration. Thirty patients undergoing open surgery under general anesthesia were included. After anesthetic induction, remifentanil was administered at a constant concentration of 2 ng/ml at the effect site followed by tetanus stimulation. MECK was defined as the minimal current needed to produce a change in K. MECK significantly (P < 0.001) correlated with the rate of change of systolic blood pressure during skin incision (ROCBP). Bland–Altman plot analysis using the predicted ROCBP calculated from MECK and the measured ROCBP showed that the prediction equation for ROCBP was highly accurate. This study showed the potential of MECK to predict blood pressure change during surgical incision under opioid analgesia.Clinical trial registration Registry: University hospital medical information network; Registration number: UMIN000041816; Principal investigator's name: Satoshi Kamiya; Date of registration: July 9th, 2019.

Auditory Brainstem Models: Adapting Cochlear Nuclei Improve Spatial Encoding by the Medial Superior Olive in Reverberation.

Listeners typically perceive a sound as originating from the direction of its source, even as direct sound is followed milliseconds later by reflected sound from multiple different directions. Early-arriving sound is emphasised in the ascending auditory pathway, including the medial superior olive (MSO) where binaural neurons encode the interaural-time-difference (ITD) cue for spatial location. Perceptually, weighting of ITD conveyed during rising sound energy is stronger at 600 Hz than at 200 Hz, consistent with the minimum stimulus rate for binaural adaptation, and with the longer reverberation times at 600 Hz, compared with 200 Hz, in many natural outdoor environments. Here, we computationally explore the combined efficacy of adaptation prior to the binaural encoding of ITD cues, and excitatory binaural coincidence detection within MSO neurons, in emphasising ITDs conveyed in early-arriving sound. With excitatory inputs from adapting, nonlinear model spherical bushy cells (SBCs) of the bilateral cochlear nuclei, a nonlinear model MSO neuron with low-threshold potassium channels reproduces the rate-dependent emphasis of rising vs. peak sound energy in ITD encoding; adaptation is equally effective in the model MSO. Maintaining adaptation in model SBCs, and adjusting membrane speed in model MSO neurons, 'left' and 'right' populations of computationally efficient, linear model SBCs and MSO neurons reproduce this stronger weighting of ITD conveyed during rising sound energy at 600 Hz compared to 200 Hz. This hemispheric population model demonstrates a link between strong weighting of spatial information during rising sound energy, and correct unambiguous lateralisation of a speech source in reverberation.

Upright head roll test: A new contribution for the diagnosis of lateral semicircular canal benign paroxysmal positional vertigo.

Diagnosing the affected side in Benign Paroxysmal Positional Vertigo (BPPV) involving the Lateral Semicircular Canal (LSC) is often challenging and uncomfortable in patients with recent onset of vertigo and intense autonomic symptoms. The Minimum Stimulus Strategy (MSS) aims to diagnose side and canal involved by BPPV causing as little discomfort as possible to the patient. The strategy applied for LSC-BPPV includes the evaluation of pseudo-spontaneous nystagmus and oculomotor responses to the Head Pitch Test (HPT) in upright position, to the seated-supine test and to the Head Yaw Test (HYT) while supine. Matching data obtained by these tests enables clinicians to diagnose the affected side in LSC-BPPV. The purpose of this preliminary study is to propose a new diagnostic test for LSC-BPPV complimentary to the HPT, the Upright Head Roll Test (UHRT), to easily determine the affected ear and the involved arm in the sitting position and to evaluate its efficiency. Our results suggest that the UHRT can increase the sensitivity of the MSS without resorting to the HYT, thus reducing patient’s discomfort.

Intense noise exposure alters peripheral vestibular structures and physiology.

The otolith organs play a critical role in detecting linear acceleration and gravity to control posture and balance. Some afferents that innervate these structures can be activated by sound and are at risk for noise overstimulation. A previous report demonstrated that noise exposure can abolish vestibular short-latency evoked potential (VsEP) responses and damage calyceal terminals. However, the stimuli that were used to elicit responses were weaker than those established in previous studies and may have been insufficient to elicit VsEP responses in noise-exposed animals. The goal of this study was to determine the effect of an established noise exposure paradigm on VsEP responses using large head-jerk stimuli to determine if noise induces a stimulus threshold shift and/or if large head-jerks are capable of evoking VsEP responses in noise-exposed rats. An additional goal is to relate these measurements to the number of calyceal terminals and hair cells present in noise-exposed vs. non-noise-exposed tissue. Exposure to intense continuous noise significantly reduced VsEP responses to large stimuli and abolished VsEP responses to small stimuli. This finding confirms that while measurable VsEP responses can be elicited from noise-lesioned rat sacculi, larger head-jerk stimuli are required, suggesting a shift in the minimum stimulus necessary to evoke the VsEP. Additionally, a reduction in labeled calyx-only afferent terminals was observed without a concomitant reduction in the overall number of calyces or hair cells. This finding supports a critical role of calretinin-expressing calyceal-only afferents in the generation of a VsEP response.NEW & NOTEWORTHY This study identifies a change in the minimum stimulus necessary to evoke vestibular short-latency evoked potential (VsEP) responses after noise-induced damage to the vestibular periphery and reduced numbers of calretinin-labeled calyx-only afferent terminals in the striolar region of the sacculus. These data suggest that a single intense noise exposure may impact synaptic function in calyx-only terminals in the striolar region of the sacculus. Reduced calretinin immunolabeling may provide insight into the mechanism underlying noise-induced changes in VsEP responses.

Selectivity of afferent microstimulation at the DRG using epineural and penetrating electrode arrays

Objective. We have shown previously that microstimulation of the lumbar dorsal root ganglia (L5-L7 DRG) using penetrating microelectrodes, selectively recruits distal branches of the sciatic and femoral nerves in an acute preparation. However, a variety of challenges limit the clinical translatability of DRG microstimulation via penetrating electrodes. For clinical translation of a DRG somatosensory neural interface, electrodes placed on the epineural surface of the DRG may be a viable path forward. The goal of this study was to evaluate the recruitment properties of epineural electrodes and compare their performance with that of penetrating electrodes. Here, we compare the number of selectively recruited distal nerve branches and the threshold stimulus intensities between penetrating and epineural electrode arrays. Approach. Antidromically propagating action potentials were recorded from multiple distal branches of the femoral and sciatic nerves in response to epineural stimulation on 11 ganglia in four cats to quantify the selectivity of DRG stimulation. Compound action potentials (CAPs) were recorded using nerve cuff electrodes implanted around up to nine distal branches of the femoral and sciatic nerve trunks. We also tested stimulation selectivity with penetrating microelectrode arrays implanted into ten ganglia in four cats. A binary search was carried out to identify the minimum stimulus intensity that evoked a response at any of the distal cuffs, as well as whether the threshold response selectively occurred in only a single distal nerve branch. Main results. Stimulation evoked activity in just a single peripheral nerve through 67% of epineural electrodes (35/52) and through 79% of the penetrating microelectrodes (240/308). The recruitment threshold (median = 9.67 nC/phase) and dynamic range of epineural stimulation (median = 1.01 nC/phase) were significantly higher than penetrating stimulation (0.90 nC/phase and 0.36 nC/phase, respectively). However, the pattern of peripheral nerves recruited for each DRG were similar for stimulation through epineural and penetrating electrodes. Significance. Despite higher recruitment thresholds, epineural stimulation provides comparable selectivity and superior dynamic range to penetrating electrodes. These results suggest that it may be possible to achieve a highly selective neural interface with the DRG without penetrating the epineurium.

Aging does not affect integration times for the perception of depth from motion parallax

To successfully navigate throughout the world, observers must rapidly recover depth information. One depth cue that is especially important for a moving observer is motion parallax. To perceive unambiguous depth from motion parallax, the visual system must integrate information from two different proximal signals, retinal image motion and a pursuit eye movement. Previous research has shown that aging affects both of these necessary components for motion parallax depth perception, but no research has yet investigated how aging affects the mechanism for integrating motion and pursuit information to recover depth from motion parallax. The goal of the current experiment was to assess the integration time required by older adults to process depth information. In four psychophysical conditions, younger and older observers made motion and depth judgments about stationary or translating random-dot stimuli. Stimulus presentations in all four psychophysical conditions were followed by a high-contrast pattern mask, and minimum stimulus presentation durations (stimulus-to-mask onset asynchrony, or SOA) were measured. These SOAs reflect the minimum neural processing time required to make motion and motion parallax depth judgments. Pursuit latency was also measured. The results revealed that, after accounting for age-related delays in motion processing and pursuit onset, older and younger adults required similar temporal intervals to combine retinal image motion with an internal pursuit signal for the perception of depth. These results suggest that the mechanism for motion and pursuit integration is not affected by age.

Intraoperative Mapping and Monitoring of the Pyramidal Tract Using Endoscopic Depth Electrodes.

To evaluate motor function during neuroendoscopic resectioning of deep-seated brain tumors using endoscopically guided depth electrodes. For 12 cases of thalamic tumors, including high-grade gliomas, germinomas, and malignant lymphomas, depth electrodes were inserted using endoscopic guides between the tumor and the pyramidal tract in the thalamus. Motor-evoked potentials (MEPs) were continuously recorded during neuroendoscopic resectioning of the tumors. Monitoring of MEP responses using depth electrodes in all 12 cases was successful. The minimum stimulus intensity threshold required to induce MEP responses was 3 mA. Gross total or subtotal resections were successful with this technique for all patients with glioma. No additional neurologic impairments were found after surgery in any of the cases. Continuous MEP measurement using depth electrodes can serve as a new monitoring technique for endoscopic resectioning of deep-seated brain tumors.

Methyl donor supplementation alters cognitive performance and motivation in female offspring from high-fat diet-fed dams.

During gestation, fetal nutrition is entirely dependent on maternal diet. Maternal consumption of excess fat during pregnancy has been linked to an increased risk of neurologic disorders in offspring, including attention deficit/hyperactivity disorder, autism, and schizophrenia. In a mouse model, high-fat diet (HFD)-fed offspring have cognitive and executive function deficits as well as whole-genome DNA and promoter-specific hypomethylation in multiple brain regions. Dietary methyl donor supplementation during pregnancy or adulthood has been used to alter DNA methylation and behavior. Given that extensive brain development occurs during early postnatal life-particularly within the prefrontal cortex (PFC), a brain region critical for executive function-we examined whether early life methyl donor supplementation (e.g., during adolescence) could ameliorate executive function deficits observed in offspring that were exposed to maternal HFD. By using operant testing, progressive ratio, and the PFC-dependent 5-choice serial reaction timed task (5-CSRTT), we determined that F1 female offspring (B6D2F1/J) from HFD-fed dams have decreased motivation (decreased progressive ratio breakpoint) and require a longer stimulus length to complete the 5-CSRTT task successfully, whereas early life methyl donor supplementation increased motivation and shortened the minimum stimulus length required for a correct response in the 5-CSRTT. Of interest, we found that expression of 2 chemokines, CCL2 and CXCL10, correlated with the median stimulus length in the 5-CSRTT. Furthermore, we found that acute adult supplementation of methyl donors increased motivation in HFD-fed offspring and those who previously received supplementation with methyl donors. These data point to early life as a sensitive time during which dietary methyl donor supplementation can alter PFC-dependent cognitive behaviors.-McKee, S. E., Grissom, N. M., Herdt, C. T., Reyes, T. M. Methyl donor supplementation alters cognitive performance and motivation in female offspring from high-fat diet-fed dams.

Intraoperative Neuromonitoring and Alarm Criteria for Judging MEP Responses to Transcranial Electric Stimulation: The Threshold-Level Method.

The motor evoked potential (MEP) is used in the operating room to gauge-and ultimately protect-the functional integrity of the corticospinal tract (CST). However, there is no consensus as to how to best interpret the MEP for maximizing its sensitivity and specificity to CST compromise. The most common way is to use criteria associated with response magnitude (response amplitude; waveform complexity, etc.). With this approach, should an MEP in response to a fixed stimulus intensity diminish below some predetermined cutoff, suggesting CST dysfunction, then the surgical team is warned. An alternative approach is to examine the minimum stimulus energy-the threshold-needed to elicit a minimal response from a given target muscle. Threshold increases could then be used as an alternative basis for evaluating CST functional integrity. As the original proponent of this Threshold-Level alarm criteria for MEP monitoring during surgery, I have been asked to summarize the basis for this method. In so doing, I have included justification for what might seem to be arbitrary recommendations. Special emphasis is placed on anesthetic considerations because these issues are especially important when weak stimulus intensities are called for. Finally, it is important to emphasize that all the alarm criteria currently in use for interpreting intraoperative MEPs have been shown to be effective for protecting CST axons during surgery. Although differences between approaches are more than academic, overall it is much better for patient welfare to be using some form of MEP monitoring than to use none at all, while you wait for consensus about alarm criteria to emerge.

Effect of laryngotracheal topical anesthesia on recurrent laryngeal nerve monitoring during thyroid Surgery

Study ObjectiveIntraoperative neuromonitoring of the recurrent laryngeal nerve (RLN) is often used as an adjunct for RLN identification and preservation during thyroidectomies. Laryngotracheal anesthesia (LTA) with topical lidocaine reduces coughing upon emergence from anesthesia and in the immediate postoperative period; however, its use is prohibited with concerns that it could decrease the sensitivity of the intraoperative neuromonitoring. We hypothesize that there is no difference in measurements of nerve conduction made before and after LTA administration. DesignAn observational study in which all patients were subjected to LTA administration was conducted. Recurrent laryngeal nerve threshold currents were measured before and after the intervention. SettingTertiary medical center operating room. PatientsEighteen patients (total of 25 nerves at risk) with American Society of Anesthesiologists classes 1 to 3 undergoing thyroid surgery. InterventionsAfter the thyroid was removed and threshold currents at the RLN were obtained, LTA with endotracheal lidocaine was applied on the left and right side of the in situ endotracheal tube (2 cc of 4% lidocaine per side). Threshold currents were reassessed at 5 and 10 minutes after LTA administration. MeasurementsThreshold currents (minimum stimulus current applied to the RLN required to generate a discernible electromyographic response at the vocal cords) were recorded along the RLN for a baseline at 5 and 10 mm from the insertion point of the RLN into the larynx. Threshold currents were reassessed at the same 2 positions on the RLN at 5 and 10 minutes after LTA administration. Differences in mean values, between threshold currents recorded at the 3 different times, at 2 positions on the RLN, were used to compare effects of LTA on nerve conduction. Main ResultsThere were no statistically significant differences when comparing threshold currents before and after LTA administration. ConclusionsLaryngotracheal anesthesia had no significant effect on RLN nerve conduction in the period assessed.