Air Puff Research Articles

Dynamics of Ketamine-induced Loss and Return of Consciousness across Primate Neocortex.

Ketamine is a noncompetitive N-methyl-D-aspartate antagonist and is known for unique electrophysiologic profiles in electroencephalography. However, the mechanisms of ketamine-induced unconsciousness are not clearly understood. The authors have investigated neuronal dynamics of ketamine-induced loss and return of consciousness and how multisensory processing is modified in the primate neocortex. The authors performed intracortical recordings of local field potentials and single unit activity during ketamine-induced altered states of consciousness in a somatosensory and ventral premotor network. The animals were trained to perform a button holding task to indicate alertness. Air puff to face or sound was randomly delivered in each trial regardless of their behavioral response. Ketamine was infused for 60 min. Ketamine-induced loss of consciousness was identified during a gradual evolution of the high beta-gamma oscillations. The slow oscillations appeared to develop at a later stage of ketamine anesthesia. Return of consciousness and return of preanesthetic performance level (performance return) were observed during a gradual drift of the gamma oscillations toward the beta frequency. Ketamine-induced loss of consciousness, return of consciousness, and performance return are all identified during a gradual change of the dynamics, distinctive from the abrupt neural changes at propofol-induced loss of consciousness and return of consciousness. Multisensory responses indicate that puff evoked potentials and single-unit firing responses to puff were both preserved during ketamine anesthesia, but sound responses were selectively diminished. Units with suppressed responses and those with bimodal responses appeared to be inhibited under ketamine and delayed in recovery. Ketamine generates unique intracortical dynamics during its altered states of consciousness, suggesting fundamentally different neuronal processes from propofol. The gradually shifting dynamics suggest a continuously conscious or dreaming state while unresponsive under ketamine until its deeper stage with the slow-delta oscillations. Somatosensory processing is preserved during ketamine anesthesia, but multisensory processing appears to be diminished under ketamine and through recovery.

Polarity- and Intensity-Independent Modulation of Timing During Delay Eyeblink Conditioning Using Cerebellar Transcranial Direct Current Stimulation.

Delay eyeblink conditioning (dEBC) is widely used to assess cerebellar-dependent associative motor learning, including precise timing processes. Transcranial direct current stimulation (tDCS), noninvasive brain stimulation used to indirectly excite and inhibit select brain regions, may be a promising tool for understanding how functional integrity of the cerebellum influences dEBC behavior. The aim of this study was to assess whether tDCS-induced inhibition (cathodal) and excitation (anodal) of the cerebellum differentially impact timing of dEBC. A standard 10-block dEBC paradigm was administered to 102 healthy participants. Participants were randomized to stimulation conditions in a double-blind, between-subjects sham-controlled design. Participants received 20-min active (anodal or cathodal) stimulation at 1.5mA (n = 20 anodal, n = 22 cathodal) or 2mA (n = 19 anodal, n = 21 cathodal) or sham stimulation (n = 20) concurrently with dEBC training. Stimulation intensity and polarity effects on percent conditioned responses (CRs) and CR peak and onset latency were examined using repeated-measures analyses of variance. Acquisition of CRs increased over time at a similar rate across sham and all active stimulation groups. CR peak and onset latencies were later, i.e., closer to air puff onset, in all active stimulation groups compared to the sham group. Thus,tDCS facilitated cerebellar-dependent timing of dEBC, irrespective of stimulation intensity and polarity. These findings highlight the feasibility of using tDCS to modify cerebellar-dependent functions and provide further support for cerebellar contributions to human eyeblink conditioning and for exploring therapeutic tDCS interventions for cerebellar dysfunction.

Distinct temporal integration of noradrenaline signaling by astrocytic second messengers during vigilance

Astrocytes may function as mediators of the impact of noradrenaline on neuronal function. Activation of glial α1-adrenergic receptors triggers rapid astrocytic Ca2+ elevation and facilitates synaptic plasticity, while activation of β-adrenergic receptors elevates cAMP levels and modulates memory consolidation. However, the dynamics of these processes in behaving mice remain unexplored, as do the interactions between the distinct second messenger pathways. Here we simultaneously monitored astrocytic Ca2+ and cAMP and demonstrate that astrocytic second messengers are regulated in a temporally distinct manner. In behaving mice, we found that while an abrupt facial air puff triggered transient increases in noradrenaline release and large cytosolic astrocytic Ca2+ elevations, cAMP changes were not detectable. By contrast, repeated aversive stimuli that lead to prolonged periods of vigilance were accompanied by robust noradrenergic axonal activity and gradual sustained cAMP increases. Our findings suggest distinct astrocytic signaling pathways can integrate noradrenergic activity during vigilance states to mediate distinct functions supporting memory.

Corneal Reflex Testing in the Evaluation of a Comatose Patient: An Ode to Precise Semiology and Examination Skills.

The corneal reflex assesses the integrity of the trigeminal and facial cranial nerves. This brainstem reflex is fundamental in neuroprognostication after cardiac arrest and in brain death determination. We sought to investigate corneal reflex testing methods among neurologists and general critical care providers in the context of neuroprognostication following cardiac arrest. This is an international cross-sectional study disseminated to members of the Neurocritical Care Society, Society of Critical Care Medicine, and American Academy of Neurology. We utilized an open Web-based survey (Qualtrics®, Provo, UT, USA) to disseminate 26 questions regarding neuroprognostication practices following cardiac arrest, in which 3 questions pertained to corneal reflex testing. Descriptive statistical measures were used, and subgroup analyses performed between neurologists and non-neurologists. Questions were not mandatory; therefore, the percentages were relative to the number of respondents for each question. There were 959 respondents in total. Physicians comprised 85.1% of practitioners (762 out of 895), of which 55% (419) identified themselves as non-neurologists and 45% (343) as neurologists. Among physicians, 85.9% (608 out of 708) deemed corneal reflex relevant for prognostication following cardiac arrest (neurologists 84.4% versus non-neurologists 87.0%). A variety of techniques were employed for corneal reflex testing, the most common being "light cotton touch" (59.2%), followed by "cotton-tipped applicator with pressure" (23.9%), "saline or water squirt" (15.9%), and "puff of air" (1.0%). There were no significant differences in the methods for testing between neurologists and non-neurologists (p = 0.52). The location of stimulus application was variable, and 26.1% of physicians (148/567) apply the stimulus on the temporal conjunctiva rather than on the cornea itself. Corneal reflex testing remains a cornerstone of the coma exam and is commonly used in neuroprognostication of unconscious cardiac arrest survivors and in brain death determination. A wide variability of techniques is noted among practitioners, including some that may provide suboptimal stimulation of corneal nerve endings. Imprecise testing in this setting may lead to inaccuracies in critical settings, which carries significant consequences such as guiding decisions of care limitations, misdiagnosisof brain death, and loss of public trust.

Classification of aspirated and unaspirated sounds in speech using excitation and signal level information

In this work, consonant aspiration and unaspiration phenomena are studied. It is known that, pronunciation of aspiration and unaspiration is characterized by the ’puff of air’ released at the place of constriction in the vocal tract also known as burst. Here, properties of the vowel immediately after the burst are studied for characterization of the burst. Excitation source signal estimated from speech as low pass filtered linear prediction residual signal is used for the task. The signal characteristics of parameters such as glottal pulse, duration of open, closed & return phases; slope of open, & return phases; duration of burst; ratio of highest and lowest frame wise energies of signal and voice onset point are explored as features to characterize aspiration and unaspiration. Three datasets namely TIMIT, IIIT Hyderabad Marathi and IIIT Hyderabad Hindi (IIIT-H Indic Speech Databases) are used to verify the proposed approach. Random forest, support vector machine and deep feed forward neural networks (DFFNNs) are used as classifiers to test the effectiveness of the features used for the task. Optimal features are selected for the classification using correlation based feature selection (CFS). From the results, it is observed that the proposed features are efficient in classifying the aspirated and unaspirated consonants. Performance of the proposed features in recognition of aspirated and unaspirated phoneme is also evaluated. IIIT Hyderabad Marathi is considered for the analysis. It is observed that the performance of recognition of aspirated and unaspirated sounds using proposed features is improved in comparison with the MFCCs based phoneme recognition system.

Biomechanical Changes after in vivo Enzyme-Induced Corneal Crosslinking in Rabbits

Introduction: Enzyme-induced corneal crosslinking (CXL) may be a promising and effective method to stiffen the cornea. However, there have been no reports on the effect of corneal CXL with enzyme in vivo. Objective: To evaluate the biomechanical efficacy after in vivo enzyme-induced corneal CXL in rabbits using noninvasive imaging. Methods: The eyes of 10 white New Zealand rabbits were unilaterally treated with CXL enzyme (transglutaminases [Tgases]). The contralateral eyes served as negative controls. In every rabbit, a 1 U/mL solution of Tgases was applied to the corneal surface. Corneal dynamic deformation by an air puff was measured using high-speed Scheimpflug imaging on day 14 after the procedure. Biomechanical parameters, central corneal thickness, and intraocular pressure were recorded and assessed. Then, corneal buttons were excised from euthanized animals for hematoxylin and eosin staining to evaluate changes in corneal collagen distribution and cell damage. Results: Some biomechanical parameters showed statistically significant changes after in vivo CXL. The deformation amplitude and maximum corneal velocity during the second applanations were significantly lower than those of the untreated control group. The second applanations were significantly increased compared to the control group. No changes were found in other parameters. The morphology of the corneal stroma was similar in CXL-treated and untreated corneas. No obvious cell apoptosis was observed. Conclusions: Corneal stiffness increased after in vivo CXL induced by Tgases. This CXL method may be useful for corneal ectasia.

Simulation of Air Puff Tonometry Test Using Arbitrary Lagrangian-Eulerian (ALE) Deforming Mesh for Corneal Material Characterisation.

Purpose: To improve numerical simulation of the non-contact tonometry test by using arbitrary Lagrangian-Eulerian deforming mesh in the coupling between computational fluid dynamics model of an air jet and finite element model of the human eye. Methods: Computational fluid dynamics model simulated impingement of the air puff and employed Spallart–Allmaras model to capture turbulence of the air jet. The time span of the jet was 30 ms and maximum Reynolds number was, with jet orifice diameter 2.4 mm and impinging distance 11 mm. The model of the human eye was analysed using finite element method with regional hyperelastic material variation and corneal patient-specific topography starting from stress-free configuration. The cornea was free to deform as a response to the air puff using an adaptive deforming mesh at every time step of the solution. Aqueous and vitreous humours were simulated as a fluid cavity filled with incompressible fluid with a density of 1000 kg/m3. Results: Using the adaptive deforming mesh in numerical simulation of the air puff test improved the traditional understanding of how pressure distribution on cornea changes with time of the test. There was a mean decrease in maximum pressure (at corneal apex) of 6.29 ± 2.2% and a development of negative pressure on a peripheral corneal region 2–4 mm away from cornea centre. Conclusions: The study presented an improvement of numerical simulation of the air puff test, which will lead to more accurate intraocular pressure (IOP) and corneal material behaviour estimation. The parametric study showed that pressure of the air puff is different from one model to another, value-wise and distribution-wise, based on cornea biomechanical parameters.

Changes in biomechanical properties of keratoconic corneas following intracorneal ring segment (ICRS) implantation

AbstractPurposeStudies using Corvis ST (CST, Oculus; Wetzlar, Germany) and Ocular Response Analyser (ORA, Reichert, Depew, NY, USA) have reported significant differences between keratoconic and healthy corneas. Implantation of intracorneal ring segments (ICRS) using a femtosecond laser represents a reliable surgical option to widen the spectrum of the stage‐related therapy of keratoconus in patients with contact lens intolerance, post‐LASIK‐keratectasia or pellucid marginal degeneration (PMD). Our aim was to evaluate the ability of the Corvis ST and Ocular Response Analyser to detect the possible stiffening effect after Intacs SK (Addition Technology, Inc.) implantation in patients with keratoconus.Patients and MethodsBetween January 2018 and January 2019, ICRS were implanted in 31 eyes of 27 patients (age 31.9 ± 10.2 years) with clear central cornea. The patients had to fulfill the corneal diagnostic tests required for femtosecond laser‐assisted Intacs SK implantation in 80% depth. The following CST/ORA parameters were recorded: deformation amplitude Ratio (DA Ratio), stiffness parameter at applanation 1 (SP A1), Corvis biomechanical index (CBI), tomographic biomechanical index (TBI), Keratoconus Match Index (KMI), corneal hysteresis (CH) and corneal resistance factor (CRF) preoperatively and 6 months after the ICRS implantation.ResultsDA Ratio (5.43 ± 1.0 vs 5.52 ± 1.1, p = 0.4), SP A1 (58.76 ± 17.5 vs 59.11 ± 17.8, p = 0.4) CBI (0.96 ± 0.1 vs 0.97 ± 0.1, p = 0.3), TBI (0.98 ± 0.0 vs 0.99 ± 0.1, p = 0.3) and KMI (−0.03 ± 0.3 vs −0.17 ± 0.2, p = 0.1) did not change significantly between both time‐points. However, CH (7.96 ± 1.2 vs 7.05 ± 0.9) and CRF (6.33 ± 1.2 vs 5.35 ± 1.2) decreased significantly from preoperative to postoperative measurement time‐point (p = 0.03 for both).ConclusionBoth devices ORA and CST are supposed to analyse the dynamic behavior of the cornea during its temporary deformation by an air puff. The lack of significant changes in the standard parameters of the CST reflects the inability of this device to document the stiffening effect of ICRS in keratoconus patients. In contrast, the standard ORA parameters CH and CRF, but not the KMI, showed a significant decrease 6 month postoperatively. The meaning of those findings in relation to the progression of a keratoconus the disease has to be evaluated further.

Is central corneal thickness a constant during air puff indentation with Corvis ST?

AbstractPurposeCorvis ST (Oculus Optikgeräte GmbH, Wetzlar, Germany) is the only commercial device that can capture corneal dynamic deformation in real time and provide a number of dynamic parameters, which include central corneal thickness (CCT). This study aimed to quantitatively analyse the change in CCT during air puff indentation using Corvis ST.MethodsSixty‐seven keratoconic eyes and 84 normal eyes were enrolled in this study. Dynamic videos were obtained from Corvis ST. An adaptive bilateral filtering method and a frame correlation method were used to remove noises. An adaptive threshold segmentation method was used to extract corneal boundary. The change in central corneal thickness, described as relative change rate of central corneal thickness (RCRCCT) and change speed of central corneal thickness (CSCCT) were compared between keratoconus group and normal cornea group.ResultsIt is shown that CCT would change and these two parameters were statistically significantly different between the keratoconus group and the normal cornea group RCRCCT, p = 0.014; CSCCT, p = 0.001.ConclusionsThe result of this study approved that CCT would change during air puff indentation. Further study is needed to develop more clinical applications based on these new findings, such as distinguishing keratoconus from normal cornea. image Fig. 1 Curves of changes in cornea and force over time. (A) Curve of corneal apex displacement and curve of air puff force; (B) A typical curve of the CCT changingover time. The red lineis the central corneal thickness‐time curve, the blue line is the force ‐time curve, and the green line is the fitting curveof force curve.

Contact lens and eye glass wearers with and witouth ocular symptoms: differences in corneal sensitivity, blinking, tearing and corneal surface temperature

AbstractPurposeTo analyze corneal sensitivity, blink frequency (BF), tearing rate (TR), TBUT, and corneal surface temperature (CST) in young contact lens (CLs) and eye glass (EGs) wearers with and without ocular discomfort symptoms.MethodsEGs (n = 18) and CLs (n = 23) young subjects (18–40 years old, both sexes) participated voluntarily. CLs were classified as asymptomatic (A) or symptomatic (S) depending on their OSDI score (< 13 or ≥ 13, respectively). Corneal sensitivity to mechanical and chemical air puffs (3s duration, applied with a gas esthesiometer) and cold (4°C) saline drops was explored. Sensations evoked by each stimulus was scored with 0 to 10 VAS. BR (1 min at rest or during a task), TR (mm of wet phenol red threads, 15 s), TBUT (s), and CST (IR video thermography) were also measured.ResultsVAS values of irritation sensation evoked by mechanical and chemical stimulation (p < 0.05) were higher in CLs than in EGs while VAS values of cold sensation evoked by saline drops were similar in both groups. Although CST and TR were similar in EGs and CLs, TBUT was significantly shorter (p < 0.001) and BR was higher in CLs both at rest (p < 0.001) and during a visual task (p < 0.01). Although VAS values scored to corneal mechanical, chemical and cold stimulation were lower in CL‐S than in CL‐A, no differences were found in BR at rest or during the task, TR, TBUT and CST. Corneal sensitivity and CST were also similar in EG‐A and EG‐S, although TR (p < 0.05) and BF at rest (p < 0.05), but not during the task, were higher in EG‐S.ConclusionsResults show a reduced corneal sensitivity in symptomatic CL wearers, which suggests that corneal sensory nerve activity must be altered in a different degree in asymptomatic and symptomatic individuals, thus leading to changes in tearing and blinking regulation.Support: AEI‐ERDF SAF‐2017‐83674‐C2‐1‐R and 2‐R

Tri-modal speech: Audio-visual-tactile integration in speech perception

Speech perception is a multi-sensory experience. Visual information enhances [Sumby and Pollack (1954). J. Acoust. Soc. Am. 25, 212-215] and interferes [McGurk and MacDonald (1976). Nature 264, 746-748] with speech perception. Similarly, tactile information, transmitted by puffs of air arriving at the skin and aligned with speech audio, alters [Gick and Derrick (2009). Nature 462, 502-504] auditory speech perception in noise. It has also been shown that aero-tactile information influences visual speech perception when an auditory signal is absent [Derrick, Bicevskis, and Gick (2019a). Front. Commun. Lang. Sci. 3(61), 1-11]. However, researchers have not yet identified the combined influence of aero-tactile, visual, and auditory information on speech perception. The effects of matching and mismatching visual and tactile speech on two-way forced-choice auditory syllable-in-noise classification tasks were tested. The results showed that both visual and tactile information altered the signal-to-noise threshold for accurate identification of auditory signals. Similar to previous studies, the visual component has a strong influence on auditory syllable-in-noise identification, as evidenced by a 28.04 dB improvement in SNR between matching and mismatching visual stimulus presentations. In comparison, the tactile component had a small influence resulting in a 1.58 dB SNR match-mismatch range. The effects of both the audio and tactile information were shown to be additive.

Recovering from a tumble and roosting bat style

Evolution has had some fun with the limbs that we call arms. From weight-bearing forelimbs, to fins and flippers, the same skeletal structures keep turning up; albeit somewhat modified. When David Boerma from Brown University, USA, gazes at the wings of a bat, he says that he literally sees himself; ‘from an anatomical perspective their wings aren't very different from my own arms and hands’, he smiles. Having traded in their manual dexterity, bats mastered an airborne lifestyle, but Boerma wondered how the mammal's elegantly elongated limbs might contribute as they navigate natural gusts and squalls. Knowing that bat wings are relatively heavy, Boerma wondered whether the mammals could capitalize on the limbs’ apparent weighty inertia to stabilise their manoeuvres when knocked off course by a gust of wind.Working with Tim Treskatis, an intern from Westphalian University of Applied Sciences, Germany, to build a laser-triggered blast of air that would unbalance Seba's short-tailed bats (Carollia perspicillata) as they flew along a narrow corridor in the lab, Boerma filmed the bats’ recoveries in 3D to reconstruct their manoeuvres. Remarkably, when Boerma, Treskatis, Kenneth Breuer and Sharon Swartz analysed the bats’ movements they were amazed that the animals were able to recover from being thrust off course within a single wing beat.Focusing on the bats that had been pitched upward when the 2.5× bodyweight puff of air hit their back end, the bats flung their wings wide at a point in the wing beat when they would normally pull them in; with the result that their wings were thrust forward, to counteract the jet of air and tip the body back down. However, when the jet glanced off one of the bats’ wings – forcing it down and sending the animal into a spin – the bats swiftly extended the unperturbed wing as it rolled upward in a bid to counteract the rotation. Then they swept the perturbed wing all the way under the body as the bat righted itself ready to resume normal wing beats. ‘By just shifting the weight of their wings around, bats can generate forces that rapidly reorient their bodies when recovering from aerial stumbles, similar to the way a gymnast or diver moves their arms and legs to spin in mid-air’, says Boerma.By this point, Boerma's appetite for research had been whetted; ‘the experience left me yearning to work with bats in the field, where I might see first-hand the kinds of environmental challenges they face and learn how they respond’, he recalls. Explaining that Spix's disk-winged bats (Thyroptera tricolor), which roost head-up inside furled Heliconia leaves in the rainforest, have evolved unconventional suction cups at the base of the thumb and at the ankle for attachment to smooth leaves, Boerma was curious how the minute mammals manage their inbound trajectory when coming in to land.Travelling to the Hacienda Baru Biological Research Station, Costa Rica, and teaming up with José Pablo Barrantes from the Universidad de Costa Rica, the duo spent two weeks tracking down the tiny mammals in their rainforest home. Returning with them briefly to the research station, the pair quickly trained the bats to land on a force plate disguised as a leaf while filming the manoeuvre. And Boerma recalls how the bats were equally happy to land on the researchers as they were on the force plate: ‘At one point José Pablo left the enclosure and I kept training the bat on my own. It flew around and then landed on my back where I couldn't reach it’, he laughs. Analysing movies of the bats landing on the force plate and within furled leaves, with the help of high-school student Charles Chung, Boerma realised that the bats fine-tune their approach by subtly adjusting their wing beats until just above the landing site. Then they pull in their wings, going into freefall as they reach forward with their thumb suction pads to latch onto the surface. Evaluating the force exerted on the force plate as the bat made contact, the duo also realised that the suction pad snaps into place as soon as it contacts the leaf.‘These kinds of studies help us to begin to apply what we learn about bat flight in the lab to understand the more complex flight they perform in their natural habitats’, says Boerma. He is now eager to understand how reeling bats coordinate their deft manoeuvres; in addition to looking for connections between the landing styles of other species to learn how the mammals have adapted to roost sites ranging from tightly furled leaves to caves and trees.

In vivo evaluation of corneal biomechanical properties by optical coherence elastography at different cross-linking irradiances.

.Corneal collagen cross-linking (CXL) strengthens the biomechanical properties of damaged corneas. Quantifying the changes of stiffness due to different CXL protocols is difficult, especially in vivo. A noninvasive elastic wave-based optical coherence elastography system was developed to construct in vivo corneal elasticity maps by excitation of air puff. Biomechanical differences were compared for rabbit corneas given three different CXL protocols while keeping the total energy delivered constant. The Young’s modulus was weaker in corneas treated with higher irradiance levels over shorter durations, and a slight increase of Young’s modulus was present in all groups one week after the recovery process. Due to the noninvasive nature and minimal force to generate corneal elastic waves, this technique has the potential for early detection and treatment of corneal diseases in clinic.

Effects of football practice on blink reflex parameters in Division I football athletes

ObjectiveThe objective was to access the effects of football practice sessions on blink reflex parameters using the Eyestat.BackgroundOur laboratory has utilized a potential objective measure to identify concussions. This technology, called Eyestat, is a noninvasive diagnostic tool measuring changes in blink reflex parameters. Prior research cited significant differences in various blink reflex parameters between active play, concussion, and baseline; however, the number of subjects for the active play population was small (N = 10). Thus, the purpose of this study was to identify blink reflex parameters during football practice, providing outcomes potentially helpful with its use for a concussed population.Design/MethodsForty-seven Division I male football players between the ages of 18-22 were evaluated on multiple sessions during a 2 week period of football practices. During various points of the practice, subjects completed the blink test and had their heart rate assessed. During the blink test, subjects placed their face against the apparatus, which directed a puff of air to the corner of the subject’s eye to stimulate the blink. Five puffs were administered in a random fashion over a 20 second period in which videography captured and recorded the blink.ResultsResults of the study found significant differences in latency (p = 0.0000), time under the threshold (p = 0.0176), oscillations (p = 0.0217) and excursion (p = 0.0003), but no significant differences in differential latency (p = 0.0626). Average heart rate was 125 BPM, with a minimum of 72 BPM and maximum of 172 BPM. The results of this study correlate with prior research in latency, time under the threshold and excursions and support the changes in blink reflex parameters after football practice.ConclusionsFuture studies need to assess if changes occur with individual physical activity or is it related only to the practice of this sport.

Temporal discrimination threshold and blink reflex recovery cycle in cervical dystonia – two sides of the same coin?

IntroductionElevated temporal discrimination thresholds (TDT) have been found in cervical dystonia (CD) and unaffected first-degree relatives, indicating autosomal dominant inheritance with reduced penetrance, serving as an endophenotype and being indicative of abnormal inhibitory processing within the brainstem-basal ganglia circuits. The blink reflex R2 recovery cycle (BRRC) is also a measure of excitability of brainstem-basal ganglia circuits, and inconsistent findings are reported in CD. The aim was to investigate TDT and BRRC in CD and evaluate its reliability as an endophenotype. Methods29 patients with isolated cervical dystonia (mean age: 56.1 ± 14.3, female n = 18) and 29 age- and gender-matched healthy controls (mean age: 56.0 ± 14.2, female n = 18) were evaluated using a TDT-paradigm, performed as previously described by testing visual, tactile and visual-tactile temporal discrimination thresholds, and the BRRC, investigated with electrical and air puff stimulation. ResultsMean visual-tactile (p = 0.001) and visual TDTs (p = 0.015) differed between CD and controls; tactile TDTs revealed no group differences (p = 0.232). No between group differences were found for BRRC using either electrical or air puff stimulation (p = 0.117). There was no correlation between the elevation of TDTs and the degree of BRRC-inhibition in CD. ConclusionOur findings support the hypothesis that the TDT is an endophenotype in CD. BRRC testing did not demonstrate disinhibition of brainstem-basal ganglia circuits in CD. In contrast to TDT, the BRRC seems not to represent an endophenotype in cervical dystonia.

Corneal Buckling during Applanation and Its Effect on the Air Pressure Curve in Ocular Response Analyzer.

The paper presents, for the first time, corneal buckling, during the air puff applanation, recorded with use of Ocular Response Analyzer (ORA), when the cornea is deeper deformed after its applanation. Precise numerical analysis of the air pressure curve from the raw data, distinct local disturbances of the curve, which appear almost exactly at the time of the first and the second applanations. Thirty measurements taken on six eyes show clear dependencies between times of both applanations and appearances of local wave disturbances on the air pressure curve as well as between the amplitude of pressure wave disturbances and the respective height of applanation curve. These findings can be interpreted as a result of very fast corneal buckling, that produces the air pressure wave, propagating from the cornea towards the device. The quantitative dependencies measured and described in this study, enable to characterize the individual buckling during respective applanations. Due to these individual characterizations and dependencies it is possible to understand and describe better the ultrafast corneal applanation process. Such phenomena could likely be employed to increase the accuracy of measured parameters by ORA or for identifying new types of biomechanical properties of the cornea.

Intraocular pressure changes in eyes with small incision lenticules and laser in situ keratomileusis

BackgroundMeasuring intraocular pressure after refractive surgery is a challenge in the diagnosis, evaluation, and treatment of glaucoma. Intraocular pressure characteristics after laser in situ keratomileusis (LASIK) are well known. However, intraocular pressure measurement and characteristics after small incision lenticule extraction (SMILE) are still unknown, providing an interesting point of comparison in terms of biomechanical differences from LASIK.MethodsAn intraocular pressure analytical model utilising fluid dynamics (simulating air puff) was developed using OpenFoam and Scilab. In addition, solid mechanics (simulating the deformation of the corneal structure) and a ray‐tracing technique (simulating applanation detection) simulated by a previously established air‐puff Tonovue tonometer were used to simulate post‐SMILE and post‐LASIK intraocular pressure.ResultsBased on the proposed model, while at a myopic correction of zero dioptres the difference in intraocular pressure before and after SMILE was 0-mmHg, whereas the difference before and after LASIK was −2.2-mmHg. This trend was observed with a myopic correction up to 12 dioptres.ConclusionIn a numerical simulation, differences in intraocular pressure in LASIK and SMILE largely resulted from the completeness of the Bowman's membrane resulting from cap or flap creation.

High-speed OCT-based ocular biometer combined with an air-puff system for determination of induced retraction-free eye dynamics.

We demonstrate a swept source OCT-based ocular biometer integrated with an air-puff stimulus to study the reaction of the eye to mechanical stimulation in vivo. The system enables simultaneous measurement of the stimulus strength and high-speed imaging of the eye dynamics along the visual axis. We characterize the stimulus and perform optimization of the data acquisition for a proper interpretation of the results. Access to the dynamics of axial eye length allows for a determination of the eye retraction, which is used to correct the air-puff induced displacement of ocular structures. We define the parameters to quantify the reaction of the eye to the air puff and determine their reproducibility in a group of healthy subjects. We observe the corneal deformation process and axial wobbling of the crystalline lens. OCT biometer combined with the air puff is the first instrument with the potential to provide comprehensive information on the biomechanics of ocular components.

Sensorimotor Coding of Vermal Granule Neurons in the Developing Mammalian Cerebellum.

The vermal cerebellum is a hub of sensorimotor integration critical for postural control and locomotion, but the nature and developmental organization of afferent information to this region have remained poorly understood in vivo Here, we use in vivo two-photon calcium imaging of the vermal cerebellum in awake behaving male and female mice to record granule neuron responses to diverse sensorimotor cues targeting visual, auditory, somatosensory, and motor domains. Use of an activity-independent marker revealed that approximately half (54%) of vermal granule neurons were activated during these recordings. A multikernel linear model distinguished the relative influences of external stimuli and co-occurring movements on neural responses, indicating that, among the subset of activated granule neurons, locomotion (44%-56%) and facial air puffs (50%) were more commonly and reliably encoded than visual (31%-32%) and auditory (19%-28%) stimuli. Strikingly, we also uncover populations of granule neurons that respond differentially to voluntary and forced locomotion, whereas other granule neurons in the same region respond similarly to locomotion in both conditions. Finally, by combining two-photon calcium imaging with birth date labeling of granule neurons via in vivo electroporation, we find that early- and late-born granule neurons convey similarly diverse sensorimotor information to spatially distinct regions of the molecular layer. Collectively, our findings elucidate the nature and developmental organization of sensorimotor information in vermal granule neurons of the developing mammalian brain.SIGNIFICANCE STATEMENT Cerebellar granule neurons comprise over half the neurons in the brain, and their coding properties have been the subject of theoretical and experimental interest for over a half-century. In this study, we directly test long-held theories about encoding of sensorimotor stimuli in the cerebellum and compare the in vivo coding properties of early- and late-born granule neurons. Strikingly, we identify populations of granule neurons that differentially encode voluntary and forced locomotion and find that, although the birth order of granule neurons specifies the positioning of their parallel fiber axons, both early- and late-born granule neurons convey a functionally diverse sensorimotor code. These findings constitute important conceptual advances in understanding the principles underlying cerebellar circuit development and function.

Role of human prefrontal cortex in the modulation of conditioned eyeblink responses

Classical conditioning of the eyeblink reflex (EBC) is a simple form of associative motor learning. EBC is heavily dependent on cerebellar function, but experimental studies also suggest that the prefrontal cortex (PFC) orchestrates a neuronal network which interacts with the cerebellum to mediate the conditioned eyeblink responses (CR).To further investigate the role of PFC for EBC in humans, we aimed in this study at assessing whether acquisition of CR can be modulated by focal repetitive transcranial magnetic stimulation (rTMS) given as theta burst stimulation (TBS) over the dorsolateral PFC (DLPFC).A standard delay conditioning paradigm with a 540 ms tone as conditioned stimulus (CS) coterminating with a 100 ms air puff as unconditioned stimulus (US) was used in a total of 60 healthy subjects (35 female, 25 male, mean age 28.4 ± 2.4 years). One hundred paired CS-US trials and 30 extinction CS alone trials were given. TBS was applied over the DLPFC ipsilaterally to the US during the acquisition phase. Subjects were randomly assigned to three groups (n = 20) using excitatory intermittent TBS (iTBS), inhibitory continuous TBS (cTBS) or sham stimulation.CR acquisition was significantly enhanced by iTBS (mean total CR incidence 63.1 ± 6.5%) and significantly reduced by cTBS (13 ± 2%) compared to sham stimulation (25.1 ± 6.7%).We provide thus physiological evidence that the acquisition of this type of associative learning is critically modulated by PFC activity in humans.