Reflexive Eye Closure in Response to Cone and Melanopsin Stimulation: A Study of Implicit Measures of Light Sensitivity in Migraine

Objective:To quantify interictal photophobia in migraine with and without aura using reflexive eye closure as an implicit measure of light sensitivity, and to assess the contribution of melanopsin and cone signals to these responses.Methods:Participants were screened to meet criteria for one of three groups: headache-free (HAf) controls, migraine without aura (MwoA), and migraine with visual aura (MwA). MwoA and MwA participants were included if they endorsed ictal and interictal photophobia. Exclusion criteria included impaired vision, inability to collect usable pupillometry, and history of either head trauma or seizure. Participants viewed light pulses that selectively targeted melanopsin, the cones, or their combination during recording of orbicularis oculi electromyography (OO-EMG) and blinking activity.Results:We studied twenty participants in each group. MwA and MwoA groups reported increased visual discomfort to light stimuli (Discomfort rating, 400% contrast, MwA: 4.84 [95% CI: 0.33, 9.35]; MwoA: 5.23 [0.96, 9.50]) as compared to HAf controls (2.71 [0, 6.47]). Time course analysis of OO-EMG and blinking activity demonstrated that reflexive eye closure was tightly coupled to the light pulses. The MwA group had greater OO-EMG and blinking activity in response to these stimuli (EMG activity, 400% contrast: 42.9%Δ [28.4, 57.4]; Blink activity, 400% contrast: 11.2% [8.8, 13.6]) as compared to the MwoA (EMG activity, 400% contrast: 9.9%Δ [5.8, 14.0]; Blink activity, 400% contrast: 4.7% [3.5, 5.9]) and HAf control (EMG activity, 400% contrast: 13.2%Δ [7.1, 19.3]; Blink activity, 400% contrast: 4.5% [3.1, 5.9]) groups.Conclusions:Our findings suggest that the intrinsically-photosensitive retinal ganglion cells (ipRGCs), which integrate melanopsin and cone signals, provide the afferent input for light-induced reflexive eye closure in a photophobic state. Moreover, we find a dissociation between implicit and explicit measures of interictal photophobia depending on a history of visual aura in migraine. This implies distinct pathophysiology in forms of migraine, interacting with separate neural pathways by which the amplification of ipRGC signals elicit implicit and explicit signs of visual discomfort.

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Enhanced reflexive eye closure is mediated by ipRGC signals and is specific to migraine with visual aura

10.1101/2020.12.12.422528 ◽

2020 ◽

Author(s):

Eric Alan Kaiser ◽

Harrison McAdams ◽

Aleksandra Igdalova ◽

Edda B Haggerty ◽

Brett Cucchiara ◽

...

Keyword(s):

Time Course ◽

Visual Stimulation ◽

Ganglion Cells ◽

Afferent Input ◽

Neural Pathways ◽

Implicit Measure ◽

Visual Aura ◽

Visual Discomfort ◽

Different Response ◽

Eye Closure

Objective: To assess the contribution of the melanopsin-containing, intrinsically photosensitive retinal ganglion cells (ipRGCs) and the cones to reflexive eye closure as an implicit measure of interictal photophobia in migraine. Methods: We studied twenty participants in each of three groups: headache-free (HAf) controls, migraine without aura (MwoA), and migraine with visual aura (MwA). Participants viewed spectral pulses that selectively targeted melanopsin, the cones, or their combination while we recorded orbicularis oculi electromyography (OO-EMG) and blinking rate. Results: Time course analysis of OO-EMG demonstrated that reflexive eye closure was tightly coupled to the spectral pulses. Compared to both the MwoA and HAf control groups, the MwA group had enhanced OO-EMG and blinking activity in response to melanopsin and cone stimulation in combination and in isolation. This response scaled with the contrast of the stimulus. Conclusions: Our findings suggest that ipRGC signals, whether elicited by melanopsin stimulation or from presumed extrinsic cone input, provide the afferent input for light-induced reflexive eye closure in a photophobic state. Participants with migraine and visual aura had a distinctly different response to visual stimulation as compared to the other two groups. This is in contrast to prior findings in this same cohort in whom higher explicit ratings of visual discomfort were found for both MwA and MwoA as compared to controls. Such a dissociation suggests distinct pathophysiology in forms of migraine, interacting with separate neural pathways by which ipRGC signals elicit implicit and explicit signs of visual discomfort.

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Acute Stroke Care during the COVID-19 Pandemic: Reduction in the Number of Admissions of Elderly Patients and Increase in Prehospital Delays

Cerebrovascular Diseases ◽

10.1159/000514140 ◽

2021 ◽

pp. 1-7

Author(s):

Gabriel Velilla-Alonso ◽

Andrés García-Pastor ◽

Ángela Rodríguez-López ◽

Ana Gómez-Roldós ◽

Antonio Sánchez-Soblechero ◽

...

Keyword(s):

Elderly Patients ◽

Acute Stroke ◽

Time Course ◽

Intravenous Thrombolysis ◽

Stroke Care ◽

Acute Stroke Care ◽

Group Data ◽

Radiological Data ◽

History Of ◽

Prehospital Delays

Introduction: We analyzed whether the coronavirus disease 2019 (COVID-19) crisis affected acute stroke care in our center during the first 2 months of lockdown in Spain. Methods: This is a single-center, retrospective study. We collected demographic, clinical, and radiological data; time course; and treatment of patients meeting the stroke unit admission criteria from March 14 to May 14, 2020 (COVID-19 period group). Data were compared with the same period in 2019 (pre-COVID-19 period group). Results: 195 patients were analyzed; 83 in the COVID-19 period group, resulting in a 26% decline of acute strokes and transient ischemic attacks (TIAs) admitted to our center compared with the previous year (p = 0.038). Ten patients (12%) tested positive for PCR SARS-CoV-2. The proportion of patients aged 65 years and over was lower in the COVID-19 period group (53 vs. 68.8%, p = 0.025). During the pandemic period, analyzed patients were more frequently smokers (27.7 vs. 10.7%, p = 0.002) and had less frequently history of prior stroke (13.3 vs. 25%, p = 0.043) or atrial fibrillation (9.6 vs. 25%, p = 0.006). ASPECTS score was lower (9 [7–10] vs. 10 [8–10], p = 0.032), NIHSS score was slightly higher (5 [2–14] vs. 4 [2–8], p = 0.122), onset-to-door time was higher (304 [93–760] vs. 197 [91.25–645] min, p = 0.104), and a lower proportion arrived within 4.5 h from onset of symptoms (43.4 vs. 58%, p = 0.043) during the COVID-19 period. There were no differences between proportion of patients receiving recanalization treatment (intravenous thrombolysis and/or mechanical thrombectomy) and in-hospital delays. Conclusion: We observed a reduction in the number of acute strokes and TIAs admitted during the COVID-19 period. This drop affected especially elderly patients, and despite a delay in their arrival to the emergency department, the proportion of patients treated with recanalization therapies was preserved.

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Time-dependent progression of neurogenic lower urinary tract dysfunction after spinal cord injury in the mouse model

AJP Renal Physiology ◽

10.1152/ajprenal.00622.2020 ◽

2021 ◽

Author(s):

Tetsuichi Saito ◽

Daisuke Gotoh ◽

Naoki Wada ◽

Pradeep Tyagi ◽

Tomonori Minagawa ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Time Course ◽

Time Dependent ◽

Lower Urinary Tract Dysfunction ◽

Emg Activity ◽

Mrna Levels ◽

Mechanosensitive Channels ◽

Reduction Time ◽

Cord Injury

This study evaluated the time-course changes in bladder and external urinary sphincter (EUS) activity as well as the expression of mechanosensitive channels in lumbosacral dorsal root ganglia (DRG) after spinal cord injury (SCI). Female C57BL/6N mice in the SCI group underwent transection of the Th8/9 spinal cord. Spinal intact mice and SCI mice at 2, 4 and 6 weeks post SCI were evaluated by single-filling cystometry and EUS-electromyography (EMG). In another set of mice, the bladder and L6-S1 DRG were harvested for protein and mRNA analyses. In SCI mice, non-voiding contractions was confirmed at 2 weeks post-SCI, and did not increase over time to 6 weeks. In 2-weeks SCI mice, EUS-EMG measurements revealed detrusor-sphincter dyssynergia (DSD), but periodic EMG reductions during bladder contraction were hardly observed. At 4 weeks, SCI mice showed increases of EMG activity reduction time with increased voiding efficiency (VE). At 6 weeks, SCI mice exhibited a further increase in EMG reduction time. RT-PCR of L6-S1 DRG showed increased mRNA levels of TRPV1 and ASIC1-3 in SCI mice with a decrease of ASIC2-3 at 6 weeks compared to 4 weeks whereas Piezo2 showed a slow increase at 6 weeks. Protein assay showed the SCI-induced overexpression of bladder BDNF with a time-dependent decrease post SCI. These results indicate that detrusor overactivity is established in the early phase whereas DSD is completed later at 4 weeks with an improvement at 6 weeks post SCI, and that mechanosensitive channels may be involved in the time-dependent changes.

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Nonlinear viscosity of human wrist

Journal of Neurophysiology ◽

10.1152/jn.1984.52.3.553 ◽

1984 ◽

Vol 52 (3) ◽

pp. 553-569 ◽

Cited By ~ 110

Author(s):

C. C. Gielen ◽

J. C. Houk

Keyword(s):

Constant Velocity ◽

Time Course ◽

Fractional Power ◽

Comparison Method ◽

Mean Value ◽

Emg Activity ◽

Triggered Reactions ◽

Nonlinear Viscosity ◽

Flexor Muscles ◽

Reflex Arc

Nonlinear viscous properties of stretch and unloading reflexes in the human wrist were examined using constant-velocity ramp stretches and releases in the range between 5 and 500 mm/s. Subjects were asked to oppose an initial flexor preload and were instructed not to intervene voluntarily when the changes in position were applied. Electromyographic (EMG) activity and net force exerted by the wrist were measured. Although subjects were instructed not to intervene to the applied stretches, even well-practiced subjects sometimes showed unintended triggered reactions, which character could be assisting or resisting. A trial comparison method was used to detect and eliminate responses contaminated by unintended reactions. Ramp stretches further loaded the preloaded flexor muscles. Responses of EMG and force increased steeply initially but after about 1-cm displacement, the slope of these responses decreased to a lower value and remained constant during the remainder of the 5-cm ramp. For higher stretch velocities, the magnitudes and slopes of the responses of EMG and force increased but less than proportionally with ramp velocity. Except for the initial transient, EMG in the loaded flexor muscles and force responses could be described by a product relationship between a linear position-related term and a low fractional power of velocity, after a correction was made for delays in the reflex arc. Mean value of the exponent in the power function of velocity was 0.3 for EMG and 0.17 for force. For higher preloads, incremental responses of force to constant-velocity stretches, plotted as a function of wrist position, shifted to higher values and the slope of increase of force with position became somewhat steeper. This upward shift of the force trace reflects a change of apparent threshold of the stretch reflex. Ramp releases shortened and unloaded the preloaded flexor muscles and stretched the initially inactive extensor muscles. Flexor EMG activity declined progressively with a time course that was independent of velocity. Extensor EMG response depended on preload. At high preloads, there was no activity except for some bursting at the highest velocities. At low preloads, EMG activity was initially absent but started part way through the ramp. The increase of activity was somewhat greater for higher ramp velocities. Force responses to shortening ramps depended on preload. At high preloads, force responses superimposed at all of the low velocities but fell to slightly lower forces at the higher velocities. At low preloads, force traces again superimposed for low velocities and at high velocities only during the initial part of the response.(ABSTRACT TRUNCATED AT 400 WORDS)

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Sudden Onset of Diplopia and a Skeletal Muscle Antibody

10.1093/med/9780197583425.003.0052 ◽

2021 ◽

pp. 160-162

Author(s):

John R. Mills

Keyword(s):

Computed Tomography ◽

Myasthenia Gravis ◽

Patent Foramen Ovale ◽

Time Course ◽

Vision Loss ◽

Sudden Onset ◽

Foramen Ovale ◽

Clinical Disorder ◽

History Of ◽

The Right

A 62-year-old man with a history of migraine came to the emergency department with sudden onset of horizontal diplopia and, subsequently, bilateral ptosis. He noted feeling unsteady when walking. He reported that the diplopia worsened throughout the day. He had a history of hepatitis C infection. He had some vision loss in his left eye, which was thought to relate to a retinopathy. He disclosed that he had a history of cold feet and had notably high arches. He had a pacemaker because of syncope attributed to sick sinus syndrome. Computed tomography angiography of the head and neck were ruled negative for intracranial stenosis, occlusions, or aneurysms. Computed tomography of the head indicated a tiny lacunar infarct in the right caudate head. Magnetic resonance imaging of the brain identified a tiny, periaqueductal, enhancing abnormality in the right midbrain that was thought to be likely ischemic, but there was some concern for a demyelinating or inflammatory lesion. Cerebrospinal fluid evaluation indicated an increased protein concentration. Serologic evaluation for myasthenia gravis striational antibodies were positive at a titer of 1:240. Serum protein studies indicated the presence of polyclonal hypergammaglobulinemia. Myasthenia gravis was effectively ruled out. Given the hyperacute time course, the patient’s clinical disorder was most probably explained by an ischemic stroke that affected the oculomotor nuclei regions causing ptosis and ophthalmoparesis. On follow-up, the patient was discovered to have a patent foramen ovale. Whether the patent foramen ovale was a contributing factor to the stroke is uncertain. The recurrence rate in this setting is thought to be low relative to other causes of stroke. Ultimately it was decided to not close the patent foramen ovale and to maintain the patient on clopidogrel and adult low-dose aspirin. The onset of diplopia is typically sudden, but this occurs exclusively with vascular pathologic processes. Diplopia that appears intermittently with diurnal variation suggests the possibility of a neuromuscular junction disease such as myasthenia gravis.

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The time course of implicit and explicit concept learning

Consciousness and Cognition ◽

10.1016/j.concog.2011.12.008 ◽

2012 ◽

Vol 21 (1) ◽

pp. 204-216 ◽

Cited By ~ 12

Author(s):

Eleni Ziori ◽

Zoltán Dienes

Keyword(s):

Concept Learning ◽

Time Course ◽

Implicit And Explicit

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Latitude Dependent Circadian Rhythms of Carabid Beetles

Zeitschrift für Naturforschung C ◽

10.1515/znc-1986-9-1021 ◽

1986 ◽

Vol 41 (9-10) ◽

pp. 935-945

Author(s):

Gisela Leyk ◽

Wolfgang Martin

Keyword(s):

Time Course ◽

Activity Patterns ◽

Carabid Beetles ◽

Constant Darkness ◽

Spectrum Estimation ◽

Program System ◽

Central European ◽

Light Pulses ◽

Different Types ◽

Periodogram Analysis

Abstract Comparative studies of circadian activity rhythms were performed with three stocks of the species Pterostichus rhaeticus Heer (from Southern Europe, Central Europe, and the Subarctic) and with one Central European stock of the sibling species Pterostichus nigrita Paykull. The hehaviour was investigated in various LD conditions, constant conditions including LL with changes of the illumination intensity and constant darkness with light pulses. The data were analysed with the program system “Timesdia” containing various techniques like power spectrum estimation, periodogram analysis and complex demodulation. This allowed to reveal the time course of rhythms and to determine the number of phase jumps as a measure for precision. With the help of these methods, the activity patterns are classified in different types of behaviour: synchronization, temporarily synchronization, aperiodic behaviour, free run, temporarily free run, relative entrainment, and relative coordination. Besides graduated differences between the populations in south-to-north direction (e.g. in the tendency to rhythmic behaviour) the analysis revealed splitting of rhythms into two or even three components of different frequencies and transitions from rhythmic to aperiodic behaviour or vice versa after arbitrarily chosen light pulses in constant darkness. This behaviour cannot be explained by a system which is composed of one single limit cycle oscillator, but the results rather support a multi-oscillator model.

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Migraine with Persistent Aura in a Mexican Patient: Case Report and Review of the Literature

Cephalalgia ◽

10.1111/j.1468-2982.2007.01307.x ◽

2007 ◽

Vol 27 (5) ◽

pp. 456-460 ◽

Cited By ~ 26

Author(s):

OD San-Juan ◽

PF Zermeño

Keyword(s):

Migraine Headache ◽

Spreading Depression ◽

International Headache Society ◽

Radiographic Evidence ◽

Visual Aura ◽

First Case ◽

Mexican Woman ◽

Persistent Aura ◽

History Of ◽

Mexican Patient

Persistent aura symptoms in patients with migraine are rare but well documented. The International Headache Society defines persistent aura without infarction as when the aura symptoms persist for >1 week without radiographic evidence of infarction. The visual aura of migraine attacks has been explained by cortical spreading depression. We describe a case of a 28-year-old Mexican woman, who presented with persistent aura symptoms, and a literature review. The patient had a 24-year history of migraine headache. In November 2005 the patient had an attack which started with scintillating scotomas bilaterally associated with photopsias and amaurosis followed by migraine headache. All imaging studies were negative. The episode lasted 35 days and probably resolved with nimodipine therapy. Persistent aura symptoms are rare entities. This is the first case documented of a Mexican patient with persistent aura without infarction and probably resolved with nimodipine therapy.

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Photoreceptor cells with unusual functional properties on the ventral nerve of Limulus

Visual Neuroscience ◽

10.1017/s0952523899166185 ◽

1999 ◽

Vol 16 (6) ◽

pp. 1191-1197 ◽

Cited By ~ 2

Author(s):

KÁROLY NAGY ◽

MARLIES DORLÖCHTER ◽

SVENJA KLÄSEN ◽

DANNY STEINBUSCH

Keyword(s):

Time Course ◽

Single Photon ◽

Receptor Potential ◽

Photoreceptor Cells ◽

Light Sensitivity ◽

Atpase Inhibitor ◽

Decay Kinetics ◽

Normal Cells ◽

Inward Current ◽

Low Efficiency

Normal photoreceptor cells on the ventral nerve of Limulus respond to a moderately intense flash with a large receptor potential or current. Occasionally, cells are found in which the same flash evokes only a small receptor potential or current. Our investigations reveal physiological reasons for the poor light sensitivity in these “unusual cells.” In unusual cells prolonged illumination with intense light evokes a step-like inward current with an amplitude of some nanoamperes, but without a large transient peak. The current appears to be summed up of single photon responses with amplitudes smaller than about 50 pA. Their time course is similar to that of small single photon responses forming the so-called macroscopic C1 component in normal cells. The macroscopic current evoked by an intense flash has slow activation and deactivation kinetics and reaches a saturated amplitude of about 4–5 nanoamperes. The light-intensity dependence of the current evoked by flashes or by prolonged illumination has a slope of about 1 in log–log plots. The decay kinetics of the current is similar to that of the C1 component measured in normal cells after the block of the C2 component. Occasionally, the step-like current is superposed by large standard bumps. These bumps are blocked by the Ca2+-ATPase inhibitor cyclopiazonic acid, while the sustained inward current persists. We conclude that in unusual cells the light-activated current is identical to the C1 component of normal cells. The phospholipase C pathway that in normal cells presumably gives rise to the C2 component functions only with a low efficiency in unusual cells.

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