Trigeminal Blink Research Articles

Short-latency prepulse inhibition of the trigeminal blink reflex.

Prepulse inhibition (PPI) is a well-established phenomenon wherein a weak sensory stimulus attenuates the startle reflex triggered by a subsequent strong stimulus. Within the circuit, variations in target responses observed for PPI paradigms represent prepulse-induced excitability changes. However, little is known about the mechanism of PPI. Here, we focused on short-latency PPI of the trigeminal blink reflex R1 signal with an oligosynaptic reflex arc through the principal sensory trigeminal nucleus and the facial nucleus. As the facial nucleus is facilitatory to any input, R1 PPI is the phenomenon in the former nucleus. Considering that GABAergic modulation may be involved in PPI, this study investigated whether the PPI mechanism includes GABA-A equivalent inhibition, which peaks at approximately 30 ms in humans. In 12 healthy volunteers, the reflex was elicited by electrical stimulation of the supraorbital nerve, and recorded at the ipsilateral lower eyelid by accelerometer. Stimulus intensity was 1.5 times the R1 threshold for test stimulus and 0.9 times for the prepulse. The prepulse-test interval (PTI) was 5-150 ms. Results showed significant inhibition at 40-and 80-150-ms PTIs but not at 20-, 30-, 50-, 60-, and 70-ms PTIs, yielding two distinct inhibitions of different time scales. This corresponds well to the early and late components of inhibitory post synaptic potentials by GABA-A and GABA-B receptor activation. Thus, the data support the contribution of inhibitory post synaptic potentials elicited by the prepulse to the observed PPI. As inhibitory function-related diseases may impair the different inhibition components to varying degrees, methods deconvoluting each inhibitory component contribution are of clinical importance.

Machine learning for exploring neurophysiological functionality in multiple sclerosis based on trigeminal and hand blink reflexes

Brainstem dysfunctions are very common in Multiple Sclerosis (MS) and are a critical predictive factor for future disability. Brainstem functionality can be explored with blink reflexes, subcortical responses consisting in a blink following a peripheral stimulation. Some reflexes are already employed in clinical practice, such as Trigeminal Blink Reflex (TBR). Here we propose for the first time in MS the exploration of Hand Blink Reflex (HBR), which size is modulated by the proximity of the stimulated hand to the face, reflecting the extension of the peripersonal space. The aim of this work is to test whether Machine Learning (ML) techniques could be used in combination with neurophysiological measurements such as TBR and HBR to improve their clinical information and potentially favour the early detection of brainstem dysfunctionality. HBR and TBR were recorded from a group of People with MS (PwMS) with Relapsing-Remitting form and from a healthy control group. Two AdaBoost classifiers were trained with TBR and HBR features each, for a binary classification task between PwMS and Controls. Both classifiers were able to identify PwMS with an accuracy comparable and even higher than clinicians. Our results indicate that ML techniques could represent a tool for clinicians for investigating brainstem functionality in MS. Also, HBR could be promising when applied in clinical practice, providing additional information about the integrity of brainstem circuits potentially favouring early diagnosis.

Target Site of Prepulse Inhibition of the Trigeminal Blink Reflex in Humans.

Despite the clinical significance of prepulse inhibition (PPI), the mechanisms are not well understood. Herein, we present our investigation of PPI in the R1 component of electrically induced blink reflexes. The effect of a prepulse was explored with varying prepulse test intervals (PTIs) of 20-600 ms in 4 females and 12 males. Prepulse-test combinations included the following: stimulation of the supraorbital nerve (SON)-SON [Experiment (Exp) 1], sound-sound (Exp 2), the axon of the facial nerve-SON (Exp 3), sound-SON (Exp 4), and SON-SON with a long trial-trial interval (Exp 5). Results showed that (1) leading weak SON stimulation reduced SON-induced ipsilateral R1 with a maximum effect at a PTI of 140 ms, (2) the sound-sound paradigm resulted in a U-shaped inhibition time course of the auditory startle reflex (ASR) peaking at 140 ms PTI, (3) facial nerve stimulation showed only a weak effect on R1, (4) a weak sound prepulse facilitated R1 but strongly inhibited SON-induced late blink reflexes (LateRs) with a similar U-shaped curve, and (5) LateR in Exp 5 was almost completely absent at PTIs >80 ms. These results indicate that the principal sensory nucleus is responsible for R1 PPI. Inhibition of ASR or LateR occurs at a point in the startle reflex circuit where auditory and somatosensory signals converge. Although the two inhibitions are different in location, their similar time courses suggest similar neural mechanisms. As R1 has a simple circuit and is stable, R1 PPI helps to clarify PPI mechanisms.SIGNIFICANCE STATEMENT Prepulse inhibition (PPI) is a phenomenon in which the startle response induced by a startle stimulus is suppressed by a preceding nonstartle stimulus. This study demonstrated that the R1 component of the trigeminal blink reflex shows clear PPI despite R1 generation within a circuit consisting of the trigeminal and facial nuclei, without startle reflex circuit involvement. Thus, PPI is not specific to the startle reflex. In addition, PPI of R1, the auditory startle reflex, and the trigeminal late blink reflex showed similar time courses in response to the prepulse test interval, suggesting similar mechanisms regardless of inhibition site. R1 PPI, in conjunction with other paradigms with different prepulse-test combinations, would increase understanding of the underlying mechanisms.

Conscious agency vs. pre-conscious sensory filtering: Disparate suppression of trigeminal blink reflex by self-stimulation and by prepulses.

Modulation of the blink reflex (BR) to supraorbital nerve (SON) stimulation by a weak somatosensory prepulse (sPP) consists of inhibition of R2 and facilitation of R1. Similar BR changes occur with self-stimulation. Our aim was to compare neurophysiological processes underlying both effects. We assessed BR parameters in 18 healthy participants following right SON stimulation either performed by an experimenter (experiment 1A) or following self-stimulation (experiments 1B, 1C). In experiments 1A and 1C, sPPs to digit 2 preceded SON stimuli by 40, 100, 200 and 500 ms. In experiment 1B: self-stimulation was delayed by 40, 100, 200, and 500 ms. In experiment 2, BRs were elicited by an experimenter randomly during a 2-s period before participants applied self-stimulation. In experiment 1, as expected, sPPs caused facilitation of R1 and inhibition of R2, which peaked at 100 ms ISI, similarly in experiments 1A and 1C. Self-stimulation caused a decrease of R2, which was evident in a broad range of time intervals. In experiment 2, R2 was already inhibited at the onset of the 2-s period, while R1 began to rise significantly 1.4s before self-stimulation. Both effects progressively increased until self-triggering. The results concur with a time-locked gating mechanism of prepulses at brainstem level, whereas self-stimulation modulates BR in a tonic manner, reflecting a cognitive influence due to self-agency.

Effects of transcranial ultrasound stimulation on trigeminal blink reflex excitability

Recent evidence indicates that transcranial ultrasound stimulation (TUS) modulates sensorimotor cortex excitability. However, no study has assessed possible TUS effects on the excitability of deeper brain areas, such as the brainstem. In this study, we investigated whether TUS delivered on the substantia nigra, superior colliculus, and nucleus raphe magnus modulates the excitability of trigeminal blink reflex, a reliable neurophysiological technique to assess brainstem functions in humans.

Effects of Transcranial Ultrasound Stimulation on Trigeminal Blink Reflex Excitability.

Recent evidence indicates that transcranial ultrasound stimulation (TUS) modulates sensorimotor cortex excitability. However, no study has assessed possible TUS effects on the excitability of deeper brain areas, such as the brainstem. In this study, we investigated whether TUS delivered on the substantia nigra, superior colliculus, and nucleus raphe magnus modulates the excitability of trigeminal blink reflex, a reliable neurophysiological technique to assess brainstem functions in humans. The recovery cycle of the trigeminal blink reflex (interstimulus intervals of 250 and 500 ms) was tested before (T0), and 3 (T1) and 30 min (T2) after TUS. The effects of substantia nigra-TUS, superior colliculus-TUS, nucleus raphe magnus-TUS and sham-TUS were assessed in separate and randomized sessions. In the superior colliculus-TUS session, the conditioned R2 area increased at T1 compared with T0, while T2 and T0 values did not differ. Results were independent of the interstimulus intervals tested and were not related to trigeminal blink reflex baseline (T0) excitability. Conversely, the conditioned R2 area was comparable at T0, T1, and T2 in the nucleus raphe magnus-TUS and substantia nigra-TUS sessions. Our findings demonstrate that the excitability of brainstem circuits, as evaluated by testing the recovery cycle of the trigeminal blink reflex, can be increased by TUS. This result may reflect the modulation of inhibitory interneurons within the superior colliculus.

Macaque monkey trigeminal blink reflex circuits targeting orbicularis oculi motoneurons.

The trigeminal blink reflex plays an important role in protecting the corneal surface from damage and preserving visual function in an unpredictable environment. The closing phase of the human reflex, produced by activation of the orbicularis oculi (ObOc) muscles, consists of an initial, small, ipsilateral R1 component, followed by a larger, bilateral R2 component. We investigated the circuitry that underlies this reflex in macaque (Macaca fascicularis and Macaca mulatta) monkeys by the use of single and dual tracer methods. Injection of retrograde tracer into the facial nucleus labeled neurons in the principal trigeminal nucleus, and in the spinal nucleus pars oralis and interpolaris, bilaterally, and in pars caudalis, ipsilaterally. Injection of anterograde tracer into the principal trigeminal nucleus labeled axons that directly terminated on ObOc motoneurons, with an ipsilateral predominance. Injection of anterograde tracer into pars caudalis of the spinal trigeminal nucleus labeled axons that directly terminated on ipsilateral ObOc motoneurons. The observed pattern of labeling indicates that the reticular formation ventromedial to the principal and spinal nuclei also contributes extensive bilateral input to ObOc motoneurons. Thus, much of the trigeminal sensory complex is in a position to supply a monosynaptic drive for lid closure, and the adjacent reticular formation can supply a disynaptic drive. These findings indicate that the assignment of the R1 and R2 components of the blink reflex to different parts of the trigeminal sensory complex cannot be exclusively based on subdivision connectional relationships with facial motoneurons. The characteristics of the R2 component may be due, instead, to other circuit properties.

Threat vs control: Potentiation of the trigeminal blink reflex by threat proximity is overruled by self-stimulation.

The magnitude of the defensive blink reflex is modulated by continuous assessment of its protective value. Here, we studied whether the trigeminal blink reflex (TBR) is modulated by a potentially offensive object close to the face, and, if so, whether self-stimulation or observation of the act of stimulus triggering counteracts such modulation. In all, 26 healthy volunteers participated in various experimental conditions. At baseline, an experimenter triggered supraorbital nerve stimuli remotely, unseen by the participants; in experimental conditions, the experimenter held a stimulation probe close to the participant's face but triggered the stimuli either remotely, "surprising" participants (S1 ), or directly on the probe, observed by participants (S2 ). In other conditions, participants triggered stimuli themselves on the probe held next to their body (S3 ) or held in front of their face (S4 ). The latter condition was repeated similarly, but pressing the button only randomly generated electrical stimuli (S5, "Russian roulette"). The size of the R2 component of the TBR (TBR-R2) was the main outcome measure. Compared to baseline, TBR-R2 area was significantly larger in S1 when the "threatening" probe was close to the face and the participant had no control over stimulation. Conversely, TBR-R2 was suppressed when participants either saw the action of triggering, thus being aware (S2 ), or had full initiative over stimulation (S3 , S4 ). Random self-generated stimuli (S5 ) inhibited TBR-R2, but to a lesser extent than S3 and S4. Perceived threat close to the face facilitates TBR-R2, but knowledge about impending stimulation or self-agency overrules this effect.

Sex, blinking, and dry eye.

Blinking sustains the corneal tear film generated by sexually dimorphic lacrimal and meibomian glands. Our study examines whether trigeminal control of blinking is also sexually dimorphic by investigating trigeminal reflex blinking, associative blink modification, and spontaneous blinking in male and female rats before and after unilateral dry eye caused by exorbital gland removal. Before gland removal, female rats exhibited a lower threshold for evoking trigeminal reflex blinks, a weaker effect of associative blink modification, and longer-duration spontaneous blinks than males. Spontaneous blink rate, reflex blink excitability, and occurrence of blink oscillations did not differ between the sexes. Reanalysis of previous data showed that humans showed the same blink sexual dimorphisms as rats. During the first 2 wk of dry eye, trigeminal blink circuit excitability and blink oscillations steadily rose in male rats, whereas excitability and blink oscillations did not change in females. Following dry eye, spontaneous blink duration increased for both males and females, whereas spontaneous blink rate remained constant for males but decreased for females. The associative modification treatment to depress trigeminal blink amplitude initially produced blink depression in males that converted to blink potentiation as trigeminal excitability rose, whereas females exhibited progressively more blink depression. These data indicated that dry eye increased excitability in male trigeminal reflex blink circuits at the expense of circuit modifiability, whereas trigeminal modifiability increased in females. This increased modifiability of female trigeminal blink circuits with dry eye may contribute to the preponderance of females developing the focal dystonia, benign essential blepharospasm.NEW & NOTEWORTHY All the elements controlling the corneal tear film are sexually dimorphic. Blinking, which smooths and maintains the tear film, also exhibits sex differences. Dry eye increases the sexual dimorphisms of blinking, including increased exaggeration of excitability in males and enhanced modifiability of the female trigeminal complex. This increased modifiability may explain female predominance in the development of the focal dystonia, benign essential blepharospasm.

Removal of inhibition uncovers latent movement potential during preparation.

The motor system prepares for movements well in advance of their execution. In the gaze control system, the dynamics of preparatory neural activity have been well described by stochastic accumulation-to-threshold models. However, it is unclear whether this activity has features indicative of a hidden movement command. We explicitly tested whether preparatory neural activity in premotor neurons of the primate superior colliculus has 'motor potential'. We removed downstream inhibition on the saccadic system using the trigeminal blink reflex, triggering saccades at earlier-than-normal latencies. Accumulating low-frequency activity was predictive of eye movement dynamics tens of milliseconds in advance of the actual saccade, indicating the presence of a latent movement command. We also show that reaching a fixed threshold level is not a necessary condition for movement initiation. The results bring into question extant models of saccade generation and support the possibility of a concurrent representation for movement preparation and generation.

A Dynamic Circuit Hypothesis for the Pathogenesis of Blepharospasm

Blepharospasm (sometimes called “benign essential blepharospasm,” BEB) is one of the most common focal dystonias. It involves involuntary eyelid spasms, eye closure, and increased blinking. Despite the success of botulinum toxin injections and, in some cases, pharmacologic or surgical interventions, BEB treatments are not completely efficacious and only symptomatic. We could develop principled strategies for preventing and reversing the disease if we knew the pathogenesis of primary BEB. The objective of this study was to develop a conceptual framework and dynamic circuit hypothesis for the pathogenesis of BEB. The framework extends our overarching theory for the multifactorial pathogenesis of focal dystonias (Peterson et al., 2010) to incorporate a two-hit rodent model specifically of BEB (Schicatano et al., 1997). We incorporate in the framework three features critical to cranial motor control: (1) the joint influence of motor cortical regions and direct descending projections from one of the basal ganglia output nuclei, the substantia nigra pars reticulata, on brainstem motor nuclei, (2) nested loops composed of the trigeminal blink reflex arc and the long sensorimotor loop from trigeminal nucleus through thalamus to somatosensory cortex back through basal ganglia to the same brainstem nuclei modulating the reflex arc, and (3) abnormalities in the basal ganglia dopamine system that provide a sensorimotor learning substrate which, when combined with patterns of increased blinking, leads to abnormal sensorimotor mappings manifest as BEB. The framework explains experimental data on the trigeminal reflex blink excitability (TRBE) from Schicatano et al. and makes predictions that can be tested in new experimental animal models based on emerging genetics in dystonia, including the recently characterized striatal-specific D1R dopamine transduction alterations caused by the GNAL mutation. More broadly, the model will provide a guide for future efforts to mechanistically link multiple factors in the pathogenesis of BEB and facilitate simulations of how exogenous manipulations of the pathogenic factors could ultimately be used to prevent and reverse the disorder.

Disruption of Fixation Reveals Latent Sensorimotor Processes in the Superior Colliculus

Executive control of voluntary movements is a hallmark of the mammalian brain. In the gaze-control network, this function is thought to be mediated by a critical balance between neurons responsible for generating movements and those responsible for fixating or suppressing movements, but the nature of this balance between the relevant elements-saccade-generating and fixation-related neurons-remains unclear. Specifically, it has been debated whether the two functions are necessarily coupled (i.e., push-and-pull) or independently controlled. Here we show that behavioral perturbation of ongoing fixation with the trigeminal blink reflex in monkeys (Macaca mulatta) alters the effective balance between fixation and saccade-generating neurons in the superior colliculus (SC) and can lead to premature gaze shifts reminiscent of compromised inhibitory control. The shift in balance is primarily driven by an increase in the activity of visuomovement neurons in the caudal SC, and the extent to which fixation-related neurons in the rostral SC play a role seems to be linked to the animal's propensity to make microsaccades. The perturbation also reveals a hitherto unknown feature of sensorimotor integration: the presence of a hidden visual response in canonical movement neurons. These findings offer new insights into the latent functional interactions, or lack thereof, between components of the gaze-control network, suggesting that the perturbation technique used here may prove to be a useful tool for probing the neural mechanisms of movement generation in executive function and dysfunction. Eye movements are an integral part of how we explore the environment. Although we know a great deal about where sensorimotor transformations leading to saccadic eye movements are implemented in the brain, less is known about the functional interactions between neurons that maintain gaze fixation and neurons that program saccades. In this study, we used a novel approach to study these interactions. By transient disruption of fixation, we found that activity of saccade-generating neurons can increase independently of modulation in fixation-related neurons, which may occasionally lead to premature movements mimicking lack of impulse control. Our findings support the notion of a common pathway for sensory and movement processing and suggest that impulsive movements arise when sensory processes become "motorized."

The Effects of Attention on the Trigeminal Blink Reflex.

During top-down processing, higher cognitive processes modulate lower sensory processing. The present experiment tested the effects of directed attention on trigeminal reflex blinks in humans (n = 8). In separate sessions, participants either attended to blink-eliciting stimuli or were given no attentional instructions during stimulation of the supraorbital branch of the trigeminal nerve. Attention to blink-eliciting stimuli significantly increased reflex blink amplitude and duration and shortened blink latency compared with the no attention condition. These results suggested that higher processes such as attention can modify the trigeminal blink reflex circuit.

Somatosensory-evoked blink reflex in peripheral facial palsy

Somatosensory-evoked blink reflex (SBR) is an eye blink response obtained from electrical stimulation of peripheral nerves or the skin area of the body away from the face. The aim of this study was to investigate the presence of SBR in peripheral facial palsy (PFP) and its relation with clinical and electrophysiological changes occurring in PFP as compared with postfacial syndrome (PFS). This was a single-center, public hospital-based electromyography laboratory study. It was designed as a cross-sectional examination of consecutive patients with PFP and PFS and apparently healthy volunteers. The study included 25 patients with PFP, 25 patients with PFS, and 31 healthy volunteers. Facial nerve motor conduction, trigeminal blink reflex, and SBR were studied. Quantitative data were compared using the Mann–Whitney test and the Kruskal–Wallis test. Qualitative data were analyzed using Pearson’s Chi-square test. SBR was elicited in 67.7% of controls, in 68% of PFS patients, and in 32% of PFP patients. In the PFP group, SBR was found on the nonparalytic side in 28% of patients with paralyzed side stimulation and in 24% of patients with healthy side stimulation. For the PFS group, SBR was found on the nonparalytic side in 48%. Bilateral SBR elicitability was higher than its unilateral elicitability. SBR occurs in patients with PFP and PFS and in healthy individuals. It has no relation with the clinical and electrophysiological changes occurring in PFP and PFS. Increased brainstem interneurons excitability is not essential to generate SBR. The hypothetical sensory-motor gating mechanism could be responsible for SBR generation.

Blink reflex studies in postparalytic facial syndrome and blepharospasm: trigeminal and extratrigeminal somatosensory stimulation.

The somatosensory-evoked blink reflex (SBR) is one of the release phenomena of blink reflex, possibly resulting from increased excitability of brainstem reticular formation. The authors investigated trigeminal blink responses and SBR in 26 patients with postparalytic facial syndrome (PFS) with synkinesia, 18 patients with essential blepharospasm, and 36 healthy volunteers (control participants). Trigeminal blink reflex responses were elicited in all participants, whereas SBRs were elicited in 44.4% of control participants, 38.9% of patients with essential blepharospasm, and 65.4% of patients with PFS. The mean R2 amplitude and duration and the mean amplitude and duration of SBR were highest in patients with essential blepharospasm. The mean latency of SBR was shorter on the symptomatic side of patients with PFS when compared with the asymptomatic side. The mean R2 duration on the symptomatic side of the patients with PFS was longer than the control participants. These results showed that somatosensory stimulation could be used as an alternative method to demonstrate increased excitability in facial motor neuron in patients with PFS and essential blepharospasm. Disease states relating to different peripheral and/or suprasegmental structures could also influence blink reflex and change its basal excitability and manner in which the reflex responds to modulatory factors.

Trigeminal high-frequency stimulation produces short- and long-term modification of reflex blink gain

Reflex blinks provide a model system for investigating motor learning in normal and pathological states. We investigated whether high-frequency stimulation (HFS) of the supraorbital branch of the trigeminal nerve before the R2 blink component (HFS-B) decreases reflex blink gain in alert rats. As with humans (Mao JB, Evinger C. J Neurosci 21: RC151, 2001), HFS-B significantly reduced blink size in the first hour after treatment for rats. Repeated days of HFS-B treatment produced long-term depression of blink circuits. Blink gain decreased exponentially across days, indicating a long-term depression of blink circuits. Additionally, the HFS-B protocol became more effective at depressing blink amplitude across days of treatment. This depression was not habituation, because neither long- nor short-term blink changes occurred when HFS was presented after the R2. To investigate whether gain modifications produced by HFS-B involved cerebellar networks, we trained rats in a delay eyelid conditioning paradigm using HFS-B as the unconditioned stimulus and a tone as the conditioned stimulus. As HFS-B depresses blink circuits and delay conditioning enhances blink circuit activity, occlusion should occur if they share neural networks. Rats acquiring robust eyelid conditioning did not exhibit decreases in blink gain, whereas rats developing low levels of eyelid conditioning exhibited weak, short-term reductions in blink gain. These results suggested that delay eyelid conditioning and long-term HFS-B utilize some of the same cerebellar circuits. The ability of repeated HFS-B treatment to depress trigeminal blink circuit activity long term implied that it may be a useful protocol to reduce hyperexcitable blink circuits that underlie diseases like benign essential blepharospasm.

Time Course of Motor Preparation during Visual Search with Flexible Stimulus-Response Association

Whether allocation of visuospatial attention can be divorced from saccade preparation has been the subject of intense research efforts. A variant of the visual search paradigm, in which a feature singleton indicates that the correct saccade should be directed to it (prosaccade) or to the opposite distractor (antisaccade), has been influential in addressing this core topic. We performed a causal assessment of this controversy by delivering an air puff to one eye to invoke the trigeminal blink reflex as monkeys performed this visual search task. Blinks effectively remove saccadic inhibition and prematurely trigger impending saccades in reaction time tasks, thus providing a behavioral readout of the premotor plan. We found that saccades accompanied blinks during the initial allocation of attention epoch and that these movements were directed to the singleton for both prosaccade and antisaccade trials. Blinks evoked at later times were accompanied with saccades to the correct end point location: the singleton on prosaccade trials and the opposite distractor on antisaccade trials. These results provide support for concurrent encoding of visuospatial attention and saccade preparation during visual search behavior.

Long‐term depression‐like plasticity of the blink reflex for the treatment of blepharospasm

Our previous work showed a beneficial therapeutic effect on blepharospasm using slow repetitive transcranial magnetic stimulation, which produces a long-term depression (LTD)-like effect. High-frequency supraorbital electrical stimulation, asynchronous with the R2 component of the blink reflex, can also induce LTD-like effects on the blink reflex circuit in healthy subjects. Patients with blepharospasm have reduced inhibition of their blink recovery curves; therefore, a LTD-like intervention might normalize the blink reflex recovery (BRR) and have a favorable therapeutic effect. This is a randomized, sham-controlled, observer-blinded prospective study. In 14 blepharospasm patients, we evaluated the effects of high-frequency supraorbital stimulation on three separate treatment days. We applied 28 trains of nine stimuli, 400 Hz, either before or after the R2 or used sham stimulation. The primary outcome was the blink rate, number of spasms rated by a blinded physician and patient rating before, immediately after and 1 hour after stimulation while resting, reading, and talking; secondary outcome was the BRR. Stimulation "before" and "after" the R2 both showed a similar improvement as sham stimulation in physician rating, but patients felt significantly better with the before condition. Improvement in recovery of the blink reflex was noted only in the before condition. Clinical symptoms differed in the three baseline conditions (resting, reading, and talking). Stimulation before R2 increased inhibition in trigeminal blink reflex circuits in blepharospasm toward normal values and produced subjective, but not objective, improvement. Inhibition of the blink reflex pathway by itself appeared to be insufficient for a useful therapeutic effect.

Animal Models for Investigating Benign Essential Blepharospasm

The focal dystonia benign essential blepharospasm (BEB) affects as many as 40,000 individuals in the United States. This dystonia is characterized by trigeminal hyperexcitability, photophobia, and most disabling of the symptoms, involuntary spasms of lid closure that can produce functional blindness. Like many focal dystonias, BEB appears to develop from the interaction between a predisposing condition and an environmental trigger. The primary treatment for blepharospasm is to weaken the eyelid-closing orbicularis oculi muscle to reduce lid spasms. There are several animal models of blepharospasm that recreate the spasms of lid closure in order to investigate pharmacological treatments to prevent spasms of lid closure. One animal model attempts to mimic the predisposing condition and environmental trigger that give rise to BEB. This model indicates that abnormal interactions among trigeminal blink circuits, basal ganglia, and the cerebellum are the neural basis for BEB.

Blink Perturbation Effects on Saccades Evoked by Microstimulation of the Superior Colliculus

Current knowledge of saccade-blink interactions suggests that blinks have paradoxical effects on saccade generation. Blinks suppress saccade generation by attenuating the oculomotor drive command in structures like the superior colliculus (SC), but they also disinhibit the saccadic system by removing the potent inhibition of pontine omnipause neurons (OPNs). To better characterize these effects, we evoked the trigeminal blink reflex by delivering an air puff to one eye as saccades were evoked by sub-optimal stimulation of the SC. For every stimulation site, the peak and average velocities of stimulation with blink movements (SwBMs) were lower than stimulation-only saccades (SoMs), supporting the notion that the oculomotor drive is weakened in the presence of a blink. In contrast, the duration of the SwBMs was longer, consistent with the hypothesis that the blink-induced inhibition of the OPNs could prolong the window of time available for oculomotor commands to drive an eye movement. The amplitude of the SwBM could also be larger than the SoM amplitude obtained from the same site, particularly for cases in which blink-associated eye movements exhibited the slowest kinematics. The results are interpreted in terms of neural signatures of saccade-blink interactions.