A pharmacological distinction between the long and short latency pathways of the human blink reflex revealed with tobacco

Summary In three, normal, human subjects, tobacco smoking was used as a pharmacological probe to modify differentially the direct and indirect pathways underlying the blink reflex. The latency of the indirect R2 component of the orbicularis oculis electromyogram evoked by electrical stimulation of the trigeminal supraorbital nerve transiently increased 20–80% after smoking, while the latency of the shorter latency, direct R1 component remained constant. The magnitude of both components of the blink reflex transiently decreased. The data demonstrate that tobacco smoking can differentially alter the long and short latency components of the blink reflex, and suggest that these effects result from modifications of central pathways sensitive to nicotine.     

Excitability recovery curves of blink reflexes in patients with athetotic cerebral palsy

We evaluated the brainstem function or its excitability by the blink reflex evoked with the electrical stimulation to the supraorbital nerve in 10 patients with athetotic cerebral palsy compared with 10 normal subjects and 7 spastic type patients. There were no differences in stimulus intensity, latency of R1 and R2 components, and duration and area of EMG activity of the R2 component of the blink reflex elicited by single stimulation among the two patients' groups and normal subjects. R1 recovery cycle to paired stimuli in the athetotic group showed a facilitation of the test responses by the conditioning stimuli at 100 and 200 ms intervals, but were not significantly different from those in the normals. On the other hand, the R2 recovery curve in the athetotic group showed a significant hyperexcitability at all intervals from 100 to 600 ms compared to the normals. Our results from the R2 hyperexcitable recovery to paired stimuli are indicative of increased brainstem interneuronal excitability in athetotic patients and similar to the results reported in the disorders of the basal ganglia, i.e. Parkinson's disease, dystonia and blepharospasm. We suggest that this hyperexcitability might be caused by abnormal input possibly from the basal ganglia upon these brainstem interneurons.     

Midbrain 6-hydroxydopamine lesions modulate blink reflex excitability

The blink reflex abnormalities present in the 6 hydroxydopamine (6-OHDA) lesioned rat model of parkinsonism mimicked those of the human with Parkinon's disease. In alert rats, we monitored the long and short latency components of the orbicularis oculi electromyographic (OOemg) response evoked by electrical stimulation of the supraorbital branch of the trigeminal nerve (SO). Two paradigms, habituation and double pulse, provided a measure of blink reflex excitability. In normal rats, repeated stimulation of the SO produced habituation of the R2 component of the blink. In the double pulse paradigm, presentation of two identical SO stimuli resulted in a reduced or suppressed OOemg response to the second stimulus relative to the first. In rats with complete, unilateral lesions of midbrain dopamine neurons, repeated SO stimulation produced facilitation rather than habituation of the R2 component of the blink reflex. This facilitation occurred only with the eyelid contralateral to the lesion. In the double pulse paradigm, the lesioned rats showed increased excitability rather than suppression. This effect occurred bilaterally, although the increased excitability was strongest contralateral to the lesion. Rats with partial lesions of midbrain dopamine neurons exhibited qualitatively similar, but less pronounced blink reflex abnormalities. The R1 component of the blink reflex was unaffected by either the complete or partial lesions. Thus, modification of the blink reflex by 6-OHDA lesions provides a reproducible parkinsonian-like symptom which is amenable to investigations of increases in reflex excitability.     

Nociceptive quality of the laser-evoked blink reflex in humans

Laser radiant-heat pulses selectively excite the free nerve endings in the superficial layers of the skin and activate mechano-thermal nociceptive afferents; when directed to the perioral or supraorbital skin, high-intensity laser pulses evoke a blink-like response in the orbicularis oculi muscle (the laser blink reflex, LBR). We investigated the functional properties (startle or nociceptive origin) of the LBR and sought to characterize its central pathways. Using high-intensity CO(2)-laser stimulation of the perioral or supraorbital regions and electromyographic (EMG) recordings from the orbicularis oculi muscles, we did five experiments in 20 healthy volunteers. First, to investigate whether the LBR is a startle response, we studied its habituation to expected rhythmic stimuli and to unexpected arrhythmic stimuli. To assess its possible nociceptive quality, we studied changes in the LBR and the R2 component of the electrical blink reflex after a lidocaine-induced supraorbital nerve block and after intramuscular injection of the opiate fentanyl and the opiate-antagonist naloxone. To characterize the central pathways for the LBR, we investigated the interaction between the LBR and the three components of the blink reflex (R1, R2, and R3) by delivering laser pulses to the perioral or supraorbital regions before or after electrical stimulation of the supraorbital nerve at various interstimulus intervals. Finally, to gain further information on the central LBR pathways, using two identical CO(2)-laser stimulators, we studied the LBR recovery curves with paired laser pulses delivered to adjacent forehead points at interstimulus intervals from 250 ms to 1.5 s. The LBR withstood relatively high-frequency rhythmic stimulations, and unexpected laser pulses failed to evoke larger responses. When lidocaine began to induce hypoalgesia (about 5 min after the injection), the LBR was abolished, whereas R2 was only partly suppressed 10 min after the injection. Fentanyl injection induced strong, naloxone-reversible, LBR suppression (the response decreased to 25.3% of predrug values at 10 min and to 4% at 20 min), whereas R2 remained appreciably unchanged. Whether directed to the perioral or supraorbital regions, preceding laser pulses strongly suppressed R2 and R3 though not R1. Conversely, preceding electrical stimuli to the supraorbital nerve suppressed the LBR. In response to paired stimuli, the LBR recovered significantly faster than R2. These findings indicate that the LBR is a nociceptive reflex, which shares part of the interneuron chain mediating the nonnociceptive R2 blink reflex, probably in the medullary reticular formation. The LBR may prove useful for studying the pathophysiology of orofacial pain syndromes.     

Neurophysiological aspects of eye and eyelid movements during blinking in humans

The neural relationships between eyelid movements and eye movements during spontaneous, voluntary, and reflex blinking in a group of healthy subjects were examined. Electromyographic (EMG) recording of the orbicularis oculi (OO) muscles was performed using surface electrodes. Concurrently, horizontal and vertical eye positions were recorded by means of the double magnetic induction (DMI) ring method. In addition, movement of the upper eyelid was measured by a specially designed search coil, placed on the upper eyelid. The reflex blink was elicited electrically by supraorbital nerve stimulation either on the right or the left side. It is found that disconjugate oblique eye movements accompany spontaneous, voluntary as well as reflex blinking. Depending on the gaze position before blinking, the amplitude of horizontal and vertical components of the eye movement during blinking varies in a systematic way. With adduction and downward gaze the amplitude is minimal. With abduction the horizontal amplitude increases, whereas with upward gaze the vertical amplitude increases. Unilateral electrical supraorbital nerve stimulation at low currents elicits eye movements with a bilateral late component. At stimulus intensities approximately two to three times above the threshold, the early ipsilateral blink reflex response (R(1)) in the OO muscle can be observed together with an early ipsilateral eye movement component at a latency of approximately 15 ms. In addition, during the electrical blink reflex, early ipsilateral and late bilateral components can also be identified in the upper eyelid movement. In contrast to the late bilateral component of upper eyelid movement, the early ipsilateral component of upper eyelid movement appears to open the eye to a greater degree. This early ipsilateral component of upper eyelid movement occurs more or less simultaneously with the early eye movement component. It is suggested that both early ipsilateral movements following electrical stimulation do not have a central neural origin. Late components of the eye movements slightly precede the late components of the eyelid movement. Synchrony between late components of eyelid movements and eye movements as well as similarity of oblique eye movement components in different types of blinking suggest the existence of a premotor neural structure acting as a generator that coordinates impulses to different subnuclei of the oculomotor nucleus as well as the facial nerve nucleus during blinking independent from the ocular saccadic and/or vergence system. The profile and direction of the eye movement rotation during blinking gives support to the idea that it may be secondary to eyeball retraction; an extra cocontraction of the inferior and superior rectus muscle would be sufficient to explain both eye retraction and rotation in the horizontal vertical and torsional planes.     

Electrophysiological findings of acute peripheral facial palsy in diabetic and non-diabetic patients

The aim of this study is to investigate the role of diabetes mellitus on the clinical and electrophysiological findings of peripheral facial palsy (PFP), the effect of the diabetes duration and polyneuropathy on the electrophysiological parameters. A total of 32 diabetic and 40 non-diabetic patients with peripheral facial palsy were included. All patients were divided into two subgroups based on the time of electrophysiological examinations: within the first 15 days versus within 16–30 days. Neuropathy symptoms and the results of neurological examinations and electrophysiological findings were recorded. The findings of electroneurography (EnoG), blink reflex (BR) evaluation, and needle electromyography (EMG) indicated statistically significant blink reflex abnormalities in diabetic patients compared to non-diabetics. Delay in the latency was more remarkable in the R2 component than in the R1 (p < 0.001). The delay in the R1 latency was also observed in the non-affected side for diabetic patients. The longer duration of the diabetes caused significant delay on the blink reflex latency on both the affected and non-affected sides for R1 component (p = 0.019, p = 0.041, respectively). In contrary, neither the diabetes duration nor the age of the patients correlated with the clinical severity of facial palsy, fiber loss, fibular nerve compound muscle action potential amplitudes, and the nerve conduction velocities.     

Modulation of trigeminal reflex excitability in migraine: effects of attention and habituation on the blink reflex.

The modulation of trigeminal reflex excitability in migraine patients was evaluated during the asymptomatic phase by studying the effects of attention, habituation and preconditioning stimulus on the R2 and R3 components of the blink reflex (BR). Fifty patients suffering from migraine without aura, 20 affected by migraine with aura and 35 sex- and age-matched controls were selected. In subgroups of migraine with-aura and without-aura patients, and normal controls, the blink reflex was elicited during different cognitive situations: (a) spontaneous mental activity; (b) stimulus anticipation; (c) recognition of target numbers. In the remaining subjects, R2 and R3 habituation was evaluated by repetitive stimulation at 1, 5, 10, 15, 20, 25 and 30 s intervals. The R2 and R3 recovery curves were also computed. A reduced R3 threshold with a normal pain threshold was found in migraine with-aura and without-aura patients; the R3 component was not significantly correlated with the pain thresholds in patients and controls. The R2 and R3 components were less influenced by the warning of the stimulus in migraine without-aura and migraine with-aura patients, in comparison with the control group. A slight increase of both R2 and R3 recovery after preconditioning stimulus was also observed in migraine patients, probably caused by a phenomenon of trigeminal hyperexcitability persisting after the last attack. The abnormal BR modulation by alerting expresses in migraine a dysfunction of adaptation capacity to environmental conditions, probably predisposing to migraine.     

Unilateral enhancement of early and late blink reflex components in hemidystonia

The side-to-side differences in the EMG activity of the early and late components of blink reflex, regarded as revealing the state of excitability of the brain stem reflex centers, have been analyzed in patients with unilateral dystonia without demonstrable brain lesions. It has been observed that both early and late responses of direct blink reflex were higher on the side affected by hemidystonia than on the contralateral one, while the latency values were in the normal range. Possibility that an abnormal output from the striatum towards the brainstem structures involved in blink reflex appears on the affected side of hemidystonic patients is discussed.     

Auditory-evoked masseter inhibitory reflex

We aimed to investigate auditory-evoked masseter inhibitory reflex and discuss possible auditory-trigeminal pathways in brainstem. Our study population consisted of 21 healthy volunteers (age-matched 7 males and 14 females). Bilateral electrical blink reflex (BR), auditory blink reflexes (ABR) and electrical MIR (MIR) were studied. After obtaining normal potentials, auditory MIR (AMIR) was studied. Electrical blink reflexes had two components as R1 and R2, and ABR had one evoked potential in all volunteers. There was no significant difference between gender, nor between right- and left-sided BR and ABR. The mean latency of ABR responses were shorter than latencies of R2 phase of BR (p = 0.013 for left-sided responses, p = 0.035 for right-sided responses). Electrical stimulation revealed two suppression periods (SP1 and SP2) in MIR responses bilaterally in all volunteers. Auditory stimulation evoked typical two suppression periods only in 11 subjects (5 males, 6 females). The mean latency of SP1 component of AMIR was significantly longer than those of MIR bilaterally in both males and females, while the SP2 component had a shorter onset. The durations of SP1, SP2 and total SP were always shorter than those obtained in MIR with smaller degree of suppressions. None of the MIR or AMIR responses showed significance difference between sexes. We assume that auditory-evoked MIR might share the similar interneurons as with other electrical or nociceptive stimulation, which connects cochlear-trigeminal neurons via pontine reticular system to premotor area for masseter muscle.     

正常学龄儿童瞬目反射的初步研究

应用电刺激法研究４０例正常学龄儿童的瞬目反射。通常能诱发出刺激侧快反应（Ｒ１）、迟反应（Ｒ２）及对侧迟反应（Ｒ２＇）。分析Ｒ１的形态、各波的潜伏期、时程、波幅，制定出正常值。瞬目反对的检查结果可作为诊断多种脑干障碍和三叉神经、面神经病变的方法。     

Modulation of electrically elicited blink reflex components by visual and acoustic prestimuli in man

The effects of a prestimulus on the electrically elicited blink reflex components were investigated in 20 healthy subjects. In the first group of 10 subjects (warned group), electric shocks were delivered in isolation or preceded, at an interstimulus interval (ISI) of 0.1 s, 1 s, or 10 s, by a visual or acoustic warning stimulus. In the second group of 10 subjects (unwarned group), the electric shocks were delivered either in isolation or preceded, at the same ISI, by visual or acoustic stimuli having no warning value. The modulation of the three blink reflex components was then analysed. Compared to the baseline condition, the R1 oligosynaptic component was enhanced at 0.1 s and 1 s ISI, in the warned group with the visual prestimulus, but only at 0.1 s after a visual and acoustic prestimulus in the unwarned group. On the contrary, the polysynaptic responses showed a different course: R2 was significantly reduced at the 0.1 s interval in the warned group with both the prestimuli, and only with the visual prestimulus in the unwarned group. The R3 was inhibited at all three intervals with the visual prestimulus, and at the 0.1 s and 1 s with the acoustic one in the warned group, and only at 0.1 s in the unwarned group, both after visual and acoustic prestimuli. The decrement in R2 and R3 observed with the shortest interval was probably related to the prepulse inhibition of startle reflex. Furthermore, only R3 was still inhibited at longer intervals, when the sustained processes of attention may have influenced this component. Perhaps this combination of events represents, in the warned group, the best preparation for voluntary reflex reaction.     

Distinct early and late subcomponents of the photic blink reflex: Response characteristics in patients with retrogeniculate lesions

To assess cortical contributions to the photic blink reflex, signal averaged electromyograms (EMG) were compared for responses to strobe flashes presented within the blind and sighted hemifields of 13 patients with occipital lobe lesions. Reflexes evoked by flashes within the scotoma were virtually identical to those evoked by flashes within the intact visual field. This suggests that both the early and late components of this reflex (R50 and R80, respectively) are mediated by subcortical structures that do not require, or benefit from, conscious visual processing. Additional findings included larger R80s at the eyelid contralateral to the lesion, regardless of stimulated hemifield. This presumably reflects the loss of a tonic descending influence of visual cortex onto the motor limb of the reflex arc. The R80 was also larger for stimuli activating the crossed (temporal hemifield) rather than the uncrossed (nasal hemifield) afferent pathway.     

Blink Reflex Magnitude During the Foreperiod of a Warned Reaction Time Task: Effects of Precueing

In a warned reaction time task blink reflexes were evoked electrically at different points in time during a 3-s foreperiod between the warning signal (WS) and the response signal (RS;. Two groups of 16 well-trained right-handed subjects participated. One group was informed by the warning signal as to whether or not a voluntary blink response was to be given following the response signal. For the other group of subjects, response-relevant information was delivered by the response signal. Reaction times were shorter when subjects were precued by the warning signal, which indicates a more efficient preparation in this condition. In the blink reflex an early ipsilateral component (R1) and a late bilateral component (R2) could be distinguished. Within 300 ms after the warning signal, an increase in R1 was seen which was more pronounced when the warning signal precued the required response. R2 was inhibited shortly after the warning signal. At the end of the foreperiod R1 increased more and R2 was more inhibited the higher the response certainty. The general conclusion is that the presentation of a warning stimulus has a facilitatory effect on R1 and an inhibitory effect on R2. A warning stimulus with more information results in an extra increase in R1 magnitude only, while preparation for a response is seen in both R1 and R2 magnitudes.     

A role for the basal ganglia in nicotinic modulation of the blink reflex

Summary In humans and rats we found that nicotine transiently modifies the blink reflex. For blinks elicited by stimulation of the supraorbital branch of the trigeminal nerve, nicotine decreased the magnitude of the orbicularis oculi electromyogram (OOemg) and increased the latency of only the long-latency (R2) component. For blinks elicited by electrical stimulation of the cornea, nicotine decreased the magnitude and increased the latency of the single component of OOemg response. Since nicotine modified only one component of the supraorbitally elicited blink reflex, nicotine must act primarily on the central nervous system rather than at the muscle. The effects of nicotine could be caused by direct action on lower brainstem interneurons or indirectly by modulating descending systems impinging on blink interneurons. Since precollicular decerebration eliminated nicotine's effects on the blink reflex, nicotine must act through descending systems. Three lines of evidence suggest that nicotine affects the blink reflex through the basal ganglia by causing dopamine release in the striatum. First, stimulation of the substantia nigra mimicked the effects of nicotine on the blink reflex. Second, haloperidol, a dopamine (D₂) receptor antagonist, blocked the effect of nicotine on the blink reflex. Third, apomorphine, a D₂ receptor agonist, mimicked the effects of nicotine on the blink reflex.     

Blink reflex to supraorbital nerve stimulation in the cat

 Neurophysiological studies of the blink reflex to supraorbital nerve stimulation were conducted in eight alert, adult male cats. The cat, like other mammals, shows both short-latency (R1) and long-latency (R2) orbicularis oculi electromyographic (OOemg) components. Measures of OOemg latency, duration, integrated area, and maximum amplitude (MA) were obtained at a stimulus magnitude of 1.5×R2 threshold. The mean (±SE) minimal latencies for R1 and R2 were 8.26±0.85 and 22.97±1.53 ms, respectively. On average, R1 MA was larger than R2 MA. R1 and R2 area measures were similar. Three stimulus paradigms were tested. In a paired-stimulus paradigm, the interstimulus interval (ISI) was randomly varied from 100 to 1200 ms. Ratios were constructed for the OOemg area and MA by dividing the test response by the conditioning response. In this paradigm, although a significant linear relationship was observed only between ISI and R2 MA, conditioning effects were noted on both R1 and R2 area and MA test responses at several ISIs. In a habituation paradigm, both R2 and R1 showed habituation at stimulus frequencies from 0.5 to 2 Hz. In a stimulus-response paradigm, stimulus magnitude was randomly varied between threshold and 2×threshold. In this paradigm, OOemg area and MA of both R1 and R2 were linearly related to stimulus magnitude. Neither the systemically administered centrally acting α₂-adrenergic antagonist yohimbine nor agonist clonidine had significant effects on blink reflex parameters, habituation, or the paired-stimulus paradigm. Overall, these results suggest that there are important similarities in the control and modulation of the R1 and R2 components of the blink reflex to supraorbital nerve stimulation in cats. Received: 18 June 1996 / Accepted: 21 February 1997     

Blink reflex in hyperthyroidism

Although there are studies regarding the effects of thyroid hormones on some neurologic reflexes, literature lacks knowledge of the effects of thyroid hormones on blink reflex circuits. To understand the behaviour of excess thyroid hormone on this circuit that involves synapses in brainstem, we studied electrically elicited blink reflexes of 7 patients with hyperthyroidism, 8 patients with hyperthyroidism who were under therapy and 14 volunteers as control by electroneuromyograph. Mean values of the latencies and amplitudes of the R1 and R2 responses were not statistically different between groups, while the duration of R2 response and controlateral R2 response were found shorter in patients with hyperthyroidism comparing to the patients under therapy and controls. We have thought that these findings might reflect the inhibitor effect of the excess thyroid hormone on polysynaptic reflex arc of the blink response.     

Somatosensory eye blink reflex in peripheral facial palsy

To investigate the association between somatosensory blink reflex (SBR) and peripheral facial palsy (PFP) severity and trigeminal blink reflex (BR) changes in cases with PFP and subsequent postparalytic facial syndrome development (PFS). One hundred and twenty subjects with peripheral facial palsy and post-facial syndrome and 44 age and gender matched healthy volunteers were enrolled to this study. Blink reflexes and somatosensory blink reflex were studied in all. The association between R1 and R2 responses of the BR and SBR positivity was investigated. SBR was elicited in 36.3% of normal subjects, in 18.3% of PFP and in 65.3% of PFS patients. In the paralytic side, the frequency of SBR positivity was significantly lower in PFP group compared to controls and SBR was most frequently observed in patients with PFS. Compared to PFP and control groups, SBR positivity on the non-paralytic side significantly revealed a higher rate in PFS patients. SBR positivity of patients in whom R1 or R2 were absent, was significantly lower than those subjects with prolonged or normal R1 or R2 responses. PFP and successive PFS are good models for the sensory motor gate mechanisms and/or excitability enhancement of brainstem neurons responsible for SBR.     

Startle reflex habituation in functional psychoses: a controlled study.

The habituation of the startle reflex in a paradigm using electrical stimulation was studied in 17 psychotic patients and 18 healthy controls. The magnitude of the R2 component of the blink reflex differed between the groups (ANOVA, F = 5.81; P = 0.022) and during the course of trials (F = 25.72; P < 0.0001). Furthermore a statistically significant interaction of diagnosis x trials (F = 3.34; P = 0.022) emerged suggesting that an impairment in habituation of startle is present in patients but not in healthy controls despite a comparable reactivity.     

Habituation and conditioning of the human long latency stretch reflex

Summary The effects of stretch repetition rate, prior warning stimuli and self administered stretch were examined on the size of the short and long latency components of the stretch reflex electromyographic EMG response in flexor pollicis longus and the flexor muscles of the wrist and fingers. Stretches of constant velocity and extent were given every 10 s, 5 s, 2 s, or 1 s to either the wrist or thumb during a small background contraction of the flexor muscles. The size of the long latency component of the stretch reflex (measured as the area under the averaged rectified EMG responses) declined dramatically at faster repetition rates, especially in the wrist and finger flexors. The size of the short latency component was relatively unaffected. The size of the electrically elicited H-reflex in forearm muscles also failed to habituate under the same conditions. If each individual trial of a series was examined, the long latency component of the stretch reflex EMG could be seen to decrease in size over the first three to six stretches if stretches were given every 1 s, but not if stretches were given every 10 s. When stretches were given every 5 s to either wrist or thumb, an electrical stimulus applied to the digital nerves of the opposite hand 1 s before stretch reduced the size of the long latency component of the reflex EMG response. The short latency component was unaffected. Self triggering of wrist or thumb stretch by the subject pressing the stimulator button himself with his opposite hand, also decreased the size of the long latency component of the reflex EMG response without affecting the short latency component. It is concluded that factors other than stretch size or velocity can have marked effects on the size of the long latency component of the stretch reflex. These factors must be taken into account when comparing values of reflex size obtained with different stretching techniques and in different disease states in man.     

Impaired attention modulation of the blink reflex R3 component in Parkinson's disease: a non-task warning paradigm study.

PURPOSE: the aim of this experimental study was to evaluate the attention modulating actions on the polysynaptic component of blink reflex responses and especially of the R3 component in patients suffering from Parkinson's Disease (PD). To this end, a non-task warning paradigm was adopted. METHODS: attention processing was evaluated by means of a non-task paradigm in 55 patients suffering from PD. Subjects were presented with a visual 'warning' prestimulus and the blink reflex (BR) analyzed with special regard for any modulation of its polysynaptic components (R2-R3). RESULTS: The mean amplitude of the post-warning R3 component (PW-R3c) of 'de novo' PD patients was 62% of the corresponding component following unannounced stimuli, a figure which differs significantly from both treated PD patients (18.9%) and control subjects (15.4%). De novo patients subsequently started on L-dopa therapy exhibited a more pronounced inhibition of the R3 component after warning stimulus, as the PW-R3c percentage decreased. Inversely, treated patients whose therapy was withheld showed decreased inhibition of this component. Regarding R2, the mean PW-R2c in the de novo patients differed slightly from that of the treated patients (P<0.05), but not from that of the control subjects. Such a finding may be attributable to a specific effects on the excitability of the polysynaptic responses. CONCLUSIONS: Attention disorders in PD have been well documented by means of this kind of non-task warning paradigm, which appears to probe the modulation of the BR R3 component, even if the interpretation of this R3 changes suggesting a specific alteration of attention processing must be put forward extremely carefully, because something similar, but less evident, appears also for R2.