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Classical conditioning of the electrically elicited blink reflex in humans: a new method of data analysis.

The eyeblink conditioning paradigm is a well-established model to study learning processes in humans and animals. Especially results from animal studies have supplied new insight into physiological pathways and brain structures involved in associative motor learning and memory. An important role of the cerebellum and its afferent fiber systems could be shown. Recent studies in humans have given evidence that results of animal experiments can be applied directly to the human condition. A high variation of baseline EMG activity and/or spontaneous blinks may influence the analysis of classical conditioning of the electrically elicited blink reflex in humans. To optimize differentiation between real conditioned responses and stimulus-independent EMG activity, we developed an algorithm which is fully automated and independent of a possible bias of an examiner. In a first step the algorithm decides whether a subject fulfills the criteria of a successful learning process or not. The second step quantifies the learning process. For quantification of the learning process, the following parameters were calculated: number of conditioned responses, onset of conditioning, time and amount of maximal conditioning, speed of conditioning and speed of habituation. According to our criteria, 80% of the healthy volunteers acquired conditioned responses. There is an age-related decline in eyeblink classical conditioning. Analysis of patient groups with different types of lesions will further improve our knowledge and understanding of pathways involved in learning processes in humans. The proposed new algorithm of data analysis takes less than 10 s on a standard computer, is more sensitive and more specific in detecting conditioned responses and, therefore, may further improve the value and reliability of the eyeblink conditioning paradigm in clinical research.

Adult↗

Diurnal variation in spontaneous eye-blink rate.

The daily pattern of spontaneous eye-blink rate (BR), a non-invasive peripheral measure of central dopamine activity, was investigated in 24 healthy subjects. The spontaneous eye-blink rate showed a stable pattern in morning, midday and afternoon hours. A significant increase was found at the evening time point (20.30 h). The finding is suggestive of a late evening increase of central dopamine activity. An increased level of subjective sleepiness was also found at the same evening point, at a time corresponding to the 'evening wake maintenance zone' or the 'forbidden zone for sleep'. A possible hypothesis is that the 'forbidden zone for sleep' may reflect a dopamine-mediated activation that counteracts a rising sleep drive. The role of diurnal variation of dopamine function should be considered both in the choice of the drug treatment regimen, and in the evaluation of biological and neuropsychological parameters.

Adolescent↗

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.

Aged↗

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.

Adult↗

Anticipation of a non-aversive reaction time task facilitates the blink startle reflex.

The conditions under which blink startle facilitation can be found in anticipation of a reaction time task were investigated to resolve inconsistent findings across previous studies. Four groups of participants (n=64) were presented with two visual stimuli, one predicting a reaction time task (S+) and the second presented alone (S-). Participants were asked to make a speeded response to the offset of the S+ (S1 paradigm) or were asked to respond to a tactile stimulus presented at the offset of the S+ (S1-S2 paradigm). Half of the participants in each paradigm condition received performance feedback. Overall, blink latency shortening and magnitude facilitation were larger during S+ than during S-. More detailed analyses, however, found these differences to be reliable only in the Feedback conditions. Ratings of S+ pleasantness did not change across the experiment. Electrodermal responses to S+ were larger than to S- in all groups with differential electrodermal responding emerging earlier in the S1 paradigm. Taken together, the data support the notion that startle facilitation can occur during non-aversive Pavlovian conditioning.

Adolescent↗

A parametric study of the separate contributions of the tactile and acoustic components of airpuffs to the blink reflex.

Airpuffs are often used as blink reflex eliciting stimuli, but the airpuff makes an abrupt noise when it leaves the tube. The present study investigated the effects of the tactile and acoustic components of airpuffs on the blink reflex in 18 human subjects. Subjects received airpuffs to the temple at 10.3, 20.7 and 31.0 kPa in a within-subjects design. The airpuff-associated noise was attenuated (Airpuff + Attenuated noise) or airpuffs were presented without noise-attenuation (Airpuff+ Unattenuated noise) in two conditions. In the third condition, the airpuff was directed away from the temple to eliminate the tactile component of the airpuff (Noise alone). Reflexes were larger, more probable and faster to the Airpuff+ Unattenuated noise compared to the Airpuff+ Attenuated noise. This indicates that there is an excitatory influence from the acoustic component of the airpuff. The findings suggest that researchers should reduce the acoustic component of airpuffs in studies that use airpuffs as reflex eliciting stimuli.

Adult↗

The blink reflex and the corneal reflex are followed by cortical activity resembling the nociceptive potentials induced by trigeminal laser stimulation in man.

Laser stimulation of the supraorbital regions evokes brain potentials (LEPs) related to trigeminal nociception. The aim of this study was to record the R2 component of the blink reflex and the corneal reflex in 20 normal subjects, comparing the scalp activity following these reflexes with the nociceptive potentials evoked by CO2 laser stimulation of supraorbital regions. Cortical and muscular reflexes evoked by stimulation of the first trigeminal branch were recorded simultaneously. The R2 component of the blink reflex and the corneal reflex were followed by two cortical peaks, which resembled morphologically N-P waves of LEPs. The two peaks demonstrated a difference in latency of approximately 40 ms, which is consistent with activation time of nociception. This finding suggests that these reflexes are induced by activation of small pain-related fibers.

Adult↗

Averaged blink reflex test.

Averaging of blink reflex responses was of particular value in detecting a very small potential of R1 in patients with severe facial nerve palsy where the conventional single stimulation method proved inefficient. To find the most suitable interval of stimulation for averaging, the recovery cycle of R1 was studied. The result showed that the R1 recovery curve could be divided into four phases. The initial facilitation phase at the interval of 5 msec was followed by a brief phase of depression. It was further followed by a second facilitation phase with a maximum of about 60 msec. Lastly the recovery curve returned to almost the 100% level after 100 msec. Due to the second facilitation phase, stimuli given at the interval of 60 msec were efficient for averaging of blink reflex responses. Though R1 to the second stimulus at this interval might have overlapped with R2 to the first stimulus, averaging of responses made R1 more prominent and R2 more inconspicuous, because R1 had a constant latency and R2 a variable one to each stimulus.

Adult↗

Blink reflex in young children with medullary kink in Chiari malformation.

We studied the blink reflex (especially the late components ipsi- and contralateral to stimulation site, R2 and R2') in 17 patients under 6 years of age; 12 with Chiari malformation, 1 with Dandy-Walker syndrome and 4 with brainstem tumor. We investigated the correlation between the R2 or R2' and neuro-image findings. Out of various features of the brainstem lesion revealed by MRI or CT examinations, the medullary kink characteristic in Chiari malformation was most responsible for abnormality of R2 and R2'. In addition, the fact that the disturbance of R2 and R2' in patients with Chiari malformation was more apparent in younger children than older ones confirms the intrinsic vulnerability of the blink reflex in the younger age groups as noted in normal children.

Aging↗

[Significance of the blink reflex in the Wallenberg syndrome].

The blink reflex was studied in 38 cases with lateral medullary lesions (Wallenberg syndrome). Twenty-one blink reflexes were abnormal. The most common abnormality is an afferent delay in the late reflex on the side of the lesion with a normal early reflex. This abnormality is not pathognomonic of the Wallenberg syndrome. The physiopathogeny is discussed.

Adult↗

A neurophysiological approach to brainstem reflexes. Blink reflex.

The blink reflex (BR) is a generalised phenomenon in mammals. Its teleological protective eye function is perhaps the reason why the BR can be provoked by a multitude of stimuli. As corneal and glabellar reflexes, BR has an inveterate use in the neurological exploration. Some of its physiopathological aspects were discussed more than 100 years ago, and soon half a century will have passed since the first electrophysiological study was published. This review focuses on the BR elicited by the electrical stimulation of the trigeminal supraorbital nerve, a controlled and reliable model in clinical neurophysiology. The electrically elicited BR is an exteroceptive-nociceptive reflex recorded on the orbicularis oculi muscle and formed by three components: the two principal ones, R1 and R2, of well-known characteristics, and a third, R3, of increasing interest, to which there is wide mention. The trigeminal afferent limb reaches the facial efferent one by means of a long and quite complex central pathway located at the brainstem bulbopontine level. The anatomical substrate and criteria of the rich topographical lesional semiology of the BR are established. The importance of the suprasegmental influences upon the reflex, coming mainly from the cerebral cortex and basal ganglia, as well as the impairment caused by their damage, will be emphasised. Special attention is paid to the relationship between the reflex and the dopaminergic system, and the consequences of its derangement. The methods of habituation and suppression-recovery of the BR are extensively and critically reviewed. These methods measure its excitability and serve in practice for the pathophysiological study of numerous diseases. The relationship of the BR with the spontaneous blinking is considered, and the existence of a primary inhibitory reflex on levator palpebrae muscles, previous to the active reflex response of the orbicularis, is proposed. The electrophysiological characteristics of the glabellar reflex, the corneal reflex, the acoustic, photic and somatosensory provoked BR, the ontogeny, and some of the common factors influencing the reflex, such as sleep, are also discussed. The strategic position of the neural structures of the BR, in an area involved in the gating of the various sensory-motor systems and the relative ease to its evaluation with common methodology used in clinical neurophysiology, makes the BR an essential tool for the diagnosis and pathophysiological insight into an important number of human neurological disorders.

Animals↗

Wavelet decomposition of the blink reflex R2 component enables improved discrimination of multiple sclerosis.

OBJECTIVES: The blink reflex R2 component was subjected to wavelet decomposition for time feature extraction in order to classify the functional status of patients with multiple sclerosis. METHODS: The blink reflex was recorded bilaterally with unilateral stimulation of the supra-orbital nerve in 37 normal subjects and 9 patients with multiple sclerosis (MS). The late component, R2, was subjected to time-frequency decomposition using the Daubechies-4 wavelet. Using the time-frequency coefficients, the mean time of the R2 wave as well as the standard deviation of the R2 interval were calculated in each trial. The wavelet transform enables noise reduction by allowing selective use of frequency bands with high signal-to-noise ratio for time feature extraction; therefore automatic estimation of time parameters is robust. The distribution densities of the mean and the standard deviation of the R2 wave duration for the set of trials for each subject were computed. RESULTS: An appreciable difference in the densities of the two parameters extracted in the wavelet domain was seen between normals and patients. This is in contrast to the onset latency of R2 which poorly discriminates MS patients from normals. CONCLUSION: The results suggest that the mean and standard deviation of the R2-time robustly estimated using wavelet decomposition can be used to support clinical diagnosis in tracking the functional status of patients with diseases like multiple sclerosis.

Automation↗

Enhanced gain of blink reflex responses to ipsilateral supraorbital nerve afferent inputs in patients with facial nerve palsy.

OBJECTIVES: Patients with peripheral facial palsy (PFP) may present with transient hyperkinetic movement disorders in the side contralateral to the paralysis. One possible cause of such enhanced motor activity is sensitization of reflex responses to afferent inputs from the unprotected cornea. We hypothesized that if this sensitization occurs, the size of the orbicularis oculi (OOc) responses induced by afferents from the ophthalmic branch of the paralyzed side would be larger than those induced by afferents from the contralateral side. METHODS: In 68 patients with complete PFP and in a group of 30 age-matched control subjects we recorded the response of the OOc muscle of one side to electrical stimulation of the supraorbital nerve of both sides, and calculated the ratio between R2c and R2 (R2c/R2). RESULTS: The mean R2c/R2 ratio was significantly larger in patients than in control subjects (unpaired t test, P<0.05). Larger R2c than R2 responses were observed in 23.1% of control subjects and in 80.9% of patients (chi(2)=13.3, P<0.01). CONCLUSIONS: Our results suggest that patients with PFP have an enhanced blink reflex gain to inputs from the paralyzed side compared to those of the non-paralyzed side. Sensitization of the blink reflex polysynaptic pathways to inputs carried by afferent fibers from the ophthalmic branch of the paralyzed side can play a role in inducing an abnormal facial motor behavior after PFP.

Adult↗

The stimulus intensity modifies the blink reflex recovery cycle in healthy subjects and in blepharospasm.

OBJECTIVE: The excitability of human brainstem interneurons is measured by the blink reflex recovery cycle and is abnormal in blepharospasm. We wondered whether the results of this paradigm depend on the stimulus intensity. METHODS: We investigated the blink reflex recovery cycle in 13 healthy control subjects and in 13 patients with blepharospasm (7 of them treated with botulinum toxin) using 4 levels of stimulus intensity (5, 12, 19 and 26 mA) and two interstimulus intervals (ISIs, 150 or 250 ms). RESULTS: In all groups the inhibition of the second R2 response was reduced with strong stimulus intensities: In controls, the inhibition of the second R2 decreased significantly (e.g. young controls, ISI 150 ms, from 89.6+/-15.6% at 5 mA to 21.9+/-49.7% at 26 mA, mean+/-standard deviation). In patients the R2 inhibition found at 5 mA was converted in an R2 facilitation at 26 mA, irrespective of the status of treatment. In addition, the patients' results at 5 mA did not differ significantly from the controls' results at 26 mA. CONCLUSIONS: The R2 inhibition and its sensitivity to detect abnormal interneuronal excitability depend on the stimulus intensity, which may act by modifying the excitability of the R2 interneurons.

Adult↗

A new method to increase nociception specificity of the human blink reflex.

OBJECTIVE: The medullary R2 response of the blink reflex can be elicited by innocuous and noxious stimuli. The purpose of this study was to elicit a nociception specific R2 response with a new surface electrode. METHODS: In 10 healthy subjects the blink reflex was elicited using a standard (10-15 mA) and a new concentric surface electrode type (0.6-1.6 mA) which produces a pin-prick-like pain. RESULTS: After topical local anaesthesia with lignocaine/prilocaine R1 was unchanged, R2 was attenuated by 12% after standard stimulation but was almost abolished (-91%) with the new electrode type. CONCLUSION: Stimulation with low stimulus intensities but electrode-dependent high current density allows preferential depolarization of superficial nociceptive A-delta fibres. This new method is less traumatic than others and is useful in the study of trigeminal nociception.

Adult↗

Brain stem auditory evoked potentials and blink reflexes in multiple sclerosis.

Brain stem auditory evoked potentials (BAEP) and the blink reflex (BR) were recorded from 50 patients with a wide spectrum of multiple sclerosis, to determine whether the combination of the two tests of brain stem function would yield a higher rate of abnormality than each test performed alone. Sixty-four per cent of patients had a BAEP abnormality and fifty-two per cent had an abnormal BR, but when the results were combined, seventy-six per cent were abnormal. The blink reflex was abnormal in all patients with symptoms suggestive of trigemino-facial pathology.

Adolescent↗

Tinnitus related to eyelid blinking.

Tinnitus due to muscular causes is rare. The commonest pathological muscular cause of tinnitus is palatal myoclonus. A case of bilateral tinnitus, related to eyelid blinking, is presented. This is the first case reported in the literature. Previous reported cases of tinnitus related to eyelid blinking have all been unilateral and associated with recovery from a VII nerve palsy. The treatment of the condition is discussed.

Adult↗

Sources of the attentional blink during rapid serial visual presentation: perceptual interference and retrieval competition.

Observers watched for 1 or 2 colored words as targets presented in lists of distractor strings (10 items/s). Identification of 1 target (T1) temporarily reduced the accuracy of reporting a 2nd target (T2). This attentional blink (AB) effect was most pronounced when T1 and T2 occurred close together in time. Use of recognition tests (instead of recall) improved performance but did not eliminate the AB effect. The AB effect was found with both word and nonword distractors, a smaller AB effect was found with consonant string distractors, and the AB effect was substantially attenuated with strings of unfamiliar characters (a false font). Analyses of errors indicated that the 2nd target is frequently replaced or corrupted by the following distractor during the blink. The AB effect appears to result from both attentional and mnemonic processes.

Adult↗