Influence of stimulus control on the excitability of the electrically elicited blink reflex in patients with schizophrenia.

BACKGROUND: In humans, the excitability of the electrically evoked blink reflex is influenced by the subject's attention to the stimulus. The early reflex component R1 has been found to be facilitated in conditions of increased selective attention, whereas the late components R2 and R3 exhibited a marked suppression. Distraction from the stimulus leads to enhanced R2 and R3 magnitudes. METHODS: We investigated the excitability of the distinct reflex components in 19 patients with schizophrenia and 19 healthy control subjects. In the control condition (EE), stimulation was elicited by the experimenter; in a second condition (SE), subjects released a key to evoke the reflex themselves. RESULTS: The SE patients with schizophrenia exhibited an abnormally increased R1 facilitation and an impaired R2 inhibition in comparison with normal control subjects. An R3 component could be registered in EE in 13 of 19 patients but only in one control subject; SE resulted in a complete suppression of this component in all but two patients with schizophrenia. CONCLUSIONS: The abnormal R1 facilitation and the impaired R2 inhibition may be regarded as neurophysiological markers of defective information processing in a condition of increased selective attention to a self-controlled stimulus in patients with schizophrenia. The enhanced excitability of the R3 component under standard conditions indicates defective attentional mechanisms in patients with schizophrenia in an uninstructed passive condition attending a stimulus triggered by the experimenter.     

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.     

Blink reflex in Parkinson's disease with levodopa-induced dyskinesia

We have studied the electrically evoked blink reflex (R1 and R2 components) in 40 parkinsonian patients with levodopa-induced dyskinesia (15 with facial dyskinesia, 13 with limb-truncal dyskinesia and 12 with mixed dyskinesia). R2 latencies (both ipsilateral and contralateral) were significantly prolonged in dyskinetic patients. These findings are indicative of decreased excitability of brainstem interneurones in the dyskinetic parkinsonians. We found no correlation between the neurophysiological pattern of blink reflex and the localization of dyskinesia.     

Pain threshold and polysynaptic components of the blink reflex in Parkinson's disease

This study was conducted on 15 outpatients with idiopathic Parkinson's disease, 10 on chronic levodopa therapy and 5 drug free, all complaining of painful syndromes. We investigated the perceptive and pain thresholds and the threshold of polysynaptic components of the blink reflex in patients and 8 controls. Our data indicate that as regards the perceptive, pain and R2, R3 thresholds, patients with and without levodopa therapy do not differ significantly from controls.     

The blink reflex in "chronic migraine".

OBJECTIVES: Activation of the trigeminovascular system and sensitisation of brainstem trigeminal nuclei are thought to play an important role in migraine. The aim of this study was to investigate the blink reflex and its habituation in patients with "chronic migraine". METHODS: We studied 35 patients suffering from "chronic migraine" (IHS classification criteria) outside and during a spontaneous attack, and 35 control subjects. An EMG device with a specific habituation test program was used to elicit and record blink reflex responses and to randomly repeat stimulations at different time intervals so as to induce habituation. RESULTS: The R(1) and R(2) latencies, amplitudes and areas of the basal blink reflex were similar in patients studied both outside and during an attack as well as in control subjects, whereas the blink reflex habituation responses were markedly reduced in patients studied outside an attack. The percent changes in the R(2) areas from the baseline values, obtained when stimuli were delivered at time intervals of 10, 5, 4, 3, 2 and 1s, were statistically different (p<0.01-p<0.001) from those of the same patients studied during a migraine attack and of those of control subjects. There was a significant correlation between decreased habituation of the blink reflex and a higher frequency of attacks. The stimulus intensities of the blink reflex (multiples of the detection threshold intensities) were significantly lower (p<0.001) on the side affected, or more severely affected, by headache in patients studied during a migraine attack. CONCLUSIONS: The decreased habituation of the blink reflex outside an attack reflects abnormal excitability in "chronic migraine", which normalizes during the attacks. The inverse correlation between the frequency of attacks and habituation responses confirms the abnormal excitability induced by the high frequency of attacks. Central sensitisation mechanisms (allodynia) may explain the lower detection thresholds observed on the side affected by headache in patients during the attacks. SIGNIFICANCE: The blink reflex and its habituation may help shed light on the subtle neurophysiological changes that occur in migraine patients between and during attacks.     

Comparative study of pain perception and polysynaptic blink reflex responses in man

Stimulation of the first trigeminal branch using a 10 ms train of 5 pulses of 0.1 ms duration is performed on 17 healthy subjects (19-65 years of age) in order to assess the relationship between polysynaptic components of the blink reflex and perceptive and pain thresholds (ths). The mean value of tactile ths (Pth) is 2.22 +/- 0.86 mA; while R2, R3 and pain threshold values are 1.25 +/- 0.34, 3.52 +/- 1.94 and 4.78 +/- 2.77 times the Pth respectively. The pain ths average is 1.47 +/- 0.92 with regard to the R3 threshold. The R2 ths are very close to those of tactile perception, while those of R3 appear significantly related to the pain ths.     

Blink reflex excitability cycle in hemifacial spasm

We studied electrically elicited blink reflex responses in patients with hemifacial spasm (HFS) by applying single isolated, as well as paired (conditioning and test), stimuli at both sides of the face. Responses after single stimuli were of larger size on the side of the spasm compared with the uninvolved side and controls. With paired stimuli, the inhibitory effect of the conditioning stimuli upon the test stimuli late response (R2), which was always observed in normals, was significantly less pronounced at short interstimuli intervals. This resulted in an enhanced recovery curve of R2, which was observed on the side of the spasm and the contralateral, clinically normal side. Patients with longer disease duration showed more striking abnormalities of the recovery curve. We suggest that there is enhanced excitability of facial motoneurons and of those brainstem interneurons that mediate the blink reflex pathway in patients with HFS.     

Blink reflex in hemiplegia.

An electrophysiological study of the blink reflex was undertaken in 20 normal subjects and in 28 patients complaining of central facial palsy caused by unilateral hemispheral damage. In normal subjects, the latency, amplitude and organization of R1 and R2 responses are well known. Habituation of R2 responses occurred between 1 and 2 c/sec stimulation rate. R1 responses habituated at a higher stimulation rate (5 c/sec). In patients with unilateral hemispheral lesion, our results showed that changes in the blink reflex responses were bilateral. On the hemiplegic side the responses showed a decreased amplitude, while they were facilitated on the "normal" side. However, there was no change in latency of the two components of the reflex, on both sides. On the other hand, habituation of the late component occurred on the hemiplegic side for low stimulation rates: (0.5--1 c/sec), while on the "normal" side there was less habituation (3--4 c/sec), as compared with normal subjects. These results agree with those of experimental studies on cortical modulatory influences on brain-stem nuclei. They suggest a tactile origin of the two components of the blink reflex.     

Prognostic significance of the electrically elicited blink reflex in neonates

The electrically elicited blink reflex was examined in ten normal neonates, 11 postasphyxial neonates, and 3 congenital hydrocephalus cases. The blink reflex was elicited in all cases. In normal neonates, the latencies and amplitudes were 10.9 +/- 0.7 msec and 159 +/- 62 microV at R1, 34.3 +/- 1.4 msec and 123 +/- 30 microV at R2, and 40.7 +/- 2.3 msec and 84 +/- 25 microV at R'2 respectively. Ischemic-hypoxic brain damage during the neonatal period mainly influenced the late components of the blink reflex. The blink reflex of the postasphyxial neonates showed significantly prolonged latencies of R2 and R'2. The amplitudes were increased in cases with a fair prognosis and decreased in cases with a poor prognosis. A case of congenital hydrocephalus with mental retardation also showed the prolonged latencies of R2 and R'2 in neonatal period. The blink reflex in neonates appears to be useful in predicting the outcome in cases of neonatal asphyxia and congenital hydrocephalus.     

Corneal reflex in normal and pathological subjects

The orbicularis oculi response can be evoked both by mechanical stimulation of the cornea (corneal reflex) and by electrical stimulation of the skin overlying the supraorbital nerve (blink reflex). Mechanical stimuli to the cornea activate A delta and C free nerve endings of the corneal mucosa. Electrical stimuli to the supraorbital nerve activate A beta, A delta and C fibers of the nerve trunk. Both reflexes present a bilateral late response, but the blink reflex shows in addition an early ipsilateral component (R1), which has never been observed with the corneal stimulation in man. We have developed a simple technique of electrical stimulation of the cornea which provides stable responses and allows precise measurements of threshold and latency of the reflex. In normal subjects, the threshold ranged from 50 to 350 microA, and the maximal stimulus that the subject could bear (tolerance level) ranged from 1000 to 2500 microA. The minimal latency to tolerance level stimuli was 39 +/- 3 msec. The latency difference between the direct responses evoked from the two opposite corneas never exceeded 8 msec and the difference between the direct and consensual responses elicited from the same cornea never exceeded 5 msec. An early ipsilateral component similar to the R1 response of the blink reflex was not observed, even with supramaximal stimulation. The electrically evoked corneal reflex was normal in 10 cases of essential trigeminal neuralgia, while the responses showed significant abnormalities in 18 subjects submitted to thermocoagulation of the Gasserian ganglion as a treatment of neuralgic pain, as well as in 2 cases of symptomatic neuralgia.(ABSTRACT TRUNCATED AT 250 WORDS)     

The three responses of the blink reflex in adult and juvenile migraine

Recent theories about migraine pathogenesis have emphasized the role of the trigeminal system in the pathogenesis of migraine attacks (Moskowitz, 1997). The blink reflex (BR) could be a suitable method to evaluate the trigeminal system in migraine, as it is generally elicited by stimulation of the trigeminal ophthalmic division (Kimura et al., 1967), involved in migraine attacks. Sixty one adult and 15 juvenile migraine without aura subjects were selected, in order to evaluate the BR features, including the subjective perceptive and pain thresholds and the R1, R2 and R3 components intensity thresholds and amplitudes. The electrophysiological procedure was carried out during the pain free phase. The findings were compared with those of 28 healthy controls, 18 adults and 10 children. In both adult and juvenile migraine sufferers an early appearance of the R3 response at almost the R2 threshold was observed in comparison with age-matched controls. Unfortunately, the anatomic and physiologic organization of the R3 component is uncertain: its early onset could suggest a dysfunction of the inhibitory control system on the trigeminal networks, which may predispose to migraine attacks.     

Corneal and blink reflexes in Parkinson's disease with "on-off" fluctuations

In 13 patients with Parkinson's disease and "on-off" fluctuations and in a control group, the electrically evoked blink (R1 and R2 component) and corneal reflexes (CR), the habituation of the glabellar reflex, and the blink rate were studied. Latency, amplitude, and recovery cycle of R1 was normal. CR latency, but not R2 latency, was significantly shorter in patients than in normal subjects. R2 recovery cycle, but not CR recovery cycle, was facilitated in "off" patients in comparison to normal subjects. CR and R2 duration was longer in "off" than in "on" patients. R2 recovery cycle became similar to that of normal subjects after fluctuation from "off" to "on" period, but CR recovery cycle varied only slightly. The habituation of the glabellar reflex and the blink rate were decreased in "off" patients. These findings indicate that the enhanced excitability of R2 is related to the central dopamine activity levels. The differences between the recovery cycles of CR and R2 may be explained with the smaller number of interneurons subserving CR than R2 circuit. The shorter latency of CR, but not of R2, both in "on" and "off" patients, may suggest that in Parkinson's disease basal ganglia exert a different control of incoming sensory input transmitted via beta and delta fibers.     

Blink reflex recovery in facial weakness: an electrophysiologic study of adaptive changes

OBJECTIVE: To study the electrophysiologic effects of unilateral facial weakness on the excitability of the neuronal circuitry underlying blink reflex, and to localize the site of changes in blink reflex excitability that occur after facial weakness. BACKGROUND: Eyelid kinematic studies suggest that adaptive modification of the blink reflex occurs after facial weakness. Such adaptations generally optimize eye closure. A report of blepharospasm following Bell's palsy suggests that dysfunctional adaptive changes can also occur. METHODS: Blink reflex recovery was evaluated with paired stimulation of the supraorbital nerve at different interstimulus intervals. Comparisons were made between normal control subjects and patients with Bell's palsy who either recovered facial strength or who had persistent weakness. RESULTS: Blink reflex recovery was enhanced in patients with residual weakness but not in patients who recovered facial strength. Facial muscles on weak and unaffected sides showed enhancement. In patients with residual weakness, earlier blink reflex recovery occurred when stimulating the supraorbital nerve on the weak side. Sensory thresholds were symmetric. CONCLUSION: Enhancement of blink reflex recovery is dependent on ongoing facial weakness. Faster recovery when stimulating the supraorbital nerve on the paretic side suggests that sensitization may be lateralized, and suggests a role for abnormal afferent input in maintaining sensitization. Interneurons in the blink reflex pathway are the best candidates for the locus of this plasticity.     

Nociceptive R3 reflex in relapsing-remitting multiple sclerosis patients.

Pain in multiple sclerosis (MS) patients has only recently been recognised as a genuine symptom of this disease. It is important to determine whether this pain is the consequence of another symptom of MS or whether it is due to a demyelinating lesion affecting pain pathways. A close relationship has been found between the R3 component of the blink reflex and the pain threshold. The aim of this work was to carry out an objective evaluation of the nociceptive system in MS patients by means of the R3 component of the blink reflex. The study was performed on 20 healthy volunteers and on 20 clinically defined relapsing-remitting MS patients with EDSS not > 3.5, normal R1 and R2 components of the blink-reflex, personal and family anamnesis negative for migraine and trigeminal neuralgia; the patients were not taking drugs at the time of the test. A significant difference was found, between healthy volunteers and patients, for R3 threshold, pain threshold and R3 latency.     

Changes in the recruitment pattern of single motor units in the blink reflex of patients with parkinsonism and hemiplegia

The recruitment pattern of single motor units (SMUs) was studied in the early (R1) and late (R2) blink reflex components in normal subjects (15), patients with parkinsonism (10) and with hemiplegia due to hemispheral lesions (5). Reflexes were evoked by constant current stimuli applied to the supraorbital nerve. SMU discharges were recorded in the preseptal part of the lower eyelid using a bipolar needle electrode. Thresholds of R1 and R2, latencies at the thresholds and the number of discharges in R2 were determined. In parkinsonism, the recruitment of SMUs in R1 was impaired, suggesting that the malfunction of the basal ganglia in this disorder is associated with a reduced excitability of neurons in the pontine brain-stem. In hemiplegia, the recruitment in both R1 and R2 could be impaired. The orderly function of neurones in the pontine and medullary pathways of these components appears to require facilitatory hemispheral influences. Signs of disinhibition occasionally found in R1 may point to an imbalance between facilitatory and inhibitory hemispheral influences upon the pontine pathway.     

Alterations in excitatory and inhibitory brainstem interneuronal circuits in fibromyalgia: Evidence of brainstem dysfunction

ObjectivePatients with fibromyalgia syndrome (FMS) perceive stimuli differently and show altered cortical sensory representation maps following peripheral stimulation. Altered sensory gating may play a causal role.MethodsBlink reflex, blink reflex excitability recovery, and prepulse inhibition of the blink reflex – representing brainstem excitability – were assessed in 10 female patients with FMS and 26 female healthy controls.ResultsUnconditioned blink reflex characteristics (R1 latency and amplitude, R2 and R2c latency and area-under-the-curve) did not differ significantly between patients and controls. Blink reflex excitability recovery was enhanced in patients versus controls at all intervals tested. Prepulses significantly suppressed R2 area and increased R2 latency in patients and controls. However, R2 area suppression was significantly less in patients than in controls (patients: to 80.0 ± 28.9%, controls: to 47.8 ± 21.7%). The general pattern of corresponding changes in R2c was similar.ConclusionsBlink reflex is normal, whereas blink reflex excitability recovery is enhanced and blink reflex prepulse inhibition is reduced in patients with FMS, suggesting functional changes at the brainstem level in FMS.SignificanceReduced blink reflex prepulse inhibition concurs with altered sensory gating in patients with FMS.     

Voluntary,spontaneous, and reflex blinking in Parkinson's disease

Blinking, a motor act consisting of a closing and an opening eyelid movement, can be performed voluntarily, spontaneously, and reflexly. In this study we investigated the kinematic features of voluntary, spontaneous, and reflex blinking in patients with Parkinson's disease (PD), OFF and ON dopaminergic treatment. Patients were asked to blink voluntarily as fast as possible. Spontaneous blinking was recorded for a minute during which the subjects just relaxed. Reflex blinking was evoked by electrical stimulation on the supraorbital nerve. Eyelid movements were recorded with the SMART analyzer motion system. Patients OFF therapy paused longer than controls during voluntary blinking but not during spontaneous and reflex blinking. The blink rate tended to be lower in patients OFF therapy than in controls and the spontaneous blinking had abnormally low amplitude and peak velocity. Finally, in patients OFF therapy the excitability of the neural circuit mediating the closing phase of the reflex blinking was enhanced. Dopaminergic treatment shortened the pause during voluntary blinking and increased the blink rate. In PD patients the longer pauses between the closing and opening phase in comparison to normal subjects, suggest bradykinesia of voluntary blinking. PD patients also display kinematic abnormalities of spontaneous blinking and changes in the excitability of the closing phase of reflex blinking. © 2007 Movement Disorder Society     

Pain-evoked blink reflex

The electrically evoked blink reflex (BR) consists of an ipsilateral R1 component (R1) at 11 ms and two bilateral components R2 at 33 ms and R3 at 83 ms. It is still unclear whether the R2 is mediated by activation of tactile or nociceptive afferents. For testing the nociceptive hypothesis, nociceptors of the supraorbital nerve were selectively activated by infrared laser stimuli in 10 subjects. Only painful laser stimuli evoked a bilateral early polyphasic BR response (LR2) at 71 ms. Stimulation of infraorbital and mental nerve dermatomes was equally effective. A late bilateral reflex response at 130 ms was occasionally observed. Regarding the nociceptor activation time of about 40 ms, onset latencies were within the range of the electrically evoked R2 and R3, respectively. The good accordance of R2 and LR2 may be due to activation of identical nociceptive fibers or to convergence of electrically evoked tactile and laser-elicited nociceptive input onto common multireceptive neurons. © 1997 John Wiley & Sons, Inc. Muscle Nerve, 20, 265–270, 1997.     

Blink reflex in patients with hemispheric cerebrovascular accident (CVA). Blink reflex in CVA

A blink reflex consists of an early unilateral component, R1, and a late bilateral component, R2. During an acute phase of hemispheric cerebrovascular accident, R1 and R2 were abnormal in 30 and 50 of 66 patients, respectively. Paired stimuli usually corrected R1 but not R2, which was profoundly suppressed. The discrepancy between polysynaptic R2 and oligosynaptic R1 indicates a greater disfacilitation at the level of interneurons than at the motoneuron, which serves as the final common path. Abnormality of R2 occurred bilaterally with stimulation on the affected side of face and contralaterally after stimulation on the normal side in 31 patients. This finding suggests a diffuse loss of internuncial excitability, contralateral to the hemispheric lesion. Changes of R2 implicated the brainstem pathways forming the afferent and efferent arc of the reflex in 7 and 8 patients, respectively. The remaining 4 comatose patients had no R2 irrespective of stimulus sites. Clinical localization of the hemispheric lesion showed no consistent correlation with the type of blink reflex abnormalities. The CT scans revealed widely scattered changes in 29 patients with abnormal blink reflex but with a tendency to overlap in the inferior Rolandic area. This contrasted with conspicuous sparing of the inferior post-central region in 10 patients with normal blink reflex. These findings suggest the presence of crossed facilitation to this reflex from wide areas of the cortex but most prominently from the sensory representation of the face.     

Blink reflex in patients with an ischaemic lesion of the brain-stem verified by MRI

The electrically elicited blink reflex was investigated in 25 patients with ischaemic lesions of the pons or the medulla oblongata. Only patients with a lesion on MRI appropriate to the clinical syndrome were included. Twenty patients had an infarction of the pons, bilateral in 5. Additional 5 patients had an infarction of the dorsolateral medulla oblongata. Patients with hemispheric lesions were excluded. Four of the 5 patients with Wallenberg's syndrome showed delayed R2 components to stimulation ipsilateral to the lesion. Additional loss of the ipsilateral R1 component was observed in 1 patient. Fifteen of the 20 patients with pontine infarctions had pathological blink reflexes. All 6 patients with a unilateral pons lesion and an abnormality of R1 had this abnormality on the side contralateral to the lesion. In 3 cases with bilateral pontine infarction R1 was abnormal on one side or on either side. Of 11 patients with a normal R1, 6 had isolated abnormalities of R2 without consistent correlation to the side of the lesion. We conclude that abnormalities of the blink reflex are of minor localizing value in pontine infarction. This may be explained by the fact that a pontine infarction affects either the reflex arch itself or descending pathways that have a modulating influence on the reflex arch. Infarctions of the medulla oblongata, however, have characteristic abnormalities that have already been described.