Electrical stimulation as a therapeutic option to improve eyelid function in chronic facial nerve disorders.
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PURPOSE: To establish whether it is possible to improve orbicularis oculi muscle function in the eyelids of patients with a chronic seventh cranial nerve palsy by using transcutaneous electrical stimulation to the point at which electrical stimulation induces a functional blink. METHODS: Ten subjects (one woman, nine men) aged 36 to 76 with chronic, moderate to severe facial nerve palsy were recruited into the study. Voluntary and spontaneous eyelid movements were assessed, using an optical measuring system, before, during, and after a 3-month treatment period. Voluntary and spontaneous lid velocities were also measured and compared with eyelid kinematic data in normal subjects (12 women, 18 men; age range, 22-56 years). RESULTS: Therapeutic electrical stimulation applied over 3 months produced improvement in eyelid movement (>2 mm) in 8 of 10 patients during voluntary eyelid closure. However, there was no significant improvement recorded in spontaneous blink amplitudes or peak downward-phase velocity of the upper eyelid. This regimen of stimulation failed to recover function well enough that a functional blink could be induced in the paretic eyelid by electrical stimulation. CONCLUSIONS: Electrical stimulation using transcutaneous electrical nerve stimulators units can improve voluntary eye closure, apparently because of a reduction in stiffness of eyelid mechanics, rather than an improvement of muscle function. Investigation of alternative stimulation regimens is warranted. (+info)
Discharge profiles of abducens, accessory abducens, and orbicularis oculi motoneurons during reflex and conditioned blinks in alert cats.
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The discharge profiles of identified abducens, accessory abducens, and orbicularis oculi motoneurons have been recorded extra- and intracellularly in alert behaving cats during spontaneous, reflexively evoked, and classically conditioned eyelid responses. The movement of the upper lid and the electromyographic activity of the orbicularis oculi muscle also were recorded. Animals were conditioned by short, weak air puffs or 350-ms tones as conditioned stimuli (CS) and long, strong air puffs as unconditioned stimulus (US) using both trace and delayed conditioning paradigms. Motoneurons were identified by antidromic activation from their respective cranial nerves. Orbicularis oculi and accessory abducens motoneurons fired an early, double burst of action potentials (at 4-6 and 10-16 ms) in response to air puffs or to the electrical stimulation of the supraorbital nerve. Orbicularis oculi, but not accessory abducens, motoneurons fired in response to flash and tone presentations. Only 10-15% of recorded abducens motoneurons fired a late, weak burst after air puff, supraorbital nerve, and flash stimulations. Spontaneous fasciculations of the orbicularis oculi muscle and the activity of single orbicularis oculi motoneurons that generated them also were recorded. The activation of orbicularis oculi motoneurons during the acquisition of classically conditioned eyelid responses happened in a gradual, sequential manner. Initially, some putative excitatory synaptic potentials were observed in the time window corresponding to the CS-US interval; by the second to the fourth conditioning session, some isolated action potentials appeared that increased in number until some small movements were noticed in eyelid position traces. No accessory abducens motoneuron fired and no abducens motoneuron modified their discharge rate for conditioned eyelid responses. The firing of orbicularis oculi motoneurons was related linearly to lid velocity during reflex blinks but to lid position during conditioned responses, a fact indicating the different neural origin and coding of both types of motor commands. The power spectra of both reflex and conditioned lid responses showed a dominant peak at approximately 20 Hz. The wavy appearance of both reflex and conditioned eyelid responses was clearly the result of the high phasic activity of orbicularis oculi motor units. Orbicularis oculi motoneuron membrane potentials oscillated at approximately 20 Hz after supraorbital nerve stimulation and during other reflex and conditioned eyelid movements. The oscillation seemed to be the result of both intrinsic (spike afterhyperpolarization lasting approximately 50 ms, and late depolarizations) and extrinsic properties of the motoneuronal pool and of the circuits involved in eye blinks. (+info)
HPLC analysis of closed, open, and reflex eye tear proteins.
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Changes in the closed, open and reflex eye tear proteins of normal subjects were compared and analysed. Tear proteins were resolved by high-performance liquid chromatography (HPLC) utilising both gel filtration (P-300 SW) and reverse-phase (C-18) columns and the HPLC fractions were further analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) under reducing and non-reducing conditions. The protein composition of the closed-eye tear was significantly different from that of the open and reflex-eye tear. Secretory IgA (sIgA) was the predominant protein in closed eye tears constituting 49% of the total protein compared to 11% in reflex tears, whereas lysozyme was the predominant protein (53%) in reflex tears. Levels of lactoferrin, lipocalin and lysozyme were relatively constant in both open and reflex tears. HPLC profiles of the closed-eye tears, upon continuous stimulation of lacrimal glands indicated that sIgA was significantly reduced whereas lactoferrin, lipocalin, and lysozyme were significantly increased. These results indicate that the tear composition upon waking attains that of the open eye within 4 to 5 minutes, and upon continuous stimulation this reflects the reflex-eye tear composition. It also indicates that mechanisms responsible for changes in concentration of constitutive and regulated tear protein with stimulus can be studied successfully using non-invasive methods to collect human tears. (+info)
Midazolam effects on prepulse inhibition of the acoustic blink reflex.
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AIMS: The eye-blink response following sudden acoustic noise bursts is part of the startle reflex. The magnitude of the startle response can be attenuated by presentation of a weak stimulus before the 'startle-eliciting' stimulus (prepulse inhibition, PPI). PPI is a stable finding in awake humans but may be altered by anaesthetic drugs. We investigated whether the application of benzodiazepines altered the magnitude of PPI in healthy male volunteers. METHODS: In an open-label noncontrolled investigation, the effect of the benzodiazepine agonist midazolam on PPI was assessed in the absence and presence of the antagonist flumazenil. After an initial control period of 60 min three consecutive periods, each of 60 min, with progressively increasing concentrations of midazolam were studied (0. 02, 0.06, 0.14 mg kg-1 h-1 ). A final 60 min period during the administration of flumazenil (0.004 mg kg-1 h-1 ) and while the agonist was still present was also studied. Drug was administered intravenuously as a combination of bolus, 50% of total dose and continuous infusion over the 60 min period. Electromyographic (EMG) response of the right orbicularis oculi muscle was used to assess the startle response to noise bursts of 50 ms duration (95 dB(A)). Noise bursts were randomly preceded by nonstartling prepulses (800 Hz sinus, 50 ms duration, 65 dB(A), prepulse to noise interval 120 ms). The magnitude of PPI was calculated by dividing the EMG response to nonprepulsed stimuli by the response to prepulsed stimuli for each individual and period. Eleven subjects participated in the study, two of them were excluded from the statistical analysis because startle responses could not be reliably elicited (final sample size n=9). RESULTS: The magnitude of PPI was inversely related to the concentration of midazolam. This relationship was described by a sigmoidal Emax model, giving an Emax of 0.65+/-0.13, an ED50 of 33.9+/-10.9 ng ml-1 and gamma of 3.5+/-1.0. During infusion of flumazenil and in the presence of midazolam, the magnitude of PPI increased by 0.11 (95% CI, 0-0.22, P+info)
Effects of paired and unpaired eye-blink conditioning on Purkinje cell morphology.
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This experiment addressed (1) the importance of conjunctive stimulus presentation for morphological plasticity of cerebellar Purkinje cells and inhibitory interneurons and (2) whether plasticity is restricted to the spiny branches of Purkinje cells, which receive parallel fiber input. These issues were investigated in naive rabbits and in rabbits that received paired or unpaired presentations of the conditioned stimulus (CS) and unconditioned stimulus (US). To direct CS input to the cerebellar cortex, pontine stimulation served as the CS. Air puffs to the cornea served as the US. Paired condition rabbits received pontine stimulation for 350 msec paired with a coterminating 100-msec air puff. Unpaired condition rabbits received the same stimuli in a pseudorandom order at 1- to 32-sec intervals. Rabbits were trained for a mean of 12 days. Naive rabbits received no treatment. In Golgi-stained Purkinje neurons in lobule HVI, total dendritic length, main branch length, total spiny branch length, and number of spiny branch arbors were all greater in the naive group than in the paired and unpaired groups, which did not differ. No differences were found between the hemispheres ipsilateral and contralateral to the trained eye. The dendritic length and number of branches for inhibitory interneurons did not differ across groups. The Purkinje cell morphological changes detected with these methods do not appear to be uniquely related to the conjunctive activation of the CS and US in the paired condition. (+info)
Learning in Parkinson's disease: eyeblink conditioning, declarative learning, and procedural learning.
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OBJECTIVE: To assess the degree of learning ability in Parkinson's disease. METHODS: Three different learning tasks: eyeblink classical conditioning with delay and trace paradigms, the California verbal learning test (CVLT), and a serial reaction time task (SRTT) were studied in patients with Parkinson's disease and normal (control) subjects. RESULTS: In the eyeblink conditioning tasks, both patients and normal subjects showed significant learning effects without between group differences. In the CVLT, patients remembered significantly fewer words than normal subjects in both short term and long term cued recall tasks. In the SRTT, normal subjects had significantly reduced response time and error rates across blocks of repeated sequence trials, whereas patients had significantly reduced error, but not response time rates. CONCLUSION: Impairment of nigrostriatal pathways selectively affects performance in complex learning tasks that are competitive and require alertness such as the SRTT, but not in simple learning procedures such as eyeblink conditioning. (+info)
New treatment of dry eye: the effect of calcium ointment through eyelid skin delivery.
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AIM: To demonstrate the efficacy of a petrolatum based calcium ointment applied to the lower lid skin in the management of dry eye. METHODS: In a controlled double masked study, the effects of water free petrolatum ointment containing calcium carbonate (10% w/w) on tear functional factors and ocular surface vital staining in dry eye patients were observed. Petrolatum without calcium carbonate served as control. Patients were instructed to place ointment to the lower lid skin twice a day. Evaluation of subjective complaints, fluorescein and rose bengal staining patterns, blink rate, tear evaporation and tear break up time (BUT) were performed before and 3 months after treatment. In order to demonstrate the movement of petrolatum from the skin to the tear film, petrolatum containing 1% sodium fluorescein was placed on the lower lid of four healthy volunteers, and the concentration of fluorescein in the tear film was followed up to 6 hours using an anterior fluorometer. RESULTS: Subjective symptoms significantly improved in both the calcium group (p=0.001) and control (p=0.012), while only the calcium group demonstrated a significant improvement in fluorescein (p=0.043), rose bengal (p=0.021) scores, and blink rate (p=0.004). Tear evaporation also significantly decreased in both the calcium group (p=0.0004) and control (0.043). BUT did not improve in either group. CONCLUSION: Petrolatum based calcium ointment significantly improved symptoms, tear dynamics, and ocular surface staining in dry eye patients. However, some of the therapeutic effects may be due to lipids in the petrolatum vehicle. Petrolatum applied to the lower lid skin is an effective drug delivery system for slowly releasing drugs to the ocular surface. (+info)
Impaired eye-blink conditioning in waggler, a mutant mouse with cerebellar BDNF deficiency.
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In addition to their trophic functions, neurotrophins are also implicated in synaptic modulation and learning and memory. Although gene knockout techniques have been used widely in studying the roles of neurotrophins at molecular and cellular levels, behavioral studies using neurotrophin knockouts are limited by the early-onset lethality and various sensory deficits associated with the gene knockout mice. In the present study, we found that in a spontaneous mutant mouse, waggler, the expression of brain-derived neurotrophic factor (BDNF) was selectively absent in the cerebellar granule cells. The cytoarchitecture of the waggler cerebellum appeared to be normal at the light microscope level. The mutant mice exhibited no sensory deficits to auditory stimuli or heat-induced pain. However, they were massively impaired in classic eye-blink conditioning. These results suggest that BDNF may have a role in normal cerebellar neuronal function, which, in turn, is essential for classic eye-blink conditioning. (+info)