Peripheral Thresholds Research Articles

Disruption of Balanced Cortical Excitation and Inhibition by Acoustic Trauma

Sensory deafferentation results in rapid shifts in the receptive fields of cortical neurons, but the synaptic mechanisms underlying these changes remain unknown. The rapidity of these shifts has led to the suggestion that subthreshold inputs may be unmasked by a selective loss of inhibition. To study this, we used in vivo whole cell recordings to directly measure tone-evoked excitatory and inhibitory synaptic inputs in auditory cortical neurons before and after acoustic trauma. Here we report that acute acoustic trauma disrupted the balance of excitation and inhibition by selectively increasing and reducing the strength of inhibition at different positions within the receptive field. Inhibition was abolished for frequencies far below the trauma-tone frequency but was markedly enhanced near the edges of the region of elevated peripheral threshold. These changes occurred for relatively high-level tones. These changes in inhibition led to an expansion of receptive fields but not by a simple unmasking process. Rather, membrane potential responses were delayed and prolonged throughout the receptive field by distinct interactions between synaptic excitation and inhibition. Far below the trauma-tone frequency, decreased inhibition combined with prolonged excitation led to increased responses. Near the edges of the region of elevated peripheral threshold, increased inhibition served to delay rather than abolish responses, which were driven by prolonged excitation. These results show that the rapid receptive field shifts caused by acoustic trauma are caused by distinct mechanisms at different positions within the receptive field, which depend on differential disruption of excitation and inhibition.

No close correlation between brainstem auditory function and peripheral auditory threshold in preterm infants at term age

Objective To determine whether central auditory function in preterm infants correlates with peripheral auditory threshold and whether threshold elevation affects central auditory function. Methods Brainstem auditory evoked response (BAER) was recorded at term age using maximum length sequence (MLS) with 91–910/s clicks in 133 preterm infants (gestation 28–36 weeks). The relationship between MLS BAER variables and BAER threshold was analyzed. Results The latencies and amplitudes of all MLS BAER waves correlated significantly with BAER threshold. However, no correlation was found between MLS BAER interpeak intervals and BAER threshold at any rates. In preterm infants with a threshold >20 dB nHL ( n = 30), MLS BAER wave latencies were all significantly longer than in those with a threshold ⩽20 dB nHL ( n = 103) ( P < 0.01–0.001). MLS BAER wave amplitudes were significantly smaller than in those ⩽20 dB nHL ( P < 0.05–0.001). However, no interpeak intervals differed significantly between the two groups of infants. V/I amplitude ratio was similar in the two groups. These findings were true of all click rates. Click rate-dependent changes in MLS BAER of the preterm infants with an elevated BAER threshold are generally similar to those with a normal threshold. Conclusions Brainstem auditory function does not closely correlate with peripheral auditory threshold at term in preterm infants. Elevation in peripheral threshold due to middle ear disorders does not significantly affect functional status of the auditory brainstem. Significance Short term peripheral conductive auditory abnormality does not significantly affect the immature central auditory function.

Effect of Needle Combination on the Analgesic Efficacy of the Tendinomuscular Meridians (TMM) System

Background: Tendinomuscular Meridians (TMM) are adopted as a treatment paradigm for studying the neuronal mechanisms of acupuncture analgesia in acute thermal pain. The effect of needle combination on analgesia and the corresponding neuronal mechanisms have yet to be fully delineated. Objective: To assess the role of different needle groups in the TMM treatment paradigms of acute pain by determining the peripheral thermal thresholds before and after electroacupuncture (EA) and the corresponding behavioral feedback of thermal pain stimulation and the De Qi sensation of EA. Design, Setting, and Participants: A prospective study of 13 individuals conducted at the University of California, San Diego Medical Center. Interventions: Participants' baseline thermal thresholds (cold, warm, cold and hot pain) were measured at premarked testing sites along the medial aspects of the bilateral lower extremities. Hot pain was delivered for 5 seconds to the testing sites and the corresponding pain visual analog scale (VA...

Development of Scotopic Visual Thresholds in Retinopathy of Prematurity

To test the hypothesis that the late-maturing parafoveal rod photoreceptors are more vulnerable than peripheral rods to the effects of retinopathy of prematurity (ROP). Twenty-four infants with a history of preterm birth (gestational age at birth </=31 weeks) participated in a longitudinal study: 12 had mild ROP that resolved without treatment, and 12 had never had ROP. Thresholds for detecting stimuli (2 degrees diameter, 50 ms duration) presented 10 degrees (parafoveal) and 30 degrees (peripheral) from a central fixation target were estimated by using a preferential-looking At each visit, thresholds at both sites were obtained in random order. Thresholds of the preterm subjects were compared with those of previously reported term infants. The course of threshold maturation in subjects with ROP was significantly prolonged (P </= 0.01) compared with those who had never had ROP and with term-born control subjects. On average, parafoveal thresholds in subjects with ROP reached the adult level at a median age of 12 (range, 6-18) months, and peripheral thresholds reached the adult level at 9 (range, 5-12) months. Median thresholds in subjects who had never had ROP reached adult levels at both sites by approximately 7 months. The slower development of parafoveal compared with peripheral thresholds in subjects with a history of ROP is evidence that the late-maturing parafoveal rods are more affected by the ROP disease process.

Contrast sensitivity loss in the peripheral visual field following laser in situ keratomileusis

We report a case of contrast sensitivity loss in the peripheral visual field following laser in situ keratomileusis (LASIK). A 50-year-old white man was referred to us for differences in visual perception in the peripheral field between the right eye, which had had LASIK, and the left eye, which was emmetropic. Linear meridional static perimetry was carried out in the 0- to 180-degree meridian using a Goldmann perimeter to assess the peripheral perimetric thresholds. There was a statistically significantly marked increased threshold in contrast sensitivity in the nasal and temporal fields from 40 degrees of eccentricity in the LASIK eye compared with that in the emmetropic eye. Eyes treated with LASIK may show higher peripheral thresholds than untreated eyes owing to poorer retinal image quality after LASIK surgery. Excimer laser surgeons should consider optical factors when post-LASIK patients complain of peripheral visual field symptoms.

Patterns of primary afferent depolarization of segmental and ascending intraspinal collaterals of single joint afferents in the cat

We have examined in the anesthetized cat the threshold changes produced by sensory and supraspinal stimuli on intraspinal collaterals of single afferents from the posterior articular nerve (PAN). Forty-eight fibers were tested in the L3 segment, in or close to Clarke's column, and 70 fibers in the L6-L7 segments within the intermediate zone. Of these, 15 pairs of L3 and L6-L7 collaterals were from the same afferent. Antidromically activated fibers had conduction velocities between 23 and 74 m/s and peripheral thresholds between 1.1 and 4.7 times the threshold of the most excitable fibers (xT), most of them below 3 xT. PAN afferents were strongly depolarized by stimulation of muscle afferents and by cutaneous afferents, as well as by stimulation of the bulbar reticular formation and the midline raphe nuclei. Stimulation of muscle nerves (posterior biceps and semitendinosus, quadriceps) produced a larger PAD (primary afferent depolarization) in the L6-L7 than in the L3 terminations. Group II were more effective than group I muscle afferents. As with group I muscle afferents, the PAD elicited in PAN afferents by stimulation of muscle nerves could be inhibited by conditioning stimulation of cutaneous afferents. Stimulation of the cutaneous sural and superficial peroneal nerves increased the threshold of few terminations (i.e., produced primary afferent hyperpolarization, PAH) and reduced the threshold of many others, particularly of those tested in the L6-L7 segments. Yet, there was a substantial number of terminals where these conditioning stimuli had minor or no effects. Autogenetic stimulation of the PAN with trains of pulses increased the intraspinal threshold in 46% and reduced the threshold in 26% of fibers tested in the L6-L7 segments (no tests were made with trains of pulses on fibers ending in L3). These observations indicate that PAN afferents have a rather small autogenetic PAD, particularly if this is compared with the effects of heterogenetic stimulation. Therefore, the depression of the PAN intraspinal fields produced by autogenetic stimulation described by Rudomin et al. (Exp Brain Res DOI 10.1007/s00221-006-0600-x, 2006) may be ascribed to other mechanisms besides a GABAa PAD. It is suggested that the small or no autogenetic PAD displayed by the examined joint afferents prevents presynaptic filtering of their synaptic actions and preserves the original information generated in the periphery. This could be important for proper adjustment of limb position.

Does peripheral auditory threshold correlate with brainstem auditory function at term in preterm infants?

Conclusion. Peripheral auditory threshold does not correlate with brainstem auditory function in preterm infants. Infants with peripheral auditory abnormality seem not to be necessarily more prone to brainstem auditory abnormality than those without the elevation, although further studies are needed in a larger number of subjects. Objective. To investigate whether peripheral auditory threshold correlates with brainstem auditory function in preterm infants and shed light on whether preterm infants with threshold elevation are prone to central auditory abnormality. Patients and methods. Brainstem auditory evoked response (BAER) was recorded with clicks at term in preterm infants (gestation 28–36 weeks). Analysis of correlation was made between BAER threshold and various BAER components. BAER data were compared between preterm infants with thresholds ≤20 dB nHL (n=113) and those >20 dB (n=32). Results. Although BAER threshold correlated significantly with BAER wave latencies and amplitudes, the threshold did not correlate significantly with I–V, I–III and III–V intervals. No significant differences were found between preterm infants with BAER thresholds ≤20 dB and those >20 dB in I–V, I–III intervals, although III–V was longer in the infants with thresholds >20 dB nHL (p<0.05).

Mechanisms of Somatosensory Neuronal Sensitivity to Alkaline pH

Life for most species is best in a very narrow range of pH. Departures of tissue pH from this narrow range are guarded against by various neural and physiological defense mechanisms. In the past few years, we have gained a much better understanding of what the sensory bases of the defenses against acid insults are. Specifically, several ion channels (TRPV1, Caterina et al., 1997; ASIC3, Waldmann et al., 1997; Ugawa, this issue) have been identified and cloned that respond to even moderately acidic pH. Less is known about the mechanisms monitoring tissue alkalinity. Although tissue acidity is the more common condition that is encountered in pathological situations, there are several conditions that give rise to alkaline tissue. Respiratory alkalosis due to hyperventilation, for instance gives rise to tingling in the extremities and lowered peripheral nerve thresholds (Tenny and Lamb, 1965; Mogyoros et al., 1997). Moreover, alkaline environmental insults to unprotected epithelium such as cornea and nasal mucosa give rise to behavioral defenses such as pain (Acosta et al., 2001) or apnea (Lindberg et al., 1987a) and the physiological defenses of vasodilatation (Izumi and Karita, 1993), tearing and increased mucociliary activity (Lindberg et al., 1987b). In the cranial region these defenses are mediated by the branches of the trigeminal nerve. Ammonia, for instance, activates fibers in the ethmoid branch of the trigeminal nerve (Sekizawa and Tsubone, 1994). To elucidate the mechanisms underlying trigeminal sensitivity to alkaline pH, responses of cultured rat trigeminal neurons to alkaline stimulation were measured using fluorescence imaging of intracellular calcium, [Ca]i (Kirifides et al., 2004) and intracellular pH (James-Kraacke, 1992). Using this approach, the influence of epithelial permeability barriers and potential stimulatory contributions of the epithelium were eliminated.

The application of chromatic dark-adapted kinetic perimetry to retinal diseases

Purpose To demonstrate the value of a 2-color perimetric procedure for determining cone and rod system contributions to the dark-adapted kinetic visual field (VF). Design Prospective evaluation of perimetric testing procedure. Participants Five patients with retinal diseases and 6 visually normal individuals. Methods Long- and short-wavelength stimuli were presented under dark-adapted conditions in a Goldmann perimeter. Visual fields were measured for the II and V test target sizes with a long-wavelength filter (cut-on at 600 nm) and a short-wavelength filter (cutoff at 510 nm). Light intensities through these filters were matched scotopically for the rod system by producing equal peripheral boundaries on 6 visually normal individuals. To validate the application of this procedure, we tested a patient with congenital achromatopsia and another patient with congenital stationary night blindness (CSNB). We then tested 2 patients with retinitis pigmentosa (RP) and 1 patient with Usher's syndrome to determine the cone and rod contributions to their VF isopters. Main outcome measures Isopters for long- and short-wavelength test stimuli, and the appearance of the test stimuli, whether reported as chromatic or achromatic. Results The patient with congenital achromatopsia showed superimposed isopters for the 2 stimuli, which were reported as achromatic, demonstrating that the peripheral field boundaries were rod mediated. The patient with CSNB showed an isopter in response to the long-wavelength stimulus that was considerably larger than that in response to the short-wavelength stimulus, both stimuli reported as chromatic, showing that the cone system determined peripheral thresholds for both stimuli. In 2 patients with RP, we observed a mixed pattern of cone or rod system detection of the chromatic stimuli. The peripheral isopters were rod mediated, whereas the cone system determined the central field isopters. In an Usher's syndrome patient, cones mediated both the peripheral and the central field isopters. Conclusions A 2-color dark-adapted Goldmann perimetric procedure was able to determine whether the VF isopters were rod or cone mediated in 5 patients with various forms of retinal disease.

What are the visual benefits of eyelid squinting?

We propose that eyelid squint can reduce the impact of several conditions known to cause eyestrain such as uncorrected refractive error, accommodative dysfunction, presbyopia, and glare. Clinicians commonly accept that squint improves visual acuity (VA) in the presence of refractive error, and even though the benefit of eyelid squint in bright light seems self-evident, data are not available to support either benefit. The purpose of this study was to measure the effect of eyelid squint on VA in the presence of refractive blur and on visual field sensitivity. Nineteen subjects with optimal refractive correction were tested, with and without squinting, as follows: (1) distance VA with induced refractive errors of +0.50, +1.00, +2.00, +3.00, +1.00 -1.00 x 90, and +1.00 -1.00 x 180; (2) near VA with induced refractive errors of -1.00 x 90 and -1.00 x 180; and (3) central and peripheral threshold visual fields with a Humphrey Field Analyzer. Differences in visual acuity between squinting and nonsquinting were tested for significance with repeated-measures analysis of variance, and differences in visual fields were tested using mixed model analysis of variance with repeated measures. Eyelid squint significantly improved (p < 00.016) distance VA measurements for 1.00 to 3.00 D of induced myopia. The squint-induced VA improvement increased from 0.06 logarithm of the minimum angle of resolution for 1.00 D to 0.24 logarithm of the minimum angle of resolution for 3.00 D of myopia. Eyelid squint also significantly reduced visual field sensitivity below the horizontal meridian by an average of 1.4 dB, by 1.6 dB on the horizontal meridian, and with increasing reductions in the vertical field up to 11.6 dB for measurements 40 degrees above fixation. This pattern of decreased superior field sensitivity would decrease visual discomfort from overhead glare. The results provide empirical support that eyelid squint improves visual acuity for subjects with refractive error and reduces glare in the superior visual field.

Neural changes in cat auditory cortex after a transient pure-tone trauma.

Here we present the changes in cortical activity occurring within a few hours after a 1-h exposure to a 120-dB SPL pure tone (5 or 6 kHz). The changes in primary auditory cortex of 16 ketamine-anesthetized cats were assessed by recording, with two 8-microelectrode arrays, from the same multiunit clusters before and after the trauma. The exposure resulted in a peripheral threshold increase that stabilized after a few hours to on average 40 dB in the frequency range of 6-32 kHz, as measured by the auditory brain stem response. The trauma induced a shift in characteristic frequency toward lower frequencies, an emergence of new responses, a broadening of the tuning curve, and an increase in the maximum of driven discharges. In addition, the onset response after the trauma was of shorter duration than before the trauma. The results suggest the involvement of both a decrease and an increase in inhibition. They are discussed in terms of changes in central inhibition and its implications for tonotopic map plasticity.

Clinical Implications in Perimetry After Photorefractive Keratectomy

Through refractive surgery, it is now possible to correct various ametropias using new techniques such as photorefractive keratectomy (PRK). We hypothesized that patients submitting to PRK show higher peripheral thresholds attributable to poorer retinal quality than normal patients. However, no difference were found when comparing glaucoma with PRK patients. Thus, early glaucoma following PRK may be masked by the previous surgery.

二硫化炭素中毒における経頭蓋超音波ドップラー所見と末梢感覚閾値

二硫化炭素中毒における経頭蓋超音波ドップラー所見と末梢感覚閾値

Aliasing for rapidly counterphasing stimuli: a failure to demonstrate an M-cell sampling limit to resolution.

We investigated whether resolution is sampling limited for stimuli optimized for detection by magnocellular mechanisms. We measured peripheral (15 degrees and 30 degrees) spatial detection and resolution thresholds using 50% and 90% contrast flicker-defined gratings (25 Hz) and 90% contrast counterphasing sinusoidal gratings (25 Hz). Direction-discrimination performance for 90% contrast counterphasing sinusoidal gratings (25 Hz) was measured foveally. Our results indicate that resolution of rapidly counterphasing stimuli is sampling limited in peripheral vision but is consistent with limiting of performance by parvocellular mechanisms. Also, undersampling may not be necessary to account for motion reversals observed with gratings that both drift and flicker.

Train duration effects on perception: sensory deficit, neglect, and cerebral lateralization.

The mechanisms of conscious perception are uncertain. In a preliminary study, dramatic effects of train duration on perception in a patient with right brain stroke were noted. In this study, the mechanisms of train duration on perception of peripheral somatosensory stimuli are examined. Subjects included healthy adults and patients with right brain infarctions. Train duration effects on perception were examined in relation to cerebral infarction, handedness, age, elevated peripheral threshold via bupivacaine, and impaired attention via diazepam or scopolamine. Perceptual thresholds to electrical pulses on the hand decreased as train duration increased, but only over the first several hundred milliseconds. Compared to controls, right brain stroke patients showed much greater lowering of threshold in the affected hand as train duration was extended. Age and bupivacaine elevated thresholds, but had little or no influence on train duration effects. Diazepam and scopolamine had no effect on thresholds. Thresholds were lower in the left than right hand of healthy dextral subjects, irrespective of age. Sinistral subjects had less left/right asymmetry. Increased train duration effect in patients is not explained by a primary elevation in threshold or by impaired vigilance. Lower perceptual thresholds in the left hand of healthy dextral subjects is consistent with right cerebral dominance for externally directed attention.

Maturation of cutaneous sensory neurons from normal and NGF-overexpressing mice.

In the rodent, cutaneous sensory neurons mature over the first two postnatal weeks, both in terms of their electrical properties and their responses to mechanical stimulation of the skin. To examine the coincidence of these events, intracellular recordings were made from neurons in the dorsal root ganglion (DRG) in an in vitro spinal cord, DRG, and skin preparation from mice between the ages of postnatal day 0 and 5 (P0-P5). We also examined mice in which nerve growth factor (NGF) is overexpressed in the skin. NGF has been shown to be involved in a number of aspects of sensory neuron development and function. Therefore we ask here whether excess target-derived NGF will alter the normal course of development, either of somal membrane properties, physiological response properties, or neuropeptide content. In wild-type mice, somal action potentials (APs) were heterogeneous, with some having simple, uninflected falling phases and some displaying an inflection or break on the falling limb. The proportion of neurons lacking an inflection increased with increasing age, as did mean conduction velocity. A variety of rapidly and slowly adapting responses could be obtained by gently probing the skin; however, due to relatively low thresholds and firing frequencies, as well as lack of mature peripheral receptors such as hairs, it was not possible to place afferents into the same categories as in the adult. No correlation was seen between the presence or absence of an inflection on the somal AP (a marker for high-threshold mechanoreceptors in adult animals) and either peripheral threshold or calcitonin-gene related peptide (CGRP) content. Small differences in the duration and amplitude of the somal AP were seen in the NGF-overexpressing mice that disappeared by P3-P5. Excess target-derived NGF did not alter physiological response properties or the types of neurons containing CGRP. The changes that did occur, including a loss of the normal relationship between AP duration and conduction velocity, and a decrease in mean conduction velocity in the inflected population, might best be explained by an increase in the relative proportions of myelinated nociceptors. Of greatest interest was the finding that in both NGF overexpressers and wild-type mice, the correlation between mechanical threshold and presence or absence of an inflection on the somal spike is not apparent by P5.

Foveal and peripheral thresholds for detection and resolution of vanishing optotype tumbling E’s

We measured detection and resolution acuity for vanishing optotype tumbling E stimuli in both the fovea and at 30° in the periphery to determine if peripheral resolution is sampling limited for this stimulus. In the fovea, where acuity is optically limited, detection and resolution were the same. At 30°, however, detection was markedly better than resolution indicating that peripheral resolution is sampling limited for this stimulus. Detection acuity was higher when contrast was 90% rather than 40%, but resolution did not change with contrast. The vanishing optotype is a legitimate perimetric stimulus to measure retinal ganglion cell density provided the task is resolution and not detection.

Recognition of band-pass filtered hand-written numerals in foveal and peripheral vision.

The purpose of the present study was to find out what differences between foveal and peripheral pattern recognition remain unexplained by the inhomogeneities of retinal sampling and the optics of the eye. We measured contrast thresholds for pattern recognition at different eccentricities. The effects of retinal sampling were homogenised by using M-scaling of the stimuli, and the effects of the optics of the eye were by-passed either by using strong external noise (signal-to-noise ratio is not affected by optical attenuation) or by computing retinal image contrast by means of the optical modulation transfer function. The stimuli were hand-written numerals filtered to two-octave bands of various centre object spatial frequencies (c/object). The results were described as contrast thresholds and recognition efficiency. At all eccentricities, lowest contrast thresholds and highest recognition efficiencies were found at medium object spatial frequencies. At high object spatial frequencies the peripheral retinal contrast thresholds and recognition efficiencies were nearly as good as at the fovea, but at low object spatial frequencies most of the data showed superiority of the fovea to the periphery. Therefore, at high object spatial frequencies peripheral recognition performance could be explained relatively well by the retinal sampling gradient, or equivalently by the cortical magnification factor, together with the effects of the optics of the eye. Some eccentricity dependent deterioration of recognition at low object spatial frequencies remained unexplained.

Vernier acuity with non-simultaneous targets: the cortical magnification factor estimated by psychophysics.

The eccentricity at which peripheral thresholds double their foveal value (E2) may relate to the visual system's anatomical organization. Using a variety of experimental approaches, previous estimates of E2 for vernier acuity have ranged from less than 0.1 deg to greater than 15.0 deg. This broad range of values seems to challenge the usefulness of E2 for determining visual topography. We explain that the varying contributions from at least two different regimes, spatial filter and local sign, may explain the broad range of E2 values found previously. We attempt to limit responses to the local sign regime, where it may be possible to determine the psychophysical analog to the gradient of the cortical spatial grain. In our experiments we measure how vernier task performance falls off with eccentricity. We hypothesize that if the vernier features are adequately separated in time, they will fall outside of the spatial filter's temporal integration span and the local sign regime would then predominate for precise positional processing. Using an interstimulus interval ranging from 20 to 200 msec between the two vernier features, we estimate that vernier thresholds in the local sign regime double at about 0.8 +/- 0.2 deg eccentricity, which is similar to anatomical estimates of the eccentricity at which the linear spacing of human cortical units doubles.

Diltiazem does not protect the ear from noise-induced hearing loss in mongolian gerbils.

Recent data suggest that diltiazem reduces noise-induced hearing loss. Our study was designed to replicate and extend the results of Maurer et al. by using the gerbil as a model. In experiment A, subjects received diltiazem (30 mg/kg/day intraperitoneally) or saline for 3 days. After peripheral thresholds were measured, each subject was exposed to a 4-kHz tone (90-dB sound pressure level) for 20 minutes. Similar amounts of temporary threshold shifts (ITS) were measured in the saline and diltiazem groups. In experiment B, subjects were given saline or diltiazem (30 mg/kg/day intraperitoneally) for 3 days and then exposed to an octave band of noise centered at 4 kHz for 5 days, during which time the subjects continued to receive the drug or saline. The TTS and permanent threshold shifts were similar in the two groups. Measures of cochlear nonlinearities also showed no effect of diltiazem, suggesting that diltiazem does not protect the ear from the effects of noise.