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Biomedical subjects

J M Wild

Publications and source records attributed to J M Wild.

At least 19 recordsLinked to original sources

MR imaging of the lungs with hyperpolarized helium-3 gas transported by air.

Hyperpolarized noble gas MRI shows promise in the functional imaging of the pulmonary air spaces. The production of hyperpolarized (HP) gas requires specialized laser optical pumping apparatus, which is not likely to be home built in the majority of clinical MRI radiology centres. There are two routes through which HP gas will be made available to hospitals for clinical use: either the apparatus will be installed locally at a considerable expense to the centre, or a central facility will produce the gas and then deliver it to remote MRI sites as and when required. In this study, the feasibility of transporting large quantities of HP gas for in vivo MR imaging from a remote production facility in Mainz, Germany, by airfreight to Sheffield, UK, was successfully demonstrated.

Air↗

Field-specific visual-evoked potentials: identifying field defects in vigabatrin-treated children.

OBJECTIVE: To derive a visual-evoked potential (VEP) technique for identifying visual field defects in children with epilepsy treated with vigabatrin and unable to perform perimetry. BACKGROUND: Studies have linked vigabatrin to a specific pattern of visual field loss. Few studies have included the pediatric population because of difficulties in assessing the visual field by perimetry below a developmental age of 9 years. METHODS: A field-specific VEP was developed with a central (0 degrees to 5 degrees radius) and peripheral stimulus (30 degrees to 60 degrees radius). Stimuli consisted of black and white checks that increased in size with eccentricity. Checks reversed at different rates, allowing separate central and peripheral responses to be recorded. Five vigabatrin-treated young adults with field defects were identified using this stimulus. Electroretinograms (ERG) were recorded to examine the effects of vigabatrin on retinal function. Thirty-nine children aged 3 to 15 years were included in the study. Twelve patients were examined by both the field-specific stimulus test and perimetry. The diagnostic performance of the field-specific stimulus test was compared with that of perimetry. RESULTS: Thirty-five of 39 children complied with the field-specific stimulus, 26 of 39 complied with the ERG, and 12 of 39 complied with perimetry. Using the summed amplitude of the peripheral response from O(2) and O(1), responses below 10 microV were deemed abnormal. The field-specific stimulus identified 3 of 4 abnormal perimetry results and 7 of 8 normal perimetry results, giving a sensitivity of 75% and a specificity of 87.5%. When comparing perimetry results with the ERG parameters, only the 30-Hz flicker amplitude, with a cutoff below 70 microV, gave a useful indication of visual field loss. CONCLUSION: Field-specific VEP are well tolerated by children older than 2 years of age and are sensitive and specific in identifying vigabatrin-associated peripheral field defects.

Anticonvulsants↗

Parvalbumin-positive projection neurons characterise the vocal premotor pathway in male, but not female, zebra finches.

Parvalbumin (PV) and calbindin (CB) immunoreactivities were assessed in nucleus robustus archistriatalis (RA) of male and female zebra finches, together with retrograde labelling of RA neurons. The results of double and triple labelling experiments suggested that, in males, moderately and faintly PV-positive neurons were projection neurons, but that all intensely PV-positive cells were not. The latter, which are presumably interneurons, were also intensely CB-positive, and may correspond to the GABAergic inhibitory interneurons identified by others. In addition, the complete RA pathway and its terminal fields in the respiratory-vocal nuclei of the brainstem were strongly PV-positive. In female zebra finches, which do not sing, no evidence was found that PV-positive RA cells were projection neurons, yet the pattern of projections of RA neurons, as determined by anterograde transport of biotinylated dextran amine, was very similar to that of RA in males. Moreover, in females, RA neurons retrogradely labelled from injections of cholera toxin B-chain into the tracheosyringeal nucleus (XIIts) were abundant and included, in the lateral part of the nucleus, a population of cells that were as large as those in the male RA. Parvalbumin immunoreactivity was also present in RA and its projections in males of several other songbird species (northern cardinal, brown headed cowbird, canary) and in the female cardinal, which sings to some extent, but the labelling was not as intense as that in male zebra finches.

Animals↗

Trigeminally innervated iron-containing structures in the beak of homing pigeons, and other birds.

The ophthalmic nerve in the upper beak was labelled with cholera toxin B-chain, and iron was identified using the Prussian Blue reaction. Iron deposits were found in the caudal part of the beak, and some were concentrated in cells that clustered in encapsulated structures densely innervated by ophthalmic nerve fibres. Such structures could form the anatomical basis of a type of mechanoreceptor that transmits magnetic sense information to the brain.

Animals↗

Short wavelength automated perimetry.

Short Wavelength Automated Perimetry (SWAP) utilizes a blue stimulus to preferentially stimulate the blue cones and a high luminance yellow background to adapt the green and red cones and to saturate, simultaneously, the activity of the rods. This review describes the theoretical aspects of SWAP, highlights current limitations associated with the technique and discusses potential clinical applications. Compared to white-on-white (W-W) perimetry, SWAP is limited clinically by: greater variability associated with the estimation of threshold, ocular media absorption, increased examination duration and an additional learning effect. Comparative studies of SWAP and W-W perimetry have generally been undertaken on small cohorts of patients. The conclusions are frequently unconvincing due to limitations for SWAP in the delineation of abnormality and of progressive field loss. SWAP is almost certainly able to identify glaucomatous visual field loss in advance of that by W-W perimetry although the incidence of progressive field loss is similar between the two techniques. Increasing evidence suggests that functional abnormality with SWAP is preceded by structural abnormality of the optic nerve head and/or the retinal nerve fibre layer. SWAP appears to be beneficial in the detection of diabetic macular oedema and possibly in some neuro-ophthalmic disorders.

Glaucoma↗

The influences of stimulus wavelength and eccentricity on short-wavelength pathway isolation in automated perimetry.

The aim of the study was to determine whether the suggested stimulus and background parameters employed in commercially available short-wavelength sensitive perimetry (SWAP) are clinically appropriate. Threshold versus intensity curves were measured using a modified Humphrey Field Analyser. The reduction in background luminance was achieved using aperture stops in order to avoid changes in the chromaticity of the background. Short-wavelength thresholds were determined for 440, 450 and 460 nm stimuli and were corrected for pre-receptoral absorption. Short-wavelength sensitive pathway isolation was approximately 1.5 log units and decreased with increases in eccentricity and in stimulus wavelength. It would seem that the use of a 450 nm narrowband stimulus filter would offer a compromise between both the physiological requirements and the physical properties of the stimulus. Such an approach would reduce some of the inherent between-subject normal variability associated with SWAP.

Adult↗

Tonotopic and somatotopic representation in the nucleus basalis of the barn owl, Tyto alba.

We have investigated the somatosensory and auditory representations in the nucleus basalis of the barn owl. In pigeons and finches, the nucleus basalis contains a representation of the beak and an auditory area. In the barn owl, the nucleus basalis also contains a complete somatotopic map of the head and body (as in the budgerigar), with a tonotopically organized auditory area in close proximity to the representation of the facial ruff and the preaural area. Recordings within and around the nucleus basalis revealed predominantly (about 80%) contralateral responses to somatic stimulation. The somatotopic map was oriented with the head down and rostral. Penetrations revealed an over-representation of the feet in dorsal basalis, followed by the rest of the body and wings more ventrally. Towards more rostral positions in nucleus basalis, responses from the head and beak predominated ventrally. The auditory response area was encountered below the region that responded to stimulation of the facial ruff and preaural flap regions and above a region responsive to beak stimulation. Auditory responses were tonotopically organized, with low best frequencies dorsal. Some penetrations yielded predominantly monaural responses with a fairly broad dynamic range, similar to those recorded from the ventral nucleus of the lateral lemniscus (LLV) and the cochlear nucleus angularis, whereas other penetrations contained predominantly binaural responses sensitive to interaural time differences (ITD). The physiological responses could be predicted on the basis of auditory projections to the nucleus basalis. An injection of biotinylated dextran amine (BDA) in the auditory region of nucleus basalis retrogradely labeled cells in both the caudal and rostral parts of the intermediate lateral lemniscal nucleus (LLIc and LLIr), and a few cells in the anterior part of the dorsal lateral lemniscal nucleus (LLDa, previously known as nucleus ventralis lemnisci lateralis, pars anterior, or VLVa) and in the posterior part of the dorsal lateral lemniscal nucleus (LLDp, previously known as nucleus ventralis lemnisci lateralis, pars posterior, or VLVp). A large injection of cholera toxin B-chain (CTB) into the nucleus basalis also produced dense retrograde labeling of a previously unidentified nucleus on the lateral aspect of the rostral pons, that we here call nucleus pontis externus (PE). An injection of CTB into PE produced dense retrograde labeling of the contralateral dorsal column nuclei and anterograde labeling of the ipsilateral lateral and dorsolateral nucleus basalis. Together these results define major somatosensory and auditory projections to the owl telencephalon that bypass the thalamus.

Afferent Pathways↗

Long-term fluctuation in short-wavelength automated perimetry in glaucoma suspects and glaucoma patients.

PURPOSE: To determine the magnitude of the homogeneous, LF(Ho), and the heterogeneous, LF(He), components of the long-term fluctuation (LF) in glaucoma suspects and in stable primary open angle glaucoma (POAG) patients undergoing short-wavelength automated perimetry (SWAP) and to compare the magnitude of the SWAP LF components with those elicited by standard white-on-white (W-W) perimetry. METHODS: The sample comprised 33 glaucoma suspects and 17 patients with early-to-moderate stable POAG who underwent W-W perimetry and SWAP at each of six visits over a mean period of 12.75 months (SD, 2.29). The LF(Ho), LF(He), and error components of the long-term fluctuation were determined between the third and seventh visual field examinations. The intervening visual field examinations and the optic nerve head parameters, derived both by stereo observation and by the Heidelberg Retinal Tomograph, were used to confirm stability over the follow-up period. RESULTS: The LF(Ho) and LF(He) components were larger in the POAG patients than in the glaucoma suspects for both W-W perimetry and SWAP; the magnitude was independent of the depth of defect and of the short-term fluctuation. All three components of long-term fluctuation were greater for SWAP than for W-W perimetry, both in the glaucoma suspects and in the POAG patients. CONCLUSIONS: SWAP exhibits greater long-term fluctuation than white-on-white perimetry. The usefulness of SWAP will be limited if the extent of this variability is not overcome in future statistical procedures developed to detect progressive visual field loss.

Adult↗

Separating the retinal electrophysiologic effects of vigabatrin: treatment versus field loss.

OBJECTIVE: To separate the retinal electrophysiologic markers associated with vigabatrin-attributed visual field loss (VGB-VFL) from those associated with current vigabatrin therapy. METHODS: A nonrandomly selected cohort of 8 previous and 18 current vigabatrin users and a reference cohort of 8 never vigabatrin-treated patients with epilepsy receiving other antiepilepsy drugs (AED) underwent electro-oculography (EOG), electroretinography (ERG), and automated static threshold perimetry. A cohort of 22 normal subjects underwent ERG. The validity of the retinal electrophysiologic variables to detect the presence and severity of VGB-VFL was assessed using receiver operator characteristic curves. RESULTS: Of 26 patients exposed to vigabatrin, 18 exhibited VGB-VFL. No patients receiving alternative AED showed this type of visual field abnormality. The presence and severity of VGB-VFL was significantly associated with the latency (implicit time) and amplitude of the ERG cone function. The amplitude of the cone flicker response was the strongest predictor of VGB-VFL and revealed a sensitivity of 100% at a specificity of 75%. The EOG, the photopic and scotopic ERG, and the latency of the ERG second oscillatory potential (OP2) were not significantly related to the presence of VGB-VFL. Vigabatrin therapy was significantly associated with the photopic amplitude, the scotopic a-wave latency, and the latency of OP2. CONCLUSION: In patients who cannot perform reliable perimetry, the cone-specific ERG flicker amplitude provides the best screening method for detecting VGB-VFL.

Adult↗

Neural pathways for bilateral vocal control in songbirds.

Ipsilateral and contralateral projections of nucleus robustus archistriatalis (RA), a telencephalic vocal premotor nucleus, to respiratory-vocal nuclei in the brainstem were defined in adult male Wasserschlager canaries, grey catbirds, and zebra finches, three songbird species that appear to differ in the degree of lateralized syringeal dominance. In all three species, ipsilateral projections of RA to the medulla included the tracheosyringeal part of the hypoglossal nucleus (XIIts), that innervates the syrinx, the bird's vocal organ, the suprahypoglossal area (SH), and two respiratory-related nuclei, retroambigualis (RAm) and parambigualis (PAm; Reinke and Wild [1998] J Comp Neurol 391:147-163). Projections of RA to the contralateral XIIts, SH and RAm, were substantial in canaries, which use the left side of the syrinx predominantly during singing; less pronounced in catbirds, which have no lateral dominance for song control; and least pronounced in zebra finches, in which there is a right-sided dominance for song control. There were no obvious differences in the number of crossed projections in birds injected in the left or right RA. Local sources of inputs to XIIts and RAm were defined anatomically in zebra finches and canaries. RAm, including neurons in close proximity to XIIts, was found to project to XIIts and the suprahypoglossal area bilaterally but predominantly ipsilaterally. RAm also had reciprocal connections with its contralateral homologue. These results suggest a pattern of connections between premotor and motor respiratory-vocal nuclei that may be involved in bilateral control of vocal output at medullary levels, a control that involves a high degree of coordination between vocal and respiratory structures on both sides of the body.

Animals↗

Rostral wulst in passerine birds. I. Origin, course, and terminations of an avian pyramidal tract.

An avian "pyramidal tract" was defined in zebra finches and green finches by making injections of neuronal tracers into the hyperstriatum accessorium (HA) of the rostral Wulst. Extratelencephalic projections of rostral HA traveled in the septomesencephalic tract (TSM) and gave rise to nuclear-specific terminal fields in the precerebellar medial spiriform nucleus of the posterior thalamus, the red nucleus in the mesencephalon, the medial pontine nucleus in the pons, and the subtrigeminal, external cuneate, cuneate, gracile, and inferior olivary nuclei in the medulla. Extensive but more diffuse terminal fields were also present in the stratum cellulare externum of the posterior hypothalamus, the central periaqueductal gray, the prerubral field, and the lateral and ventrolateral tegmentum of the pons and medulla. There was also a sparse projection to the dorsal thalamic nucleus intermedius ventralis anterior, which supplies the somatosensory input to the rostral Wulst, and distinct projections to the intercollicular region surrounding the central nucleus of the inferior colliculus, where they partly overlapped the projections of the dorsal column nuclei. Projections from HA to the cerebellum via the TSM are described separately. In the brainstem the ventral ramus of TSM was situated ventral to the medial lemniscus at the base of the brain, entered the spinal cord in the inner margin of the lateral funiculus, predominantly ipsilaterally, and terminated bilaterally but predominantly contralaterally in the medial part of the base of the dorsal horn of the upper six or seven cervical segments. After injections of tracers into putative targets, numerous retrogradely labeled cells were found in the rostral HA, predominantly ventrally. The results confirm the presence of a major descending fiber system in passerine birds that resembles in its brainstem course and several of its terminations the pyramidal tract of mammals. The reciprocal projections of HA with the hypothalamus suggest that rostral HA may also incorporate neuronal components that in mammals would be considered parts of prefrontal cortex.

Animals↗

A direct cerebrocerebellar projection in adult birds and rats.

The rostral Wulst of birds, like the somatosensory cortex of mammals, receives somatosensory information from the thalamus and projects to the brainstem and spinal cord via a pyramidal-like tract. Using anterograde and retrograde tract-tracers, we show here, in adult zebra finches, that the rostral Wulst also projects directly to the cerebellar cortex and deep nuclei. In the cortex, the cerebrocerebellar fibers resemble neither mossy nor climbing fibers, but more closely resemble the multilayer fibers shown to originate from the hypothalamus in mammals. We also show that a sparse projection to the cerebellum from the mammalian neocortex, originally thought to be lost during early development, is present in the adult rat. Although the functional implications of these results are obscure, they suggest a revision of the concept of the "cerebrocerebellar system", which is generally considered to involve a pontine relay.

Animals↗

Electro-oculography, electroretinography, visual evoked potentials, and multifocal electroretinography in patients with vigabatrin-attributed visual field constriction.

PURPOSE: Symptomatic visual field constriction thought to be associated with vigabatrin has been reported. The current study investigated the visual fields and visual electrophysiology of eight patients with known vigabatrin-attributed visual field loss, three of whom were reported previously. Six of the patients were no longer receiving vigabatrin. METHODS: The central and peripheral fields were examined with the Humphrey Visual Field Analyzer. Full visual electrophysiology, including flash electroretinography (ERG), pattern electroretinography, multifocal ERG using the VERIS system, electro-oculography, and flash and pattern visual evoked potentials, was undertaken. RESULTS: Seven patients showed marked visual field constriction with some sparing of the temporal visual field. The eighth exhibited concentric constriction. Most electrophysiological responses were usually just within normal limits; two patients had subnormal Arden electro-oculography indices; and one patient showed an abnormally delayed photopic b wave. However, five patients showed delayed 30-Hz flicker b waves, and seven patients showed delayed oscillatory potentials. Multifocal ERG showed abnormalities that sometimes correlated with the visual field appearance and confirmed that the deficit occurs at the retinal level. CONCLUSION: Marked visual field constriction appears to be associated with vigabatrin therapy. The field defects and some electrophysiological abnormalities persist when vigabatrin therapy is withdrawn.

Adult↗

N-acetylaspartate distribution in proton spectroscopic images of ischemic stroke: relationship to infarct appearance on T2-weighted magnetic resonance imaging.

BACKGROUND AND PURPOSE: It is generally considered that tissue that appears abnormal on T2 MRI is already infarcted and that any penumbra lies outside the T2-visible lesion. We investigated the distribution of infarcted tissue using proton spectroscopic MRI. METHODS: In patients with symptoms of acute hemispheric ischemic stroke, imaged within a maximum of 3 days of stroke, we explored the distribution of N:-acetylaspartate (NAA), a marker of intact neurons, within and around the abnormal (hyperintense) areas on T2-weighted MR images, using proton spectroscopic MRI. RESULTS: In 11 patients, imaged 24 to 72 hours after stroke onset, there was little evidence of damaged neurons (reduced NAA) beyond the margins of hyperintensity on the T2 image. However, within the abnormal T2 area, there were statistically significant differences in the amount of NAA (ie, the proportion of intact neurons) between areas that were obviously abnormal on T2 (very hyperintense) and those that were only slightly abnormal (slightly hyperintense). CONCLUSIONS: The extent and degree of hyperintensity of the T2-visible lesion directly reflect the amount of neuronal damage; lack of a T2-visible lesion would suggest predominantly intact neurons at the time of imaging. We hypothesize that once tissue damage has reached a critical (probably irreversible) level, the T2 image quickly becomes abnormal without any significant time lag between the pathological staging of the infarct and its visualization on T2. Further testing in a larger study with information on blood flow levels would be required to confirm this.

Acute Disease↗

The long-term fluctuation of the visual field in stable glaucoma.

PURPOSE: To determine, in stable glaucoma, the characteristics of the between-examination variability of the visual field recorded with the Humphrey Field Analyser (HFA; Humphrey Systems, Dublin, CA) using the homogeneous, LF(Ho), and heterogeneous, LF(He), components of the long-term fluctuation (LF), thereby providing a technique for separating progressive loss from fluctuation in sensitivity. METHODS: The LF components were calculated using a two-factor analysis of variance (ANOVA) with replications and were determined between each pair of three successive HFA program 30-2 fields for each patient from two groups, each containing 30 patients with primary open-angle glaucoma. The interval between examinations for the first group was 6 to 9 months and for the second group was 3 weeks. RESULTS: The group mean values for LF(Ho) ranged from 1.50 to 2.19 dB and for LF(He) from 1.70 to 2.05 dB. The average difference between examinations was within +/-0.35 dB for each component, and the 95% limits of agreement for the two groups, respectively, were +/- 2.31 and +/- 2.39 dB for the LF(Ho) and +/- 2.36 and +/- 2.09 dB for the LF(He). The estimate of the 90% confidence limit for the LF(Ho) was 3.30 dB and for the LF(He), 3.60 dB. Little relationship was present between the LF components and the modulus differences in mean deviation (MD), the corrected pattern SD (CPSD), or the mean MD, mean short-term fluctuation, and mean CPSD, of the two fields. CONCLUSIONS: Estimation of the LF components and of the corresponding confidence limits yields an expression of the normal between-examination variability of two consecutive fields that can be used as a reliability index. A value outside the confidence limits indicates the necessity for a confirmatory follow-up field.

Aged↗

Rostral wulst of passerine birds: II. Intratelencephalic projections to nuclei associated with the auditory and song systems.

We have previously shown that the hyperstriatum accessorium (HA) of the rostral wulst in zebra finches and green finches is the origin of a pyramidal-like tract with substantial projections to the brainstem and cervical spinal cord. Here, we show that the HA also is the origin of a set of intratelencephalic projections with terminal fields in the lateral part of the frontal neostriatum, the shell surrounding the lateral magnocellular nucleus of the anterior neostriatum, the lobus parolfactorius surrounding area X, the nucleus interface, auditory fields L1 and L3, the shelf underlying the high vocal center, the dorsolateral caudal neostriatum, the dorsocaudal part of the nucleus robustus archistriatalis, and the ventral archistriatum. The cells of origin of these projections are located predominantly laterally in the HA, close to and sometimes within the intercalated HA, which receives somatosensory projections from the dorsal thalamus. The specific implications of these findings for auditory and vocal function are unclear, but the apparent overlap of auditory and somatosensory inputs in several of these regions suggests the possibility of mechanisms for stimulus enhancement or depression, depending on the congruence of stimuli within a cell's "in-register" multiple receptive fields.

Animals↗

Trigeminal disynaptic circuit mediating corneal afferent input to M. depressor palpebrae inferioris motoneurons in the pigeon (Columba livia).

Corneal afferent projections to the trigeminal brainstem nuclear complex (TBNC) and associated structures, as determined by transganglionic transport of various tracers, were found to be predominantly concentrated in two distinct patches in the dorsolateral medulla at periobex levels. One was in the external cuneate nucleus, and the other was in the ventralmost part of the ophthalmic division of the TBNC. The projections of putative second-order neurons in these regions, as determined by injections of wheat germ agglutinin conjugated to horseradish peroxidase into the dorsolateral medulla, were found to include the dorsal trigeminal motor nucleus (Vd), which innervates the M. depressor palpebrae inferioris. Electrical stimulation of Vd, which elicited lower eyelid movements, was then used to guide injections of tracer into Vd, which retrogradely labeled clusters of neurons in the corneal afferent recipient regions of the dorsolateral medulla. The lower eyelid of pigeons, unlike the nictitating membrane and upper lid, does not appear to be appreciably involved in either reflex blinking in response to relatively mild stimulation of the cornea (e.g., air puff), or in eye closure during the saccade-like head movements associated with walking, or in eye closure during pecking; but in response to a stimulus that makes corneal contact, an upward movement of the lower lid follows descent of the nictitating membrane and upper lid as part of a defensive eye-closing mechanism. The anatomical results thus appear to define a dedicated disynaptic trigeminal sensorimotor circuit for the control of lower eyelid motility in response to mechanical or noxious stimuli of the cornea. Injections of tracers into the lower and upper eyelids labeled palpebral sensory afferents that terminated predominantly in maxillary and ophthalmic portions, respectively, of the dorsal horn of upper cervical spinal segments. These terminal fields were therefore largely separate from those of corneal afferents. There were no specific corneal afferent projections upon accessory abducens motoneurons that innervate the two muscles controlling the nictitating membrane.

Animals↗