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Biomedical subjects

P Dean

Publications and source records attributed to P Dean.

At least 19 recordsLinked to original sources
PubMed1995

Time estimation deficits in developmental dyslexia: evidence of cerebellar involvement.

In addition to their language-related difficulties, dyslexic children suffer problems in motor skill, balance, automatization and speeded performance. Given the recent evidence for cerebellar involvement in the acquisition of language fluency, these problems suggest cerebellar deficit. To test the hypothesis of cerebellar dysfunction in dyslexia, a time estimation task considered to be a sensitive index of cerebellar function was administered to matched groups of dyslexic and control children. The dyslexic children showed the predicted deficit on time estimation (among the most severe obtained in our research programme) but not on a control, loudness estimation, task. Cerebellar dysfunction, therefore, provides a parsimonious account of otherwise disparate data on deficits in dyslexia.

Acoustic Stimulation↗
PubMed1995

The dorsal midbrain anticonvulsant zone--I. Effects of locally administered excitatory amino acids or bicuculline on maximal electroshock seizures.

Microinjections of bicuculline methiodide into the dorsal midbrain anticonvulsant zone, a region which includes the caudal deep layers of the superior colliculus, the adjacent mesencephalic reticular formation and the intercollicular nucleus, suppress tonic hindlimb extension induced by maximal electroshock. The purpose of the present experiments was to establish the most effective and convenient method for eliciting anticonvulsant properties from the dorsal midbrain using the electroshock model of epilepsy. A comparison of different injections of excitatory amino acids and bicuculline into the dorsal midbrain of the rat showed: (i) injections of kainate suppressed hindlimb extension but only at substantially larger doses (i.e. 200-400 pmol) than 50 pmol of bicuculline, which produced generally superior effects; (ii) quisqualate provided only weak protection against tonic seizures at doses that produced neurotoxic effects (2-40 nmol); (iii) N-methyl-D-aspartate was ineffective at doses which produced mild clonic seizure in their own right (2-4 nmol) and also produced some evidence of neurotoxicity; (iv) the suppression of hindlimb extension by bicuculline was dose related, and the lowest bilateral dose for producing reliable suppression was 50 pmol/400 nl per side; and (v) a unilateral injection of 100 pmol/400 nl also reliably suppressed hindlimb extension. The latter finding had important implications for the design and interpretation of the following lesion study. Injections of bicuculline into the dorsal midbrain also produced defence-like behavioural responses that included running and biting; the intensity of these responses correlated with the suppression of hindlimb extension.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

The dorsal midbrain anticonvulsant zone--II. Efferent connections revealed by the anterograde transport of wheatgerm agglutinin-horseradish peroxidase from injections centred on the intercollicular area in the rat.

Activation of the dorsal midbrain has a powerful anticonvulsant effect in the maximal electroshock model of epilepsy. The suppression of tonic seizures can be obtained most reliably from an area centred on the intercollicular nucleus overlapping into the deep layers of the superior colliculus and adjacent mesencephalic reticular formation. As part of a series of investigations to identify neural mechanisms responsible for mediating the anticonvulsant properties of the dorsal midbrain, the present study provides an anatomical description of the efferent projections of this region. Small amounts of wheatgerm agglutinin-horseradish peroxidase (10-30 nl of a 1% solution) were injected into the intercollicular nucleus and surrounding tissue. The resulting anterograde transport of the tracer was plotted on a set of standard atlas sections. Four major output pathways were identified: (i) an ipsilateral descending projection which had terminations in the microcellular tegmental nucleus, lateral and ventral pontine reticular nucleus pars oralis, ventrolateral tegmental nucleus, ventral and caudal pontine reticular nucleus pars caudalis, raphe magnus nucleus and the gigantocellular nucleus; (ii) a contralateral descending projection which for the most part targeted the same brainstem structures but with weaker terminal labelling; (iii) a projection to the contralateral dorsal midbrain with comparatively weak terminal label in the contralateral superior colliculus, intercollicular nucleus, periaqueductal gray, mesencephalic reticular formation and cuneiform area; (iv) ipsilateral ascending pathway with terminations in the red nucleus, zona incerta, peripeduncular area, parafascicular nucleus, lateral hypothalamus, parts of the pretectum and caudal thalamus. At a general level the dorsal midbrain anticonvulsant zone shares its major output projections and efferent targets with at least one of its near neighbours, including the superior colliculus, periaqueductal gray, the cuneiform nucleus and pedunculopontine nucleus. The possibility that anticonvulsant properties of the intercollicular area can simply be attributed to a unique set of efferent projections is therefore not supported by the anatomy.

Animals↗
PubMed1995

The dorsal midbrain anticonvulsant zone--III. Effects of efferent pathway transections on suppression of electroshock seizures and defence-like reactions produced by local injections of bicuculline.

Having provided an anatomical description of the efferent projections of the dorsal midbrain anticonvulsant zone [Shehab S. et al. (1995) Neuroscience 65, 681-695], our purpose in the present study was to establish which outputs from this region are responsible for mediating the anticonvulsant and behavioural properties of dorsal midbrain activation. The ability of unilateral injections of bicuculline into the dorsal midbrain anticonvulsant zone to suppress tonic hindlimb extension in the electroshock model of epilepsy was tested before and after three different knife cuts: (i) a transection of ipsilateral descending projections on the same side as the injection of bicuculline; (ii) an identical cut except it was placed contralateral to the injection; (iii) a cut which transected rostral projecting fibres from the dorsal midbrain anticonvulsant zone including most ipsilateral ascending and crossed descending projections. A fourth group of operated control animals was included to establish a baseline for the schedule of repeated testing. Qualitative observations of behaviour were taken immediately prior to administration of the electroshocks. Unilateral transection of ipsilateral descending efferents prevented the suppression of electroshock-induced hindlimb extension by injections of bicuculline into the dorsal midbrain anticonvulsant zone on the same side of the brain. Both the control cuts on the opposite side of the brain and the rostral cuts were ineffective. Transection of the ipsilateral descending projection on the same side as the injection of bicuculline also reduced the incidence of defensive reactions induced by the GABA antagonist, including explosive motor behaviour, oral attack and vocalization. Damage to this projection on the opposite side had little effect on the expression of behavioural reactions, neither did transection of the ascending efferents. These data suggest that ipsilateral descending efferents are critical for the suppression of electroshock-induced extension of the hindlimbs and the expression of defensive reactions elicited by activation of the dorsal midbrain.

Animals↗
PubMed1995

Modelling the role of the cerebellar fastigial nuclei in producing accurate saccades: the importance of burst timing.

Clinical and experimental data indicate that damage to the cerebellar vermis results in permanent loss of saccadic accuracy. Models of saccade production therefore need to provide a role for the cerebellum. It has been proposed that the vermis adjusts the gain of the saccadic internal feedback loop in response to information about the amplitude of the intended saccade. A model of how the fastigial nuclei (through which vermal output is channelled) influence brainstem saccadic circuitry to achieve this effect was constructed in three stages. (1) The brainstem was represented by a version of Robinson's internal feedback model, which relates excitatory burst neuron discharge to horizontal saccade dynamics. (2) The original model was lesioned to simulate the effects of bilateral inactivation of the fastigial nuclei, namely slow hypermetric saccades. This required reducing the synaptic weight of the internal feedback pathway, and lowering the gain of the excitatory burst neurons. The resultant brainstem-only model served as a preparation for testing the effects of neuronal discharge patterns within the fastigial nuclei. (3) These discharge patterns were simulated using measurements from recent electrophysiological studies. It was found that saccadic accuracy and normal dynamics were restored in the model if the simulated burst from neurons in the contralateral fastigial nucleus were subtracted from the feedback signal (i.e. added to the command signal) early in the saccade, and the burst from neurons in the ipsilateral fastigial nucleus were added to the feedback signal later in the saccade. This pattern corresponds to the observed timing of neuronal bursts in the fastigial nuclei, and accounts qualitatively for the effects of unilateral stimulation and inactivation of both the fastigial nuclei and the cerebellar vermis. This method of producing accurate saccades also contributes to time optimal control, by increasing both saccadic acceleration and deceleration. Appropriate timing of burst onset and duration in the fastigial nuclei is essential for these roles. Evidence concerning the effects of cerebellar damage on fast movements of other parts of the body suggests that the cerebellum may use similar strategies for controlling a wide range of simple movements.

Brain Stem↗
PubMed1994

Opposing excitatory and inhibitory influences from the cerebellum and basal ganglia converge on the superior colliculus: an electrophysiological investigation in the rat.

We recently showed (Westby et al., Eur. J. Neurosci., 5, 1378-1388, 1993) that the cerebellar interpositus nucleus is a source of excitatory drive for a population of spontaneously active neurons in the lateral intermediate layers of the contralateral superior colliculus. Anatomical and physiological studies have shown that this region of the colliculus contains cells of origin of the crossed descending tectoreticulospinal tract and receives GABAergic input from the ipsilateral basal ganglia. In the present study we tested the hypothesis that the same neurons receiving excitatory drive from the cerebellum also receive tonic inhibitory input from the substantia nigra pars reticulata. From a sample of 73 spontaneously active collicular cells we found that in 53% the firing rate was suppressed by GABA microinjection into the contralateral deep cerebellar nuclei; a further 15% showed a frequency increase. Of the collicular cells identified as receiving excitatory cerebellar input, 85% were found to be disinhibited by nigral GABA microinjection. The remainder were all inhibited by nigral GABA. These data show that the main excitatory influence from the cerebellum and the main inhibitory influence from the substantia nigra converge on at least one population of spontaneously active cells in the lateral intermediate layers of the superior colliculus. This finding is discussed in relation to the possible function of these spontaneous cells in movement control and nociception.

Animals↗
PubMed1994

A visual programming environment for bioprocess control.

The paper introduces the use of a visual programming environment (LabVIEW) to program custom control functions for bioprocess research. The time taken for a bioprocess scientist to program new functions compared well with typical times expected for experienced programmers using conventional languages. Experienced LabVIEW programmers will develop applications significantly faster. The package described was flexible, easy to use and was ideally suited to developing new applications for control of bioprocesses. It was demonstrated with the development of a system to control specific growth rate in a fed-batch culture.

Recombinant Proteins↗
PubMed1994

Mood-lowering effect of tryptophan depletion. Enhanced susceptibility in young men at genetic risk for major affective disorders.

METHODS: A double-blind placebo-controlled cross-over study in which plasma tryptophan was manipulated by administration of a tryptophan-deficient amino acid mixture. In the placebo condition, all subjects received a nutritionally balanced amino acid mixture that contained tryptophan. To further standardize baseline amino acids, each subject was provided with a low-protein diet the day before amino acid challenges. Subjects were euthymic, healthy men aged 18 to 30 years with either a multigenerational family history of affective illness or no family history of psychiatric illness in the present or in the two previous generations. Each subject was screened with a structured clinical interview to rule out a personal history of psychiatric illness. RESULTS: Plasma tryptophan was reduced by 89% 5 hours after the administration of the tryptophan-deficient amino acid mixture. Six of 20 subjects with a family history of affective illness and none of 19 subjects without a family history of psychiatric illness showed a lowering of mood of 10 or more points on the Profile of Mood States depression scale (P = .012, Fisher's Exact Test) 5 hours after tryptophan depletion. No significant mood changes were observed following the control treatment (balanced amino acid mixture) in either group. CONCLUSIONS: Our data support the hypothesis that subjects with no prior depressive episodes but with a multigenerational family history of major affective disorder show a greater reduction in mood after tryptophan depletion. They are also consistent with theories that implicate deficient serotonergic function as one possible etiological factor in major depressive disorders.

Adolescent↗
PubMed1994

Grids for kids: the pediatric patient undergoing invasive extraoperative EEG monitoring.

Surgical intervention is an acceptable treatment modality for children with intractable epilepsy. However, many children require a complicated evaluation process that involves placement of intracranial electrodes for purpose of extraoperative recording. The management of the child undergoing extraoperative electroencephalography (EEG) monitoring requires active participation by the nursing staff. An understanding of the electrode placement and functional mapping, proper preparation of the child and family and early detection of complications by nursing staff members is necessary to ensure a successful and safe evaluation.

Cerebral Cortex↗
PubMed1993

Comparative evidence indicating neural specialization for predatory behaviour in mammals.

The evolution of cognitive and sensory specializations must involve concomitant modifications of neural substrates. Ecological correlates of species differences in brain structure are intriguing sources of evidence about such evolutionary specialization but, to date, these have been identified only for gross parameters, such as overall brain size and the size of major brain regions. Here we show that a behavioural specialization in mammals, predation, is associated with species differences in the fine structure of a single neural pathway, the tectospinal tract. Both the relative number of neurons in this pathway and the relative size of their cell bodies were greater in more predatory species than in their less predatory counterparts within each of four separate mammalian orders. Expansion of these analyses to consider comparisons between taxa at a variety of taxonomic levels gave further support to the idea of a relation between predatory habits and the evolution of the tectospinal tract. In addition, within the primates, the number of neurons in the tectospinal tract was significantly correlated with the proportion of prey in the diet. These results therefore appear to provide an example of correlated evolution between a specific neural system and behaviour which applies generally within the mammals. They also help to unify findings from physiological and anatomical studies on a wider range of vertebrate taxa, including reptiles and amphibians.

Adaptation, Physiological↗
PubMed1993

Excitatory drive from deep cerebellar neurons to the superior colliculus in the rat: an electrophysiological mapping study.

The cerebello-tectal projection arising from the interpositus nucleus was investigated electrophysiologically to test the hypothesis that the deep cerebellar nuclei constitute a source of tonic excitation in the superior colliculus. A total of 117 spontaneously active collicular neurons were recorded during GABA microinjection into 26 interpositus sites, where tonic single-cell deep cerebellar activity was also simultaneously recorded. GABA injection always led to suppression of interpositus activity, while in the colliculus a clear pattern of results emerged. 58% of superior colliculus cells showed no response to suppression of interpositus activity, 35% showed a frequency decrease and 7% showed a frequency increase. The majority of these responsive cells were found in a laterally located sheet of cells mainly restricted to the intermediate white layer, in close register with the known cells of origin of the predorsal bundle and completely overlapping the terminals of the nigrotectal pathway originating in dorsolateral substantia nigra pars reticulata. The implications of these results for cooperative theories of head movement control involving the superior colliculus, cerebellum and precerebellar nuclei are discussed.

Afferent Pathways↗
PubMed1992

Epistaxis in two horses with dacryohemorrhea.

Unilateral epistaxis in 2 horses was caused by inflammation of the distal portion of the lacrimal system. The origin of epistaxis was identified during physical examination by observing hemorrhage emanating from the nasal opening of the nasolacrimal duct. Dacryohemorrhea caused by bacterial infection was successfully treated with antibacterial drugs administered systemically and instilled into the lacrimal system.

Animals↗
PubMed1992

Regional expression of fos-like immunoreactivity following seizures induced by pentylenetetrazole and maximal electroshock.

The expression of fos-like immunoreactivity (FLI) has been used widely as a marker of neural activation following the induction of seizures in several experimental models of epilepsy. The purpose of the present study was to provide a more detailed regional analysis of FLI expression following the induction of seizures by maximal electroshock (MES) and pentylenetetrazole (PTZ). Tonic-clonic seizures, matched for duration, were induced by MES applied by earclips (40 mA, 1 s) and intraperitoneal injections of PTZ (60 mg/kg); tonic hindlimb extension was present only after MES. Two hours after the induction of seizures brain tissue was processed for FLI. High levels of FLI were induced by both convulsion-inducing processes in a range of structures, including the dentate gyrus, the caudal amygdala, parts of the cerebral cortex, the bed nucleus of stria terminalis, various thalamic nuclei, the lateral parabranchial nucleus, and the nucleus of the solitary tract. In other structures, such as the medial and rostral amygdala, the ventromedial hypothalamic nucleus, the peripeduncular area, the central gray, and parts of the pretectum and superior colliculus, significantly greater FLI was induced by MES. Only in relatively few structures, such as the reticular thalamic nucleus and arcuate nucleus of the hypothalamus, did PTZ cause a much larger expression of FLI than MES. Insofar as the c-fos technique reflects neuronal activation, the present data reveal potentially important differences in the circuitry underlying the seizures induced in two major experimental models of epilepsy.

Animals↗
PubMed1992

Anticonvulsant role of nigrotectal projection in the maximal electroshock model of epilepsy--I. Mapping of dorsal midbrain with bicuculline.

Previous work has indicated that the anticonvulsant effect of nigral inactivation on the maximal electroshock model of generalized seizures is mediated by the projection from substantia nigra to superior colliculus. In accordance with this idea, and with the GABAergic nature of the nigrotectal pathway, microinjections of the GABAA antagonist bicuculline methiodide into the superior colliculus have been reported to block tonic hindlimb extension induced by maximal electroshock. To characterize the relevant circuitry more precisely, the present study sought to determine which region of the superior colliculus was important for the anticonvulsant effect of bicuculline by systematic mapping in the rat. Bilateral injections of bicuculline methiodide (50 pmol in 400 nl/side) were most effective in the caudal deep layers of the superior colliculus and adjoining midbrain reticular formation. These results suggest that the well-known projection from substantia nigra pars reticulata to the superior colliculus may not be involved in the anticonvulsant effect of nigral inactivation in the electroshock model, because this pathway terminates primarily in the intermediate layers of the superior colliculus throughout its rostrocaudal extent. Instead, some other pathway from ventral midbrain to a dorsal midbrain anticonvulsant zone appears to be part of the brain's anticonvulsant circuitry. The following paper [Redgrave et al. (1991) Neuroscience 46, 391-406] describes an anatomical study to characterize this pathway.

Animals↗
PubMed1992

Anticonvulsant role of nigrotectal projection in the maximal electroshock model of epilepsy--II. Pathways from substantia nigra pars lateralis and adjacent peripeduncular area to the dorsal midbrain.

Lesion evidence suggests that the superior colliculus is essential for mediating the anticonvulsant properties of nigral suppression in the electroshock model of epilepsy. However, our companion paper [Redgrave et al. (1991) Neuroscience 46, 379-390] established that the region of dorsal midbrain where bicuculline was most effective in suppressing tonic hindlimb extension did not correspond well with the known distribution of nigrotectal terminals. The purpose of the present anatomical study was, therefore, to investigate in more detail ventral midbrain connections to the dorsal midbrain anticonvulsant zone in rat. Small injections (10-20 nl) of a 1% solution of wheatgerm agglutinin conjugated with horseradish peroxidase were made specifically into the region of dorsal midbrain where bicuculline was maximally effective. Numerous retrogradely labelled cells were found in substantia nigra pars lateralis and adjacent peripeduncular area but not in substantia nigra pars reticulata. Retrogradely labelled cells were also located in ventral zona incerta. When wheatgerm agglutinin-horseradish peroxidase injections were made into lateral substantia nigra, a region of anterogradely transported reaction product characteristic of nerve terminals was observed in the caudolateral deep layers and underlying reticular tissue; this area corresponded well to the dorsal midbrain anticonvulsant zone. These data suggest that, in the electroshock model of epilepsy, direct connections between substantia nigra pars lateralis and adjacent peripeduncular area and the dorsal midbrain anticonvulsant zone could be critical for mediating the anticonvulsant properties previously attributed to substantia nigra pars reticulata. During the course of this study, anterograde projections from substantia nigra pars lateralis and adjacent peripeduncular area to both superficial and intermediate layers of the ipsilateral superior colliculus were noted. Additional experiments using retrograde transport of the fluorescent tracer Fast Blue confirmed these projections.

Amidines↗
PubMed1992

Topographical organization of the nigrotectal projection in rat: evidence for segregated channels.

Recent evidence suggests that projections from the superior colliculus to the brainstem in rat are organized into a series of anatomically segregated output channels. To understand how collicular function may be modified by the basal ganglia it is important to know whether particular output modules of the superior colliculus can be selectively influenced by input from substantia nigra. The purpose of the present study was, therefore, to examine in more detail topography within the nigrotectal system in the rat. Small injections (10-50 nl) of a 1% solution of wheatgerm agglutinin conjugated with horseradish peroxidase were made at different locations within substantia nigra and surrounding structures. A discontinuous puff-like pattern of anterogradely transported label was found in medial and caudal parts of the ipsilateral intermediate layers of the superior colliculus. In contrast, the rostrolateral enlargement of the intermediate layers contained a greater density of more evenly distributed terminal label. Injection sites associated with this dense pattern of laterally located label were concentrated in lateral pars reticulata, while the puff-like pattern was produced by injections into ventromedial pars reticulata. Retrograde tracing experiments with the fluorescent dyes True Blue and Fast Blue revealed that injections involving the rostrolateral intermediate layers were consistently associated with a restricted column of labelled cells in the dorsolateral part of ipsilateral pars reticulata. Comparable injections into medial and caudal regions of the superior colliculus produced retrograde labelling in ventral and medial parts of the rostral two-thirds of pars reticulata. Both anterograde and retrograde tracing data indicated that contralateral nigrotectal projections arise from cells located in ventral and medial pars reticulata. The present results suggest that the main ipsilateral projection from substantia nigra pars reticulata to the superior colliculus comprises two main components characterized by regionally segregated populations of output cells and spatially separated zones of termination. Of particular interest is the apparent close alignment between terminal zones of the nigrotectal channels and previously defined populations of crossed descending output cells in the superior colliculus. Thus, the rostrolateral intermediate layers contain a concentration of terminals specifically from dorsolateral pars reticulata and output cells which project to the contralateral caudal medulla and spinal cord. Conversely, the medial and caudal intermediate layers receive terminals from ventral and medial pars reticulata and contain cells which project specifically to contralateral regions of the paramedian pontine and medullary reticular formation.(ABSTRACT TRUNCATED AT 400 WORDS)

Amidines↗