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Biomedical subjects

B Rydenhag

Publications and source records attributed to B Rydenhag.

At least 37 records · Page 2Linked to original sources

Dendritic morphology in epileptogenic cortex from TRPE patients, revealed by intracellular Lucifer Yellow microinjection and confocal laser scanning microscopy.

Biopsy material was obtained from cortical epileptogenic zones (eight temporal, one occipital, one parietal and one frontal) of eleven patients aged 1.5-47 years with therapy-resistant partial epilepsy (TRPE) undergoing epilepsy surgery. Control autopsy material (two temporal, two occipital, one parietal and one frontal) was removed from six neurologically healthy cases within 6-10 hours postmortem delay. In each specimen, 100-300 pyramidal and non-pyramidal neurons were visualized by intracellular Lucifer Yellow microinjection. Single neurons were imaged using CLSM generated serial optical sections; 2-D reconstruction of each neuron was made using z-projection of serial optical images, and 3-D reconstructions and rotations were computerized. Neuronal maps from TRPE biopsies, compared to control autopsies, show markedly increased numbers of dendritic abnormalities of single pyramidal and non-pyramidal neurons in layers I, II-III, V-VII, and in the subcortical white matter. The abnormalities include: (1) increased number of non-pyramidal cells in layer I; (2) many pyramidal cells with two or three dendrites originating apically, rather than one single apical dendrite, in layers II-III; (3) atypical orientation of oblique apical and basal dendrites in pyramidal neurons of layers II-VII; (4) increased number of atypical 'dinosaur-like' and fusiform cells in layers V-VII; (5) numerous neurons in the white matter. These abnormalities may be etiological in cases with early onset, and predisposing in cases with late onset.

Adolescent↗

The effects of epilepsy surgery on the sensorimotor function of children.

The motor and sensory functions of 50 children were investigated before and six months after epilepsy surgery; 34 infants were assessed 24 months after surgery. Postoperatively, 20 children were seizure-free and 22 had a significant reduction of seizures. Epilepsy surgery was found to be an effective mode of treatment for intractable seizures in childhood, even in multiply handicapped individuals. Motor and sensory functions did not deteriorate after surgery; in fact, significant improvements were found in more than half of the children, including those with multiple handicaps. Improvements were most obvious in the seizure-free group, but were also noted in those with reduced seizure frequency. The younger children benefited more from surgery as regards sensorimotor function than did older children and adolescents.

Adolescent↗

Alterations in cortical visual evoked response following ethanol feeding in adult rats.

A study was performed on the visual-evoked response (VER) in adult rats that were given an ethanol containing liquid diet for 2 months and examined directly after the exposure period or subjected to a gradual decrease in ethanol over 3 days and total abstinence for 1 week. Control rats showed a first negative peak (N1) directly following the first positive peak (P1). In ethanol-exposed rats examined without withdrawal, the VER showed an increase in onset latency and a marked distorsion of the N1 region. The existing N1 potential was very sensitive to high-frequency stimulation. The alterations were partly normalized 1 week after withdrawal. There was no increase in latency to onset of the response or to P1. There remained an increase of latency and a reduced relative amplitude upon high-frequency stimulation of the N1 peak in ethanol-exposed rats compared with controls. The mechanisms underlying the changes in the cortical potentials are not clear, but they may be related to the cholinergic, glutamatergic/NMDA and/or noradrenergic cortical systems. The lack of persistent changes in onset and P1 latency may be related to the circumstance that the retinogeniculate impulses are transmitted over glutamatergic kainate receptors, which are relatively resistant to ethanol.

Alcoholic Intoxication↗

Thalamic nociceptive mechanisms in cats, influenced by central conditioning stimuli.

Field potentials and single cell activity evoked by tooth pulp (TP) stimulation were studied in the ventrobasal (VB) complex of the cat. The experiments were performed using a conditioning-test paradigm. Evoked cell activity or field potentials following TP stimulation was used as a test. Conditioning stimulus was given to different regions of the thalamic central lateral nucleus (CL). Conditioning electrical stimulation in medial (ML 2.8-3.6 mm) parts of CL induced a depression of the TP evoked response in 10 cells. Stimulation sites in lateral CL (ML 3.6-4.2 mm) induced facilitation in eight cells and decreased activity in seven cells. Tooth pulp evoked field potentials in thalamus were facilitated by a preceding stimulation in lateral CL. Cells in the lateral parts of CL are suggested to induce an increased activity in cells in the VB complex which mediate nociceptive information. This effect is suggested to be mediated via a CL induced disinhibition at a reticular thalamic (RE) or at a VB complex level. The medial parts of CL seem to give a traditional feedback inhibition on VB cells. Such an effect is also suggested to be mediated via the RE complex. The importance of these findings are discussed with relation to changes in the thalamus that may occur following long lasting nociceptive stimulation.

Animals↗

Properties of single neurons in the cat midsuprasylvian gyrus.

Responses of cells in the midsuprasylvian gyrus (MSSG) of cats were investigated following electrical stimulation of the central lateral nucleus (CL) of the thalamus and tooth pulp, low-threshold cutaneous or visual afferents. Electrical stimulation in CL induced excitation in many cells located in cortical areas 5 and 7. Cells in these areas also received input from somato-sensory and visual afferents. Cells in MSSG showed a wide convergence from tooth pulp, low-threshold cutaneous afferents and from the CL. The majority of wide convergent cells in area 5 were found in layers IV and V, while cells excited by CL and tooth pulp were found in layers II and III. Similarities were found between CL and tooth pulp evoked responses with regard to the excitation-inhibition pattern. The excitation evoked from CL and tooth pulp was less often followed by a hyperpolarizing potential compared to that seen after low-threshold lip, paw and visual afferent stimulation. Stimulation sites in the lateral parts of CL-evoked responses with the shortest latencies in area 5. In this part of the cortex, short latency synaptic potentials were found in cells in superficial layers. In the same area, synaptic potentials of short latency were also evoked by electrical stimulation of tooth pulp, lip and paw. Light-flash stimulation evoked responses with the shortest latencies in area 7. The results of this study demonstrate that putative nociceptive information reaches the parietal association cortex and that part of this input may be relayed via CL. We suggest that the excitatory influences of nociceptive and CL stimulation is related to behavioral arousal and attention mechanisms.

Afferent Pathways↗

Sympathetic activity influences the vascular axon reflex in the skin.

The interaction between changes of skin blood flow evoked by centrally mediated reflexes and local axon reflexes was studied in healthy subjects. Axon reflexes were evoked on the dorsum of the hand by transcutaneous electrical stimulation and reflex changes of blood flow by changes of ambient temperature, deep breath and emotional changes of blood flow by changes of ambient temperature, deep breath and emotional stress. Skin blood flow was measured by two laser-Doppler flowmeters, the probes of which were situated 6-8 mm from the stimulating electrode (monitoring net flow responses) and several centimetres away (monitoring generalized reflex responses only). The axon reflex responses were markedly diminished by body cooling but did not change during body warming. In warm subjects, a deep breath and emotional stress caused transient reductions of the flow response evoked by the electrical stimulation. Regional anaesthesia of the nerve(s) innervating the stimulated skin area led to marked increases of axon reflex responses in cold subjects, but no changes occurred in warm subjects. The anaesthesia also eliminated the transient flow reductions evoked by deep breaths and emotional stress. Since the applied stimuli are known to change skin sympathetic activity, it is concluded that sympathetic (presumably vasoconstrictor) impulses destined for the skin may reduce axon reflex responses.

Adult↗

Projection from the thalamic intralaminar nuclei on the isocortex of the rat: a surface potential study.

Cortical surface potentials evoked from thalamic intralaminar nuclei have been studied in rats anaesthetized with chloralose. Stimulation with low current intensity in central lateral nucleus (CL), evoked potentials in large areas of the rat isocortex. In the posterior parietal cortex responses with a short latency negativity were evoked which followed high frequency repetitive stimulation. Its latency and ability to follow high frequency stimulation indicated a monosynaptic connection from CL to this part of the cortex. The short latency potential was followed by a second negativity with longer latency and varying amplitude. This second negativity did not follow repetitive stimulation exceeding 10 Hz, and was also reduced by supplementary doses of anaesthetics, indicating a polysynaptic origin. Stimulation at different CL sites elicited cortical potentials with short latency in a topographical pattern. Laminar analysis in the parietal and motor cortex suggested both a superficial and a deep layer termination of afferents from CL. Similar topografical relations and afferent layer distributions have previously been found in cats. The role of the thalamocortical projection from CL to parietal cortex in arousal, attention and pain mechanisms is discussed.

Action Potentials↗

Functional development of the visual system in normal and protein-deprived rats. VIII. Post-natal development of optic nerve axons.

Protein deprivation results in a persistent impairment of transmission of impulses from the specific cortical projection within the visual cortex. In order to evaluate changes in subcortical structures during pre-weaning development, a study was made on number, calibre and myelination of optic nerve axons in control (C) and protein-deprived (PD) rats 5, 12, 20 and 30 days of age. Protein deprivation was induced by giving rat mothers a diet containing 7% protein by weight (control diet 14%, during gestation and lactation. The cross-sectional area of the nerve was measured on a digitizer. Between 3000 and 4000 axons collected from 7-13 field areas sampled by a random, systematic procedure from a cross-shaped area of the nerve were counted and measured. Between 5 and 12 days after birth, the number of axons was reduced by 50% in C rats. The total number of optic nerve axons was not significantly different in PD compared to C rats, indicating that protein deprivation does not affect the formation or naturally occurring nerve cell death of retinal ganglion cells. At all ages examined there were significant reductions in the number of axons larger than 0.52 micron as well as the number of myelinated axons. The rates of growth/maturation and myelination of axons in C rats and PD rats suggested that the reductions seen in PD rats up to 20 days of age may represent a developmental delay of approximately 4 days. At 30 days, a delay or a distortion of development may present. The retarded development of optic nerve axons is discussed in relation to delays, distortions and deficits during visual system maturation in protein-deprived rats.

Animals↗

Field potential analysis of the cortical projection of the central lateral nucleus in the cat.

A previous field potential study has indicated a monosynaptic projection of fibres from the central lateral nucleus (CL) to the mid-suprasylvian gyrus (MSSG). The present study, which is based on an analysis of current source density (CSD), aims to investigate further the sites of major localized synaptic activities in different layers of the MSSG after electrical stimulation in the CL. An initial positive surface potential was evoked in the MSSG with a latency of 3-5 ms and followed by a large negative potential with a peak latency of 8-15 ms. The initial positivity was only found in the rostral part of the MSSG, which corresponds to area 5. The positivity reversed in deeper layers. The CSD analysis showed a sink at a depth from 650 to 1050 microns. A corresponding source was found more superficially at 400-600 microns. This indicates that CL fibres have an excitatory synaptic termination on the soma or proximal dendrites of neurons in layers III and IV. The surface negative potential reversed at the border between layers II and III, suggesting a superficial CL projection. The CSD analysis of potentials in superficial layers showed a sink appearing between the pial surface and a depth of 350 microns, and a source lying in layers below. This indicates a depolarization of apical dendrites of cells in layers II and III. The superficial sink appeared in a large part of the MSSG. Application of a solution of 0.5% gamma-aminobutyric acid (GABA) on the surface of the cortex blocked the superficial sink and source and revealed a prominent sink current in layers III and IV in agreement with a deep termination of CL fibres. Application of a solution of 25 mM DL-2-amino-5-phosphono-valeric acid (APV) abolished CL-evoked cortical responses indicating that N-methyl-D-aspartate (NMDA) receptors are involved in the cortical activation. The CSD analysis confirms that CL has a wide superficial projection to the MSSG. It also confirms a deeper monosynaptic projection from CL to area 5.

Animals↗

Influence of changes of tooth temperature on reflex and central activity evoked by stimulation of tooth pulp afferents.

The importance of the temperature of the dentine was studied in teeth prepared for electrical stimulation. During experiments with the mouth open, the temperature of teeth covered by cement was normal. The digastric EMG and the brainstem--evoked response following electrical stimulation of the tooth pulp as well as the threshold for eliciting a jaw-opening response remained constant throughout prolonged experiments. However, heat produced by the cement used to fixate the tooth electrodes could have damaged the tooth if the dentine temperature had exceeded 45 degrees C. A careful preparation of the tooth pulp by repeated application of thin layers of cement allowed an adequate preparation without damage to tooth pulp afferents.

Animals↗

Localized responses in the midsuprasylvian gyrus of the cat following stimulation of the central lateral nucleus in thalamus.

Evoked responses were mapped in the cerebral cortex following low intensity electrical stimulation in serial penetrations of the medial and intralaminar nuclei of the thalamus of the cat. A projection was found from one of the intralaminar nuclei, the central lateral nucleus (CL) to the midsuprasylvian gyrus, mainly areas 5 and 7. The projection is suggested to be direct, since the evoked responses had a short latency initial positivity. The most characteristic type of response consisted of this early positivity followed by two successive negativities. The earlier, so called first negativity followed high frequency stimulation and was recorded in a smaller area of the cortex than the later, so called second negativity. The first negativity is suggested to depend on monosynaptic depolarization and activation of cortical cells. The second negativity failed at frequencies higher than 10 Hz and was strongly depressed by the administration of barbiturates; it is suggested to depend on polysynaptic depolarization and cellular activity. In electrode penetrations of the cortex both negativities reversed at the border between cortical layers II and III, indicating a superficial termination of thalamic afferents in the cortex. The cortical evoked response to CL stimulation was facilitated by light mechanical and low intensity electrical stimulation of the periphery, as well as by electrical stimulation of the tooth pulp. The possible significance and function of this projection is discussed in relation to arousal, attention and pain.

Animals↗

Projection of tooth pulp afferents to the thalamus of the cat. I. Focal potentials and thalamocortical connections.

Electrical stimulation of tooth pulp afferents in cats evoked short latency focal potentials in the basal ventromedial nucleus of thalamus (VMB), in the border zone between this nucleus and the arcuate nucleus of the ventrobasal complex (VBA), and in the marginal zone of VBA and the external nucleus of the ventrobasal complex (VBX). No responses were found in the centre of VBA and VBX. Very few responses were found in the intralaminar region. The projection from the tooth pulps was bilateral, but the best responses following stimulation of the ipsi- and the contralateral tooth pulps could be evoked at slightly different locations within VMB. The mean latency of the responses was shorter following stimulation of the contralateral tooth pulp than following stimulation of the ipsilateral one. Electrical stimulation in VMB, VBA, and VBX evoked focal potentials in thalamocortical projection fibres, which were recorded from in the white matter below areas SI and SII after decortication by suction. Conditioning stimulation of the tooth pulps suppressed these responses within 200 ms if the stimulating electrode was placed at the border between VBA and VMB, suggesting that tooth pulp stimulation activates a thalamocortical projection with a postexcitatory inhibition. Finally, lesions were made in the thalamus and their effects were checked on the cortical responses to tooth pulp stimulation. If the lesion included the region of VMB bordering to VBA the cortical responses decreased in amplitude. It is concluded that VMB and the borderzone between VMB and VBA are important relays between the nociceptors of the tooth pulp and the sensory cortex.

Animals↗

Projection of tooth pulp afferents to the thalamus of the cat. II. Distribution and characteristics of single units.

Single unit activity was recorded extra- and intracellularly in the thalamus of the cat following electrical stimulation of tooth pulp afferents. Cells activated by noxious stimuli were found in the basal ventromedial nucleus (VMB), the marginal zones of the arcuate and external nuclei of the ventrobasal complex (VBA and VBX) and the intralaminar complex. Cells found in any of these locations showed a variety of properties; they were activated at different latencies and had different patterns of input. However, cells with responses of short latency and low convergence were with few exceptions found in or close to VMB. Stimulation of tooth pulp evoked both EPSP's and IPSP's in these cells. A subpopulation of cells were found that responded to stimulation of either right or left tooth pulp afferents. 22 units, mainly located in VMB, were found that responded exclusively to stimulation of tooth pulp afferents. In the laterodorsal part of VMB cells influenced by tooth pulp stimulation were found to be antidromically activated by stimulation of the cortical tooth pulp projection area. No such cells were seen at other locations. The results of this study is in agreement with the conclusions in the companion paper (Rydenhag et al. 1986a) that VMB and the border zone between VMB and VBA are the most likely relay nuclei between tooth pulp nociceptive afferents and the cortex. The intralaminar complex is suggested to be important in the cortical arousal reactions and direction of attention following a painful stimulus.

Afferent Pathways↗

Effects of naloxone on dental pain threshold following muscle exercise and low frequency transcutaneous nerve stimulation: a comparative study in man.

Previous studies have shown that muscle exercise and low frequency transcutaneous nerve stimulation (TNS) give rise to an analgesic effect in humans and animals. Endorphin has been proposed to mediate this analgesia. In this investigation, the effect of muscle exercise and low frequency TNS, on dental pain thresholds was studied and the possible involvement of endorphinergic mechanisms was investigated using naloxone as an antagonist. Dental pain thresholds were measured in 11 volunteers following leg or arm exercise and after low frequency TNS of the hands or face. After exercise (20 min) or stimulation (30 min) either 0.8 mg naloxone (2 ml) or saline (2 ml) was injected i.v. in a double-blind fashion. Pain thresholds were measured repetitively before and after exercise or stimulation. Both leg and arm exercise increased pain threshold. Stimulation of the hands also increased pain threshold, but less than arm exercise. A marked increase in pain threshold was seen after face stimulation. These changes in pain threshold were unaffected following injections of either naloxone or saline, except for an early and short-lasting reduction when naloxone was injected following arm exercise. The increases in pain threshold following muscle exercise and after low frequency TNS, showed similarities suggesting that a common mechanism might be involved. The pain threshold increase after arm exercise could only be partially mediated by endorphinergic mechanisms.

Adult↗

Cortical nociceptive systems.

There is evidence that the cerebral cortex is involved in the perception of pain but no specific area appears to be the 'pain centre'. Limited knowledge exists on the cortical processing of the noxious input. The nociceptors are most likely to activate at least two different systems with different characteristics. One has a bilateral cortical projection, no apparent topographical pattern, low synaptic security and excites cells in large areas. This system may give rise to the widespread increase in blood flow and the widely distributed surface potentials recorded in man following a painful stimulus. Noxious stimuli also excite a system with contralateral topographical projection, high synaptic security and termination in lamina IV. This system produces EPSP-IPSP sequences in cells in a restricted cortical area. Pronounced inhibition of cells in lamina IV and more superficial layers is induced by activity in low threshold afferents. Thus, similarly as at the segmental spinal level, the nociceptive input to cortical cells is processed and integrated with the activity in other afferent systems.

Anesthetics↗

Activity in cortical cells after stimulation of tooth pulp afferents in the cat. Intracellular analysis.

The projection of tooth pulp afferents to cortical cells was studied in intracellular recordings. In a small region of the coronal gyrus, cells in lamina IV were responding at stimulation of contralateral tooth pulp afferents with short latency, steeply rising EPSPs, and one or two action potentials followed by an IPSP. These cells received convergence from skin afferents. In a large cortical area in the coronal, anterior suprasylvian and anterior ectosylvian gyri, tooth pulp stimulation elicited long latency, long lasting EPSPs not succeeded by hyperpolarization mainly in superficial cortical cells. These EPSPs could elicit trains of spikes. A complex type of responses consisted of a short latency EPSP with one or two spikes followed by hyperpolarization which in part was counteracted by a second, long latency EPSP of long duration. Stimulation of low threshold contralateral skin afferents usually gave short latency EPSPs with spikes followed by long lasting hyperpolarization. A common feature of many cells was a high convergence from tooth pulp afferents and bilateral low threshold skin afferents. The response characteristics at tooth pulp stimulation compared to low threshold input are discussed in relation to cortical mechanisms of pain.

Action Potentials↗

Activity in cortical cells after stimulation of tooth pulp afferents in the cat. Extracellular analysis.

The cortical projection of tooth pulp afferents has been investigated by extracellular recordings in lightly chloralose anaesthetized cats. The results indicate two different projection systems from the tooth pulp afferents terminating on the cortical cells. One system appears to be specific with topographical distribution and activates cells mainly in lamina IV in a restricted region of the coronal gyrus. The cells in this area receive excitation also from restricted cutaneous fields. At stimulation of the tooth pulps with single electrical pulses cells are activated with high discharge probability and with a stable latency. The other system projects mainly to cells in the superficial cortical laminae in a much larger area. These cells receive input from large bilateral cutaneous fields but show less discharge probability and require often temporal summation to discharge at tooth pulp stimulation.

Action Potentials↗

Cortical responses evoked by tooth pulp stimulation in the cat. Surface and intracortical responses.

In lightly chloralose-anaesthetized cats selective stimulation of tooth pulp afferents elicited responses in coronal, anterior suprasylvian and adjacent cortical gyri. In the lateral part of coronal gyrus the potentials evoked from the contralateral canine tooth pulps were initially positive. Such responses from the upper and lower teeth had different cortical distribution suggesting a topographical organization. In the regions adjacent to those with initially positive responses stimulation of the same tooth pulp evoked initially negative potentials. Stimulation of ipsilateral tooth pulp afferents elicited almost exclusively initially negative potentials with a similar distribution as the responses of contralateral teeth but with longer latency. Laminar analysis showed that the region with initial positivity in the response to stimulation of the tooth pulp coincided with an intracortical negative focal potential of maximum amplitude mainly in lamina IV. In areas with initially negative responses the maximum of the focal potential following tooth pulp stimulation was obtained in superficial cortical layers. It is postulated that the projection system underlying the initially positive cortical responses has a topographically arranged cortical projection terminating mainly in lamina IV. The projection system eliciting the initially negative potentials, has a widespread cortical distribution and produces excitation predominantly in the superficial laminae.

Afferent Pathways↗