Trond Ganes

Effect of near normoglycaemia for two years on progression of early diabetic retinopathy, nephropathy, and neuropathy: the Oslo study.

Forty five insulin dependent diabetics were randomised to treatment with continuous subcutaneous insulin infusion (CSII), multiple insulin injections (five or six daily), or conventional twice daily insulin injections. Near normoglycaemia was obtained with CSII and multiple injections but not with conventional treatment (p less than 0.01). Hypoglycaemic coma was observed less frequently with CSII than with multiple injections and conventional treatment (p less than 0.001), but blood glucose concentrations below 2.5 mmol/l (45 mg/100 ml) were more common. After two years fewer retinal microaneurysms and haemorrhages had developed in the patients given CSII and multiple injections compared with those given conventional treatment, in whom the number had increased significantly (p less than 0.01). Motor nerve conduction velocity deteriorated in the patients given conventional treatment; in those given CSII it was unchanged during the first year but had improved after two years (p less than 0.01). Glomerular hyperfiltration was reduced with CSII, but no change occurred in urine albumin excretion rates. Long term near normoglycaemia may prevent the progression of early stages of late diabetic complications.

Two generators of hippocampal theta activity in rabbits

Spontaneous and hypothalamically induced theta activity was studied in rabbits lightly anaesthetized with urethane or urethane-chloralose. Well-developed theta activity was found over a large area of the dorsal part of the hippocampal formation, roughly corresponding to the CA1 field. Cross-correlation analysis between a stationary and a moving electrode showed that a large sheet of tissue oscillated in remarkable synchrony. This region was at least 8 mm along the longitudinal axis of the hippocampus and 6 mm in a plane transverse to this axis, thus comprising the whole of the rostro-caudal extension of the CA1 region. For technical reasons the temporal half was not explored. Depth recordings showed two foci of theta activity, one in the basal part of CA1 (stratum oriens) and a second, separate region with considerably larger amplitudes in the dentate region, having its maximum in the molecular layer. Due to the folded nature of the dentate fascia, an electrode often recorded two maxima corresponding to its upper and lower blades. Wave form analysis showed that the dentrate and CA1 rhythmic activity was roughly 180 degrees out of phase. The dentate theta activity remained in conditions where the CA1 theta activity was absent, either spontaneously or due to experimental interference. Systematic micro-electrode tracking showed absence of theta activity in the CA3 region. Nor was convincing theta activity found in the subiculum, parasubiculum, presubiculum or entohinal areas.

Automated analysis of rhythmicity of physiologically identified hippocampal formation neurons

SummaryThe participation of physiologically identified hippocampal neurons in spontaneous and hypothalamically induced theta activity was studied in rabbits lightly anaesthetized with urethane. Dentate granule cells were identified by their orthodromic response to perforant path stimulation, CA1 and CA3 pyramids by antidromic activation from the alveus and Schaffer collaterals, respectively, and basket cells by their response to increasing orthodromic activation.The discharges of many hippocampal cells were grossly correlated to the pattern of slow wave activity. Few cells were spontaneously active during irregular slow wave activity. With the appearance of rhythmical slow wave activity of 4–6 Hz, the unit discharges also increased in frequency. Dentate granule cells had the lowest threshold for activation and also a longer duration of the increased discharge frequency, compared to other cell types.There was a characteristic pattern of transition for dentate granule cells and CA1 pyramidal cells from a silent to an active state. The cell discharges paralleled the changes in amplitude, regularity, and frequency of theta slow waves. Large-amplitude, high-frequency theta was correlated with rhythmic burst discharges of up to 2–3 spikes per burst. As theta amplitude and frequency decreased, the number of spikes per burst reduced until only regular single spikes occurred. When theta activity was replaced by irregular slow wave activity, the cell discharges became irregular and sometimes ceased entirely. At high levels of activation, CA1 pyramids often showed clusters of high-frequency discharges with declining amplitude (complex spikes).For each cell a cycle histogram was constructed, placing the discharges in one of 20 bins according to their time relation to the simultaneously recorded slow theta waves. In addition, by Fourier transformation of the cycle histograms, the technique allowed a quantitative description of the degree and type of rhythmicity.The analysis indicated that virtually all dentate granule cells and CA1 pyramidal cells were phaselocked to the negative portion of the theta waves recorded from the corresponding region.The cells differed in their degree of coupling, as expressed by the modulation index of their cyclic histograms. Dentate granule cells had higher modulation indices than the CA1 pyramids. There was a suggestion that basket cells and CA3 cells had smaller modulation indices, but the low number of cells recorded mitigate against any strong conclusions.The results are interpreted as corroborating earlier findings that the dentate granule region and the CA1 pyramidal region are the main generators of hippocampal theta activity.A “size principle” was proposed to explain the role of synaptic depolarizing pressure in the rhythmic activation of hippocampal neurons and the fact that small neurons (dentate granules and CA1 pyramids) were better driven than larger neurons.

Childhood autism: the need for physical investigations

In this paper the results of an extensive medical investigation of 25 children with childhood autism are presented and compared with those found in a group of non-autistic individuals matched for sex, age and intellectual level, all referred for developmental deviancy of unknown etiology. The examination included a psychiatric assessment and a neurological examination in addition to neurophysiological, chromosomal, metabolic and neuroimaging evaluation. In the clinical examination macrocephaly was found only among the autistic individuals, while the frequency of pathological cerebral CT and clinical parameters such as tendon reflexes and mobility problems was significantly greater in the control group. All the other pathological findings were found to occur with the same frequency in the two groups. Except for research purposes this study did not lend support to those who argue for extensive medical examinations for all children with autism. Based on the present findings, ordinary procedures for assessment of developmentally delayed children should be followed. This should include a systematic clinical neuropaediatric examination, an assessment of vision and hearing and a chromosome study, including that for fragile X.

Distribution of GABA Sensitive Areas on Hippocampal Pyramidal Cells

SummaryIn isolated transverse hippocampal slices GABA (gamma-amino-butyric acid) was applied iontophoretically to various parts of the dendritic tree of CA1 pyramidal cells. Indices of GABA effects were reduced amplitude of orthodromically driven CA1 population spikes and inhibition of single CA1 units driven by orthodromic stimulation or by application of L-glutamate.Weak iontophoretic currents of GABA (3–6 nA, backing current -3 nA) effectively reduced the amplitude of the population spike and arrested unit activity when applied in a position close to the soma. The effect was halved when GABA was applied 25–30 μm away at right angles to the main dendritic axis. In the direction of the main dendritic axis, GABA was effective as far as 250 and 150 μm from the soma in the apical and basal dendritic directions, respectively, corresponding to about 50% of the total dendritic length. The best effect was usually found at a depth corresponding to that of the recording electrode, probably because the main dendritic axis was parallel to the slice surface.The sharp localization of GABA sensitivity when applied in the pyramidal layer supports earlier evidence that GABA mediates the basket cell inhibition on the soma of the pyramidal hippocampal cells. In the dendritic tree, GABA may also have an inhibitory function with an effectiveness matching that of the soma application.

Barbiturate spindle activity in functionally corresponding thalamic and cortical somato-sensory areas in the cat

(1) Spontaneous barbiturate spindles were recorded from a locus in the thalamic nucleus ventralis postero-lateralis (VPL) and the corresponding projection area in the somato-sensory cortex (SI) in the cat. (2) Type I spindles32 recorded from such sites in the thalamus and cortex, regarded as being functionally on line, were cross-correlated. The analysis gave high negative cross-correlation coefficients, indicating that a considerable degree of wave synchrony existed between the spindles. Maximal wave synchrony was present in the first and middle part of the spindle. (3) The thalamo-cortical spindle wave synchrony was reduced by a small displacement of the cortical electrode within the somato-sensory cortex. Starting with a very lightly anaesthetized animal, small amounts of barbiturate did not influence the size of the cortical area which had spindles in synchrony with the thalamic spindles. (4) Spindles recorded from a VPL locus and from its cortical projection site started simultaneously. When the thalamic and cortical electrodes were positioned functionally off line this spindle coincidence decreased. The intervals between the spindle onsets increased with increasing off line positions of the electrodes. Those few thalamic and cortical spindles which occurred simultaneously showed no, or only weak, spindle wave synchrony. (5) These data suggest a point-to-point topographical relation between thalamic and cortical loci engaged in barbiturate spindle activity. (6) Type I and type II spindles32 differed with respect to spindle characteristics (amplitude, duration, incidence) and also with respect to corresponding thalamic rhythmic activity. These spindle types are, therefore, probably produced by different mechanisms. We suggest that type II spindles represent a purely cortical process initiated by type I spindles.

Barbiturate spindle activity in the thalamic lateral ventro-posterior nucleus and the second somato-sensory area of the cortex.

(1) Barbiturate spindles recorded from the second somato-sensory cortical area (SII) were similar to spindles in the primary somato-sensory area (SI) both with respect to incidence, duration of each spindle and per cent spindle time. The spindle wave amplitude was smaller in SII. The highest spindle wave amplitude was observed in the anterior part of SII which receives input from nucleus ventralis postero-lateralis (VPL). No spindle activity was observed in the posterior part of SII which receives input from the posterior nuclear group (PO) of the thalamus. (2) Barbiturate spindles recorded from a locus in VPL and its projection area in SII were cross-correlated. The analysis resulted in high cross-correlation factors, indicating that a considerable degree of spindle wave synchrony existed between the spindles. This wave synchrony was reduced by moving the cortical electrode a short distance. (3) Cortical spindles recorded from corresponding sites in SI and SII were cross-correlated, and gave a high cross-correlation coefficient. This synchrony was markedly reduced if one of the electrodes was moved a few millimetres away from the optimal point. (4) Spindles started simultaneously in corresponding sites of SI and SII. A high degree of coincidence was found also between spindles in a VPL locus and the corresponding projection site in SII. Local anaesthesia applied to or total removal of SI failed to influence the spindle activity in SII and vice versa. Similarly, the SI-SII synchrony survived a deep incision cutting all connections between the two areas. (6) It is suggested that spindles in corresponding sites of SII and SI have a common thalamic pacemaker which probably projects to both areas by axonal branching.

Hypoxemic Resuscitation in Newborn Piglets: Recovery of Somatosensory Evoked Potentials, Hypoxanthine, and Acid-Base Balance

We tested the hypothesis that hypoxic newborn piglets can be successfully resuscitated with lower O2 concentrations than 21%. Severely hypoxic, 2-4-d-old, anesthetized piglets were randomly divided into five resuscitation groups: 21% O2 (n = 10), 18% O2 (n = 9), 15% O2 (n = 9), 12% O2 (n = 8), all normoventilated, and a hypoventilated 21% O2 group (PaCO2; 7.0-8.0 kPa, n = 9). Base excess (BE) reached -20 ± 1 mmol/L at the end of hypoxia. After 3 h of resuscitation, BE had risen to -4 ± 1 mmol/L in the 21% O2, 18% O2, and hypoventilated groups, but was -10 ± 2 mmol/L in the 15% O2 group (p < 0.05versus 21% O2 group) and -22 ± 2 mmol/L in the 12% O2 group (p < 0.05 versus 21% O2 group). Four animals died during resuscitation, all allocated to the 12% O2 group (p < 0.05 versus 21% O2 group). Somatosensory evoked potentials (SEPs) recovered in 39 of 45 piglets, and remained present during resuscitation in all except the 12% O2 group. SEP recovered initially even in six of eight animals in the 12% O2 group, but disappeared again in all later during resuscitation. The SEP amplitude recovered to levels not significantly different from the 21% O2 group in all groups except the 12% O2 group. Plasma hypoxanthine concentrations and extracellular hypoxanthine concentrations in the striatum decreased during resuscitation to levels not significantly different from the 21% O2 group in all but the 12% O2 group(p < 0.05 versus 21% O2 group). In conclusion, severely hypoxic newborn piglets were resuscitated as efficiently with both hypoventilation and 18% O2 as with 21% O2.

Spindle wave synchrony in the somatosensory cortex of the cat

(1) Spontaneous barbiturate spindles were recorded from the primary and secondary somatosensory cortex. The recordings were concentrated to areas surrounding several reference loci. The recording sites producing the maximal response evoked by stimulation of an exposed nerve in a contralateral limb were used as reference loci. (2) Spindles recorded at various distances from the respective reference loci were cross-correlated to spindles developing simultaneously in the latter. High correlation coefficients, indicating a considerable degree of wave synchrony, were obtained between spindles in the reference locus and spindles recorded a few millimeters from this site. The correlation coefficients decreased with increasing interelectrode distance. A relatively sharp fall in the correlation coefficients was generally found 2-3 mm from the reference locus. Small amounts of sodium pentobarbital, given intravenously at intervals of 5 min, had no effect upon this pattern. (3) The change in the correlation coefficients was followed by a parallel change in the amplitude of the evoked potentials. The iso-correlation lines of spindle wave synchrony and the iso-amplitude lines of the evoked potentials had a similar distribution and extension for each particular reference locus. (4) Lateral spread of spindle waves in the cortex seems to be of minor importance, since a vertical lesion cutting the cortico-cortical fibres did not reduce the wave synchrony of the spindles recorded from either side of the lesion. (5) The majority of the spindles recorded in the close vicinity of a reference locus started simultaneously within +/- 0.1 sec. This pattern changed with increasing distance from the reference locus and 5.6 mm away only a fraction of the spindles started simultaneously. However, within the entire primary somatosensory cortex a small but significant coupling existed between onset of the spindles.

Barbiturate spindle activity in the association cortex of the cat and its relation to spindle activity in the somatosensory system

(1) Spontaneous barbiturate spindle activity was recorded simultaneously from nucleus ventralis poster-lateralis (VPL) of the thalamus, from the corresponding projection site in the primary somatosensory cortex (SI) and from the lateral (LAT) and middle suprasylvian (SSM) gyri. (2) Barbiturate spindles occurred more frequently in LAT and SSM than in the somatosensory cortex. Spindles in LAT and SSM were of longer duration than SI spindles while the intraspindle frequency was higher in spindles from the latter areas. The amplitude of the spindle waves was significantly higher in LAT and SSM than in SI. The largest spindle waves were recorded from the anterior part of LAT and SSM. (3) Barbiturate spindles recorded at various interelectrode distances were cross-correlated. In LAT and SSM the cross-correlation coefficients remained high up to an interelectrode distance of 4-5 mm while spindles recorded at this distance in SI gave low coefficients when cross-correlated. (4) Extensive removal of the somatosensory cortex had no effect on spindle formation in LAT or SSM. Furthermore, cutting of the cortico-cortical connections between two recording sites in either of these gyri produced no reduction in spindle wave synchrony between the recording sites. (5) Spindles in the VPL-SI only rarely started simultaneously with spindles in LAT and SSM. Those few coincident spindles which occurred were cross-correlated. The cross-correlation coefficients were invariably low suggesting that no wave synchrony existed between spindles in the VPL-SI system and those in the LAT and SSM.