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Biomedical subjects

H Bergman

Publications and source records attributed to H Bergman.

At least 91 records · Page 5Linked to original sources
PubMed1995

Neuropsychological changes during steady-state drug use, withdrawal and abstinence in primary benzodiazepine-dependent patients.

Impairment on neuropsychological tests during steady-state drug use and withdrawal, and after discontinuation of benzodiazepines, was studied in primary benzodiazepine-dependent patients. One group of patients was tested before and the other group after the initiation of a gradual tapering-off of the drug, and both groups were tested approximately 1 year later. At the initial assessment, both groups of patients showed impairment on most of the tests of general intelligence and on several of the tests in the Halstead-Reitan battery, as well as on a test of nonverbal memory, in comparison with healthy controls. At follow-up the patient groups had reached the level of the control group. This study confirmed earlier observations of neuropsychological deficits in long-term benzodiazepine-using patients and demonstrated that these changes are at least partly reversible by discontinuing drug intake.

Adult↗
PubMed1995

Neurons in the globus pallidus do not show correlated activity in the normal monkey, but phase-locked oscillations appear in the MPTP model of parkinsonism.

1. To test the mode of functional connectivity in the basal ganglia circuitry, we studied the activity of simultaneously recorded neurons in the globus pallidus (GP) of a behaving rhesus monkey. The cross-correlograms of pairs of neurons in the GP were compared with those of neurons in the thalamus and frontal cortex and to the cross-correlograms of pallidal pairs after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment. 2. In contrast with cortical and thalamic neuronal activity, almost all pairs (n = 76/81 pairs; 93.8%, 1,629/1,651 histograms; 98.7%) of GP neurons in the normal monkey were not driven by a common input. 3. The monkey was systemically treated with MPTP until the appearance of parkinsonian signs and an intermittent 7- to 11-Hz action/postural tremor. After the MPTP treatment, many pallidal neurons (49/140; 35%) became oscillatory, and 19% (n = 31/162) of pallidal pairs had oscillatory cross-correlograms. 4. These results support the model of parallel processing in the basal ganglia of normal monkeys and suggest a breakdown of the independent activity in the parkinsonian state.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1994

Increased semantic priming in patients with dementia of the Alzheimer's type.

Semantic priming on a lexical decision task(LDT) was examined in 50 patients with mild to moderate dementia of the Alzheimer's Type(DAT), and 25 normal age-matched controls. DAT patients were slower in their responses, and showed significantly greater priming effects (mean 54 ms vs. 27 ms in controls). The size of the priming effect correlated with the speed of response on the LDT task for the individual DAT patients but not for controls. Twenty of the DAT patients (vs. one control) showed priming greater than 60 ms. This subgroup of DAT patients with "hyperpriming" was slower than the nonhyperpriming group on "yes" responses to targets preceded by unassociated prime words and more impaired on tests of clock drawing and verbal fluency. Slowing of responses alone, however, seems unable to account for the presence of increased priming in DAT patients. Its presence may reflect semantic memory deficits, as well as impaired attentional processing and supervisory control systems. The exact mechanism of this increased priming remains to be established.

Aged↗
PubMed1994

The primate subthalamic nucleus. I. Functional properties in intact animals.

1. The present study tests several key aspects of the current model of the intrinsic circuitry of the basal ganglia, in particular the degree to which basal ganglia-thalamocortical circuits are functionally segregated at the level of the subthalamic nucleus (STN). To this end the responses of STN cells to somatosensory examination (n = 301 cells), the polarity and latencies of neuronal responses to passive and active movements (n = 223 cells), responses to microstimulation (n = 1589 sites), and cross-correlation functions of pairs of neighboring neurons (n = 72 pairs) were studied in STNs of three African green monkeys. 2. The activity of 55% of cells examined in STN was briskly modulated in response to passive movements of individual contralateral body parts. Of these, 86% responded to passive joint rotation of muscle palpation, but in some cases (25% of responding cells) responses were also elicited by light touch. In 91% of the responding cells responses were elicited by manipulations around a single joint only. 3. The caudoventral sector in STN was largely devoid of cells with responses to somatosensory stimulation. Within the rostrodorsal zone a lateral region containing neurons that responded to arm movements and a more medial region with neurons responding to leg movement were found. Cells responding to orofacial movements were located more dorsally and rostrally. Neurons with similar responses to active and passive movements of the limbs tended to be clustered within "arm" and "leg" zones. 4. Of identified arm cells in STN (n = 80), 36% responded to the application of torque pulses to the elbow (43 responses overall). Forty-eight percent of these cells responded to both extension and flexion torques. Ninety-three percent of the responses were initial increases in discharge, which characteristically occurred earlier and were shorter than initial decreases. Fifty-three percent of the responses were biphasic or multiphasic. 5. During active step tracking movements 40% of STN arm cells (n = 53 cells) responded with significant changes in activity. Thirty-six percent of these cells showed responses with both extension and flexion movements. Of the responses, 90% were increases in discharge. Only 14% of all responses were biphasic or multiphasic. Responses tended to occur around the time of movement onset (average latency 2 ms after movement onset). 6. Microstimulation (bipolar pulses, 40 microA, 200-500 ms train duration, 400 Hz) of the core of STN itself did not appear to produce movement.4+ synchronized activity in only 11% of pairs.(ABSTRACT TRUNCATED AT 400 WORDS)

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1994

The primate subthalamic nucleus. II. Neuronal activity in the MPTP model of parkinsonism.

1. The neuronal mechanisms underlying the major motor signs of Parkinson's disease were studied in the basal ganglia of parkinsonian monkeys. Three African green monkeys were systemically treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) until parkinsonian signs, including akinesia, rigidity, and a prominent 4- to 8-Hz tremor, appeared. The activity of neurons in the subthalamic nucleus (STN) and in the internal segment of the globus pallidus (GPi) was recorded before (STN, n = 220 cells; GPi, n = 175 cells) and after MPTP treatment (STN, n = 326 cells; GPi, n = 154 cells). 2. In STN the spontaneous firing rate was significantly increased from 19 +/- 10 (SD) spikes/s before to 26 +/- 15 spikes/s after MPTP treatment. Division of STN neurons recorded after MPTP treatment into cells with rhythmic bursts of discharge occurring at 4-8 Hz (as defined by autocorrelation analysis) and neurons without 4- to 8-Hz periodic activity revealed an even more prominent increase in the firing rate of the 4- to 8-Hz oscillatory neurons. 3. In GPi overall changes in the average firing rate of cells were inconsistent between different animals and behavioral states. However, the average firing rate of the subpopulation of neurons with 4- to 8-Hz periodic oscillatory activity after treatment with MPTP was significantly increased over that of all neurons before MPTP treatment (from 53 to 76 spikes/s, averaged across monkeys). 4. In the normal state the percentage of neurons with burst discharges (as defined by autocorrelation analysis) was 69% and 78% in STN and GPi, respectively. After MPTP treatment the percentage of cells that discharged in bursts was increased to 79% and 89%, respectively. At the same time the average burst duration decreased (from 121 +/- 98 to 81 +/- 99 ms in STN and from 213 +/- 120 to 146 +/- 134 ms in GPi) with no significant change in the average number of spikes per burst. 5. Periodic oscillatory neuronal activity at low frequency, highly correlated with tremor, was detected in a large number of cells in STN and GPi after MPTP treatment (average oscillation frequency 6.0 and 5.1 Hz, respectively). The autocorrelograms of spike trains of these neurons confirm that the periodic oscillatory activity was very stable. The percentage of cells with 4- to 8-Hz periodic activity significantly increased from 2% to 16% in STN and from 0.6% to 25% in GPi with the MPTP treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1994

The primate subthalamic nucleus. III. Changes in motor behavior and neuronal activity in the internal pallidum induced by subthalamic inactivation in the MPTP model of parkinsonism.

1. The effects of reversible and irreversible pharmacological manipulations of the neuronal activity in the subthalamic nucleus (STN) on parkinsonian motor signs and neuronal activity in the internal segment of the globus pallidus (GPi) were studied in African green monkeys rendered parkinsonian by treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. 2. Muscimol injections (< or = 1 microliter, 1 microgram/microliter) into STN reduced neuronal activity recorded at the injection site within minutes. This was immediately followed by reduced akinesia, tremor, and rigidity, as well as the emergence of dyskinesias in contralateral limbs. The motor effects were accompanied by generalized behavioral activation, lasted between 10 and 60 min, and were strongly dependent on the site of injection, with injections into the lateral "arm area" of STN first affecting contralateral arm movements and injections into the "leg" area affecting leg movements first. 3. Bicuculline injections (< or = 1 microliter, 1 microgram/microliter) into STN marginally increased the neuronal activity and induced neuronal discharge in bursts. Rigidity, akinesia, and tremor in the contralateral limbs were not changed. 4. Injections of ibotenic acid in two animals (2 and 7 microliters, 10 micrograms/microliters) resulted in 70 and 51% destruction of STN, respectively. Similarly to the muscimol injections, this resulted in a reduction of the neuronal activity, a reversal of parkinsonian motor signs, and the development of dyskinesias in the contralateral limbs. 5. Although tremor was significantly reduced after STN lesions, periodic oscillatory neuronal activity in GPi persisted. The strength of modulation of the neuronal oscillation was not significantly changed after STN lesion. 6. The percentage of cells in GPi exhibiting increases in discharge in response to torque application was significantly reduced after STN lesion. The magnitude and duration of the responses with increase in firing rate were reduced after STN lesioning. 7. These results support the hypothesis that abnormally increased tonic and phasic activity in STN leads to abnormal GPi activity and is a major factor in the development of parkinsonian motor signs. Furthermore they imply that cells in the basal ganglia have the intrinsic property of discharging in periodic bursts, which is unmasked under parkinsonian conditions.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1994

UREA PRODUCTION, ACID-BASE REGULATION AND THEIR INTERACTIONS IN THE LAKE MAGADI TILAPIA, A UNIQUE TELEOST ADAPTED TO A HIGHLY ALKALINE ENVIRONMENT

The Lake Magadi tilapia, Oreochromis alcalicus grahami, thrives in highly alkaline geothermal springs and pools surrounding Lake Magadi, Kenya (control pH=9.9, CCO2=173 mmol l-1), has a functional hepatic ornithine&shy;urea cycle (OUC) and excretes all nitrogenous waste as urea-N at variable rates (JUrea) related to O2 consumption (M&middot;O2). The mean value of JUrea/M&middot;O2 (N/O2=0.183) was high for fish but below the theoretical maximum (approximately 0.27) for 100 % aerobic respiration of protein, so an exogenous source of substrates is not required to explain the observed JUrea. JUrea was insensitive to thiourea. Urea excretion occurred largely (80 %) through the gills, but urea-N was also present in bile and urine. Control blood pHe, pHi and [HCO3-] (approximately 8.1, 7.6 and 15 mmol l-1, respectively, at approximately 32&deg;C) were extremely high. When fish were exposed to lake water titrated with HCl and aerated to remove CO2, N/O2 progressively declined. At a lake water pH of 7.05 and CCO2 of 0 mmol l-1, N/O2 was reduced by 80 % and an intense metabolic acidosis occurred (pHe=7.04, [HCO3-]=1.5 mmol l-1). Restoration of control water pH 9.9 at a CCO2 of 0 mmol l-1 resulted in intermediate levels of N/O2 and internal acid&shy;base status. Additional experiments confirmed that urea production was inhibited by low pHe, was dependent on blood [HCO3-] with a Km of 3.06 mmol l-1 and was insensitive to acetazolamide. While metabolic acidosis clearly inhibited OUC ureagenesis, the system appeared to be saturated with HCO3- under control conditions so that additional basic equivalent loading would not stimulate ureagenesis. Urea production in the Lake Magadi tilapia does not appear to remove exogenous HCO3- or to play a role in normal acid&shy;base regulation.

Journal Article↗
PubMed1993

Blood-brain barrier penetration and in vivo activity of an NGF conjugate.

Nerve growth factor (NGF) is essential for the survival of both peripheral ganglion cells and central cholinergic neurons of the basal forebrain. The accelerated loss of central cholinergic neurons during Alzheimer's disease may be a determinant of dementia in these patients and may therefore suggest a therapeutic role for NGF. However, NGF does not significantly penetrate the blood-brain barrier, which makes its clinical utility dependent on invasive neurosurgical procedures. When conjugated to an antibody to the transferrin receptor, however, NGF crossed the blood-brain barrier after peripheral injection. This conjugated NGF increased the survival of both cholinergic and noncholinergic neurons of the medial septal nucleus that had been transplanted into the anterior chamber of the rat eye. This approach may prove useful for the treatment of Alzheimer's disease and other neurological disorders that are amenable to treatment by proteins that do not readily cross the blood-brain barrier.

Animals↗
PubMed1993

Spatiotemporal firing patterns in the frontal cortex of behaving monkeys.

1. Activity of up to 10 single units was recorded in parallel from frontal areas of behaving monkeys. 2. Spatiotemporal firing patterns were revealed by a method that detects all excessively repeating patterns regardless of their complexity or single-unit composition. 3. Excess of repeating patterns was found in 30-60% of the cases examined when timing jitter of 1-3 ms was allowed. 4. An independent test refuted the hypothesis that these patterns represented chance events. 5. In a given behavioral condition there were usually many different patterns, each repeating several times, and not one (or a few) pattern repeating many times. 6. In 13 out of 20 cases, when a single unit elevated its firing rate in association with an external event beyond 40/s, most of the spikes within that period were associated with excessively repeating spatiotemporal patterns. 7. Of 157 types of patterns whose excess was most marked, 107 were composed of spikes from one single unit, 45 of the patterns contained spikes from two single units, and only one was composed of spikes from three different single units. 8. These properties suggest that the patterns were generated by reverberations in a synfire mode within self-exciting cell assemblies.

Animals↗
PubMed1993

Detection of neuronal periodic oscillations in the basal ganglia of normal and parkinsonian monkeys.

A feature-extracting program for detecting and quantifying periodic oscillations in auto- and cross-correlograms is described. The program performs like an "expert system" for extracting and evaluating neuronal periodic oscillations. A series of parameters (oscillation frequency, number of repeated cycles, modulation depth, etc.) is calculated, and used for grading (0 to 10) the periodic activity. The program has been applied to single-unit records from the basal ganglia of normal and parkinsonian (MPTP treated) monkeys, and the results have confirmed its accuracy and advantages over other methods.

Algorithms↗
PubMed1992

Dependence of cortical plasticity on correlated activity of single neurons and on behavioral context.

It has not been possible to analyze the cellular mechanisms underlying learning in behaving mammals because of the difficulties in recording intracellularly from awake animals. Therefore, in the present study of neuronal plasticity in behaving monkeys, the net effect of a single neuron on another neuron (the "functional connection") was evaluated by cross-correlating the times of firing of the two neurons. When two neurons were induced to fire together within a short time window, the functional connection between them was potentiated, and when simultaneous firing was prevented, the connection was depressed. These modifications were strongly dependent on the behavioral context of the stimuli that induced them. The results indicate that changes in the temporal contingency between neurons are often necessary, but not sufficient, for cortical plasticity in the adult monkey: behavioral relevance is required.

Acoustic Stimulation↗
PubMed1992

Development of synapsin I and synapsin II in intraocular hippocampal transplants.

Previous studies have indicated that the appearance of synaptic vesicle-associated proteins known as the synapsins is one indicator of synapse formation. In this study, the levels and morphological distribution of synapsin I and synapsin IIa and IIb were studied in intraocular hippocampal transplants and in situ in the intact hippocampus. No detectable levels of either synapsin I or synapsin II were found in the fetal brain. The in situ levels of the synapsins exhibited parallel increases rapidly after birth, reaching peak levels at 8 weeks, after which a slight decline was noted in synapsin I and synapsin IIb. In hippocampal transplants, a comparable increase in the synapsins was seen during the first 8 weeks in oculo. It is likely that the synapse formation in the hippocampal transplants represents synapses from neurons within the transplant, as well as from various peripheral ganglia that send collaterals into the graft. Peripheral and central synapses express different synapsin I: synapsin IIa and IIb ratios. When the ratios of the synapsin proteins in hippocampal transplants were examined ratios essentially identical to those seen in the normal hippocampus were found, despite the numerous peripheral neurites innervating the grafts. Immunohistochemical studies supported the immunoblot data, showing no detectable immunofluorescence with synapsin antibodies in fetal or newborn hippocampal formation. The density of immunoreactive profiles increased substantially both in transplants and in the hippocampal formation in situ during the first 2 postnatal months. In conclusion, the present data demonstrate that hippocampal transplants in oculo can develop significant levels of the synapsins and that there is no time lag in development in these levels compared to the hippocampal formation in situ.

Animals↗
PubMed1992

A personal computer-based spike detector and sorter: implementation and evaluation.

Many studies of neuronal activity require isolation of the extracellular wave form (spike) of a single neuron from the potentials generated by nearby cells. A variety of methods for spike sorting exists, but most are expensive and require specialized hardware and software. Moreover, there is no easy and objective way for evaluating and comparing the performance of spike sorting devices. We describe here a system for on-line spike sorting that is implemented on an IBM PC/AT computer using commercially available hardware and C-language software. Spikes are detected after crossing an amplitude threshold and are sorted or rejected by template matching. The templates are constructed in a learning phase, using a fast manual sorting of all detected spikes. Later, each detected spike is matched against all defined templates. A detected spike which does not match any template, or matches more than one, is rejected. A continuous display of the wave forms of the last 256 sorted, double-matched, and rejected spikes is used as the main tool for parameter adjustment and error detection. Also described is a new and highly versatile tool for generating appropriate wave forms for critical evaluation of sorter performance. Using the same hardware and software tools, a simulation program mimics the extra-cellular activity of several neurons by linear combination of two vectors and added random noise. The size, shape and the variability of the action potential, as well as its firing pattern, can be adjusted. Comparison of the sorter output with the known simulated activity is used to examine the sorter performance and limitations.

Action Potentials↗