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Biomedical subjects

H Bergman

Publications and source records attributed to H Bergman.

At least 19 recordsLinked to original sources

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

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

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

Encoding of sound-source location and movement: activity of single neurons and interactions between adjacent neurons in the monkey auditory cortex.

1. Neuronal mechanisms for decoding sound azimuth and angular movement were studied by recordings of several single units in parallel in the core areas of the auditory cortex of the macaque monkey. The activity of 180 units was recorded during the presentation of moving and static sound stimuli. Both the activity of single units and the interactions between neighboring neurons in response to each stimulus were analyzed. 2. Sixty-two percent of the units showed significant modulation of their firing rates as a function of the stimulus azimuth. Contralateral stimuli were preferred by the majority (approximately 60%) of these neurons. Thirty-five percent of the units showed mild but statistically significant modulation of their firing rates, which was specifically attributed to the angular movement of the sound source. 3. Eighty-nine percent of the "movement-sensitive" units were also "azimuth sensitive." The sound source's azimuth determined the pattern of the response components (on, sustained, off), whereas the source's movement affected only the magnitude of these components, typically the sustained component. Most neurons for which the sustained response to static sounds was greater for contralateral than ipsilateral stimuli preferred moving sounds that were moving into the contralateral hemifield. 4. Cross-correlation analysis was carried out for 245 neuron pairs. Cross-correlograms were computed for each pair under all stimulus conditions to allow comparison of the neuronal interactions under the various conditions. The shapes of some correlograms (after subtraction of direct stimulus effects) were dependent on specific stimulus conditions, suggesting that the effective connectivity between these neurons depended on the location and/or movement of the sound stimuli. Furthermore, joint peristimulus time (JPST) analysis indicated that modifications of connectivity may be temporally related to the stimulus and may occur over short periods of time. These results could not have been predicted from analysis of the independent single-unit responses to the stimuli. 5. The data suggest that both firing rates and correlated activity between adjacent neurons in the auditory cortex encode sound location and movement.

Acoustic Stimulation

Medical home care services for the housebound elderly.

In our health jurisdiction the proportion of elderly people is more than double the national average, and there is a severe shortage of both home care services and long-term care beds. To help the many elderly housebound people without primary medical care we initiated a medical services home care program. The goals were patient identification, clinical assessment, medical and social stabilization, matching of the housebound patient with a nearby family physician willing and able to provide home care and provision of a backup service to the physician for consultation and help in arranging admission to hospital if necessary. In the program's first 2 years 105 patients were enrolled; the average age was 78.9 years. More than 50% were widowed, single, separated or divorced, over 25% lived alone, and more than 40% had no children living in the city. In almost one-third of the cases there had never been a primary care physician, and in another third the physician refused to do home visits. Before becoming housebound 15% had been seeing only specialists. Each patient had an average of 3.2 active medical problems and was functionally quite dependent. Thirty-five of the patients were surveyed after 1 year: 24 (69%) were still at home, and only 1 (3%) was in a long-term care institution; 83% were satisfied with the care provided, and 79% felt secure that their health needs were being met. One-third of the patients or their families said that it was not easy to reach the physician when necessary. We recommend that programs similar to ours be set up in health jurisdictions with a high proportion of elderly people. To recruit and retain cooperative physicians hospital geriatric services must be willing to provide educational, consultative and administrative support.

Aged

Appropriateness of patient transfer from a nursing home to an acute-care hospital: a study of emergency room visits and hospital admissions.

OBJECTIVE: To determine the appropriateness of transfers to acute care hospitals from a nursing home. DESIGN: Nursing home and hospital records of all the nursing home residents during the 3-year study period were reviewed retrospectively to determine: number and type of transfers; problems identified in the nursing home justifying the transfers; diagnoses made at the hospitals; length of hospital stays; outcome of hospital visits. SETTING: An 80-bed public nursing home. SUBJECTS: 112 residents in the nursing home over the 3-year study period. MAIN OUTCOME MEASURES: Based on the decision of the hospital physician, those transfers resulting in hospital admissions were considered appropriate. As well, transfers to the emergency room with return to the nursing home without hospital admission were also judged to be appropriate if the problems required diagnostic and therapeutic procedures not available in the nursing home. RESULTS: During the 3-year study period, 55 residents (49%) were transferred a total of 102 times. An average of 26% of patients were transferred each year. Direct admissions to acute hospitals accounted for 17% of the transfers, transfers to the emergency room with subsequent admission for 34%, and transfers to the emergency room with subsequent return to the nursing home without admission for 45%. Four percent of patients transferred died in the emergency room. On the basis of the outcome measure, 7% of all transfers could have been diagnosed and treated in the nursing home and were considered inappropriate. CONCLUSIONS: The majority of transfers from this nursing home to acute-care hospitals were appropriate.

Aged

Neural interactions in the frontal cortex of a behaving monkey: signs of dependence on stimulus context and behavioral state.

In order to gain an understanding of the processes taking place within and between neuronal assemblies, we made simultaneous recordings of spike trains from groups of up to 11 neurons in the frontal cortex of a rhesus monkey, that was trained to perform a sensorimotor behavioral task. We report here on preliminary results from correlation analysis of these neuronal activities, with special emphasis on signs of behaviorally induced modifications of neural interaction, possibly due to rapid modulations of discharge synchronization among the neurons. Our findings suggest that different functional groups of neurons may co-exist within each small volume of cortex, and that neurons may be dynamically recruited into such a group to fulfil a specific function.

Animals

Reversal of experimental parkinsonism by lesions of the subthalamic nucleus.

Although it is known that Parkinson's disease results from a loss of dopaminergic neurons in the substantia nigra, the resulting alterations in activity in the basal ganglia responsible for parkinsonian motor deficits are still poorly characterized. Recently, increased activity in the subthalamic nucleus has been implicated in the motor abnormalities. To test this hypothesis, the effects of lesions of the subthalamic nucleus were evaluated in monkeys rendered parkinsonian by treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The lesions reduced all of the major motor disturbances in the contralateral limbs, including akinesia, rigidity, and tremor. This result supports the postulated role of excessive activity in the subthalamic nucleus in Parkinson's disease.

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

Tetrahydroaminoacridine-lecithin combination treatment in patients with intermediate-stage Alzheimer's disease. Results of a Canadian double-blind, crossover, multicenter study.

We studied the efficacy and safety of oral tetrahydroaminoacridine (THA) combined with lecithin in 52 patients with Alzheimer's disease. The maximal tolerated dose of THA (up to 100 mg per day) was determined during an eight-week titration period, after which the tolerated dose of THA or placebo was given during two sequential randomized periods of treatment lasting eight weeks each. Highly purified lecithin (4.7 g per day) was administered during all phases of the study. Efficacy was expressed in terms of scores on the Mini-Mental State (MMS) test, the modified MMS test, the Hierarchic Dementia Scale, the Rapid Disability Rating Scale-II, and the behavioral scale of Reisberg et al. Safety was assessed by careful clinical monitoring as well as serial measurements of liver aminotransferases. Forty-six patients completed the titration period, and 39 completed the double-blind period, during which only the MMS score showed a small but significant increase (P less than 0.05) after four weeks of treatment with THA. Autonomic side effects of THA were common but mild. Reversible elevations of serum aspartate and alanine aminotransferase levels to three or more times the upper limit of normal occurred in 17 percent of patients; most of the patients affected were women. A liver biopsy performed in one patient showed resolving focal liver-cell necrosis. These studies fail to demonstrate a significant clinical benefit of THA given orally in a maximal dose of 100 mg per day over a period of eight weeks in combination with lecithin.

Administration, Oral

Intraocular hypothalamic transplants containing histaminergic neurons: innervation of host iris and hippocampal cografts.

Hypothalamic tissue containing the tuberomammillary nucleus was dissected from fetuses of Embryonic Day 17 and inserted into the anterior chamber of the eye of young adult recipient rats. The growth of hypothalamic grafts was monitored through the translucent cornea and transplants were found to double in size over the 8 first weeks in oculo. After 4 weeks fetal hippocampal formation (Embryonic Day 18) was inserted into the eye chamber in half of the previously grafted animals and placed in contact with the first grafts. Double grafts were allowed to mature for up to 18 weeks before sacrifice. Recipient rats were anesthetized and superfused with carbodiimide and paraformaldehyde, after which transplants were removed, frozen, sectioned on a cryostat, and incubated with histamine antibodies. Immunohistochemical evaluations revealed a large number of histamine-positive nerve cell bodies with processes innervating the entire hypothalamic graft with a dense plexus of varicose fibers. Such histamine-positive fibers were also seen to invade the surrounding host iris in some cases with thick axon bundles as well as with single fibers. When hypothalamic transplants were combined with hippocampal grafts numerous histamine-immunoreactive fibers invaded the hippocampal tissue to form a plexus of varicose terminals throughout the cografts. After 4 weeks in oculo only a sparse histamine-positive innervation of hippocampal grafts was found, while 18-week-old double grafts contained a considerably larger amount of immunoreactive neurites.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Predictors and consequences of aggressive behavior by community-based dementia patients.

The frequency, nature, context, and caregivers' reactions to aggressive behavior in 213 dementia patients residing in the community was studied. Aggression was reported in 57.2% of the patients and in 10.6% of the caregivers. Predictors of patient aggression were greater frequency of behavior and memory problems, premorbid aggression, and a more troubled premorbid social relationship between patient and caregiver. Patient aggression predicted the decision to discontinue home care.

Aged

Urea excretion as a strategy for survival in a fish living in a very alkaline environment.

Ammonia is toxic to all vertebrates. It can be converted to the less toxic urea, but this is a metabolically expensive process found only in terrestrial vertebrates that cannot readily excrete ammonia and marine fish that use urea as an osmotic filler. Freshwater fish mostly excrete ammonia with only a small quantity of urea. It seems the ornithine cycle for urea production has been suppressed in all freshwater teleosts except for some airbreathers which, when exposed to air, increase urea synthesis via the cycle. Here we show that the tilapia fish Oreochromis alcalicus grahami, the only fish living in Lake Magadi, an alkaline soda lake (pH = 9.6-10) in the Kenyan Rift Valley, excretes exclusively urea and has ornithine-urea cycle enzymes in its liver. A closely related species that lives in water at pH 7.1 lacks these enzymes and excretes mainly ammonia with small amounts of urea produced via uricolysis. It dies within 60 min when placed in water from Lake Magadi. We suggest that urea production via the ornithine-urea cycle permits O. a. grahami to survive the very alkaline conditions in Lake Magadi.

Acclimatization