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Biomedical subjects

S Fusi

Publications and source records attributed to S Fusi.

At least 19 recordsLinked to original sources

Forming classes by stimulus frequency: behavior and theory.

Visual classification is the way we relate to different images in our environment as if they were the same, while relating differently to other collections of stimuli (e.g., human vs. animal faces). It is still not clear, however, how the brain forms such classes, especially when introduced with new or changing environments. To isolate a perception-based mechanism underlying class representation, we studied unsupervised classification of an incoming stream of simple images. Classification patterns were clearly affected by stimulus frequency distribution, although subjects were unaware of this distribution. There was a common bias to locate class centers near the most frequent stimuli and their boundaries near the least frequent stimuli. Responses were also faster for more frequent stimuli. Using a minimal, biologically based neural-network model, we demonstrate that a simple, self-organizing representation mechanism based on overlapping tuning curves and slow Hebbian learning suffices to ensure classification. Combined behavioral and theoretical results predict large tuning overlap, implicating posterior infero-temporal cortex as a possible site of classification.

Adult↗

Spike-driven synaptic plasticity: theory, simulation, VLSI implementation.

We present a model for spike-driven dynamics of a plastic synapse, suited for aVLSI implementation. The synaptic device behaves as a capacitor on short timescales and preserves the memory of two stable states (efficacies) on long timescales. The transitions (LTP/LTD) are stochastic because both the number and the distribution of neural spikes in any finite (stimulation) interval fluctuate, even at fixed pre- and postsynaptic spike rates. The dynamics of the single synapse is studied analytically by extending the solution to a classic problem in queuing theory (Takacs process). The model of the synapse is implemented in aVLSI and consists of only 18 transistors. It is also directly simulated. The simulations indicate that LTP/LTD probabilities versus rates are robust to fluctuations of the electronic parameters in a wide range of rates. The solutions for these probabilities are in very good agreement with both the simulations and measurements. Moreover, the probabilities are readily manipulable by variations of the chip's parameters, even in ranges where they are very small. The tests of the electronic device cover the range from spontaneous activity (3-4 Hz) to stimulus-driven rates (50 Hz). Low transition probabilities can be maintained in all ranges, even though the intrinsic time constants of the device are short (approximately 100 ms). Synaptic transitions are triggered by elevated presynaptic rates: for low presynaptic rates, there are essentially no transitions. The synaptic device can preserve its memory for years in the absence of stimulation. Stochasticity of learning is a result of the variability of interspike intervals; noise is a feature of the distributed dynamics of the network. The fact that the synapse is binary on long timescales solves the stability problem of synaptic efficacies in the absence of stimulation. Yet stochastic learning theory ensures that it does not affect the collective behavior of the network, if the transition probabilities are low and LTP is balanced against LTD.

Action Potentials↗

Collective behavior of networks with linear (VLSI) integrate-and-fire neurons.

We analyze in detail the statistical properties of the spike emission process of a canonical integrate-and-fire neuron, with a linear integrator and a lower bound for the depolarization, as often used in VLSI implementations (Mead, 1989). The spike statistics of such neurons appear to be qualitatively similar to conventional (exponential) integrate-and-fire neurons, which exhibit a wide variety of characteristics observed in cortical recordings. We also show that, contrary to current opinion, the dynamics of a network composed of such neurons has two stable fixed points, even in the purely excitatory network, corresponding to two different states of reverberating activity. The analytical results are compared with numerical simulations and are found to be in good agreement.

Afferent Pathways↗

Inter-trial neuronal activity in inferior temporal cortex: a putative vehicle to generate long-term visual associations.

When monkeys perform a delayed match-to-sample task, some neurons in the anterior inferotemporal cortex show sustained activity following the presentation of specific visual stimuli, typically only those that are shown repeatedly. When sample stimuli are shown in a fixed temporal order, the few images that evoke delay activity in a given neuron are often neighboring stimuli in the sequence, suggesting that this delay activity may be the neural correlate of associative long-term memory. Here we report that stimulus-selective sustained activity is also evident following the presentation of the test stimulus in the same task. We use a neural network model to demonstrate that persistent stimulus-selective activity across the intertrial interval can lead to similar mnemonic representations (distributions of delay activity across the neural population) for neighboring visual stimuli. Thus, inferotemporal cortex may contain neural machinery for generating long-term stimulus-stimulus associations.

Animals↗

Learning attractors in an asynchronous, stochastic electronic neural network.

LANN27 is an electronic device implementing in discrete electronics a fully connected (full feedback) network of 27 neurons and 351 plastic synapses with stochastic Hebbian learning. Both neurons and synapses are dynamic elements, with two time constants--fast for neurons and slow for synapses. Learning, synaptic dynamics, is analogue and is driven in a Hebbian way by neural activities. Long-term memorization takes place on a discrete set of synaptic efficacies and is effected in a stochastic manner. The intense feedback between the nonlinear neural elements, via the learned synaptic structure, creates in an organic way a set of attractors for the collective retrieval dynamics of the neural system, akin to Hebbian learned reverberations. The resulting structure of the attractors is a record of the large-scale statistics in the uncontrolled, incoming flow of stimuli. As the statistics in the stimulus flow changes significantly, the attractors slowly follow it and the network behaves as a palimpsest--old is gradually replaced by new. Moreover, the slow learning creates attractors which render the network a prototype extractor: entire clouds of stimuli, noisy versions of a prototype, used in training, all retrieve the attractor corresponding to the prototype upon retrieval. Here we describe the process of studying the collective dynamics of the network, before, during and following learning, which is rendered complex by the richness of the possible stimulus streams and the large dimensionality of the space of states of the network. We propose sampling techniques and modes of representation for the outcome.

Animals↗

Free radial artery grafts: surgical technique and results.

In the search for alternative conduits, the use of radial artery (RA) grafts has found renewed interest. This study sought to evaluate prospectively the perioperative morbidity, including the postoperative complications in the donor forearm, and mortality in the routine use of RA grafts in coronary artery bypass surgery. Data were obtained prospectively on 200 consecutive patients who underwent coronary revascularization using at least one RA graft from January 1995 to April 1997. The mean age of the patents was 61.9+/-10.5 years (mean+/-standard deviation [SD]). The RA was obtained from one forearm in 197 patients and both forearms in 3 patients. Two patients (1%) required exploration for donor site hematomas, 4 patients (2%) had temporary perioperative dysesthesias in the region of the lateral cutaneous nerve of the forearm, and none had donor site wound infection. Two patients (1%) had a myocardial infarction with electrocardiographic changes in the areas grafted by the RA in the immediate postoperative period, indicating graft failure. The two deaths in the series were due to comorbid factors. Our data suggest that the RA is a safe and suitable conduit for coronary revascularization, and it provides good clinical results. Long-term follow-up of these patients is necessary to confirm the patency of RA conduits. Free RA grafts have the potential for use in other areas of surgery where a conduit is necessary for revascularization procedures.

Coronary Artery Bypass↗

Slow stochastic Hebbian learning of classes of stimuli in a recurrent neural network.

We study unsupervised Hebbian learning in a recurrent network in which synapses have a finite number of stable states. Stimuli received by the network are drawn at random at each presentation from a set of classes. Each class is defined as a cluster in stimulus space, centred on the class prototype. The presentation protocol is chosen to mimic the protocols of visual memory experiments in which a set of stimuli is presented repeatedly in a random way. The statistics of the input stream may be stationary, or changing. Each stimulus induces, in a stochastic way, transitions between stable synaptic states. Learning dynamics is studied analytically in the slow learning limit, in which a given stimulus has to be presented many times before it is memorized, i.e. before synaptic modifications enable a pattern of activity correlated with the stimulus to become an attractor of the recurrent network. We show that in this limit the synaptic matrix becomes more correlated with the class prototypes than with any of the instances of the class. We also show that the number of classes that can be learned increases sharply when the coding level decreases, and determine the speeds of learning and forgetting of classes in the case of changes in the statistics of the input stream.

Generalization, Stimulus↗

Paradigmatic working memory (attractor) cell in IT cortex.

We discuss paradigmatic properties of the activity of single cells comprising an attractor-a developed stable delay activity distribution. To demonstrate these properties and a methodology for measuring their values, we present a detailed account of the spike activity recorded from a single cell in the inferotemporal cortex of a monkey performing a delayed match-to-sample (DMS) task of visual images. In particular, we discuss and exemplify (1) the relation between spontaneous activity and activity immediately preceding the first stimulus in each trial during a series of DMS trials, (2) the effect on the visual response (i.e., activity during stimulation) of stimulus degradation (moving in the space of IT afferents), (3) the behavior of the delay activity (i.e., activity following visual stimulation) under stimulus degradation (attractor dynamics and the basin of attraction), and (4) the propagation of information between trials-the vehicle for the formation of (contextual) correlations by learning a fixed stimulus sequence (Miyashita, 1988). In the process of the discussion and demonstration, we expose effective tools for the identification and characterization of attractor dynamics.

Animals↗

The carpal boss. A 20-year review of operative management.

Between 1969 and 1989, 116 patients were evaluated and treated surgically for symptomatic carpal boss. Their mean age was 32 years and male and female patients were equally affected. 28 patients gave a history of previous injury. Surgical treatment consisted of excision of the localized bony abnormality and the associated degenerative arthritic process to the level of normal articular surfaces and normal adjacent cancellous bone. The mean follow-up period for the patients in this study was 42 months. Complete symptomatic relief was observed in 94% of the patients undergoing surgical treatment. Recurrence or persistence of symptoms developed in seven surgical patients. Six had a second operation with more extensive removal of sclerotic bone and degenerate cartilage, and all patients had relief of symptoms.

Adolescent↗

Immediate tendon Achilles reconstruction with composite palmaris longus grafts.

Full-thickness defects of the posterior heel constitute a continuing reconstructive challenge due to a relative lack of regional tissues in this area and the inherent avascularity of the tendo-Achilles. Wound closure and tendon reconstruction with composite flaps can potentially accelerate healing, reduce scarring, and improve tendon function. In 2 patients, a radial forearm-palmaris longus composite free flap was used to reconstruct full-thickness defects of the heal and tendo-Achilles. Rapid healing and return of function were obtained without significant donor site disability.

Achilles Tendon↗

Data on first recurrence after treatment for malignant melanoma in a large patient population.

Recurrent malignant melanoma is a clinical entity that behaves distinctly differently from the primary disease. The purpose of this study was to determine whether there are significant trends in the prognostic factors or in the timing and sites of recurrence. We reviewed 250 patients with recurrent malignant melanoma from the Sydney Melanoma Unit in Australia who were followed in their Tumor Registry between 1960 and 1981 (median follow-up was 7 years). Fifty-two percent of all first recurrences were to regional nodes, 17 percent were local recurrences, 8 percent were in-transit metastases, and 23 percent of all first recurrences were to a distant organ. We found that 67 percent of all recurrences were diagnosed within 24 months and 81 percent were diagnosed by 36 months after the primary melanoma. Regional nodal recurrences were diagnosed earlier (with 63 percent at 18 months and 74 percent at 24 months). Local recurrences and in-transit metastases were comparable (with 55 percent of each at 18 months and about 66 percent of each at 24 months), and systemic recurrences were diagnosed later (52 percent at 24 months and 71 percent at 36 months). Of significant interest was the fact that survival after the diagnosis of recurrence was independent of thickness of the primary tumor or duration of disease-free interval (local, in-transit, or regional nodal). Only the diagnosis of distant organ metastasis correlated with shorter survival; local recurrence, in-transit metastasis, and regional nodal metastasis were all associated with comparable survivals.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Treatment of the particularly fatty neck and the short-interval secondary facelift.

In patients with normal body weight but with large accumulations of submental and cervical fat, good results can be obtained by an extensive subcutaneous dissection, carefully sculpted removal of the excess fat, and relatively limited work on the platysema. For some patients there may be an indication for a secondary facelift involving skin dissection alone within a relatively short interval.

Adipose Tissue↗

Cyclical Cushing's disease: report of a case cured by conventional cobaltotherapy.

Preliminary hormonal studies in a 18-y old man with the clinical features of Cushing's syndrome showed inconclusive and conflicting results both in basal conditions and after metyrapone and dexamethasone administration. Therefore the possibility of a cyclical or acyclical fluctuation of adrenal hypersecretion was suspected and the patient was observed for an extended period of time free of hormonal manipulations. Regular cycles of cortisol hyperproduction, with peaks occurring every 6.0 days were found. Ectopic ACTH production was ruled out and, even in the absence of radiological evidence of a pituitary adenoma, conventional cobaltotherapy was suggested after refusal of transsphenoidal pituitary surgery. About 8 months later a marked clinical improvement was evident as well as normalization of hormonal data with loss of the cyclical pattern. Remission of the disease was still persistent 15 and 28 months later. A recent control, approximately 4 1/2 yr after treatment confirmed the normalization of biochemical data, suggesting a cure of the disease.

Adolescent↗

Study of endocrine function in myotonic dystrophy.

Endocrine function was studied in 12 patients, 7 men and 5 women, with myotonic dystrophy (MD). Growth hormone (GH) was within normal limits in all the patients and there was no response to arginine stimulation. Prolactin (PRL) was above normal in only 2 cases (one man and one woman) and the response to TRH was below normal in 2 patients and slightly above in one. The GnRH test yielded a reduced LH response in 4 of the 7 men and none at all in the 4 women in whom it was done. The FSH response was below normal in only one of the 7 men and in 3 out of 4 women. The testosterone assay after HCG stimulation was borderline high in 2 out of 6 men and below normal in one. The level of thyroid hormones (T3, T4, FTI, TSH) was normal in all patients except one, whose FTI and T4 level were below normal. In the TRH test TSH was raised in only one of the 6 patients tested. The circadian rhythm of cortisol was absent in 3 out of 10 patients and 3 out of 8 patients showed no response to ACTH stimulation. The results of the study suggest that endocrine alterations are fairly frequent in MD but that they are neither specific nor correlated with disease severity or duration.

Adrenal Cortex↗

Reversal of postburn immunosuppression by the administration of vitamin A.

The effect of high doses of vitamin A was evaluated on the suppression of cellular immunity after a 30% body surface area experimental scald burn in a mouse model. Male CBA/J mice were treated postburn with daily intraperitoneal injections of either 3000 IU of vitamin A or an equal volume of 0.9N saline. Similar groups of unburned mice were also studied as controls. At the seventh postburn day, one-way mixed lymphocyte reactions were tested for each group with whole spleen cells of CBA/J mice used as responders and mitomycin C-treated whole spleen cells of C57 BL/6 mice used as stimulators. When results were expressed as mean percentage of the values of control animals, no significant difference was observed between the saline-injected unburned control group (taken as 100%) and the vitamin A-treated unburned control groups (89%). The burned animals treated with saline showed suppression to 21% of the control values. However, the burned animals treated postburn with vitamin A improved the response rate dramatically to 52% of control values. This improvement over the untreated burned animals was significant in all experiments performed (p less than 0.02). This study suggests that vitamin A may be an effective agent in the reversal of cellular immunosuppression after burns.

Animals↗

Effects of pharmacological doses of testosterone and dihydrotestosterone on the hypothalamic-pituitary axis function of Klinefelter patients.

Six patients affected by Klinefelter's syndrome (KS) were treated with testosterone propionate (TP) 100 mg im daily for 4 days and one month later the same patients received dihydrotestosterone propionate (DHTP) 100 mg im daily for 4 days. Plasma levels of LH, FSH, PRL, testosterone (T) and dihydrotestosterone (DHT) have been measured in these patients for 8 days during and after TP and DHTP treatment. TP administration reduced LH levels only transiently, while a more prolonged reduction was observed for FSH. DHTP administration produced a late and transient reduction of LH and a very late reduction of FSH. PRL levels increased significantly during and after TP administration. Our data suggest that in Klinefelter patients: i) DHT is less effective than T in suppressing gonadotropin concentrations, ii) the increased PRL levels observed during and after TP administration are not due to a pure androgenic effect, but are probably related to an increased conversion rate of T to estradiol.

Adolescent↗

Parameters of interferon action: I. Immunological effects of whole cell leukocyte interferon (IFN-alpha) in phase I-II trials.

The antitumor mechanisms of the interferons (IFN) have yet to be fully elucidated. Augmentation of natural killer (NK) cell activity in vitro and in vivo by IFN has regularly been assessed in clinical trials. We have measured NK activity against K562 target cells at various effector-to-target ratios, in patients receiving leukocyte IFN-alpha (HuLeIFN) in various schedules, as well as T-cell subsets determined by indirect immunofluorescence using Leu series monoclonal antibodies (Becton-Dickinson). The effect of HuLeIFN on the endocrine system has also been examined in selected trials. The preliminary results of these studies reveal that NK activity rose during the first 8 days of HuLeIFN therapy in patients with initially low levels of target cell lysis (less than 50% NK activity at either 50:1 or 25:1 ratios). Tachyphylaxis, with a decremental effect of HuLeIFN on NK activity, ensued during treatment, whether at the same or escalated doses. NK activity rose repeatedly during intermittent schedules of i.m. HuLeIFN given daily x 5 every 21 days with escalation cycles. A decreasing trend in the ratio of Leu 3a to Leu 2a (helper phenotype/suppressor phenotype) was also seen overall. Of the endocrine parameters evaluated, the only remarkable finding was an increase in serum cortisol level following ACTH stimulation following HuLeIFN. Intramuscular HuLeIFN has been shown to augment NK activity, to perturb the T-cell-lymphocyte balance, and to affect the pituitary-adrenal axis in vivo.

Adenocarcinoma↗