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M Bodner

Publications and source records attributed to M Bodner.

At least 19 recordsLinked to original sources
PubMed2001

Reliable short-term memory in the trion model: toward a cortical language and grammar.

It has previously been shown that Hebb learning in a single column in the trion model of cortical organization occurs by selection. Motivated by von Neumann's solution for obtaining reliability and by models of circulating cortical activity, we introduce Hebb intercolumnar couplings to achieve dramatic enhancements in reliability in the firing of connected columns. In order for these enhancements to occur, specific temporal phase differences must exist between the same inherent spatial-temporal memory patterns in connected columns. We then generalize the criteria of large enhancements in the global firing of the entire connected columnar network to investigate the case when different inherent memory patterns are in the columns. The spatial rotations as well as the temporal phases now are crucial. Only certain combinations of inherent memory patterns meet these criteria with the symmetry properties playing a major role. The columnar order of these memory patterns not in the same symmetry family can be extremely important. This yields the first higher-level architecture of a cortical language and grammar within the trion model. The implications of this result with regard to an innate human language and grammar are discussed.

Cerebral Cortex↗
PubMed2000

Cross-modal and cross-temporal association in neurons of frontal cortex.

The prefrontal cortex is essential for the temporal integration of sensory information in behavioural and linguistic sequences. Such information is commonly encoded in more than one sense modality, notably sight and sound. Connections from sensory cortices to the prefrontal cortex support its integrative function. Here we present the first evidence that prefrontal cortex cells associate visual and auditory stimuli across time. We gave monkeys the task of remembering a tone of a certain pitch for 10 s and then choosing the colour associated with it. In this task, prefrontal cortex cells responded selectively to tones, and most of them also responded to colours according to the task rule. Thus, their reaction to a tone was correlated with their subsequent reaction to the associated colour. This correlation faltered in trials ending in behavioural error. We conclude that prefrontal cortex neurons are part of integrative networks that represent behaviourally meaningful cross-modal associations. The orderly and timely activation of neurons in such networks is crucial for the temporal transfer of information in the structuring of behaviour, reasoning and language.

Action Potentials↗
PubMed2000

Generation of retroviral packaging and producer cell lines for large-scale vector production and clinical application: improved safety and high titer.

For many applications, human clinical therapies using retroviral vectors still require many technological improvements in key areas of vector design and production. These improvements include higher unprocessed manufacturing titers, complement-resistant vectors, and minimized potential to generate replication-competent retrovirus (RCR). To address these issues, we have developed a panel of human packaging cell lines (PCLs) with reduced homology between retroviral vector and packaging components. These reduced-homology PCLs allowed for the use of a novel high multiplicity of transduction ("high m.o. t.") method to introduce multiple copies of provector within vector-producing cell lines (VPCLs), resulting in high-titer vector without the generation of RCR. In a distinct approach to increase vector yields, we integrated manufacturing parameters into screening strategies and clone selection for large-scale vector production. Collectively, these improvements have resulted in the development of diverse VPCLs with unprocessed titers exceeding 2 x 10(7) CFU/ml. Using this technology, human Factor VIII VPCLs yielding titers as high as 2 x 10(8) CFU/ml unprocessed supernatant were generated. These cell lines produce complement-resistant vector particles (N. J. DePolo et al., J. Virol. 73: 6708-6714, 1999) and provide the basis for an ongoing Factor VIII gene therapy clinical trial.

Base Sequence↗
PubMed2000

Increasing epithelial junction permeability enhances gene transfer to airway epithelia In vivo.

Gene transfer to airway epithelia is the most direct approach for treating the progressive lung disease associated with cystic fibrosis. However, the transduction efficiency is poor when viral vectors are applied to the mucosal surface. We reported previously that gene transfer via the apical surface of human airway epithelia in vitro was improved by formulating vectors with ethyleneglycol-bis-(2-aminoethyl ether)- N,N,N',N'-tetraacetic acid (EGTA) in a hypotonic buffer. First, we investigated the mechanism for this enhancement. When 100-nm fluorescent beads were applied to the apical surface in the presence of EGTA, paracellular deposition of the particles was noted. Transmission electron microscopy verified that the epithelial junction complex was disrupted under these conditions. The Ca(2+) chelators EGTA, 1,2-bis (2-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (BAPTA), and ethylenediaminetetraacetic acid all caused a rapid, reversible drop in transepithelial resistance and facilitated gene transfer with retrovirus or adenovirus in vitro. When Ca(2+) chelators were applied to rabbit tracheal epithelia or human nasal epithelia in vivo, the transepithelial voltage decreased, and amiloride sensitivity was lost, suggesting that epithelial junctions opened. Importantly, this novel formulation enhanced both retroviral- and adenoviral-mediated gene transfer to rabbit tracheal epithelia in vivo. This technique may have applications for vector or drug delivery to airway epithelia and other polarized cells.

Amiloride↗
PubMed1999

The resistance of retroviral vectors produced from human cells to serum inactivation in vivo and in vitro is primate species dependent.

The ability to deliver genes as therapeutics requires an understanding of the vector pharmacokinetics similar to that required for conventional drugs. A first question is the half-life of the vector in the bloodstream. Retroviral vectors produced in certain human cell lines differ from vectors produced in nonhuman cell lines in being substantially resistant to inactivation in vitro by human serum complement (F. L. Cosset, Y. Takeuchi, J. L. Battini, R. A. Weiss, and M. K. Collins, J. Virol. 69:7430-7436, 1995). Thus, use of human packaging cell lines (PCL) may produce vectors with longer half-lives, resulting in more-efficacious in vivo gene therapy. However, survival of human PCL-produced vectors in vivo following systemic administration has not been explored. In this investigation, the half-lives of retroviral vectors packaged by either canine D17 or human HT1080 PCL were measured in the bloodstreams of macaques and chimpanzees. Human PCL-produced vectors exhibited significantly higher concentrations of circulating biologically active vector at the earliest time points measured (>1, 000-fold in chimpanzees), as well as substantially extended half-lives, compared to canine PCL-produced vectors. In addition, the circulation half-life of human PCL-produced vector was longer in chimpanzees than in macaques. This was consistent with in vitro findings which demonstrated that primate serum inactivation of vector produced from human PCL increased with increasing phylogenetic distance from humans. These results establish that in vivo retroviral vector half-life correlates with in vitro resistance to complement. Furthermore, these findings should influence the choice of animal models used to evaluate retroviral-vector-based therapies.

Animals↗
PubMed1999

Detecting symmetric patterns in EEG data: a new method of analysis.

Theoretical models of higher cognitive function predict that cortical activity will exhibit families of spatial-temporal patterns of activity whose individual members are related to each other by specific symmetry transformations. In the trion model, it is suggested that these inherent symmetries play a vital role in how we think and reason. We have developed a method of analysis (SYMMETRIC analysis), which detects families of patterns in EEG data, and characterizes the symmetry relationships between members of those pattern families. Using this analysis, significant symmetry families have been found in EEG and single unit spike train data. If symmetry is a crucial aspect of brain function, it is possible that different pathologies are associated with specific types of symmetry relationships in brain activity that could be detected in EEG data by a SYMMETRIC analysis.

Electroencephalography↗
PubMed1999

Music enhances spatial-temporal reasoning: towards a neurophysiological basis using EEG.

Motivated by predictions from the structured trion model of the cortex, based on Mountcastle's columnar organizational principle, behavioral experiments have demonstrated a causal short-term enhancement of spatial-temporal reasoning in college students following listening to a Mozart Sonata (K.448) but not in control conditions. An EEG coherence study reported presence of right frontal and left temporoparietal activity induced by listening to the Mozart Sonata, which carried over into the spatial-temporal tasks in three of the seven subjects. In this paper, we present further predictions from the trion model and discuss how the new SYMMETRIC analysis method can be used in EEG recordings to help determine the neurophysiological basis of specific music enhancing spatial-temporal reasoning. We conclude with potential clinical applications of major significance.

Child, Preschool↗
PubMed1998

Effects of keratinocyte and hepatocyte growth factor in vivo: implications for retrovirus-mediated gene transfer to liver.

We have previously shown that intravenous administration of keratinocyte growth factor (KGF) induces hepatocyte proliferation, allowing for efficient and noninvasive in vivo gene transfer with high-titer retroviral vectors in mice. The distinctive periportal distribution of transduced cells led us to investigate the ability of virus-sized particles to perfuse the liver adequately after growth factor treatment. We found that perfusion was adequate, and that transduction was limited to the periportal region because only those cells were stimulated to divide. Cells in this region also showed increased expression of Ram-1, the receptor for the murine Moloney leukemia virus (MoMLV) amphotropic envelope, after KGF treatment. In further studies we found that recombinant hepatocyte growth factor (HGF) induces a different population of hepatocytes to divide and upregulate Ram-1. The differential pattern of induction suggested that combining KGF and HGF would improve gene transfer efficiency further. Indeed, simultaneous delivery of both growth factors leads to an overall increase in the number of proliferating cells. Importantly, when coupled with MoMLV delivery, efficiency of gene transfer increased. These results confirm the utility of growth factors for noninvasive hepatic gene transfer in mice, and demonstrate how experiments to define the mechanism of transduction can be taken advantage of to develop improved gene transfer protocols.

Animals↗
PubMed1998

High-frequency transitions in cortical spike trains related to short-term memory.

Single-unit spike trains recorded from parietal cortex of monkeys performing a tactile short-term memory task show characteristic fluctuations (transitions) in their firing frequency that are related to memory. Spike trains recorded during the memory period, when the animal must retain information for the short term, show a higher rate of such transitions than spike trains recorded during intertrial baseline periods. In the present study, an analysis of multiple temporal resolutions over which these transitions are observed reveals that the memory-related transitions occur most prominently in the 25-50 Hz range. The results of this study suggest that, in the monkey, high frequency fluctuations of neuronal discharge in the parietal cortex are correlated with haptic short-term memory. The presence of such fluctuations are also consistent with theoretical models of short-term memory.

Animals↗
PubMed1998

Influence of cell polarity on retrovirus-mediated gene transfer to differentiated human airway epithelia.

Gene transfer with recombinant murine leukemia viruses (MuLV) provides the potential to permanently correct inherited lung diseases, such as cystic fibrosis (CF). Several problems prevent the application of MuLV-based recombinant retroviruses to lung gene therapy: (i) the lack of cell proliferation in mature pulmonary epithelia, (ii) inefficient gene transfer with a vector applied to the apical surface, and (iii) low titers of many retroviral preparations. We found that keratinocyte growth factor (KGF) stimulated proliferation of differentiated human tracheal and bronchial epithelia. Approximately 50% of epithelia divided in response to KGF as assessed by bromodeoxyuridine histochemistry. In airway epithelia stimulated to divide with KGF, high-titer ampho- and xenotropic enveloped vectors preferentially infected cells from the basal side. However, treatment with hypotonic shock or EGTA transiently increased transepithelial permeability, enhancing gene transfer with the vector applied to the mucosal surfaces of KGF-stimulated epithelia. Up to 35% of cells expressed the transgene after gene transfer. By using this approach, cells throughout the epithelial sheet, including basal cells, were targeted. Moreover, the Cl- transport defect in differentiated CF airway epithelia was corrected. These findings suggest that barriers to apical infection with MuLV can be overcome.

Bronchi↗
PubMed1997

Symmetric temporal patterns in cortical spike trains during performance of a short-term memory task.

The trion model is a highly structured representation of cortical organization, which predicts families of symmetric spatial-temporal firing patterns inherent in cortical activity. The symmetries of these inherent firing patterns are used by the brain in short-term memory to perform higher level computations. In the present study, symmetric temporal patterns were searched for in spike trains recorded from cells in parietal cortex of a monkey performing a short-term memory task. A new method of analysis was used to map neuronal firing into sequences of integers representing relative levels of firing rate about the mean (i.e. -1, 0 and 1). The results of this analysis show families of patterns related by symmetry operations. These operations are: i. the interchanging of all the +1's and -1's in a given pattern sequence (C symmetry), ii. the inverting of the temporal sequence of the mapping (T symmetry), and iii. the combination of the two previous operations (CT symmetry). Patterns of a given family are found across cells, especially in the memory periods of the task; in most cases they reoccur within a given spike train. The pattern families predicted by the model and reported here should be further investigated in multiple microelectrode and EEG recordings.

Action Potentials↗
PubMed1997

Binary mapping of cortical spike trains in short-term memory.

Microelectrode studies in monkeys performing short-term memory tasks show the sustained elevated discharge of cortical neurons during the retention of recalled sensory information. Cortical cells that are part of memory networks are assumed to receive numerous inputs of excitatory as well as inhibitory nature and local as well as remote. Thus it is reasonable to postulate that the temporal and spatial summation of diverse inputs on any cell in an activated network will result in temporally discrete groups of spikes in its firing. The activation of a network in active memory supposedly increases the magnitude and diversity of those inputs and thus increases the discontinuities and frequency fluctuations in the firing of cells in the network. In this study we use a new method of analysis that allows the quantification of firing discontinuities in a spike train. We apply it to parietal cells recorded from monkeys during the performance of a tactile short-term memory task. In our method, time is divided into bins of equal duration and the measure of discontinuities is the total count of the number of transitions between consecutive time bins with and without spikes. The results of the analysis show that in many of the cells studied, discontinuities (transitions between spiking and nonspiking) reflect memory-related activity obscured in the measures of raw spike frequency over a wide range of frequencies. These cells show more firing transitions in active short-term memory than in baseline (intertrial) conditions.

Animals↗
PubMed1996

Auditory memory cells in dorsolateral prefrontal cortex.

The activity of single neurons was recorded extracellularly from dorsolateral prefrontal cortex (DPC) of monkeys during the performance of a cross-modal audio-visual short-term memory task. Cells in DPC show sustained elevated firing levels (higher than spontaneous discharge) during the retention of the auditory stimulus. In some cells this elevated firing was significantly different depending on the particular auditory memorandum of each trial. These results support the notion that DPC participates in auditory short-term memory and the integration of auditory and visual information for prospective action.

Animals↗
PubMed1991

Recovery profile after desflurane-nitrous oxide versus isoflurane-nitrous oxide in outpatients.

Thirty-eight healthy outpatients undergoing elective surgical procedures lasting 1-3 h were randomly assigned to receive either desflurane 3% (approximately 0.5 MAC) or isoflurane 0.6% (approximately 0.5 MAC) for maintenance of general anesthesia with nitrous oxide 60% in oxygen after a standardized induction sequence consisting of fentanyl 3 micrograms.kg-1, thiopental 4 mg.kg-1, and succinylcholine 1-1.5 mg.kg-1, intravenously. Although anesthetic conditions were similar during operations in the two treatment groups, significant differences were noted in the recovery profiles as measured by elimination kinetics, psychometric testing, and visual analog scales (to assess subjective feelings). The time required for the end-tidal concentration to decrease by 50% was 2.5 +/- 0.8 min for desflurane vs. 9.5 +/- 3.4 min for isoflurane (mean +/- standard deviation [SD]). Times to awakening and ability to follow simple commands were significantly shorter after desflurane than after isoflurane (5.1 +/- 2.4 vs. 10.2 +/- 7.7 min 6.5 +/- 2.3 min vs. 11.1 +/- 7.9 min, respectively). Postoperatively, patients who received desflurane exhibited less impairment of cognitive function (as measured using the Digit-Symbol Substitution Test) than did those who received isoflurane. Furthermore, visual analog scores indicated that patients receiving desflurane experienced significantly less discomfort (pain), drowsiness, fatigue, clumsiness, and confusion in the early postoperative period. We conclude that desflurane may offer clinical advantages over isoflurane when used for maintenance of anesthesia during outpatient surgical procedures.

Adult↗
PubMed1991

Antiemetic efficacy of ondansetron after outpatient laparoscopy.

The safety and efficacy of ondansetron were evaluated for the treatment of postoperative nausea and vomiting after laparoscopic surgical procedures. Seventy-one healthy, consenting outpatients were randomly assigned to one of two treatment groups according to a double-blind, placebo-controlled protocol. A standardized anesthetic technique consisting of alfentanil-thiopental-succinylcholine for induction and alfentanil-nitrous oxide-succinylcholine for maintenance of anesthesia was used. Patients in whom postoperative nausea and/or vomiting developed and persisted for greater than or equal to 10 min received equivolemic intravenous injections of either ondansetron (8 mg) or saline (placebo) over a 2-5 min period. Ondansetron significantly decreased the posttreatment nausea scores (vs placebo) without increasing sedation or producing changes in cardiorespiratory parameters. In the placebo-treated group, 92% of the patients experienced subsequent episodes of vomiting in the postanesthesia care unit compared with 51% of the patients in the ondansetron group. Finally, only 43% of the ondansetron-treated patients required a "rescue" antiemetic compared with 86% in the placebo group. Thus, ondansetron (8 mg IV) was associated with a decreased incidence of nausea and vomiting after outpatient laparoscopic procedures.

Adolescent↗