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Biomedical subjects

C Koch

Publications and source records attributed to C Koch.

At least 91 records · Page 5Linked to original sources

A direct quantitative relationship between the functional properties of human and macaque V5.

The nature of the quantitative relationship between single-neuron recordings in monkeys and functional magnetic resonance imaging (fMRI) measurements in humans is crucial to understanding how experiments in these different species are related, yet it remains undetermined. We measured brain activity in humans attending to moving visual stimuli, using blood oxygenation level-dependent (BOLD) fMRI. Responses in V5 showed a strong and highly linear dependence on increasing strength of motion signal (coherence). These population responses in human V5 had a remarkably simple mathematical relationship to previously observed single-cell responses in macaque V5. We provided an explicit quantitative estimate for the interspecies comparison of single-neuron activity and BOLD population responses. Our data show previously unknown dissociations between the functional properties of human V5 and other human motion-sensitive areas, thus predicting similar dissociations for the properties of single neurons in homologous areas of macaque cortex.

Adult↗

Category-specific visual responses of single neurons in the human medial temporal lobe.

The hippocampus, amygdala and entorhinal cortex receive convergent input from temporal neocortical regions specialized for processing complex visual stimuli and are important in the representation and recognition of visual images. Recording from 427 single neurons in the human hippocampus, entorhinal cortex and amygdala, we found a remarkable degree of category-specific firing of individual neurons on a trial-by-trial basis. Of the recorded neurons, 14% responded selectively to visual stimuli from different categories, including faces, natural scenes and houses, famous people and animals. Based on the firing rate of individual neurons, stimulus category could be predicted with a mean probability of error of 0.24. In the hippocampus, the proportion of neurons responding to spatial layouts was greater than to other categories. Our data provide direct support for the role of human medial temporal regions in the representation of different categories of visual stimuli.

Action Potentials↗

The role of single neurons in information processing.

Neurons carry out the many operations that extract meaningful information from sensory receptor arrays at the organism's periphery and translate these into action, imagery and memory. Within today's dominant computational paradigm, these operations, involving synapses, membrane ionic channels and changes in membrane potential, are thought of as steps in an algorithm or as computations. The role of neurons in these computations has evolved conceptually from that of a simple integrator of synaptic inputs until a threshold is reached and an output pulse is initiated, to a much more sophisticated processor with mixed analog-digital logic and highly adaptive synaptic elements.

Action Potentials↗

Protective copolymers for nonviral gene vectors: synthesis, vector characterization and application in gene delivery.

Uncontrolled interactions of gene vectors and drug carriers in and with an in vivo environment pose serious limitations to their applicability. In order to reduce such interactions we have designed, synthesized and applied novel copolymers of poly(ethylene glycol) and reactive linkers which are derivatized with anionic peptides after copolymerization. The anionic copolymer derivatives are used to coat positively charged nonviral gene vectors by electrostatic interactions. The copolymer coat confers to polyelectrolyte colloids of DNA and polycations steric stabilization in their minimal size and prevents salt- and serum albumin-induced aggregation. Furthermore, complement activation and the interaction with serum proteins are drastically reduced or abolished in contrast to unprotected DNA complexes. The designed vectors are compatible with the intracellular steps of gene delivery and can even enhance transfection efficiency as demonstrated with various adherent and nonadherent cell lines in culture. The synthetic concept is amenable to the principles of combinatorial chemistry and the copolymeric products may be applicable beyond gene delivery in targeted drug delivery. Gene Therapy (2000) 7, 1183-1192.

Cells, Cultured↗

Perception of parental acceptance in women with binge eating disorder.

The authors contribute to the validating literature for binge eating disorder (BED) by examining perceptions of parents and satisfaction with life among obese women with and without BED. Participants were female patients, recruited through a private medical clinic, who were assigned to groups on the basis of body mass index (BMI) and scores on the Questionnaire on Eating and Weight Patterns (QEWP; R. L. Spitzer et al., 1992). Groups consisted of (a) obese women with BED (n = 32), (b) obese women who had no eating disorders (n = 51), and (c) nonobese women with no eating disorders (n = 30). All participants completed the Parental Acceptance/Rejection Questionnaire (PARQ; R. P. Rohner, 1986), the Satisfaction with Life Scale (SWLS; J. Fischer & K. Corcoran, 1994), and the Beck Depression Inventory (BDI; A. T. Beck & R. A. Steer, 1987). Obese women with BED perceived their fathers as more rejecting than did women in the other groups. Moreover, obese women with BED perceived their fathers as significantly more rejecting than their mothers. The BED group indicated lower satisfaction with life and higher levels of depression than the groups without eating disorders. These findings further validate the diagnostic category of BED. Obese women with BED appear to be a distinct subgroup of the obese population. The results indicate a need for further assessment of the father-daughter relationship in connection to BED and other eating disorders.

Compulsive Behavior↗

Activity and immunohistochemical localization of porphobilinogen deaminase in rat tissues.

Porphobilinogen deaminase (PBGD) is an enzyme involved in the synthesis of heme. Acute intermittent porphyria (AIP) is an inherited disease resulting from a reduced activity of PBGD. The symptoms seem to be due to a neurological dysfunction. Attacks of AIP are often provoked by conditions where the PBGD activity becomes insufficient as a result of an increased synthesis of heme in the liver. How this affects the nervous tissue is still unknown. It may well be that a reduced activity of PBGD in other tissues than the liver is of importance too. The aim of the present study was to examine the activity and the immunohistochemical localization of PBGD in the following tissues of wistar female rats: brain, heart, submandibular gland, liver, kidney, pancreas, ovary, stomach, duodenum, jejunum, ileum, colon and musculature. The PBGD activity varied considerably among the tissues. It was highest in the liver, 14 pkat/g, and lowest in the jejunum, 0.7 pkat/g. The immunohistochemical localization of PBGD was studied by antibodies raised against a 40 amino acid synthetic peptide that corresponds to a segment in the C-terminal part of PBGD. The study demonstrated that the PBGD immunoreactivity was not evenly distributed among the various cell types in a given tissue. Immunohistochemical reactions were pronounced in Kupffer cells in the liver, in smooth muscle cells of arteries and arterioles, in distal and collecting tubules in the kidney, in nerve axons in the brain and in ganglionic cells in the intestine. Especially, the immunohistochemical reaction in nerve cells is notable considering the nervous dysfunction in AIP.

Amino Acid Sequence↗

Pelvic fractures in pregnant multiple trauma patients.

OBJECTIVE: To study the outcome of pelvic fractures and fetuses in pregnant patients involved in blunt multiple trauma. DESIGN: Retrospective follow-up study. SETTING: Level I trauma center. PATIENTS: Pregnant multiple trauma patients with pelvic fractures between 1974 and 1998. INTERVENTIONS: Conservative and operative treatment of pelvic fractures adapted to the clinical status of the mother. MAIN OUTCOME MEASURES: Clinical, functional, and social outcomes were evaluated. RESULTS: Out of 4,196 patients with blunt multiple trauma treated between 1974 and June 1998, seven demonstrated the combination of blunt multiple trauma, pregnancy, and pelvic fractures. These patients had a mean Injury Severity Score of 29.9 points. Five mothers and three fetuses survived their injuries. All dead fetuses died on the scene. One surviving fetus was found to have hydrocephalus unrelated to the injury; the remaining fetuses had an uneventful delivery and were healthy. In two of the three patients whose fetuses survived, the treatment of the pelvic fracture was modified for the sake of fetal well-being. In all of these patients, acceptable outcome was achieved. CONCLUSION: Modification of the treatment of the pelvic fracture in pregnant women with multiple trauma may be necessary to minimize the risk of fetal injury. In our experience with these rare cases, this modified treatment did not severely alter the clinical outcome of the mother's pelvic fracture.

Acetabulum↗

Robustness and variability of neuronal coding by amplitude-sensitive afferents in the weakly electric fish eigenmannia.

We investigated the variability of P-receptor afferent spike trains in the weakly electric fish, Eigenmannia, to repeated presentations of random electric field AMs (RAMs) and quantified its impact on the encoding of time-varying stimuli. A new measure of spike timing jitter was developed using the notion of spike train distances recently introduced by Victor and Purpura. This measure of variability is widely applicable to neuronal responses, irrespective of the type of stimuli used (deterministic vs. random) or the reliability of the recorded spike trains. In our data, the mean spike count and its variance measured in short time windows were poorly correlated with the reliability of P-receptor afferent spike trains, implying that such measures provide unreliable indices of trial-to-trial variability. P-receptor afferent spike trains were considerably less variable than those of Poisson model neurons. The average timing jitter of spikes lay within 1-2 cycles of the electric organ discharge (EOD). At low, but not at high firing rates, the timing jitter was dependent on the cutoff frequency of the stimulus and, to a lesser extent, on its contrast. When spikes were artificially manipulated to increase jitter, information conveyed by P-receptor afferents was degraded only for average jitters considerably larger than those observed experimentally. This suggests that the intrinsic variability of single spike trains lies outside of the range where it might degrade the information conveyed, yet still allows for improvement in coding by averaging across multiple afferent fibers. Our results were summarized in a phenomenological model of P-receptor afferents, incorporating both their linear transfer properties and the variability of their spike trains. This model complements an earlier one proposed by Nelson et al. for P-receptor afferents of Apteronotus. Because of their relatively high precision with respect to the EOD cycle frequency, P-receptor afferent spike trains possess the temporal resolution necessary to support coincidence detection operations at the next stage in the amplitude-coding pathway.

Action Potentials↗

Diagnosis and treatment of cystic fibrosis.

This review discusses some diagnostic aspects of cystic fibrosis (CF) including direct mutational analysis. Treatment of major disease manifestations is discussed in more detail with an emphasis on lung disease, in particular chronic infection with Pseudomonas aeruginosa which is responsible for the majority of excess morbidity and mortality. Centralised care and aggressive antimicrobial treatment have led to increased life expectancy and this may be even further increased by the demonstration that chronic P. aeruginosa infection may be prevented, or at least postponed for many years in a majority of patients. Adjunct treatment such as the use of local and systemic anti-inflammatory agents and inhalation of human recombinant DNase are also briefly touched upon. It is emphasised that important questions concerning the link(s) between the mutated gene and lung disease are still missing but that current research raises hope of a more causal treatment in the near future.

Clinical Trials as Topic↗

A silicon implementation of the fly's optomotor control system.

Flies are capable of stabilizing their body during free flight by using visual motion information to estimate self-rotation. We have built a hardware model of this optomotor control system in a standard CMOS VLSI process. The result is a small, low-power chip that receives input directly from the real world through on-board photoreceptors and generates motor commands in real time. The chip was tested under closed-loop conditions typically used for insect studies. The silicon system exhibited stable control sufficiently analogous to the biological system to allow for quantitative comparisons.

Animals↗

Revisiting spatial vision: toward a unifying model.

We report contrast detection, contrast increment, contrast masking, orientation discrimination, and spatial frequency discrimination thresholds for spatially localized stimuli at 4 degrees of eccentricity. Our stimulus geometry emphasizes interactions among overlapping visual filters and differs from that used in previous threshold measurements, which also admits interactions among distant filters. We quantitatively account for all measurements by simulating a small population of overlapping visual filters interacting through divisive inhibition. We depart from previous models of this kind in the parameters of divisive inhibition and in using a statistically efficient decision stage based on Fisher information. The success of this unified account suggests that, contrary to Bowne [Vision Res. 30, 449 (1990)], spatial vision thresholds reflect a single level of processing, perhaps as early as primary visual cortex.

Computer Simulation↗

Influences of occlusion, color, and luminance on the perception of fragmented pictures.

The contribution of the magnocellular (M) pathway to perceptual completion and depth processing was examined by comparing performance under black-and-white conditions with isoluminant color and diffuse red background conditions expected to suppress M pathway activity. Participants identified the repeated figure in pictures where only fragments of the figures were visible. The fragments were presented either alone (unoccluded) or with an occluder (occluded) filling the space between them. Identification with an occluder involved amodally completing the fragments behind it, i.e., depth processing. All unoccluded versions were easy to identify indicating perceptual completion of the fragments was not influenced by suppressing M pathway activity. Black-and-white occluded versions were also easy to identify. The significantly longer identification times for occluded versions under isoluminant and diffuse red background conditions indicates amodal completion of the fragments was hindered when M pathway activity was reduced, supporting the importance of M pathway activity for depth processing.

Color Perception↗

Detecting and estimating signals in noisy cable structure, I: neuronal noise sources.

In recent theoretical approaches addressing the problem of neural coding, tools from statistical estimation and information theory have been applied to quantify the ability of neurons to transmit information through their spike outputs. These techniques, though fairly general, ignore the specific nature of neuronal processing in terms of its known biophysical properties. However, a systematic study of processing at various stages in a biophysically faithful model of a single neuron can identify the role of each stage in information transfer. Toward this end, we carry out a theoretical analysis of the information loss of a synaptic signal propagating along a linear, one-dimensional, weakly active cable due to neuronal noise sources along the way, using both a signal reconstruction and a signal detection paradigm. Here we begin such an analysis by quantitatively characterizing three sources of membrane noise: (1) thermal noise due to the passive membrane resistance, (2) noise due to stochastic openings and closings of voltage-gated membrane channels (NA+ and K+), and (3) noise due to random, background synaptic activity. Using analytical expressions for the power spectral densities of these noise sources, we compare their magnitudes in the case of a patch of membrane from a cortical pyramidal cell and explore their dependence on different biophysical parameters.

Animals↗

Detecting and estimating signals in noisy cable structures, II: information theoretical analysis.

This is the second in a series of articles that seek to recast classical single-neuron biophysics in information-theoretical terms. Classical cable theory focuses on analyzing the voltage or current attenuation of a synaptic signal as it propagates from its dendritic input location to the spike initiation zone. On the other hand, we are interested in analyzing the amount of information lost about the signal in this process due to the presence of various noise sources distributed throughout the neuronal membrane. We use a stochastic version of the linear one-dimensional cable equation to derive closed-form expressions for the second-order moments of the fluctuations of the membrane potential associated with different membrane current noise sources: thermal noise, noise due to the random opening and closing of sodium and potassium channels, and noise due to the presence of "spontaneous" synaptic input. We consider two different scenarios. In the signal estimation paradigm, the time course of the membrane potential at a location on the cable is used to reconstruct the detailed time course of a random, band-limited current injected some distance away. Estimation performance is characterized in terms of the coding fraction and the mutual information. In the signal detection paradigm, the membrane potential is used to determine whether a distant synaptic event occurred within a given observation interval. In the light of our analytical results, we speculate that the length of weakly active apical dendrites might be limited by the information loss due to the accumulated noise between distal synaptic input sites and the soma and that the presence of dendritic nonlinearities probably serves to increase dendritic information transfer.

Animals↗

Adaptive neural coding dependent on the time-varying statistics of the somatic input current.

It is generally assumed that nerve cells optimize their performance to reflect the statistics of their input. Electronic circuit analogs of neurons require similar methods of self-optimization for stable and autonomous operation. We here describe and demonstrate a biologically plausible adaptive algorithm that enables a neuron to adapt the current threshold and the slope (or gain) of its current-frequency relationship to match the man (or dc offset) and variance (or dynamic range or contrast) of the time-varying somatic input current. The adaptation algorithm estimates the somatic current signal from the spike train by way of the intracellular somatic calcium concentration, thereby continuously adjusting the neurons' firing dynamics. This principle is shown to work in an analog VLSI-designed silicon neuron.

Adaptation, Physiological↗

Human ATP-binding cassette transporter 1 (ABC1): genomic organization and identification of the genetic defect in the original Tangier disease kindred.

Tangier disease is characterized by low serum high density lipoproteins and a biochemical defect in the cellular efflux of lipids to high density lipoproteins. ABC1, a member of the ATP-binding cassette family, recently has been identified as the defective gene in Tangier disease. We report here the organization of the human ABC1 gene and the identification of a mutation in the ABC1 gene from the original Tangier disease kindred. The organization of the human ABC1 gene is similar to that of the mouse ABC1 gene and other related ABC genes. The ABC1 gene contains 49 exons that range in size from 33 to 249 bp and is over 70 kb in length. Sequence analysis of the ABC1 gene revealed that the proband for Tangier disease was homozygous for a deletion of nucleotides 3283 and 3284 (TC) in exon 22. The deletion results in a frameshift mutation and a premature stop codon starting at nucleotide 3375. The product is predicted to encode a nonfunctional protein of 1,084 aa, which is approximately half the size of the full-length ABC1 protein. The loss of a Mnl1 restriction site, which results from the deletion, was used to establish the genotype of the rest of the kindred. In summary, we report on the genomic organization of the human ABC1 gene and identify a frameshift mutation in the ABC1 gene of the index case of Tangier disease. These results will be useful in the future characterization of the structure and function of the ABC1 gene and the analysis of additional ABC1 mutations in patients with Tangier disease.

ATP Binding Cassette Transporter 1↗