Biomedical subjects

D T Liley

Publications and source records attributed to D T Liley.

5 recordsLinked to original sources

PubMed1999

Theoretical electroencephalogram stationary spectrum for a white-noise-driven cortex: evidence for a general anesthetic-induced phase transition.

We present a model for the dynamics of a cerebral cortex in which inputs to neuronal assemblies are treated as random Gaussian fluctuations about a mean value. We incorporate the effect of general anesthetic agents on the cortex as a modulation of the inhibitory neurotransmitter rate constant. Stochastic differential equations are derived for the state variable h(e), the average excitatory soma potential, coherent fluctuations of which are believed to be the source of scalp-measured electroencephalogram (EEG) signals. Using this stochastic approach we derive a stationary (long-time limit) fluctuation spectrum for h(e). The model predicts that there will be three distinct stationary (equilibrium) regimes for cortical activity. In region I ("coma"), corresponding to a strong inhibitory anesthetic effect, h(e) is single valued, large, and negative, so that neuronal firing rates are suppressed. In region II for a zero or small anesthetic effect, h(e) can take on three values, two of which are stable; we label the stable solutions as "active" (enhanced firing) and "quiescent" (suppressed firing). For region III, corresponding to negative anesthetic (i.e., analeptic) effect, h(e) again becomes single valued, but is now small and negative, resulting in strongly elevated firing rates ("seizure"). If we identify region II as associated with the conscious state of the cortex, then the model predicts that there will be a rapid transit between the active-conscious and comatose unconscious states at a critical value of anesthetic concentration, suggesting the existence of phase transitions in the cortex. The low-frequency spectral power in the h(e) signal should increase strongly during the initial stage of anesthesia induction, before collapsing to much lower values after the transition into comatose-unconsciousness. These qualitative predictions are consistent with clinical measurements by Bührer et al. [Anaesthesiology 77, 226 (1992)], MacIver et al. [ibid. 84, 1411 (1996)], and Kuizenga et al. [Br. J. Anaesthesia 80, 725 (1998)]. This strong increase in EEG spectral power in the vicinity of the critical point is similar to the divergences observed during thermodynamic phase transitions. We show that the divergence in low-frequency power in our model is a natural consequence of the existence of turning points in the trajectory of stationary states for the cortex.

Action Potentials↗

PubMed1999

Alpha rhythm emerges from large-scale networks of realistically coupled multicompartmental model cortical neurons.

Conical pyramidal and stellate neurons were simulated using the GENESIS simulation package. Model neurons were leaky integrate-and-fire and consisted of from four to nine passive compartments. Neurophysiological measurements, based on single-cell recordings and patch-clamp experiments, provided estimations for the simulation of cortical neurons: transmitter-activated conductances, passive membrane time constants and axonal delays. Network connectivity was generated using a previously described probabilistic scheme based on known cortical histology, in which the probability of connections forming between one neuron and another fell off monotonically with increasing inter-cellular separation. Simulations of up to 6400 cortical neurons, approaching the scale of an individual cortical column, confirmed previous findings with smaller networks. Limit-cycle behaviour emerged in the network, in the frequency in the range of the mammalian alpha and beta rhythms (8-20 Hz). Contrary to expectation, near-linear relationships were found between the mean soma membrane potential and and neuronal firing probability. Some of the implications for cortical information processing, in particular the dynamical interactions between the neuronal and larger scales, are discussed.

Alpha Rhythm↗

PubMed1995

Simulation of electrocortical waves.

We report simulations of the electrocorticogram of the cat and human, based on estimates of fibre range, fibre density, axonal and dendritic delays, and cortical synaptic density. The long-range cortical connections of real cortex were simplified to couplings of symmetric density, decreasing in density with range, on a closed (toroidal) surface. Non-specific cortical activation was modelled as a diffuse global input and specific sensory input as a localised white noise input. Spectral properties of output included peak densities at the frequencies of the major cerebral rhythms, a '1/f' spectral envelope and 'shift to the right' with increasing total power as non-specific activation increased. Steady-state travelling waves with a velocity of 5-7 m/s (human) and < 1 m/s (cat) were produced. Frequency/wavenumber analysis revealed an additional class of activity with wavenumbers independent of temporal frequency. All these findings accord qualitatively and quantitatively with existing physiological results. Global resonant modes were not prominent, but the simulations obey a restricted case of the analytical results of Nunez (1994). Wave/pulse relations resemble the findings of Freeman (1975).

Animals↗

PubMed1994

Computer simulation of electrocortical activity at millimetric scale.

We report a simulation of electrocortical wave activity at millimetric scale, during the "desynchronised" state. Asymmetric sigmoid pulse/wave relations, short-range excitatory/inhibitory interactions and long-range excitatory couplings of pools of cortical cells were modelled. Frequency/wave number analysis of cat electrocorticogram was compared with the results of simulation. Local standing waves, with wave numbers from about 0.25/mm to 3.3/mm independent of temporal frequency, appeared in real and simulated ECoG. These arise from interactions of excitatory and inhibitory cells and reciprocal excitation of pyramidal cells. The simulation also exhibits long wave length activity consistent with that of the real ECoG. Serial relay of excitation gives rise to travelling waves with a velocity of about 0.6 m/sec, which approximates earlier experimental estimates based on coherence. Interaction of the local and travelling waves results in group waves with high phase velocities (32 m/sec at 5 Hz, to 0.6 m/sec at 50 Hz). Such group waves have not yet been experimentally identified and would be readily confused with effects of volume conduction. However, the frequency response characteristics of the simulation, along with the group waves, may account for experimental findings of action potential correlation with local field potentials at 40-50 Hz and long-range synchronisation of action potentials.

Animals↗

PubMed1989

Localization of a nonintercalative DNA binding antitumour drug in mitochondria: relationship to multidrug resistance.

The bis-(n-butyl) quaternary salt of N,N'-bis-(6-quinolyl)terephthalamide (QBQ), a fluorescent antitumour compound in the phthalanilide series which is thought to bind to the minor groove of the DNA double helix, has been investigated with respect to its in vitro activity and subcellular localization. Cultured MCF-7 human breast carcinoma cells concentrated QBQ in mitochondria by a time-dependent process which was inhibited by the ionophore valinomycin, suggesting a possible mode of antitumour action of QBQ through mitochondrial poisoning. Growth of cultured P388 murine leukaemia cells was inhibited 50% in the presence of 0.52 microM QBQ and multidrug-resistant P388 sublines developed for resistance to actinomycin D, vincristine, Adriamycin and the phthalanilide NSC 38280 were cross-resistant to the drug. Cross-resistance was reduced in all lines by the presence of 11 microM verapamil, suggesting that a transport resistance mechanism operates on QBQ. The actinomycin D-resistant P388 cell line was found to be cross-resistant to the aromatic cations rhodamine 123, which binds to proteins, and ethidium and pyronin Y, which bind intercalatively to DNA. Thus mitochondrion-specific drugs with different macromolecular binding properties all appear to be excluded by multidrug-resistant cells.

Animals↗