PubMed Health⌕ Search

Biomedical subjects

C J Rennie

Publications and source records attributed to C J Rennie.

At least 19 recordsLinked to original sources

BOLD responses to stimuli: dependence on frequency, stimulus form, amplitude, and repetition rate.

A quantitative theory is developed for the relationship between stimulus and the resulting blood oxygen level-dependent (BOLD) functional MRI signal. The relationship of stimuli to neuronal activity during evoked responses is inferred from recent physiology-based quantitative modeling of evoked response potentials (ERPs). A hemodynamic model is then used to calculate the BOLD response to neuronal activity having the form of an impulse, a sinusoid, or an ERP-like damped sinusoid. Using the resulting equations, the BOLD response is analyzed for different forms, frequencies, and amplitudes of stimuli, in contrast with previous research, which has mostly concentrated on sustained stimuli. The BOLD frequency response is found to be closely linear in the parameter ranges of interest, with the form of a low-pass filter with a weak resonance at approximately 0.07 Hz. An improved BOLD impulse response is systematically obtained which includes initial dip and post-stimulus undershoot for some parameter ranges. It is found that the BOLD response depends strongly on the precise temporal course of the evoked neuronal activity, not just its peak value or typical amplitude. Indeed, for short stimuli, the linear BOLD response is closely proportional to the time-integrated activity change evoked by the stimulus, regardless of amplitude. It is concluded that there can be widely differing proportionalities between BOLD and peak activity, that this is the likely reason for the low level of correspondence seen experimentally between ERP sources and BOLD measurements and that non-BOLD measurements, such as ERPs, can be used to correct for this effect to obtain improved activity estimates. Finally, stimulus sequences that optimize the signal-to-noise ratio in event-related BOLD fMRI (efMRI) experiments are derived using the hemodynamic transfer function.

Brain↗

Multiscale brain modelling.

A central difficulty of brain modelling is to span the range of spatio-temporal scales from synapses to the whole brain. This paper overviews results from a recent model of the generation of brain electrical activity that incorporates both basic microscopic neurophysiology and large-scale brain anatomy to predict brain electrical activity at scales from a few tenths of a millimetre to the whole brain. This model incorporates synaptic and dendritic dynamics, nonlinearity of the firing response, axonal propagation and corticocortical and corticothalamic pathways. Its relatively few parameters measure quantities such as synaptic strengths, corticothalamic delays, synaptic and dendritic time constants, and axonal ranges, and are all constrained by independent physiological measurements. It reproduces quantitative forms of electroencephalograms seen in various states of arousal, evoked response potentials, coherence functions, seizure dynamics and other phenomena. Fitting model predictions to experimental data enables underlying physiological parameters to be inferred, giving a new non-invasive window into brain function that complements slower, but finer-resolution, techniques such as fMRI. Because the parameters measure physiological quantities relating to multiple scales, and probe deep structures such as the thalamus, this will permit the testing of a range of hypotheses about vigilance, cognition, drug action and brain function. In addition, referencing to a standardized database of subjects adds strength and specificity to characterizations obtained.

Axons↗

Estimation of multiscale neurophysiologic parameters by electroencephalographic means.

It is shown that new model-based electroencephalographic (EEG) methods can quantify neurophysiologic parameters that underlie EEG generation in ways that are complementary to and consistent with standard physiologic techniques. This is done by isolating parameter ranges that give good matches between model predictions and a variety of experimental EEG-related phenomena simultaneously. Resulting constraints range from the submicrometer synaptic level to length scales of tens of centimeters, and from timescales of around 1 ms to 1 s or more, and are found to be consistent with independent physiologic and anatomic measures. In the process, a new method of obtaining model parameters from the data is developed, including a Monte Carlo implementation for use when not all input data are available. Overall, the approaches used are complementary to other methods, constraining allowable parameter ranges in different ways and leading to much tighter constraints overall. EEG methods often provide the most restrictive individual constraints. This approach opens a new, noninvasive window on quantitative brain analysis, with the ability to monitor temporal changes, and the potential to map spatial variations. Unlike traditional phenomenologic quantitative EEG measures, the methods proposed here are based explicitly on physiology and anatomy.

Adult↗

Nonuniform corticothalamic continuum model of electroencephalographic spectra with application to split-alpha peaks.

Recent theoretical work has successfully predicted electroencephalographic spectra from physiology using a model corticothalamic system with spatially uniform parameters. The present work incorporates parameter nonuniformities into this model via the coupling they induce between spatial eigenmodes. Splitting of the spectral alpha peak, an effect seen in a small percentage of the normal population, is investigated as an illustrative special case. It is confirmed that weak splitting can arise from mode structure if the peak is sufficiently sharp, even for uniform parameters. However, it is further demonstrated that greater splitting can result from nonuniformities, and it is argued that this mechanism for split alpha is better able to account quantitatively for this effect than previously suggested alternatives of pacemakers or purely cortical resonances. On introducing nonuniformities in corticothalamic loop time delays, we find that the alpha frequency also varies as one moves from the front to the back of the head, in accord with observations, and that analogous (but less distinct) variations are seen in the beta peak. Analysis shows realistic variations of around +/-10 ms relative to the mean loop delay of approximately 80 ms can account for observed splittings of about 1 Hz. It is also suggested that subjects who display clear alpha splitting form the tail of a distribution of magnitude of cortical inhomogeneity, rather than a separate population.

Algorithms↗

Simulated electrocortical activity at microscopic, mesoscopic, and global scales.

Simulation of electrocortical activity requires (a) determination of the most crucial features to be modelled, (b) specification of state equations with parameters that can be determined against independent measurements, and (c) explanation of electrical events in the brain at several scales. We report our attempts to address these problems, and show that mutually consistent explanations, and simulation of experimental data can be achieved for cortical gamma activity, synchronous oscillation, and the main features of the EEG power spectrum including the cerebral rhythms and evoked potentials. These simulations include consideration of dendritic and synaptic dynamics, AMPA, NMDA, and GABA receptors, and intracortical and cortical/subcortical interactions. We speculate on the way in which Hebbian learning and intrinsic reinforcement processes might complement the brain dynamics thus explained, to produce elementary cognitive operations.

Animals↗

Neurophysical modeling of brain dynamics.

A recent neurophysical model of brain electrical activity is outlined and applied to EEG phenomena. It incorporates single-neuron physiology and the large-scale anatomy of corticocortical and corticothalamic pathways, including synaptic strengths, dendritic propagation, nonlinear firing responses, and axonal conduction. Small perturbations from steady states account for observed EEGs as functions of arousal. Evoked response potentials (ERPs), correlation, and coherence functions are also reproduced. Feedback via thalamic nuclei is critical in determining the forms of these quantities, the transition between sleep and waking, and stability against seizures. Many disorders correspond to significant changes in EEGs, which can potentially be quantified in terms of the underlying physiology using this theory. In the nonlinear regime, limit cycles are often seen, including a regime in which they have the characteristic petit mal 3 Hz spike-and-wave form.

Brain↗

Dynamics of large-scale brain activity in normal arousal states and epileptic seizures.

Links between electroencephalograms (EEGs) and underlying aspects of neurophysiology and anatomy are poorly understood. Here a nonlinear continuum model of large-scale brain electrical activity is used to analyze arousal states and their stability and nonlinear dynamics for physiologically realistic parameters. A simple ordered arousal sequence in a reduced parameter space is inferred and found to be consistent with experimentally determined parameters of waking states. Instabilities arise at spectral peaks of the major clinically observed EEG rhythms-mainly slow wave, delta, theta, alpha, and sleep spindle-with each instability zone lying near its most common experimental precursor arousal states in the reduced space. Theta, alpha, and spindle instabilities evolve toward low-dimensional nonlinear limit cycles that correspond closely to EEGs of petit mal seizures for theta instability, and grand mal seizures for the other types. Nonlinear stimulus-induced entrainment and seizures are also seen, EEG spectra and potentials evoked by stimuli are reproduced, and numerous other points of experimental agreement are found. Inverse modeling enables physiological parameters underlying observed EEGs to be determined by a new, noninvasive route. This model thus provides a single, powerful framework for quantitative understanding of a wide variety of brain phenomena.

Adult↗

Unified neurophysical model of EEG spectra and evoked potentials.

Evoked potentials -- the brain's transient electrical responses to discrete stimuli -- are modeled as impulse responses using a continuum model of brain electrical activity. Previous models of ongoing brain activity are refined by adding an improved model of thalamic connectivity and modulation, and by allowing for two populations of excitatory cortical neurons distinguished by their axonal ranges. Evoked potentials are shown to be modelable as an impulse response that is a sum of component responses. The component occurring about 100 ms poststimulus is attributed to sensory activation, and this, together with positive and negative feedback pathways between the cortex and thalamus, results in subsequent peaks and troughs that semiquantitatively reproduce those of observed evoked potentials. Modulation of the strengths of positive and negative feedback, in ways consistent with psychological theories of attentional focus, results in distinct responses resembling those seen in experiments involving attentional changes. The modeled impulse responses reproduce key features of typical experimental evoked response potentials: timing, relative amplitude, and number of peaks. The same model, with further modulation of feedback, also reproduces experimental spectra. Together, these results mean that a broad range of ongoing and transient electrocortical activity can be understood within a common framework, which is parameterized by values that are directly related to physiological and anatomical quantities.

Cerebral Cortex↗

Modal analysis of corticothalamic dynamics, electroencephalographic spectra, and evoked potentials.

The effects of cortical boundary conditions and resulting modal aspects of continuum corticothalamic electrodynamics are explored, including feedbacks. Dispersion relations, electroencephalographic spectra, and stimulus response functions are calculated from the underlying physiology, and the effects of discrete mode structure are determined. Conditions under which modal effects are important are obtained, along with estimates of the point at which modal series can be truncated, and the limit in which only a single globally uniform mode need be retained. It is found that for physiologically plausible parameters only the lowest cortical spatial eigenmode together with the set of next-lowest modes can produce distinct modal structure in spectra and response functions, and then only at frequencies where corticothalamic resonances reduce dissipation to the point where the spatial eigenmodes are weakly damped. The continuum limit is found to be a good approximation, except at very low frequencies and, under some circumstances, near the alpha resonance. It is argued that the major electroencephalographic rhythms result from corticothalamic feedback resonances, but that cortical modal effects can contribute to weak substructure in the alpha resonance. This mechanism is compared and contrasted with purely cortical and pacemaker-based alternatives and testable predictions are formulated to enable experimental discrimination between these possibilities.

Analysis of Variance↗

Prediction of electroencephalographic spectra from neurophysiology.

A recent neurophysical model of propagation of electrical waves in the cortex is extended to include a physiologically motivated subcortical feedback loop via the thalamus. The electroencephalographic spectrum when the system is driven by white noise is then calculated analytically in terms of physiological parameters, including the effects of filtering of signals by the cerebrospinal fluid, skull, and scalp. The spectral power at low frequencies is found to vary as f(-1) when awake and f(-3) when asleep, with a breakpoint to a steeper power-law tail at frequencies above about 20 Hz in both cases; the f(-1) range concurs with recent magnetoencephalographic observations of such a regime. Parameter sensitivities are explored, enabling a model with fewer free parameters to be proposed, and showing that spectra predicted for physiologically reasonable parameter values strongly resemble those observed in the laboratory. Alpha and beta peaks seen near 10 Hz and twice that frequency, respectively, in the relaxed wakeful state are generated via subcortical feedback in this model, thereby leading to predictions of their frequencies in terms of physiological parameters, and of correlations in their occurrence. Subcortical feedback is also predicted to be responsible for production of anticorrelated peaks in deep sleep states that correspond to the occurrence of theta rhythm at around half the alpha frequency and sleep spindles at 3/2 times the alpha frequency. An additional positively correlated waking peak near three times the alpha frequency is also predicted and tentatively observed, as are two new types of sleep spindle near 5/2 and 7/2 times the alpha frequency, and anticorrelated with alpha. These results provide a theoretical basis for the conventional division of EEG spectra into frequency bands, but imply that the exact bounds of these bands depend on the individual. Three types of potential instability are found: one at zero frequency, another in the theta band at around half the alpha frequency, and a third at the alpha frequency itself.

Adult↗

Mechanisms of cortical electrical activity and emergence of gamma rhythm.

A continuum model of the electrical activity of the cerebral cortex is described which predicts the occurrence of a resonance in the gamma range near 40 Hz. The emergence of this resonance is due to two refinements to a previous model, namely the inclusion of a modulation of synaptic strength due to finite reversal potentials, and use of parameters that better match physiological measurements. Analytical expressions for the fixed points of the system and for its linear dynamics are found in terms of average neuronal properties, and together explain the occurrence and modulation of the gamma-like resonance. The analytical results are confirmed by a numerical simulation.

Cerebral Cortex↗

Eye movements reflect impaired face processing in patients with schizophrenia.

BACKGROUND: Impaired processing of faces in patients with schizophrenia may underlie aspects of disturbance in their social interaction. This study examined patterns of eye fixation in subjects with schizophrenia and non-psychiatric controls, while processing a high resolution picture of a neutral face and a nonbiological complex geometric stimulus. METHODS: Ten-second sequences of eye movement were recorded video-oculographically (50 samples/sec) while subjects were "free-viewing" the stimuli. An essential element of the study was customized software that ensured stimulus presentation on a video display only after subjects were fixated upon a centre-screen cue, so that all subjects began stimulus processing from the same point. RESULTS: Compared with the control group, subjects with schizophrenia exhibited reduced scanpath lengths and a tendency toward fewer fixations for the face stimulus. They also showed an initial relative right spatial hemineglect (for the first voluntary fixation) when viewing the Rey figure, but not when viewing the face stimulus. Overall, there were no significant differences between the schizophrenia and control groups in the lateral distribution of subsequent fixations for either stimulus. CONCLUSIONS: Disturbed spatial and temporal patterns of eye movement in some people with schizophrenia may reflect sub-optimal processing of face stimuli, that may predispose these individuals to dysfunctional interpretation of facial communication cues.

Adult↗

Observations of vaginal calculi in dolphins.

Vaginal calculi have been described from the common (Delphinus delphis), Pacific white-sided (Lagenorhynchus obliquidens) and spotted (Stenella attenuata) dolphins. We describe additional calculi found in six sexually mature D. delphis from southern California. Three calculi were large (ca. 7 x 5 cm), exhibited concentric layer crystallization, and were unique from previously published descriptions. One calculus described previously and one in our sample appeared to be a fetal skeleton and skull respectively. Using CAT scans of a first trimester northern right whale dolphin (Lissodelphis borealis) and of a near term Delphinus delphis, we discuss the potential origin and development of vaginal calculi through analysis of ossification in embryonic delphinids. We hypothesize that the calculi represented spontaneous incomplete abortion with retention of part or all of the fetus in the distal reproductive tract. The form of the calculus relates to the degree of skeletal development at the time of fetal death. Calculi from a pregnant dolphin provided one measure of residence time.

Abortion, Veterinary↗

Prevalence of in-flight medical emergencies on commercial airlines.

In-flight medical emergencies were evaluated among passengers arriving at Los Angeles International Airport (LAX) from October 1985 through March 1986. All emergency department, LAX first-aid station, and paramedic records were examined. There were 8,735,000 passenger arrivals at LAX during the study period; 260 passengers (0.003%) developed medical complaints in flight, and of these 260, 115 (44.2%) had symptoms that lasted for more than one hour. Only 20 (8%) had in-flight physician assistance. One hundred thirty-seven (52.6%) passengers required only first-aid station treatment or signed out against medical advice, 123 (47.3%) were triaged to the ED, and 25 (9.6%) were admitted to the hospital. Seven passengers had fatal events while in flight. Most of the illnesses encountered did not require advanced medical treatment. We conclude that while in-flight medical illnesses occur more frequently than believed by airlines, true emergencies are rare. The rarity of true in-flight medical emergencies coupled with low physician availability bring into question the benefit of any comprehensive medical kit on airliners.

Aerospace Medicine↗

Postcountershock pulseless rhythms: hemodynamic effects of glucagon in a canine model.

Defibrillation after prolonged ventricular fibrillation (VF) is frequently followed by asystole or electromechanical dissociation (EMD) which are usually fatal. We studied the effects of glucagon, a known inotropic and chronotropic agent, during 19 episodes of postcountershock asystole/EMD in nine dogs. Systolic and diastolic aortic (Ao), left ventricular, pulmonary arterial, and right atrial (RA) pressures were recorded as was the instantaneous Ao-RA difference (coronary perfusion pressure) and coronary sinus blood flow (CSF) during closed-chest CPR. VF was induced electrically; 2 min later, a 400-J transthoracic shock was given. Countershock was always followed by asystole (n = 12) or EMD (n = 7). Conventional closed-chest CPR with a mechanical device was begun 30 to 60 sec after countershock and continued for 2 to 3 min. If a perfusing rhythm did not occur, glucagon (1 mg) was given iv and CPR continued for 2 to 3 min more. Glucagon had no significant effect on intravascular pressures, the coronary perfusion gradient, or CSF when compared to CPR alone. However, in 14 or 19 postcountershock episodes unresponsive to CPR alone, glucagon restored effective spontaneous circulation, i.e., successful cardiac resuscitation, due to its effects on the intrinsic pacemaker discharge rate. Glucagon has been previously shown to stimulate myocardial adenyl cyclase via nonadrenergic mechanisms. We conclude that when postcountershock asystole/EMD occurs, glucagon has a direct and favorable effect on cardiac resuscitation outcome due to its effects on pacemaker discharge rate which is not mediated by changes in myocardial blood flow or coronary perfusion pressure.

Animals↗

Postcountershock pulseless rhythms: response to CPR, artificial cardiac pacing, and adrenergic agonists.

Clinically, countershock of ventricular fibrillation (VF) may result in asystole or a pulseless rhythm in more than 50% of attempts. We conducted a study to assess the effects of immediate artificial pacing, CPR, and adrenergic drug therapy in the management of postcountershock pulseless rhythms. Thirty-four episodes of VF followed by countershock were studied in eight anesthetized dogs. Transducer-tipped catheters were positioned in the ascending aorta (Ao) and right atrium (RA). A bipolar pacing catheter was advanced to the apex of the right ventricle and a catheter for measurement of coronary sinus blood flow (CSQ) (continuous thermodilution technique) was positioned in the coronary sinus. VF was induced electrically and a countershock at 400 J was given two minutes later; CPR was not performed during VF episodes. Countershock was followed by asystole or a pulseless rhythm in all animals. Immediate endocardial pacing (0.1 to 5 mA) of bradyarrhythmias produced electrical capture but did not result in arterial pressure pulses in any animal. After pacing, CPR was performed for two minutes or until restoration of spontaneous circulation (ROSC). During CPR, the diastolic coronary perfusion gradient (Ao-RA) was 20 +/- 7 mm Hg (mean +/- SD) and CSQ was 14 +/- 7 mL/min/100 g (53% +/- 43% of control). ROSC followed CPR of less than two minutes duration in 24% of VF study episodes. If ROSC did not follow two minutes of CPR, 1 mg epinephrine, or 50 micrograms or 100 micrograms isoproterenol was given IV.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Use of naloxone during cardiac arrest and CPR: potential adjunct for postcountershock electrical-mechanical dissociation.

Naloxone has been shown to increase arterial pressure in hemorrhagic and septic shock. To determine if naloxone has salutary effects during cardiac arrest with conventional closed-chest cardiopulmonary resuscitation (CPR), ten dogs were studied during 20 minutes of ventricular fibrillation (VF) and CPR and during a 30-minute postcountershock period. Central aortic (Ao) and right atrial (RA) systolic and end-diastolic (EDP) pressures, instantaneous Ao-RA pressure difference (coronary perfusion pressure), and electromagnetic Ao flow were measured. Ao and RA samples were analyzed during a control period and at five-minute intervals during CPR for PO2, PCO2, and pH. During VF, a piston-cylinder device was used to perform anteroposterior sternal depressions and positive pressure ventilations (100% O2) at standard rates and ratios. After 15 minutes of CPR, animals were randomized and given either naloxone (5 mg/kg) or epinephrine (1 mg). Defibrillation was attempted five minutes later using 1 J/kg and then, if necessary, 2, 4, 8, 12, and 16 J/kg until VF was terminated or the maximum energy dose was reached. If VF persisted or if countershock resulted in asystole or a nonperfusing rhythm (electrical-mechanical dissociation [EMD]), the alternate drug (naloxone or epinephrine) was then given. Measured systolic pressures, coronary perfusion pressures, aortic flow, and blood gases were not significantly different during the control period or at five, ten, and 15 minutes of VF and CPR between animal groups prior to drug administration. When compared to hemodynamic values measured at 15 minutes, naloxone had no significant effect on pressures or aortic flow measured five minutes after administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗