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Biomedical subjects

W J Freeman

Publications and source records attributed to W J Freeman.

At least 19 recordsLinked to original sources
PubMed2001

Response dynamics of entorhinal cortex in awake, anesthetized, and bulbotomized rats.

The generation of oscillatory activity may be crucial to brain function. The coordination of individual neurons into rhythmic and coherently active populations is thought to result from interactions between excitatory and inhibitory cells mediated by local feedback connections. By using extracellular recording wires and silicon microprobes to measure electrically evoked damped oscillatory responses at the level of neural populations in the entorhinal cortex, and by using current-source density analysis to determine the spatial pattern of evoked responses, we show that the propagation of activity through the cortical circuit and consequent oscillations in the local field potential are dependent upon background neural activity. Pharmacological manipulations as well as surgical disconnection of the olfactory bulb serve to quell the background excitatory input incident to entorhinal cortex, resulting in evoked responses without characteristic oscillations and showing no signs of polysynaptic feedback. Electrical stimulation at 200 Hz applied to the lateral olfactory tract provides a substitute for the normal background activity emanating from the bulb and enables the generation of oscillatory responses once again. We conclude that a non-zero background level of activity is necessary and sufficient to sustain normal oscillatory responses and polysynaptic transmission through the entorhinal cortex.

Action Potentials↗
PubMed2001

Change in pattern of ongoing cortical activity with auditory category learning.

Humans are able to classify novel items correctly by category; some other animals have also been shown to do this. During category learning, humans group perceptual stimuli by abstracting qualities from similarity relationships of their physical properties. Forming categories is fundamental to cognition and can be independent of a 'memory store' of information about the items or a prototype. The neurophysiological mechanisms underlying the formation of categories are unknown. Using an animal model of category learning, in which frequency-modulated tones are distinguished into the categories of 'rising' and 'falling' modulation, we demonstrate here that the sorting of stimuli into these categories emerges as a sudden change in an animal's learning strategy. Electro-corticographical recording from the auditory cortex shows that the transition is accompanied by a change in the dynamics of cortical stimulus representation. We suggest that this dynamic change represents a mechanism underlying the recognition of the abstract quality (or qualities) that defines the categories.

Animals↗
PubMed2001

Biocomplexity: adaptive behavior in complex stochastic dynamical systems.

Existing methods of complexity research are capable of describing certain specifics of bio systems over a given narrow range of parameters but often they cannot account for the initial emergence of complex biological systems, their evolution, state changes and sometimes-abrupt state transitions. Chaos tools have the potential of reaching to the essential driving mechanisms that organize matter into living substances. Our basic thesis is that while established chaos tools are useful in describing complexity in physical systems, they lack the power of grasping the essence of the complexity of life. This thesis illustrates sensory perception of vertebrates and the operation of the vertebrate brain. The study of complexity, at the level of biological systems, cannot be completed by the analytical tools, which have been developed for non-living systems. We propose a new approach to chaos research that has the potential of characterizing biological complexity. Our study is biologically motivated and solidly based in the biodynamics of higher brain function. Our biocomplexity model has the following features, (1) it is high-dimensional, but the dimensionality is not rigid, rather it changes dynamically; (2) it is not autonomous and continuously interacts and communicates with individual environments that are selected by the model from the infinitely complex world; (3) as a result, it is adaptive and modifies its internal organization in response to environmental factors by changing them to meet its own goals; (4) it is a distributed object that evolves both in space and time towards goals that is continually re-shaping in the light of cumulative experience stored in memory; (5) it is driven and stabilized by noise of internal origin through self-organizing dynamics. The resulting theory of stochastic dynamical systems is a mathematical field at the interface of dynamical system theory and stochastic differential equations. This paper outlines several possible avenues to analyze these systems. Of special interest are input-induced and noise-generated, or spontaneous state-transitions and related stability issues.

Adaptation, Physiological↗
PubMed2000

Spatial spectral analysis of human electrocorticograms including the alpha and gamma bands.

Spatial spectral analysis is essential for deriving spatial patterns from simultaneous recordings of electrocorticograms (ECoG), in order to determine the optimal interval between electrodes in arrays, and to design spatial filters, particularly for extraction of information about the dynamics of human gamma activity. ECoG were recorded from up to 64 electrodes 0.5 mm apart in a linear array 3.2 cm long, which was placed on the exposed superior temporal gyrus or motor cortex of volunteers undergoing diagnostic surgery. Visual displays of multiple traces revealed broad spectrum oscillations in episodic bursts having a common aperiodic wave form with recurring patterns of spatial amplitude modulation (AM patterns) on selected portions of the array. The one-dimensional spatial spectrum of the human ECoG was calculated at successive time samples and averaged over periods of up to 20 s. Log power decreased monotonically with increasing log spatial frequency in cycles/mm (c/mm) to the noise level approximately 2 log units below maximal power at minimal frequency (0.039+/-0.002 c/mm). The inflection point at 0.40+/-0.05 c/mm specified an optimal value for a low pass spatial filter to remove noise, and an optimal interelectrode spacing of 1.25 mm to avoid undersampling and aliasing. An 8 x 8 array with that spacing would be 10 x 10 mm.

Adolescent↗
PubMed2000

Topographic analysis of epidural pure-tone-evoked potentials in gerbil auditory cortex.

This study investigated the tonotopic organization of pure-tone-evoked middle latency auditory evoked potentials (MAEPs) recorded at the auditory cortical surface in unanesthetized gerbils. Multielectrode array recording and multiple linear regression analysis of the MAEP demonstrated different degrees of tonotopic organization of early and late MAEP components. The early MAEP components P1 and N1 showed focal topography and clear dependence in location and size of cortical area covered on pure-tone frequency. The later components P2 and N2 showed a widespread topography which was largely unaffected in location and size of cortical area covered by pure-tone frequency. These results allow delimitation of the neural generators of the early and late MAEP components in terms of the spectral properties of functionally defined neural populations.

Acoustic Stimulation↗
PubMed2000

Analysis of spatial patterns of phase in neocortical gamma EEGs in rabbit.

Arrays of 64 electrodes (8 x 8, 7 x 7 mm) were implanted epidurally on the surface of the visual, auditory or somatosensory cortex of rabbits trained to discriminate conditioned stimuli in the corresponding modality. The 64 electroencephalographic (EEG) traces at all times displayed a high degree of spatial coherence in wave form, averaging >90% of the variance in the largest principal components analysis component. The EEGs were decomposed with the fast Fourier transform (FFT) to give the spatial distributions of amplitude and phase modulation (AM and PM) in segments 128 ms in duration. Spatial (2-dimensional) and temporal (1-dimensional) filters were designed to optimize classification of the spatial AM patterns in the gamma range (20-80 Hz) with respect to discriminative conditioned stimuli. No evidence was found for stimulus-dependent classification of the spatial PM patterns. Instead some spatial PM distributions conformed to the pattern of a cone. The location and sign (maximal lead or lag) of the conic apex varied randomly with each recurrence. The slope of the phase gradient varied in a range corresponding to that of the conduction velocities reported of axons to extend parallel to the cortical surfaces. The durations and times of recurrence of the phase cones corresponded to those of the optimally classified spatial AM patterns. The interpretation is advanced that the phase cones are manifestations of state transitions in the mesoscopic dynamics of sensory cortices by which the intermittent AM patterns are formed. The phase cones show that the gamma EEG spatial coherence is not due to volume conduction from a single deep-lying dipole generator nor to activity at the site of the reference lead on monopolar recording. The random variation of the apical sign shows that gamma AM patterns are self-organized and are not imposed by thalamic pacemakers. The half-power radius of the phase gradient provides a useful measure of the soft boundary condition for the formation and read-out of cooperative cortical domains responsible for binding sensory information into the context of prior experience in the process of perception.

Animals↗
PubMed1999

Statistical evaluation of clusters derived by nonlinear mapping of EEG spatial patterns.

New methods were devised to improve the discrimination of EEG spatial amplitude patterns recorded from arrays of 64 electrodes placed on visual, auditory or somatic cortex. The 64 traces shared a spatially coherent, aperiodic carrier wave with a spatial pattern of amplitude modulation (AM). Previous observations on AM patterns from rabbits trained to discriminate conditioned stimuli with reinforcement (CS+) and without (CS-) had revealed epochs between the CS and the CR in which AM patterns on CS+ trials could be distinguished from AM patterns on CS- trials. The AM patterns were expressed by points in 64-space that formed clusters. Levels of CS-/CS+ pattern separation were quantified by a pair-wise Euclidean distance method with cross-validation. The present study documents use of the technique for nonlinear mapping (NLM) to project the 64-dimensional structure onto a plane while preserving the relative distances between all points. The goodness of classification by the Euclidean distance measure was the same or improved after projection. Whereas the Euclidean distance measure only gave pair-wise classifications, the planar displays showed the patterns for multiple clusters simultaneously. These NLM-based methods revealed previously unrecognized structures within distributions of AM patterns in sensory cortices in the time period between the CS and CR.

Animals↗
PubMed1998

Bidirectional processing in the olfactory-limbic axis during olfactory behavior.

Field potentials were recorded simultaneously from the olfactory bulb (OB), prepyriform cortex (PPC), entorhinal cortex (EC), and dentate gyrus (DG) of rats trained to respond to appetitively reinforced odors. Preafferent anticipatory events in the beta band (12-35 Hz) suggest transmission from EC to OB before the odorant stimulus. Gamma band (35-120 Hz) power in olfactory regions is significantly reduced during stimulus presentation as compared with high values during preafferent expectation. High coherence of OB and PPC gamma activity during the preodorant control period is interrupted before the stimulus and is followed by increased gamma coherence among OB, EC, and DG. These results suggest that olfactory perceptual processing is bidirectional and covers a wide frequency range.

Afferent Pathways↗
PubMed1997

Neurohumoral brain dynamics of social group formation. Implications for autism.

Brains are dynamic systems in which learning tends towards isolation by increasing specialization of cognitive skills. Induction of social skills for cooperative behavior requires "unlearning" in social contexts. A hypothesis is proposed by which oxytocin and related neuropeptides play a key role in meltdown of prior learning in preparation for new learning. This has implications for clinical management of disorders of the socialization processes in children.

Animals↗
PubMed1996

Spatio-temporal correlations in human gamma band electrocorticograms.

Animal electrocorticogram (ECoG) studies have shown that spatial patterns in the gamma band (>20 Hz) reflect perceptual categorization. Spatio-temporal correlations were investigated in the 20-50 Hz range in search for similar phenomena in human ECoG. ECoGs were recorded in a somatosensory discrimination task from 64-electrode subdural grid arrays, with inter-electrode spacing of 1 cm, overlying somatosensory, motor and superior temporal cortices in 2 patients with intractable epilepsy. Bootstrap techniques were devised to analyze the spatial and temporal characteristics of the correlations. Despite an extensive search, no evidence was found for globally correlated activity related to behavior either in narrow (1.e., 35-45 Hz) or broad (i.e., 20-50 Hz) bands. Spatial patterns, extracted using principal component analysis, could not be classified with respect to stimulus type in any time interval. Instead, spatially and temporally intermittent synchronization was observed between pairs of electrodes in 1 cm X 1 cm regions with high variability within and across trials. The distribution of correlation coefficients differed substantially from background levels at inter-electrode distances of 1 cm and 1.4 cm but not 2 cm or more. The minimum duration of correlation, the decorrelation time, of the ECoG was about 50 msec; the average correlation duration at 1 cm inter-electrode distance was about 150 msec; and the recurrence rate of significant correlation peaks was about 1.3/sec. The findings suggest that the surface diameters of domains of spatially correlated activity underlying perceptual categorization in human gamma band ECoG are limited to less than 2 cm and that the intermittent synchronization observed across separations of 1 cm and 1.4 cm is not solely due to volume conduction. Thus, if such gamma band spatial patterns exist in the human brain, no existing technology would be capable of measuring them at the scalp, and subdural electrode arrays for cortical surface recording would have to have spacings under 5 mm.

Adult↗
PubMed1996

Random activity at the microscopic neural level in cortex ("noise") sustains and is regulated by low-dimensional dynamics of macroscopic cortical activity ("chaos").

In this review I posit two levels of neural function. Microscopic activity is generated by neurons, to the extent that they act autonomously or in concert with networks of finite numbers of other neurons. Macroscopic activity is found in neuropil, where it depends on the sustained interaction of innumerable neurons. These levels coexist in cerebral cortex. Microscopic activity is manifested in the fraction of the variance of single neuron pulse trains (> 99.9%) that is both random and uncorrelated with pulse trains of other neurons in the neuropil. Macroscopic activity is revealed in the < 0.1% of the total variance of each neuron that is covariant with all other neurons in an area of neuropil comprising a population. It is best observed in dendritic potentials recorded as surface EEGs. The "spontaneous" background activity of neuropil at both levels arises from mutual excitation within a population of excitatory neurons. It is governed by a point attractor of the neuropil, which is actualized by the microscopic activity engendering the macroscopic state, and which acts as an order parameter to regulate the contributing neurons. The point attractor manifests a homogeneous field of white noise, into which sensory receptors send their microscopic stimuli. When neuropil comprises both excitatory and inhibitory neurons, the interactions at the macroscopic level lead to oscillations, manifesting a limit cycle attractor. When multiple areas of neuropil comprising a sensory system interact, then owing to their incommensurate characteristic frequencies and the long axonal delays between them, the system maintains a global chaotic attractor having multiple wings, one for each discriminable class of stimuli. Access to each wing is by stimulus-induced state transitions, leading to the construction of macroscopic chaotic patterns, that are carried to targets of cortical transmission by the microscopic noise. The chaotic modulation of the carrier noise is extracted by the targets through spatiotemporal integration, thereby retrieving the small covariance comprising the chaotic signal. Thus, controlled noise is the substrate for the meanings of stimuli that are expressed in chaotic patterns of sensory cortical activity.

Animals↗
PubMed1996

Reafference and attractors in the olfactory system during odor recognition.

Olfactory bulb activity has been postulated to be chaotic, as measured in the EEG, and to be subject to an attractor with many "wings" enabling classification of different learned odor classes. Two parallel questions are thus addressed by the work presented here: (1) what is the evidence for attractors in the olfactory system, which can mediate learned odor classes? and (2) how does the olfactory system enter a specific attractor or attractor wing associated with the learned odor during the classification process? Both of these questions address the wider notion of endogenous activity preparing the system for an expected stimulus, which is at the basis of the reafference principle. By viewing the brain as a distributed complex dynamical system with global attractors, these questions can be answered together. Rats were implanted with bipolar macroelectrodes in the Olfactory Bulb (OB), Prepyriform Cortex (PPC), Entorhinal Cortex (EC), and Dentate Gyrus (DG), and then trained in an operant paradigm to press a bar for a reward in the presence of one odor and to receive no reward in the presence of another odor. Local Field Potentials (LFP) were recorded simultaneously from the structures during the operant task. We present evidence for three endogenous events: (1) preafference, which is manifested both by the EC entering an attractor and a mid-range signal (15-30 Hz) which appears to be passed from the EC to the OB just before the OB enters an attractor; (2) afference, where the OB enters an attractor during the odor recognition period of the experiment and the LFP recordings indicate that the OB drives the other structures in all frequency bands, especially the high gamma band (65-100 Hz) associated with the OB burst frequency; and (3) reafference or post-afference, which is accompanied by a lower frequency gamma band signal (40-60 Hz) originating in the PPC and passed to both the OB and the EC just before the onset of the motor response to the odor. We use a new method, NECTAR (Nonparametric Exact Contingency Table Association Routine), related to mutual information, to verify what is seen with coherence and phase estimates, the apparent driving of each structure at different times in the odor trials, and to display evidence for non-periodic attractors governing both individual physiological structures and the system of structures. This is the first evidence of an endogenous, limbic event associated with sensory perceptual tuning in a mammal. These results are also the first experimental confirmation that the attractors governing olfactory activity involve multiple sites in the olfactory/limbic system and implement the process of attention.

Adaptation, Physiological↗
PubMed1996

Spatiotemporal analysis of prepyriform, visual, auditory, and somesthetic surface EEGs in trained rabbits.

1. Spatial ensemble averages were computed for 64 traces of electroencephalograms (EEGs) simultaneously recorded from 8 x 8 arrays over the epidural surfaces of the prepyriform cortex (PPC) and visual, somatic, and auditory cortices. They revealed a common waveform across each array. Examination of the spatial amplitude modulation (AM) of the waveform revealed classifiable spatial pattern in short time segments. The AM patterns varied within trials after presentation of identical conditioned stimuli, and also between trials with differing stimuli. 2. PPC EEGs revealed strong correlates with the respiratory rhythm; neocortical EEGs did not. 3. Time ensemble averaging of the PPC EEG attenuated the oscillatory bursts, indicating that olfactory gamma oscillations (20-80 Hz) were not phase-locked to the times of stimulus delivery but instead to inhalations. Time ensemble averages of neocortical recordings across trials revealed average evoked potentials starting 30-50 ms after the arrival of the stimulus. 4. Average temporal fast Fourier transform (FFT) power spectral densities (PSDs) from pre- and poststimulus PPC EEG segments revealed a peak of gamma activity in olfactory bursts. 5. The logarithm of the average temporal FFT PSDs from pre- and poststimulus neocortical EEG segments, when plotted against log frequency, revealed 1/f-type spectra in both pre- and poststimulus segments for negative/aversive conditioned stimuli (CS-) and positive/rewarding conditioned stimuli (CS+). The alpha'- and beta'-coefficients from the regression of Eq. 2 onto the average PSDs were significantly different between pre- and poststimulus segments, owing to the evoked potentials, but not between CS- and CS+ stimulus segments. 6. Spatiotemporal patterns were invariant over all frequency bins in the 1/f domain (20-100 Hz). Spatiotemporal patterns in the 2- to 20-Hz domain progressively differed from the invariant patterns with decreasing frequency. 7. In the spatial frequency domain, the logarithm of the average spatial FFT power spectra from pre- and poststimulus neocortical EEG segments, when plotted against the log spatial frequency, fell monotonically from the maximum at the lowest spatial frequency, downwardly curving to a linear 1/f spectral domain. This curve in the 1/f spectral domain extended from 0.133 to 0.880 cycles/mm in the PPC and from 0.095 to 0.624 cycles/mm in the neocortices. 8. Methods of FFT and principal component analysis (PCA) EEG decomposition were used to extract the broad-spectrum waveform common to all 64 EEGs from an array. AM patterns for the FFT and PCA components were derived by regression. They were shown by cross-correlation to yield spatial patterns that were equivalent to each other and to AM patterns from calculation of the 64 root-mean-square amplitudes of the segments. 9. Each spatial AM pattern was expressed by a 1 x 64 column vector and a point in 64-space. Similar patterns formed clusters, and dissimilar patterns gave multiple clusters. A statistical test was devised to evaluate dissimilarity by a Euclidean distance metric in 64-space. 10. Significant spatial pattern classification of CS- versus CS+ trials (below the 1% confidence limit for 20 of each) was found in discrete temporal segments of poststimulus data after digital temporal and spatial filter optimization. 11. Varying the analysis window duration from 10 to 500 ms yielded a window length of 120 ms as optimal for pattern classification. A 120-ms window was subsequently stepped across each record in overlapping intervals of 20 ms. Windows in which episodic, significant CS+/CS- differences occurred lasted 50-200 ms and were separated by 100-200 ms in the poststimulus period. 12. Neocortical spatial patterns changed under reinforcement contingency reversal, showing a lack of invariance in respect to stimuli and a dependence on context and learning, as previously found for the olfactory bulb and PPC.

Animals↗
PubMed1995

Chloride is preferentially accumulated in a subpopulation of dendrites and periglomerular cells of the main olfactory bulb in adult rats.

GABA is predominantly an inhibitory transmitter. Mediated by GABAA receptors, GABA opens chloride channels, induces a passive flux of chloride ions, which is usually directed from extracellular to intracellular space, and hyperpolarizes postsynaptic neurons. Recent electrophysiological data suggested that GABA may also depolarize neurons and exert excitatory actions. However, it remained unclear whether excitatory GABA effects are based on reversed transmembrane chloride gradient due to modifications in extracellular or intracellular chloride concentrations. Here, the first histochemical evidence is provided for local redistribution of chloride in the CNS of healthy adult rats. Olfactory bulbs were examined using freeze substitution, silver trapping of chloride and intensification techniques at light and electron microscopic level. The chloride content of precipitates was evidenced by electron spectroscopic imaging using a CEM 902 (Zeiss) electron microscope. Chloride concentration was high in a subpopulation of some periglomerular cell bodies and isolated dendritic profiles, while it seemed to be very low in certain parts of the glomerular neuropil including intercellular clefts. Data suggest that reversed chloride gradients can be demonstrated by cytochemical methods, and may be responsible for excitatory GABA effects on selected periglomerular neurons and dendrites in the olfactory glomeruli. Conditions leading to chloride redistribution in the CNS of normal adult rats remain to be determined.

Animals↗
PubMed1994

Role of chaotic dynamics in neural plasticity.

Mathematical models are essential for the study of complex neural systems at all levels of the hierarchy from macromolecules through neurons to brain systems. ANN are readily available, but most of them are inappropriate for modeling brain function in normal behavior, because they stem from studies of neural systems in anesthetized or paralyzed animals which are capable only of reflux output. That class of models lacks the goal-directed, self-organizing properties of neural systems in behaving animals. In contrast to the stability of ANN and their reliance on asymptotic convergence to steady states (point attractors) and periodic oscillations (limit cycle attractors), BNN are intrinsically unstable. They continuously generate 'spontaneous' aperiodic activity that manifests the operation of chaotic dynamics undergoing repeated state transitions. Observations on the activity patterns of sensory cortex reveal that the perceptual outputs of BNN are by construction of spatial patterns and dynamic trajectories and not by computation using symbolic representations. Chaotic dynamics plays essential roles both in the construction of perceptions and in the continuing update of cortical populations, which requires selective synaptic modification during associative learning and habituation. Simultaneous multichannel recording from the olfactory bulb and cortex has given the following experimental results. (1) The cortical activity that relates to the perception of a sensory stimulus is carried macroscopically by a smaller number of single neurons e.g. 'units', 'feature detectors'. (2) The macroscopic activity reflects the meaning and significance of the stimulus for the experimental subject and not the stimulus as it is known to the observer. (3) The activity carries the meaning in spatial patterns, not in time series (the difference between a phonograph or radio and movie or TV). (4) The spatial patterns of activity that accompany previously learned stimuli or responses are changed by the introduction of new stimuli and also by modifications in reinforcement contingencies. There is no invariance in the memory store within the populations. (5) The patterns of activity are created by dynamic neural interactions in sensory cortex, not by registration or filtering of stimuli. There is no evidence for storage, retrieval, cross-correlation or logical tree search. (6) The dynamics is chaotic, not merely noisy, so that each act of perception involves a new construction by the cortex not by mere information processing. From these findings we infer that chaotic dynamics plays a crucial role in the construction of the associational contexts comprising the memory systems of experimental subjects.

Animals↗