PART I: INTRODUCTION AND BIOGRAPHIES PART II: BACKGROUND TO OUR RESEARCH PART III: NORMAL PHYSIOLOGY AND ANATOMY PART IV: DEPRIVATION AND DEVELOPMENT PART V: THREE REVIEWS

Brain and visual perception: The story of a 25‐year collaboration

Suppose that we have a set of p-dimensional random variables x. Typically we will be in a situation where we have n observations of these random variables, and the parameters of their distribution, such as means, variances and covari-ances are estimated from the values of the observations, but for the moment we think about the distribution of the underlying random variables rather than the particular observations. The basic idea of principal components is to try to describe p dimensional data in as small a number of dimensions (less than p) as possible, while preserving as much as possible of the structures involved. In doing this, we concentrate on variances. The rst step is to look for a linear function z 1 = 1 T x or z 1 = 1 T (x ?) of the elements of x which has maximum variance, where 1 is a vector of p components 11 , 21 , : : : , p1 (beware that some other authors write the suuces the other way round). Note we often subtract the mean. Then 1 T x = 11 x 1 + 21 x 2 + + p1 x p = p X j=1 j1 x j : Next, we look for a linear function z 2 = 2 T x uncorrelated with 1 T x which has maximum variance subject to this condition, and so on, so that at the kth stage a linear function z k = k x is found which has maximum variance subject to being uncorrelated with 1 T x, 2 T x, : : : , k?1 T x. We refer to the kth derived variable k T x as the kth principal component. We stop after the mth stage when, in some sense, the majority of the variation has been accounted for. Before proceeding further, let us recall some results on means and variances of linear functions. Suppose x is any p-dimensional random variable, and that is any constant p-dimensional vector. Then the mean of T x is

主成分分析(Principal Components)の経済分析への応用

We developed a neural network model that can account for major elements common to human focal seizures. These include the tonic-clonic transition, slow advance of clinical semiology and corresponding seizure territory expansion, widespread EEG synchronization, and slowing of the ictal rhythm as the seizure approaches termination. These were reproduced by incorporating usage-dependent exhaustion of inhibition in an adaptive neural network that receives global feedback inhibition in addition to local recurrent projections. Our model proposes mechanisms that may underline common EEG seizure onset patterns and status epilepticus, and postulates a role for synaptic plasticity in the emergence of epileptic foci. Complex patterns of seizure activity and bi-stable seizure end-points arise when stochastic noise is included. With the rapid advancement of clinical and experimental tools, we believe that this model can provide a roadmap and potentially an in silico testbed for future explorations of seizure mechanisms and clinical therapies.

/pdf/a-model-for-focal-seizure-onset-propagation-evolution-and-1zr62eeq8a.pdf

A model for focal seizure onset, propagation, evolution, and progression.

PURPOSE OF REVIEW

Epilepsy is a dynamical disorder of the brain characterized by sudden, seemingly unpredictable transitions to the ictal state. When and how these transitions occur remain unresolved questions in neurology.

RECENT FINDINGS

Modelling work based on dynamical systems theory proposed that a slow control parameter is necessary to explain the transition between interictal and ictal states. Recently, converging evidence from chronic EEG datasets unravelled the existence of cycles of epileptic brain activity at multiple timescales - circadian, multidien (over multiple days) and circannual - which could reflect cyclical changes in a slow control parameter. This temporal structure of epilepsy has theoretical implications and argues against the conception of seizures as completely random events. The practical significance of cycles in epilepsy is highlighted by their predictive value in computational models for seizure forecasting.

SUMMARY

The canonical randomness of seizures is being reconsidered in light of cycles of brain activity discovered through chronic EEG. This paradigm shift motivates development of next-generation devices to track more closely fluctuations in epileptic brain activity that determine time-varying seizure risk.

Chance and risk in epilepsy.

Developmental, cellular, and subcellular variations in the direction of neuronal Cl- currents elicited by GABAA receptor activation have been frequently reported. We found a corresponding variance in the reversal potential (EGABA) for synapses originating from individual interneurons onto a single pyramidal cell. These findings suggest a corresponding variance in the cytoplasmic concentration of Cl- ([Cl-i]) in individual dendrites. We determined [Cl-]i in the murine hippocampus and cerebral cortex of both sexes by: 1) two-photon imaging of the Cl- sensitive, ratiometric fluorescent protein SuperClomeleon (sCLM); 2) Fluorescence Lifetime IMaging (FLIM) of the Cl- sensitive fluorophore MEQ; and 3) electrophysiological measurements of EGABA by pressure application of GABA and RuBi-GABA uncaging. Fluorometric and electrophysiological estimates of local [Cl-]i were highly correlated. [Cl-]i microdomains persisted after pharmacological inhibition of cation-chloride cotransporters (CCCs), but were progressively modified after inhibiting the polymerization of the anionic macromolecule actin. These methods collectively demonstrated stable [Cl-]i microdomains in individual neurons in vitro and in vivo and the role of immobile anions on its stability. Our results highlight the existence of functionally significant neuronal Cl- microdomains that modify the impact of GABAergic inputs. Significant Statement: Microdomains of varying chloride concentrations in the neuronal cytoplasm are a predictable consequence of the inhomogeneous distribution of anionic polymers such as actin, tubulin, and nucleic acids. Here, we demonstrate the existence and stability of these microdomains, as well as the consequence for GABAergic synaptic signaling: each interneuron produces a postsynaptic GABAA response with a unique reversal potential. In individual hippocampal pyramidal cells, the range of GABAA reversal potentials evoked by stimulating different interneurons was over 20 mV. Some interneurons generated postsynaptic responses in pyramidal cells that reversed at potentials beyond what would be considered purely inhibitory. Cytoplasmic chloride microdomains enable each pyramidal cell to maintain a compendium of unique postsynaptic responses to the activity of individual interneurons.

Unique Actions of GABA Arising from Cytoplasmic Chloride Microdomains.

Epileptic networks are characterized by two outputs: brief interictal spikes and rarer, more prolonged seizures. Although either output state is readily modeled in silico and induced experimentally, the transition mechanisms are unknown, in part because no models exhibit both output states spontaneously. In silico small-world neural networks were built using single-compartment neurons whose physiological parameters were derived from dual whole-cell recordings of pyramidal cells in organotypic hippocampal slice cultures that were generating spontaneous seizure-like activity. In silico, neurons were connected by abundant local synapses and rare long-distance synapses. Activity-dependent synaptic depression and gradual recovery delimited synchronous activity. Full synaptic recovery engendered interictal population spikes that spread via long-distance synapses. When synaptic recovery was incomplete, postsynaptic neurons required coincident activation of multiple presynaptic terminals to reach firing threshold. Only local connections were sufficiently dense to spread activity under these conditions. This coalesced network activity into traveling waves whose velocity varied with synaptic recovery. Seizures were comprised of sustained traveling waves that were similar to those recorded during experimental and human neocortical seizures. Sustained traveling waves occurred only when wave velocity, network dimensions, and the rate of synaptic recovery enabled wave reentry into previously depressed areas at precisely ictogenic levels of synaptic recovery. Wide-field, cellular-resolution GCamP7b calcium imaging demonstrated similar initial patterns of activation in the hippocampus, although the anatomical distribution of traveling waves of synaptic activation was altered by the pattern of synaptic connectivity in the organotypic hippocampal cultures.SIGNIFICANCE STATEMENT When computerized distributed neural network models are required to generate both features of epileptic networks (i.e., spontaneous interictal population spikes and seizures), the network structure is substantially constrained. These constraints provide important new hypotheses regarding the nature of epileptic networks and mechanisms of seizure onset.

A Proposed Mechanism for Spontaneous Transitions between Interictal and Ictal Activity.

A neural model for straight line detection in the human visual cortex

Developmental, cellular, and subcellular variations in the direction of neuronal Cl- currents elicited by GABAA receptor activation have been frequently reported, and we found a corresponding variance in the reversal potential (EGABA) for individual interneurons synapsing on a single pyramidal cell These findings suggest a corresponding variance in the cytoplasmic concentration of Cl- ([Cl-i]) We determined [Cl-]i by: 1) two-photon imaging of the Cl- sensitive, ratiometric fluorescent protein SuperClomeleon (sCLM); 2) Fluorescence Lifetime IMaging (FLIM) of the Cl- sensitive fluorophore MEQ; and 3) electrophysiological measurements of EGABA These methods collectively demonstrated stable [Cl-]i microdomains in individual neurons in vivo Fluorometric and electrophysiological estimates of local [Cl-]i were highly correlated [Cl-]i microdomains persisted after pharmacological inhibition of cation-chloride cotransporters (CCCs) but steadily decreased after inhibiting the polymerization of the anionic macromolecule actin These studies highlight the existence of functionally significant neuronal Cl- microdomains that modify the impact of GABAergic inputs

/pdf/unique-actions-of-gaba-arising-from-cytoplasmic-chloride-6kwiyqmrlg.pdf

Unique actions of GABA arising from cytoplasmic chloride microdomains

Many problems in information theory feature an index into a random codebook being encoded with a fixed length scheme. We propose to purposefully select the index in a manner that skews its distribution, thus making variable length entropy coding of the index more attractive. In an application to lossy compression of a Bernoulli source, we illustrate that variable length coding yields a reduction in the rate over fixed length coding, and allows to reach a requisite rate distortion performance level using a smaller codebook.

/pdf/variable-length-compression-of-codeword-indices-for-lossy-3kfi0hgswl.pdf

Theju Jacob

Papers

Unique Actions of GABA Arising from Cytoplasmic Chloride Microdomains.

A Proposed Mechanism for Spontaneous Transitions between Interictal and Ictal Activity.

A neural model for straight line detection in the human visual cortex

Unique actions of GABA arising from cytoplasmic chloride microdomains

Variable Length Compression of Codeword Indices for Lossy Compression