Biomedical subjects

Hiroyuki Nakahara

Publications and source records attributed to Hiroyuki Nakahara.

At least 19 recordsLinked to original sources

PubMed2006

Extended LATER model can account for trial-by-trial variability of both pre- and post-processes.

We present a new decision-making model that can account for trial-by-trial variability induced by a process ("pre-process") that occurs before an explicit sensory signal specifying a later motor response. A process after explicit sensory signals, referred to herein as the "post-process", has been investigated by a variety of so-called rise-to-threshold models including the LATER model. The LATER model formulates post-process variability but treats the pre-process as fixed within a block of an experiment. We propose an extension of the LATER model, which we call the extended LATER (ELATER) model, to account for trial-by-trial variability of both pre- and post-processes together. We present the mathematical formulation of the ELATER model and analyze its characteristics, including numerical examples and an example of saccade latency data in reward-manipulated conditions with caudate activity. The ELATER model is useful for investigating decision making by taking account of trial-by-trial variability of both pre- and post-processes.

Animals↗

PubMed2006

Saccade-related spread of activity across superior colliculus may arise from asymmetry of internal connections.

The superior colliculus (SC) receives a retinotopic projection of the contralateral visual field in which the representation of the central field is expanded with respect to the peripheral field. The visual projection forms a nonlinear, approximately logarithmic, map on the SC. Models of the SC commonly assume that the function defining the strength of neuronal connections within this map (the kernel) depends only on the distance between two neurons, and is thus isotropic and homogeneous. However, if the connection strength is based on the distance between two stimuli in sensory space, the kernel will be asymmetric because of the nonlinear projection onto the brain map. We show, using a model of the SC, that one consequence of these asymmetric intrinsic connections is that activity initiated at one point spreads across the map. We compare this simulated spread with the spread observed experimentally around the time of saccadic eye movements with respect to direction of spread, differing effects of local and global inhibition, and the consequences of localized inactivation on the SC map. Early studies suggested that the SC spread was caused by feedback of eye displacement during a saccade, but subsequent studies were inconsistent with this feedback hypothesis. In our new model, the spread is autonomous, resulting from intrinsic connections within the SC, and thus does not depend on eye movement feedback. Other sensory maps in the brain (e.g., visual cortex) are also nonlinear and our analysis suggests that the consequences of asymmetric connections in those areas should be considered.

Algorithms↗

PubMed2006

Basal ganglia orient eyes to reward.

Expectation of reward motivates our behaviors and influences our decisions. Indeed, neuronal activity in many brain areas is modulated by expected reward. However, it is still unclear where and how the reward-dependent modulation of neuronal activity occurs and how the reward-modulated signal is transformed into motor outputs. Recent studies suggest an important role of the basal ganglia. Sensorimotor/cognitive activities of neurons in the basal ganglia are strongly modulated by expected reward. Through their abundant outputs to the brain stem motor areas and the thalamocortical circuits, the basal ganglia appear capable of producing body movements based on expected reward. A good behavioral measure to test this hypothesis is saccadic eye movement because its brain stem mechanism has been extensively studied. Studies from our laboratory suggest that the basal ganglia play a key role in guiding the gaze to the location where reward is available. Neurons in the caudate nucleus and the substantia nigra pars reticulata are extremely sensitive to the positional difference in expected reward, which leads to a bias in excitability between the superior colliculi such that the saccade to the to-be-rewarded position occurs more quickly. It is suggested that the reward modulation occurs in the caudate where cortical inputs carrying spatial signals and dopaminergic inputs carrying reward-related signals are integrated. These data support a specific form of reinforcement learning theories, but also suggest further refinement of the theory.

Animals↗

PubMed2006

A comparison of descriptive models of a single spike train by information-geometric measure.

In examining spike trains, different models are used to describe their structure. The different models often seem quite similar, but because they are cast in different formalisms, it is often difficult to compare their predictions. Here we use the information-geometric measure, an orthogonal coordinate representation of point processes, to express different models of stochastic point processes in a common coordinate system. Within such a framework, it becomes straightforward to visualize higher-order correlations of different models and thereby assess the differences between models. We apply the information-geometric measure to compare two similar but not identical models of neuronal spike trains: the inhomogeneous Markov and the mixture of Poisson models. It is shown that they differ in the second- and higher-order interaction terms. In the mixture of Poisson model, the second- and higher-order interactions are of comparable magnitude within each order, whereas in the inhomogeneous Markov model, they have alternating signs over different orders. This provides guidance about what measurements would effectively separate the two models. As newer models are proposed, they also can be compared to these models using information geometry.

Action Potentials↗

PubMed2006

Correlation and independence in the neural code.

The decoding scheme of a stimulus can be different from the stochastic encoding scheme in the neural population coding. The stochastic fluctuations are not independent in general, but an independent version could be used for the ease of decoding. How much information is lost by using this unfaithful model for decoding? There are discussions concerning loss of information (Nirenberg & Latham, 2003; Schneidman, Bialek, & Berry, 2003). We elucidate the Nirenberg-Latham loss from the point of view of information geometry.

Brain↗

PubMed2005

Difficulty of singularity in population coding.

Fisher information has been used to analyze the accuracy of neural population coding. This works well when the Fisher information does not degenerate, but when two stimuli are presented to a population of neurons, a singular structure emerges by their mutual interactions. In this case, the Fisher information matrix degenerates, and the regularity condition ensuring the Cramér-Rao paradigm of statistics is violated. An animal shows pathological behavior in such a situation. We present a novel method of statistical analysis to understand information in population coding in which algebraic singularity plays a major role. The method elucidates the nature of the pathological case by calculating the Fisher information. We then suggest that synchronous firing can resolve singularity and show a method of analyzing the binding problem in terms of the Fisher information. Our method integrates a variety of disciplines in population coding, such as nonregular statistics, Bayesian statistics, singularity in algebraic geometry, and synchronous firing, under the theme of Fisher information.

Action Potentials↗

PubMed2004

Dopamine neurons can represent context-dependent prediction error.

Midbrain dopamine (DA) neurons are thought to encode reward prediction error. Reward prediction can be improved if any relevant context is taken into account. We found that monkey DA neurons can encode a context-dependent prediction error. In the first noncontextual task, a light stimulus was randomly followed by reward, with a fixed equal probability. The response of DA neurons was positively correlated with the number of preceding unrewarded trials and could be simulated by a conventional temporal difference (TD) model. In the second contextual task, a reward-indicating light stimulus was presented with the probability that, while fixed overall, was incremented as a function of the number of preceding unrewarded trials. The DA neuronal response then was negatively correlated with this number. This history effect corresponded to the prediction error based on the conditional probability of reward and could be simulated only by implementing the relevant context into the TD model.

Algorithms↗

PubMed2004

Information processing in a neuron ensemble with the multiplicative correlation structure.

The present study investigates the performance of population codes when the fluctuations in neural activity have mutual correlation with strength being proportional to the neuronal firing rate (multiplicative noise). The neural field is used to calculate the Fisher information, which is decomposed in two parts, one due to the tuning function and spatial correlation, and the other due to the multiplicative structure. Their different characteristics are studied. The paper also investigates three types of maximum likelihood method, namely, decoding by using faithful and unfaithful models and the Center of Mass strategy, and compares their performances in terms of decoding accuracy and computational complexity.

Models, Neurological↗

PubMed2004

Improved parameter estimation for variance-stabilizing transformation of gene-expression microarray data.

A gene-expression microarray datum is modeled as an exponential expression signal (log-normal distribution) and additive noise. Variance-stabilizing transformation based on this model is useful for improving the uniformity of variance, which is often assumed for conventional statistical analysis methods. However, the existing method of estimating transformation parameters may not be perfect because of poor management of outliers. By employing an information normalization technique, we have developed an improved parameter estimation method, which enables statistically more straightforward outlier exclusion and works well even in the case of small sample size. Validation of this method with experimental data has suggested that it is superior to the conventional method.

Algorithms↗

PubMed2003

Gene interaction in DNA microarray data is decomposed by information geometric measure.

MOTIVATION: Given the vast amount of gene expression data, it is essential to develop a simple and reliable method of investigating the fine structure of gene interaction. We show how an information geometric measure achieves this. RESULTS: We introduce an information geometric measure of binary random vectors and show how this measure reveals the fine structure of gene interaction. In particular, we propose an iterative procedure by using this measure (called IPIG). The procedure finds higher-order dependencies which may underlie the interaction between two genes of interest. To demonstrate the method, we investigate the interaction between the two genes of interest in the data from human acute lymphoblastic leukemia cells. The method successfully discovered biologically known findings and also selected other genes as hidden causes that constitute the interaction. AVAILABILITY: Softwares are currently not available but are possibly made available in future at http://www.mns.brain.riken.go.jp/~nakahara/DNA_pub.html where all the related information is also linked.

Algorithms↗

PubMed2003

Structure-stability-function relationships of dendritic spines.

Dendritic spines, which receive most of the excitatory synaptic input in the cerebral cortex, are heterogeneous with regard to their structure, stability and function. Spines with large heads are stable, express large numbers of AMPA-type glutamate receptors, and contribute to strong synaptic connections. By contrast, spines with small heads are motile and unstable and contribute to weak or silent synaptic connections. Their structure-stability-function relationships suggest that large and small spines are "memory spines" and "learning spines", respectively. Given that turnover of glutamate receptors is rapid, spine structure and the underlying organization of the actin cytoskeleton are likely to be major determinants of fast synaptic transmission and, therefore, are likely to provide a physical basis for memory in cortical neuronal networks. Characterization of supramolecular complexes responsible for synaptic memory and learning is key to the understanding of brain function and disease.

Animals↗

PubMed2003

Correlation of primate caudate neural activity and saccade parameters in reward-oriented behavior.

Changes in the reward context are associated with changes in neuronal activity in the basal ganglia as well as changes in motor outputs. A typical example is found in the caudate (CD) projection neurons and saccade parameters. It raised the possibility that the changes in CD neuronal activity contribute to the changes in saccade parameters. To examine this possibility, we calculated the correlation coefficients (CORs) of the firing rates of each neuron with saccade parameters (peak saccade velocity and latency) on a trial-by-trial basis. We then calculated the mean CORs separately for two CD populations: reward-enhanced type neurons (RENs) that showed enhanced activity and reward-depressed type neurons (RDNs) that showed depressed activity when reward was expected. The activity of RENs was positively correlated with the saccadic peak velocity and negatively correlated with the saccade latency. The activity of RDNs was not significantly correlated with the saccade parameters. We further analyzed the CORs for RENs, a major type of CD neurons. First, we examined the time courses of the CORs using a moving time window (duration: 200 ms). The positive correlation with the saccade velocity and the negative correlation with the saccade latency were present not only in the peri-saccadic period but also during the pre- and postcue periods. Second, we asked whether the CORs with the saccade parameters were direction-selective. A majority of RENs were more active before contralateral saccades (contralateral-preferring neurons) and their activity was correlated more strongly with contralateral saccades than with ipsilateral saccades. A minority of RENs, ipsilateral-preferring neurons, showed no such preference. These results are consistent with the hypothesis that CD neuronal activity exerts facilitatory effects on contralateral saccades and that the effects start well before saccade execution. Furthermore, a multiple regression analysis indicated that changes in activity of some, but not all, CD neurons could be explained by changes in saccade parameters; a major determinant was reward context (presence or absence of reward). These results suggest that, while a majority of CD neurons receive reward-related signals, only some of them can make a significant contribution to change saccadic outputs based on expected reward.

Animals↗

PubMed2003

Synchronous firing and higher-order interactions in neuron pool.

The stochastic mechanism of synchronous firing in a population of neurons is studied from the point of view of information geometry. Higher-order interactions of neurons, which cannot be reduced to pairwise correlations, are proved to exist in synchronous firing. In a neuron pool where each neuron fires stochastically, the probability distribution q(r) of the activity r, which is the fraction of firing neurons in the pool, is studied. When q(r) has a widespread distribution, in particular, when q(r) has two peaks, the neurons fire synchronously at one time and are quiescent at other times. The mechanism of generating such a probability distribution is interesting because the activity r is concentrated on its mean value when each neuron fires independently, because of the law of large numbers. Even when pairwise interactions, or third-order interactions, exist, the concentration is not resolved. This shows that higher-order interactions are necessary to generate widespread activity distributions. We analyze a simple model in which neurons receive common overlapping inputs and prove that such a model can have a widespread distribution of activity, generating higher-order stochastic interactions.

Neurons↗

PubMed2003

[Effects of prenatal exposure to phthalate ester on both testicular descent and urogenital development in rats].

Mono-n-butyl phthalate (MBP) was administered to pregnant rats to investigate the effect of phthalate ester on both testicular descent and urogenital development in prenatal rats. Ten pregnant rats were separated into two groups. In-group 1; rats were fed with special rat chow containing 1% of MBP from the 14th to the 19th gestational days. In group 2; rats fed with normal rat chow were used as control. At birth, reduced anogenital distance was seen in MBP-treated male offspring, and additional adverse effects on androgen-dependent organs were seen at the age of 70-80 days. Undescended testis, hypospadias, short prepuce, prostatic hypoplasia and hypolastic seminal vesicles were seen in mature male offspring. The results suggest that prenatal administration of MBP may act as an antiandrogenic chemical and thereby inhibit testicular descent and urogenital development in rats.

Animals↗

PubMed2002

Effects of drug treatment on bone strength and structural changes with aging: an experimental study in rats.

The purpose of the present study was to evaluate the profiles of the bone strength of rats treated from infancy with various drugs. Young female Sprague-Dawley rats were classified into five groups according to the composition of their diets. They underwent resection of their femurs for a three-point flexion test and an impaction test at 6, 8, 12, and 16 months of age. A microcomputed tomography unit was used to evaluate the microstructure of their femoral condyles at 16 months of age. The diet given to the rats in the control group contained 0.5% Ca. The rats in groups A, B, C, and D were placed on the following regimens, respectively: vitamin K mixed diet, vitamin D oral administration, 1.8% Ca-fortified diet, and 1.8% Ca-fortified diet plus vitamin K and vitamin D. In the impaction tests conducted on the rats at each age, the results from groups A and B were nearly the same as those from the control group. At 16 months of age, the rats in groups C and D had significantly higher test results than those in the control group. In the three-point flexion tests at 16 months of age, the results from groups A, B, and C were nearly the same as those from the control group. The results from group D, however, showed a significant increase. Examination of the microstructure of the femoral condyles at 16 months of age revealed controlled destruction of the trabecular structure in groups C and D. These findings suggest that supplementing the diet from infancy with Ca, vitamin K, and vitamin D might prevent bone fractures due to osteoporosis.

Animals↗

PubMed2002

Central mechanisms of motor skill learning.

Recent studies have shown that frontoparietal cortices and interconnecting regions in the basal ganglia and the cerebellum are related to motor skill learning. We propose that motor skill learning occurs independently and in different coordinates in two sets of loop circuits: cortex-basal ganglia and cortex-cerebellum. This architecture accounts for the seemingly diverse features of motor learning.

Animals↗

PubMed2002

Self-organization in the basal ganglia with modulation of reinforcement signals.

Self-organization is one of fundamental brain computations for forming efficient representations of information. Experimental support for this idea has been largely limited to the developmental and reorganizational formation of neural circuits in the sensory cortices. We now propose that self-organization may also play an important role in short-term synaptic changes in reward-driven voluntary behaviors. It has recently been shown that many neurons in the basal ganglia change their sensory responses flexibly in relation to rewards. Our computational model proposes that the rapid changes in striatal projection neurons depend on the subtle balance between the Hebb-type mechanisms of excitation and inhibition, which are modulated by reinforcement signals. Simulations based on the model are shown to produce various types of neural activity similar to those found in experiments.

Algorithms↗

PubMed2002

Information-geometric measure for neural spikes.

This study introduces information-geometric measures to analyze neural firing patterns by taking not only the second-order but also higher-order interactions among neurons into account. Information geometry provides useful tools and concepts for this purpose, including the orthogonality of coordinate parameters and the Pythagoras relation in the Kullback-Leibler divergence. Based on this orthogonality, we show a novel method for analyzing spike firing patterns by decomposing the interactions of neurons of various orders. As a result, purely pairwise, triple-wise, and higher-order interactions are singled out. We also demonstrate the benefits of our proposal by using several examples.

Action Potentials↗