Publications by authors named "Masayuki Matsumoto"

79 Publications

Neural Population Dynamics Underlying Expected Value Computation.

J Neurosci 2021 Feb 13;41(8):1684-1698. Epub 2021 Jan 13.

Division of Biomedical Science, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8577, Ibaraki, Japan.

Computation of expected values (i.e., probability × magnitude) seems to be a dynamic integrative process performed by the brain for efficient economic behavior. However, neural dynamics underlying this computation is largely unknown. Using lottery tasks in monkeys (, male; , female), we examined (1) whether four core reward-related brain regions detect and integrate probability and magnitude cued by numerical symbols and (2) whether these brain regions have distinct dynamics in the integrative process. Extraction of the mechanistic structure of neural population signals demonstrated that expected value signals simultaneously arose in the central orbitofrontal cortex (cOFC; medial part of area 13) and ventral striatum (VS). Moreover, these signals were incredibly stable compared with weak and/or fluctuating signals in the dorsal striatum and medial OFC. Temporal dynamics of these stable expected value signals were unambiguously distinct: sharp and gradual signal evolutions in the cOFC and VS, respectively. These intimate dynamics suggest that the cOFC and VS compute the expected values with unique time constants, as distinct, partially overlapping processes. Our results differ from those of earlier studies suggesting that many reward-related regions in the brain signal probability and/or magnitude and provide a mechanistic structure for expected value computation employed in multiple neural populations. A central part of the orbitofrontal cortex (cOFC) and ventral striatum (VS) can simultaneously detect and integrate probability and magnitude into an expected value. Our empirical study on these neural population dynamics raises a possibility that the cOFC and VS cooperate on this computation with unique time constants as distinct, partially overlapping processes.
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http://dx.doi.org/10.1523/JNEUROSCI.1987-20.2020DOI Listing
February 2021

Nonhuman Primate Optogenetics: Current Status and Future Prospects.

Adv Exp Med Biol 2021 ;1293:345-358

Systems Neuroscience Section, Primate Research Institute, Kyoto University, Inuyama, Aichi, Japan.

Nonhuman primates (NHPs) have widely and crucially been utilized as model animals for understanding various higher brain functions and neurological disorders since their behavioral actions mimic both normal and disease states in humans. To know about how such behaviors emerge from the functions and dysfunctions of complex neural networks, it is essential to define the role of a particular pathway or neuron-type constituting these networks. Optogenetics is a potential technique that enables analyses of network functions. However, because of the large size of the NHP brain and the difficulty in creating genetically modified animal models, this technique is currently still hard to apply effectively and efficiently to NHP neuroscience. In this article, we focus on the issues that should be overcome for the development of NHP optogenetics, with special reference to the gene introduction strategy. We review the recent breakthroughs that have been made in NHP optogenetics to address these issues and discuss future prospects regarding more effective and efficient approaches to successful optogenetic manipulation in NHPs.
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http://dx.doi.org/10.1007/978-981-15-8763-4_22DOI Listing
February 2021

An Open Resource for Non-human Primate Optogenetics.

Authors:
Sébastien Tremblay Leah Acker Arash Afraz Daniel L Albaugh Hidetoshi Amita Ariana R Andrei Alessandra Angelucci Amir Aschner Puiu F Balan Michele A Basso Giacomo Benvenuti Martin O Bohlen Michael J Caiola Roberto Calcedo James Cavanaugh Yuzhi Chen Spencer Chen Mykyta M Chernov Andrew M Clark Ji Dai Samantha R Debes Karl Deisseroth Robert Desimone Valentin Dragoi Seth W Egger Mark A G Eldridge Hala G El-Nahal Francesco Fabbrini Frederick Federer Christopher R Fetsch Michal G Fortuna Robert M Friedman Naotaka Fujii Alexander Gail Adriana Galvan Supriya Ghosh Marc Alwin Gieselmann Roberto A Gulli Okihide Hikosaka Eghbal A Hosseini Xing Hu Janina Hüer Ken-Ichi Inoue Roger Janz Mehrdad Jazayeri Rundong Jiang Niansheng Ju Kohitij Kar Carsten Klein Adam Kohn Misako Komatsu Kazutaka Maeda Julio C Martinez-Trujillo Masayuki Matsumoto John H R Maunsell Diego Mendoza-Halliday Ilya E Monosov Ross S Muers Lauri Nurminen Michael Ortiz-Rios Daniel J O'Shea Stéphane Palfi Christopher I Petkov Sorin Pojoga Rishi Rajalingham Charu Ramakrishnan Evan D Remington Cambria Revsine Anna W Roe Philip N Sabes Richard C Saunders Hansjörg Scherberger Michael C Schmid Wolfram Schultz Eyal Seidemann Yann-Suhan Senova Michael N Shadlen David L Sheinberg Caitlin Siu Yoland Smith Selina S Solomon Marc A Sommer John L Spudich William R Stauffer Masahiko Takada Shiming Tang Alexander Thiele Stefan Treue Wim Vanduffel Rufin Vogels Matthew P Whitmire Thomas Wichmann Robert H Wurtz Haoran Xu Azadeh Yazdan-Shahmorad Krishna V Shenoy James J DiCarlo Michael L Platt

Neuron 2020 12 19;108(6):1075-1090.e6. Epub 2020 Oct 19.

Department of Neuroscience, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Psychology, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Marketing, Wharton School, University of Pennsylvania, Philadelphia, PA 19104, USA.

Optogenetics has revolutionized neuroscience in small laboratory animals, but its effect on animal models more closely related to humans, such as non-human primates (NHPs), has been mixed. To make evidence-based decisions in primate optogenetics, the scientific community would benefit from a centralized database listing all attempts, successful and unsuccessful, of using optogenetics in the primate brain. We contacted members of the community to ask for their contributions to an open science initiative. As of this writing, 45 laboratories around the world contributed more than 1,000 injection experiments, including precise details regarding their methods and outcomes. Of those entries, more than half had not been published. The resource is free for everyone to consult and contribute to on the Open Science Framework website. Here we review some of the insights from this initial release of the database and discuss methodological considerations to improve the success of optogenetic experiments in NHPs.
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http://dx.doi.org/10.1016/j.neuron.2020.09.027DOI Listing
December 2020

Endogenous hydrogen sulfide maintains eupnea in an in situ arterially perfused preparation of rats.

Commun Biol 2020 Oct 16;3(1):583. Epub 2020 Oct 16.

Department of Physiology, Division of Biomedical Science, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, 305-8575, Japan.

Hydrogen sulfide (HS) is constitutively generated in the human body and works as a gasotransmitter in synaptic transmission. In this study, we aimed to evaluate the roles of endogenous HS in generating eupnea at the respiratory center. We employed an in situ arterially perfused preparation of decerebrated rats and recorded the central respiratory outputs. When the HS-producing enzyme cystathionine β-synthase (CBS) was inhibited, respiration switched from the 3-phase eupneic pattern, which consists of inspiration, postinspiration, and expiration, to gasping-like respiration, which consists of inspiration only. On the other hand, when HS synthesis was inhibited via cystathionine γ-lyase (CSE) or when HS synthesis was activated via CBS, eupnea remained unchanged. These results suggest that HS produced by CBS has crucial roles in maintaining the neuronal network to generate eupnea. The mechanism of respiratory pattern generation might be switched from a network-based system to a pacemaker cell-based system in low HS conditions.
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http://dx.doi.org/10.1038/s42003-020-01312-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7568547PMC
October 2020

Signal dynamics of midbrain dopamine neurons during economic decision-making in monkeys.

Sci Adv 2020 Jul 1;6(27). Epub 2020 Jul 1.

Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.

When we make economic choices, the brain first evaluates available options and then decides whether to choose them. Midbrain dopamine neurons are known to reinforce economic choices through their signal evoked by outcomes after decisions are made. However, although critical internal processing is executed while decisions are being made, little is known about the role of dopamine neurons during this period. We found that dopamine neurons exhibited dynamically changing signals related to the internal processing while rhesus monkeys were making decisions. These neurons encoded the value of an option immediately after it was offered and then gradually changed their activity to represent the animal's upcoming choice. Similar dynamics were observed in the orbitofrontal cortex, a center for economic decision-making, but the value-to-choice signal transition was completed earlier in dopamine neurons. Our findings suggest that dopamine neurons are a key component of the neural network that makes choices from values during ongoing decision-making processes.
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http://dx.doi.org/10.1126/sciadv.aba4962DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458464PMC
July 2020

Primate Nigrostriatal Dopamine System Regulates Saccadic Response Inhibition.

Neuron 2018 12 8;100(6):1513-1526.e4. Epub 2018 Nov 8.

Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan; Division of Biomedical Science, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan; Transborder Medical Research Center, University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan. Electronic address:

Animals need to inhibit inappropriate actions that would lead to unwanted outcomes. Although this ability, called response inhibition, is impaired in neurological/psychiatric disorders with dopaminergic dysfunctions, how dopamine regulates response inhibition remains unclear. Here we investigated neuronal signals of the nigrostriatal dopamine system in monkeys performing a saccadic countermanding task. Subsets of dopamine neurons in the substantia nigra and striatal neurons receiving the dopaminergic input were activated when the monkey was required to cancel a planned saccadic eye movement. These activations were stronger when canceling the eye movements was successful compared with failed and were enhanced in demanding trials. The activated dopamine neurons were distributed mainly in the dorsolateral, but not in the ventromedial, part of the nigra. Furthermore, pharmacological blockade of dopaminergic neurotransmission in the striatum dampened the performance of canceling saccadic eye movements. The present findings indicate that disruption of nigrostriatal dopamine signaling causes impairments in response inhibition.
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http://dx.doi.org/10.1016/j.neuron.2018.10.025DOI Listing
December 2018

Causal Role of Neural Signals Transmitted From the Frontal Eye Field to the Superior Colliculus in Saccade Generation.

Front Neural Circuits 2018 28;12:69. Epub 2018 Aug 28.

Systems Neuroscience Section, Primate Research Institute, Kyoto University, Inuyama, Japan.

The frontal eye field (FEF) and superior colliculus (SC) are major and well-studied components of the oculomotor system. The FEF sends strong projections to the SC directly, and neurons in these brain regions transmit a variety of signals related to saccadic eye movements. Electrical microstimulation and pharmacological manipulation targeting the FEF or SC affect saccadic eye movements. These data suggest the causal contribution of each region to saccade generation. To understand how the brain generates behavior, however, it is critical not only to identify the structures and functions of individual regions, but also to elucidate how they interact with each other. In this review article, we first survey previous works that aimed at investigating whether and how the FEF and SC interact to regulate saccadic eye movements using electrophysiological and pharmacological techniques. These works have reported what signals FEF neurons transmit to the SC and what roles such signals play in regulating oculomotor behavior. We then highlight a recent attempt of our own that has applied an optogenetic approach to stimulate the neural pathway from the FEF to the SC in nonhuman primates. This study has shown that optogenetic stimulation of the FEF-SC pathway is sufficiently effective not only to modulate SC neuron activity, but also to evoke saccadic eye movements. Although the oculomotor system is a complex neural network composed of numbers of cortical and subcortical regions, the optogenetic approach will provide a powerful strategy for elucidating the role of each neural pathway constituting this network.
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http://dx.doi.org/10.3389/fncir.2018.00069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6120992PMC
March 2019

Preferential Representation of Past Outcome Information and Future Choice Behavior by Putative Inhibitory Interneurons Rather Than Putative Pyramidal Neurons in the Primate Dorsal Anterior Cingulate Cortex.

Cereb Cortex 2019 06;29(6):2339-2352

Division of Biomedical Science, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.

The dorsal anterior cingulate cortex (dACC) plays crucial roles in monitoring the outcome of a choice and adjusting a subsequent choice behavior based on the outcome information. In the present study, we investigated how different types of dACC neurons, that is, putative pyramidal neurons and putative inhibitory interneurons, contribute to these processes. We analyzed single-unit database obtained from the dACC in monkeys performing a reversal learning task. The monkey was required to adjust choice behavior from past outcome experiences. Depending on their action potential waveforms, the recorded neurons were classified into putative pyramidal neurons and putative inhibitory interneurons. We found that these neurons do not equally contribute to outcome monitoring and behavioral adjustment. Although both neuron types evenly responded to the current outcome, a larger proportion of putative inhibitory interneurons than putative pyramidal neurons stored the information about the past outcome. The putative inhibitory interneurons further represented choice-related signals more frequently, such as whether the monkey would shift the last choice to an alternative at the next choice opportunity. Our findings suggest that putative inhibitory interneurons, which are thought not to project to brain areas outside the dACC, preferentially transmit signals that would adjust choice behavior based on past outcome experiences.
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http://dx.doi.org/10.1093/cercor/bhy103DOI Listing
June 2019

The Lateral Habenula Circuitry: Reward Processing and Cognitive Control.

J Neurosci 2016 11;36(45):11482-11488

Division of Neuroscience and Basic Behavioral Science, National Institute of Mental Health, Rockville, Maryland 20892

There has been a growing interest in understanding the role of the lateral habenula (LHb) in reward processing, affect regulation, and goal-directed behaviors. The LHb gets major inputs from the habenula-projecting globus pallidus and the mPFC, sending its efferents to the dopaminergic VTA and SNc, serotonergic dorsal raphe nuclei, and the GABAergic rostromedial tegmental nucleus. Recent studies have made advances in our understanding of the LHb circuit organization, yet the precise mechanisms of its involvement in complex behaviors are largely unknown. To begin to address this unresolved question, we present here emerging cross-species perspectives with a goal to provide a more refined understanding of the role of the LHb circuits in reward and cognition. We begin by highlighting recent findings from rodent experiments using optogenetics, electrophysiology, molecular, pharmacology, and tracing techniques that reveal diverse neural phenotypes in the LHb circuits that may underlie previously undescribed behavioral functions. We then discuss results from electrophysiological studies in macaques that suggest that the LHb cooperates with the anterior cingulate cortex to monitor action outcomes and signal behavioral adjustment. Finally, we provide an integrated summary of cross-species findings and discuss how further research on the connectivity, neural signaling, and physiology of the LHb circuits can deepen our understanding of the role of the LHb in normal and maladaptive behaviors associated with mental illnesses and drug abuse.
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http://dx.doi.org/10.1523/JNEUROSCI.2350-16.2016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5125215PMC
November 2016

[Multiple Dopamine Signals and Their Contributions to Reinforcement Learning].

Brain Nerve 2016 Oct;68(10):1139-1147

Laboratory of Cognitive and Behavioral Neuroscience, Faculty of Medicine, University of Tsukuba.

Midbrain dopamine neurons are activated by reward and sensory cue that predicts reward. Their responses resemble reward prediction error that indicates the discrepancy between obtained and expected reward values, which has been thought to play an important role as a teaching signal in reinforcement learning. Indeed, pharmacological blockade of dopamine transmission interferes with reinforcement learning. Recent studies reported, however, that not all dopamine neurons transmit the reward-related signal. They found that a subset of dopamine neurons transmits signals related to non-rewarding, salient experiences such as aversive stimulations and cognitively demanding events. How these signals contribute to animal behavior is not yet well understood. This article reviews recent findings on dopamine signals related to rewarding and non-rewarding experiences, and discusses their contributions to reinforcement learning.
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http://dx.doi.org/10.11477/mf.1416200567DOI Listing
October 2016

A Primary Role for Nucleus Accumbens and Related Limbic Network in Vocal Tics.

Neuron 2016 Jan;89(2):300-7

Systems Neuroscience Section, Primate Research Institute, Kyoto University, Inuyama, Aichi 484-8506, Japan; Laboratory of Cognitive and Behavioral Neuroscience, Division of Biomedical Science, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan.

Inappropriate vocal expressions, e.g., vocal tics in Tourette syndrome, severely impact quality of life. Neural mechanisms underlying vocal tics remain unexplored because no established animal model representing the condition exists. We report that unilateral disinhibition of the nucleus accumbens (NAc) generates vocal tics in monkeys. Whole-brain PET imaging identified prominent, bilateral limbic cortico-subcortical activation. Local field potentials (LFPs) developed abnormal spikes in the NAc and the anterior cingulate cortex (ACC). Vocalization could occur without obvious LFP spikes, however, when phase-phase coupling of alpha oscillations were accentuated between the NAc, ACC, and the primary motor cortex. These findings contrasted with myoclonic motor tics induced by disinhibition of the dorsolateral putamen, where PET activity was confined to the ipsilateral sensorimotor system and LFP spikes always preceded motor tics. We propose that vocal tics emerge as a consequence of dysrhythmic alpha coupling between critical nodes in the limbic and motor networks. VIDEO ABSTRACT.
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http://dx.doi.org/10.1016/j.neuron.2015.12.025DOI Listing
January 2016

Roles of the Lateral Habenula and Anterior Cingulate Cortex in Negative Outcome Monitoring and Behavioral Adjustment in Nonhuman Primates.

Neuron 2015 Nov 17;88(4):792-804. Epub 2015 Oct 17.

Systems Neuroscience Section, Department of Cellular and Molecular Biology, Primate Research Institute, Kyoto University, Inuyama, Aichi 484-8506, Japan; Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan; Division of Biomedical Science, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan. Electronic address:

Animals monitor the outcome of their choice and adjust subsequent choice behavior using the outcome information. Together with the anterior cingulate cortex (ACC), the lateral habenula (LHb) has recently attracted attention for its crucial role in monitoring negative outcome. To investigate their contributions to subsequent behavioral adjustment, we recorded single-unit activity from the LHb and ACC in monkeys performing a reversal learning task. The monkey was required to shift a previous choice to the alternative if the choice had been repeatedly unrewarded in past trials. We found that ACC neurons stored outcome information from several past trials, whereas LHb neurons detected the ongoing negative outcome with shorter latencies. ACC neurons, but not LHb neurons, signaled a behavioral shift in the next trial. Our findings suggest that, although both the LHb and the ACC represent signals associated with negative outcome, these structures contribute to subsequent behavioral adjustment in different ways.
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http://dx.doi.org/10.1016/j.neuron.2015.09.030DOI Listing
November 2015

Neuronal and behavioural modulations by pathway-selective optogenetic stimulation of the primate oculomotor system.

Nat Commun 2015 Sep 21;6:8378. Epub 2015 Sep 21.

Systems Neuroscience Section, Primate Research Institute, Kyoto University, Inuyama, Aichi 484-8506, Japan.

Optogenetics enables temporally and spatially precise control of neuronal activity in vivo. One of the key advantages of optogenetics is that it can be used to control the activity of targeted neural pathways that connect specific brain regions. While such pathway-selective optogenetic control is a popular tool in rodents, attempts at modulating behaviour using pathway-selective optogenetics have not yet been successful in primates. Here we develop a methodology for pathway-selective optogenetics in macaque monkeys, focusing on the pathway from the frontal eye field (FEF) to the superior colliculus (SC), part of the complex oculomotor network. We find that the optogenetic stimulation of FEF projections to the SC modulates SC neuron activity and is sufficient to evoke saccadic eye movements towards the response field corresponding to the stimulation site. Thus, our results demonstrate the feasibility of using pathway-selective optogenetics to elucidate neural network function in primates.
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http://dx.doi.org/10.1038/ncomms9378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4595751PMC
September 2015

Dopamine signals and physiological origin of cognitive dysfunction in Parkinson's disease.

Mov Disord 2015 Apr 15;30(4):472-83. Epub 2015 Mar 15.

Laboratory of Cognitive and Behavioral Neuroscience, Division of Biomedical Science, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.

The pathological hallmark of Parkinson's disease (PD) is the degeneration of midbrain dopamine neurons. Cognitive dysfunction is a feature of PD patients even at the early stages of the disease. Electrophysiological studies on dopamine neurons in awake animals provide contradictory accounts of the role of dopamine. These studies have established that dopamine neurons convey a unique signal associated with rewards rather than cognitive functions. Emphasizing their role in reward processing leads to difficulty in developing hypothesis as to how cognitive impairments in PD are associated with the degeneration of dopamine circuitry. A hint to resolve this contradiction came from recent electrophysiological studies reporting that dopamine neurons transmit more diverse signals than previously thought. These studies suggest that dopamine neurons are divided into at least two functional subgroups, one signaling "motivational value" and the other signaling "salience." The former subgroup fits well with the conventional reward theory, whereas the latter subgroup has been shown to transmit signals related to salient but non-rewarding experiences such as aversive stimulations and cognitively demanding situations. This article reviews recent advances in understanding the non-reward functions of dopamine, and then discusses the possibility that cognitive dysfunction in PD is at least partially caused by the degeneration of the dopamine neuron subgroup signaling the salience of events in the environment.
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http://dx.doi.org/10.1002/mds.26177DOI Listing
April 2015

Information-rate analysis of a fiber-optic transmission system including 2R signal regenerators.

Opt Express 2013 Nov;21(22):26762-73

Performance of a single-channel fiber-optic transmission system in which signal regenerators are periodically inserted is analyzed in terms of information rate (IR) considering channel memory. Limitations in using regenerators in a system having non-zero residual dispersion between the regenerators are discussed. It is shown that a type of signal impairment caused by the interaction between the transmission-fiber dispersion and the regenerator nonlinearity is pattern-dependent and will be mitigated by the use of sequence estimation after detection at the receiver.
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http://dx.doi.org/10.1364/OE.21.026762DOI Listing
November 2013

Distinct representations of cognitive and motivational signals in midbrain dopamine neurons.

Neuron 2013 Sep 8;79(5):1011-24. Epub 2013 Aug 8.

Systems Neuroscience Section, Department of Cellular and Molecular Biology, Primate Research Institute, Kyoto University, Inuyama, Aichi 484-8506, Japan; Division of Biomedical Science, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan; Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan. Electronic address:

Dopamine is essential to cognitive functions. However, despite abundant studies demonstrating that dopamine neuron activity is related to reinforcement and motivation, little is known about what signals dopamine neurons convey to promote cognitive processing. We therefore examined dopamine neuron activity in monkeys performing a delayed matching-to-sample task that required working memory and visual search. We found that dopamine neurons responded to task events associated with cognitive operations. A subset of dopamine neurons were activated by visual stimuli if the monkey had to store the stimuli in working memory. These neurons were located dorsolaterally in the substantia nigra pars compacta, whereas ventromedial dopamine neurons, some in the ventral tegmental area, represented reward prediction signals. Furthermore, dopamine neurons monitored visual search performance, becoming active when the monkey made an internal judgment that the search was successfully completed. Our findings suggest an anatomical gradient of dopamine signals along the dorsolateral-ventromedial axis of the ventral midbrain.
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http://dx.doi.org/10.1016/j.neuron.2013.07.002DOI Listing
September 2013

Adaptive delay control for time-interleaved multi-channel amplitude limiter based on saturation of four-wave mixing in a fiber.

Opt Express 2011 Oct;19(22):21246-57

Graduate School of Engineering, Osaka University, 2-1 Yamada-oka, Suita, Osaka 565-0871, Japan.

An adaptive delay control to maintain time-interleaving condition of multi-channel input signals of all-optical amplitude limiter based on saturation of four-wave mixing (FWM) in a nonlinear fiber is demonstrated. The delay control utilizes as a monitor signal the optical power after the nonlinear fiber at a wavelength that is affected by interchannel FWM in the fiber. When the scheme is applied to 2 x 10 Gbit/s return-to-zero differential phase-shift keying signals where the time separation between the input channels is intentionally changed randomly, the delay control works well and error free detection after transmission is obtained.
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http://dx.doi.org/10.1364/OE.19.021246DOI Listing
October 2011

Electrical stimulation of the primate lateral habenula suppresses saccadic eye movement through a learning mechanism.

PLoS One 2011 24;6(10):e26701. Epub 2011 Oct 24.

Laboratory of Sensorimotor Research, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States of America.

The lateral habenula (LHb) is a brain structure which represents negative motivational value. Neurons in the LHb are excited by unpleasant events such as reward omission and aversive stimuli, and transmit these signals to midbrain dopamine neurons which are involved in learning and motivation. However, it remains unclear whether these phasic changes in LHb neuronal activity actually influence animal behavior. To answer this question, we artificially activated the LHb by electrical stimulation while monkeys were performing a visually guided saccade task. In one block of trials, saccades to one fixed direction (e.g., right direction) were followed by electrical stimulation of the LHb while saccades to the other direction (e.g., left direction) were not. The direction-stimulation contingency was reversed in the next block. We found that the post-saccadic stimulation of the LHb increased the latencies of saccades in subsequent trials. Notably, the increase of the latency occurred gradually as the saccade was repeatedly followed by the stimulation, suggesting that the effect of the post-saccadic stimulation was accumulated across trials. LHb stimulation starting before saccades, on the other hand, had no effect on saccade latency. Together with previous studies showing LHb activation by reward omission and aversive stimuli, the present stimulation experiment suggests that LHb activity contributes to learning to suppress actions which lead to unpleasant events.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0026701PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3200355PMC
February 2012

Optical filter highlighting spectral features part II: quantitative measurements of cosmetic foundation and assessment of their spatial distributions under realistic facial conditions.

Opt Express 2011 Mar;19(7):6031-41

Department of Computer Science and Engineering, Toyohashi University of Technology, Toyohashi, Aichi, Japan.

We previously proposed a filter that could detect cosmetic foundations with high discrimination accuracy [Opt. Express 19, 6020 (2011)]. This study extends the filter's functionality to the quantification of the amount of foundation and applies the filter for the assessment of spatial distributions of foundation under realistic facial conditions. Human faces that are applied with quantitatively controlled amounts of cosmetic foundations were measured using the filter. A calibration curve between pixel values of the image and the amount of foundation was created. The optical filter was applied to visualize spatial foundation distributions under realistic facial conditions, which clearly indicated areas on the face where foundation remained even after cleansing. Results confirm that the proposed filter could visualize and nondestructively inspect the foundation distributions.
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http://dx.doi.org/10.1364/OE.19.006031DOI Listing
March 2011

Optical filter for highlighting spectral features part I: design and development of the filter for discrimination of human skin with and without an application of cosmetic foundation.

Opt Express 2011 Mar;19(7):6020-30

Department of Computer Science and Engineering, Toyohashi University of Technology, Toyohashi, Aichi, Japan.

Light reflected from an object's surface contains much information about its physical and chemical properties. Changes in the physical properties of an object are barely detectable in spectra. Conventional trichromatic systems, on the other hand, cannot detect most spectral features because spectral information is compressively represented as trichromatic signals forming a three-dimensional subspace. We propose a method for designing a filter that optically modulates a camera's spectral sensitivity to find an alternative subspace highlighting an object's spectral features more effectively than the original trichromatic space. We designed and developed a filter that detects cosmetic foundations on human face. Results confirmed that the filter can visualize and nondestructively inspect the foundation distribution.
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http://dx.doi.org/10.1364/OE.19.006020DOI Listing
March 2011

Dopamine in motivational control: rewarding, aversive, and alerting.

Neuron 2010 Dec;68(5):815-34

Laboratory of Sensorimotor Research, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.

Midbrain dopamine neurons are well known for their strong responses to rewards and their critical role in positive motivation. It has become increasingly clear, however, that dopamine neurons also transmit signals related to salient but nonrewarding experiences such as aversive and alerting events. Here we review recent advances in understanding the reward and nonreward functions of dopamine. Based on this data, we propose that dopamine neurons come in multiple types that are connected with distinct brain networks and have distinct roles in motivational control. Some dopamine neurons encode motivational value, supporting brain networks for seeking, evaluation, and value learning. Others encode motivational salience, supporting brain networks for orienting, cognition, and general motivation. Both types of dopamine neurons are augmented by an alerting signal involved in rapid detection of potentially important sensory cues. We hypothesize that these dopaminergic pathways for value, salience, and alerting cooperate to support adaptive behavior.
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http://dx.doi.org/10.1016/j.neuron.2010.11.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3032992PMC
December 2010

Multiple timescales of memory in lateral habenula and dopamine neurons.

Neuron 2010 Aug;67(3):499-510

Laboratory of Sensorimotor Research, National Eye Institute, Bethesda, MD 20892, USA.

Midbrain dopamine neurons are thought to signal predictions about future rewards based on the memory of past rewarding experience. Little is known about the source of their reward memory and the factors that control its timescale. Here we recorded from dopamine neurons, as well as one of their sources of input, the lateral habenula, while animals predicted upcoming rewards based on the past reward history. We found that lateral habenula and dopamine neurons accessed two distinct reward memories: a short-timescale memory expressed at the start of the task and a near-optimal long-timescale memory expressed when a future reward outcome was revealed. The short- and long-timescale memories were expressed in different forms of reward-oriented eye movements. Our data show that the habenula-dopamine pathway contains multiple timescales of memory and provide evidence for their role in motivated behavior.
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http://dx.doi.org/10.1016/j.neuron.2010.06.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2920878PMC
August 2010

Distinct tonic and phasic anticipatory activity in lateral habenula and dopamine neurons.

Neuron 2010 Jul;67(1):144-55

Laboratory of Sensorimotor Research, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Dopamine has a crucial role in anticipation of motivational events. To investigate the underlying mechanisms of this process, we analyzed the activity of dopamine neurons and one of their major sources of input, neurons in the lateral habenula, while animals anticipated upcoming behavioral tasks. We found that lateral habenula and dopamine neurons anticipated tasks in two distinct manners. First, neurons encoded the timing distribution of upcoming tasks through gradual changes in their tonic activity. This tonic signal encoded rewarding tasks in preference to punishing tasks and was correlated with classic phasic coding of motivational value. Second, neurons transmitted a phasic signal marking the time when a task began. This phasic signal encoded rewarding and punishing tasks in similar manners, as though reflecting motivational salience. Our data suggest that the habenula-dopamine pathway motivates anticipation through a combination of tonic reward-related and phasic salience-related signals.
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http://dx.doi.org/10.1016/j.neuron.2010.06.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2905384PMC
July 2010

A pallidus-habenula-dopamine pathway signals inferred stimulus values.

J Neurophysiol 2010 Aug 10;104(2):1068-76. Epub 2010 Jun 10.

Laboratory of Sensorimotor Research, National Eye Institute, National Institutes of Health, Bldg. 49, Rm. 2A50, Bethesda, Maryland 20892-4435, USA.

The reward value of a stimulus can be learned through two distinct mechanisms: reinforcement learning through repeated stimulus-reward pairings and abstract inference based on knowledge of the task at hand. The reinforcement mechanism is often identified with midbrain dopamine neurons. Here we show that a neural pathway controlling the dopamine system does not rely exclusively on either stimulus-reward pairings or abstract inference but instead uses a combination of the two. We trained monkeys to perform a reward-biased saccade task in which the reward values of two saccade targets were related in a systematic manner. Animals used each trial's reward outcome to learn the values of both targets: the target that had been presented and whose reward outcome had been experienced (experienced value) and the target that had not been presented but whose value could be inferred from the reward statistics of the task (inferred value). We then recorded from three populations of reward-coding neurons: substantia nigra dopamine neurons; a major input to dopamine neurons, the lateral habenula; and neurons that project to the lateral habenula, located in the globus pallidus. All three populations encoded both experienced values and inferred values. In some animals, neurons encoded experienced values more strongly than inferred values, and the animals showed behavioral evidence of learning faster from experience than from inference. Our data indicate that the pallidus-habenula-dopamine pathway signals reward values estimated through both experience and inference.
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http://dx.doi.org/10.1152/jn.00158.2010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2934919PMC
August 2010

In vivo measurement of the water content in the dermis by confocal Raman spectroscopy.

Skin Res Technol 2010 May;16(2):137-41

Kanebo Cosmetics Inc., Basic Research Laboratory, Kanagawa, Japan.

Background/purpose: Dermal water plays an important role in the physical properties of the skin. Recently, researchers have attempted to directly measure the dermal water content in vivo using magnetic resonance imaging, near infrared spectroscopy, and Raman spectroscopy. However, these methods have limitations. Although confocal Raman spectroscopy has been developed to measure the water content in the skin, no reports have suggested that this instrument can measure the dermal water content. This report describes a method for measuring the dermal water content in vivo using confocal Raman spectroscopy.

Methods: We used a confocal Raman spectrometer and adjusted the laser exposure time and depth increments according to the skin depth. Age-related changes in the dermal water content of the forearm were examined in 30 young and 30 elderly male subjects. Diurnal changes in the dermal water content of the forearm were examined in 12 elderly male subjects.

Results: Adjusting the exposure time and depth increment dramatically improved the signal-to-noise ratios of the Raman spectra. Elderly dermis had significantly higher water content than young dermis. Moreover, the dermal water content displayed a diurnal change.

Conclusion: This study demonstrates that the dermal water content can be measured in vivo using confocal Raman spectroscopy.
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http://dx.doi.org/10.1111/j.1600-0846.2009.00410.xDOI Listing
May 2010

All-optical DQPSK signal regeneration using 2R amplitude regenerators.

Opt Express 2010 Jan;18(1):10-24

Graduate School of Engineering, Osaka University, 2-1 Yamada-Oka, Suita, Osaka 565-0871, Japan.

An all-optical regeneration scheme for DQPSK signals is proposed and analyzed. In the regenerator, an incoming DQPSK signal is demodulated to two parallel OOK signals by one-symbol delay interferometers. After the amplitude noise is removed by 2R (reamplifying and reshaping) regenerators and the power levels are suitably amplified, the OOK signals modulate the phase of clocked probe pulses in the subsequent all-optical phase modulators by which the noise-reduced (D)QPSK signal is generated. The alteration of phase data encoded on the pulses in the regeneration process can be undone by suitable encoding or decoding. Numerical simulation for short-pulse RZ-DQPSK signals at 160 Gbit/s (80 Gsymbol/s) shows that reduction in both phase and amplitude noise can be obtained by the regeneration scheme where fiber-based 2R amplitude regenerators and phase modulators using self- and cross-phase modulation, respectively, are employed.
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http://dx.doi.org/10.1364/OE.18.000010DOI Listing
January 2010

Relationship between dermal birefringence and the skin surface roughness of photoaged human skin.

J Biomed Opt 2009 Jul-Aug;14(4):044032

Kanebo Cosmetics, Inc., Basic Research Laboratory, 5-3-28, Kotobuki, Odawara, Kanagawa 250-0002, Japan.

The dermal degeneration accompanying photoaging is considered to promote skin roughness features such as wrinkles. Our previous study demonstrated that polarization-sensitive spectral domain optical coherence tomography (PS-SD-OCT) enabled noninvasive three-dimensional evaluation of the dermal degeneration of photoaged skin as a change in dermal birefringence, mainly due to collagenous structures. Our purpose is to examine the relationship between dermal birefringence and elasticity and the skin morphology in the eye corner area using PS-SD-OCT. Nineteen healthy male subjects in their seventees were recruited as subjects. A transverse dermal birefringence map, automatically produced by the algorithm, did not show localized changes in the dermal birefringence in the part of the main horizontal wrinkle. The averaged upper dermal birefringence, however, showed depth-dependent correlation with the parameters of skin roughness significantly, suggesting that solar elastosis is a major factor for the progress of wrinkles. Age-dependent parameters of skin elasticity measured with Cutometer did not correlate with the parameters. These results suggest that the analysis of dermal birefringence using PS-SD-OCT enables the evaluation of photoaging-dependent upper dermal degeneration related to the change of skin roughness.
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http://dx.doi.org/10.1117/1.3207142DOI Listing
December 2009

Two types of dopamine neuron distinctly convey positive and negative motivational signals.

Nature 2009 Jun 17;459(7248):837-41. Epub 2009 May 17.

Laboratory of Sensorimotor Research, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892-4435, USA.

Midbrain dopamine neurons are activated by reward or sensory stimuli predicting reward. These excitatory responses increase as the reward value increases. This response property has led to a hypothesis that dopamine neurons encode value-related signals and are inhibited by aversive events. Here we show that this is true only for a subset of dopamine neurons. We recorded the activity of dopamine neurons in monkeys (Macaca mulatta) during a Pavlovian procedure with appetitive and aversive outcomes (liquid rewards and airpuffs directed at the face, respectively). We found that some dopamine neurons were excited by reward-predicting stimuli and inhibited by airpuff-predicting stimuli, as the value hypothesis predicts. However, a greater number of dopamine neurons were excited by both of these stimuli, inconsistent with the hypothesis. Some dopamine neurons were also excited by both rewards and airpuffs themselves, especially when they were unpredictable. Neurons excited by the airpuff-predicting stimuli were located more dorsolaterally in the substantia nigra pars compacta, whereas neurons inhibited by the stimuli were located more ventromedially, some in the ventral tegmental area. A similar anatomical difference was observed for their responses to actual airpuffs. These findings suggest that different groups of dopamine neurons convey motivational signals in distinct manners.
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http://dx.doi.org/10.1038/nature08028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2739096PMC
June 2009

[Role of the lateral habenula and dopamine neurons in reward processing].

Brain Nerve 2009 Apr;61(4):389-96

Laboratory of Sensorimotor Research, National Eye Institute, National Institutes of Health, 49 Convent Drive, Bldg. 49, Rm. 2A50, Bethesda, MD 20892-4435, USA.

Dopamine neurons in the substantia nigra pars compacta and ventral tegmental area have been implicated in reward-related functions. These neurons are excited by reward and sensory stimuli that predict reward and inhibited by reward omission. These excitatory and inhibitory responses are thought to guide reward-seeking behaviors. Indeed, reward-seeking behaviors can be impaired by injecting dopamine antagonists into the brain areas targeted by dopamine neurons (e.g., caudate nucleus). However, it was unknown which parts of the brain provide dopamine neurons with reward-related signals necessary to induce their responses. Recent studies showed evidence that the lateral habenula, a part of the structure called the epithalamus, is a good candidate for a source of reward-related signals in dopamine neurons. The lateral habenula projects to midbrain structures such as the substantia nigra pars compacta and ventral tegmental area which contain dopamine neurons. Electrical stimulation of the lateral habenula inhibits the activity of dopamine neurons. Neurons in the lateral habenula also encode reward-related signals but in a manner opposite to that obeerved for dopamine neurons (i.e., lateral habenula neurons are inhibited by reward and sensory stimuli predicting reward and excited by reward omission). These anatomical and physiological findings suggest that the lateral habenula transmits reward-related signals to dopamine neurons by inhibiting them. Thereby, the lateral habenula could contribute to reward-seeking behaviors through its projections to the dopaminergic systems.
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April 2009

Fiber-based all-optical regeneration of DPSK signals degraded by transmission in a fiber.

Opt Express 2009 Apr;17(8):6913-9

Graduate School of Engineering, Osaka University, 2-1 Yamada-Oka, Suita, Osaka 565-0871, Japan.

An experiment of all-optical regeneration of short-pulse differential phase-shift keying (DPSK) signals using fiber nonlinearity is reported. Bit error rate (BER) performance is measured for a two-span transmission system where the regenerator is inserted between the spans. Two cases are examined where the signal degradation before the regenerator is due mainly to nonlinearity of the transmission fiber, i.e., the nonlinear phase noise, and is due to addition of amplified spontaneous emission (ASE). The regenerator is shown to be more effective in recovering signal quality in the former case of degradation due to phase noise.
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http://dx.doi.org/10.1364/oe.17.006913DOI Listing
April 2009