I have developed "tennis elbow" from lugging this book around the past four weeks, but it is worth the pain, the effort, and the aspirin. It is also worth the (relatively speaking) bargain price. Including appendixes, this book contains 894 pages of text. The entire panorama of the neural sciences is surveyed and examined, and it is comprehensive in its scope, from genomes to social behaviors. The editors explicitly state that the book is designed as "an introductory text for students of biology, behavior, and medicine," but it is hard to imagine any audience, interested in any fragment of neuroscience at any level of sophistication, that would not enjoy this book. The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or

Principles of Neural Science

The study of decision making spans such varied fields as neuroscience, psychology, economics, statistics, political science, and computer science. Despite this diversity of applications, most decisions share common elements including deliberation and commitment. Here we evaluate recent progress in understanding how these basic elements of decision formation are implemented in the brain. We focus on simple decisions that can be studied in the laboratory but emphasize general principles likely to extend to other settings.

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The Neural Basis of Decision Making

中枢神経系疾患の治療は正常細胞（ニューロン）の機能維持を目的とするが，脳血管障害のように機能障害の原因が細胞の死滅に基づくことは多い．一方，脳腫瘍の治療においては薬物療法や放射線療法といった腫瘍細胞の死滅を目標とするものが大きな位置を占める．いずれの場合にも，細胞死の機序を理解することは各種病態や治療法の理解のうえで重要である．現在のところ最も研究の進んでいる細胞死の型はアポトーシスである．そのなかで重要な位置を占めるミトコンドリアにおける反応および抗アポトーシス因子について概要を紹介する．

Neuroscience 細胞死：最近の知見

When we learn a new motor skill, such as playing an approaching tennis ball, both our sensors and the task possess variability. Our sensors provide imperfect information about the ball's velocity, so we can only estimate it. Combining information from multiple modalities can reduce the error in this estimate. On a longer time scale, not all velocities are a priori equally probable, and over the course of a match there will be a probability distribution of velocities. According to bayesian theory, an optimal estimate results from combining information about the distribution of velocities-the prior-with evidence from sensory feedback. As uncertainty increases, when playing in fog or at dusk, the system should increasingly rely on prior knowledge. To use a bayesian strategy, the brain would need to represent the prior distribution and the level of uncertainty in the sensory feedback. Here we control the statistical variations of a new sensorimotor task and manipulate the uncertainty of the sensory feedback. We show that subjects internally represent both the statistical distribution of the task and their sensory uncertainty, combining them in a manner consistent with a performance-optimizing bayesian process. The central nervous system therefore employs probabilistic models during sensorimotor learning.

Bayesian integration in sensorimotor learning

We recorded the activity of single neurons in the posterior parietal cortex (area LIP) of two rhesus monkeys while they discriminated the direction of motion in random-dot visual stimuli. The visual task was similar to a motion discrimination task that has been used in previous investigations of motion-sensitive regions of the extrastriate cortex. The monkeys were trained to decide whether the direction of motion was toward one of two choice targets that appeared on either side of the random-dot stimulus. At the end of the trial, the monkeys reported their direction judgment by making an eye movement to the appropriate target. We studied neurons in LIP that exhibited spatially selective persistent activity during delayed saccadic eye movement tasks. These neurons are thought to carry high-level signals appropriate for identifying salient visual targets and for guiding saccadic eye movements. We arranged the motion discrimination task so that one of the choice targets was in the LIP neuron's response field (RF) while the other target was positioned well away from the RF. During motion viewing, neurons in LIP altered their firing rate in a manner that predicted the saccadic eye movement that the monkey would make at the end of the trial. The activity thus predicted the monkey's judgment of motion direction. This predictive activity began early in the motion-viewing period and became increasingly reliable as the monkey viewed the random-dot motion. The neural activity predicted the monkey's direction judgment on both easy and difficult trials (strong and weak motion), whether or not the judgment was correct. In addition, the timing and magnitude of the response was affected by the strength of the motion signal in the stimulus. When the direction of motion was toward the RF, stronger motion led to larger neural responses earlier in the motion-viewing period. When motion was away from the RF, stronger motion led to greater suppression of ongoing activity. Thus the activity of single neurons in area LIP reflects both the direction of an impending gaze shift and the quality of the sensory information that instructs such a response. The time course of the neural response suggests that LIP accumulates sensory signals relevant to the selection of a target for an eye movement.

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Neural Basis of a Perceptual Decision in the Parietal Cortex (Area LIP) of the Rhesus Monkey

Complex visual scenes require that a target for an impending saccadic eye movement be selected from a larger number of possible targets. We investigated whether changing the probability that a visual stimulus would be selected as the target for a saccade altered activity of monkey superior colliculus (SC) neurons in two experiments. First, we changed the number of possible targets on each trial. Second, we kept the visual display constant and presented a single saccade target repeatedly so that target probability was established over time. Buildup neurons in the SC, those with delay period activity, showed a consistent reduction in activity as the probability of the saccade decreased, independent of the visual stimulus configuration. Other SC neurons, fixation and burst, were largely unaffected by the changes in saccade target probability. Because we had monkeys making saccades to many locations within the visual field, we could examine activity associated with saccades outside of the movement field of neurons. We found the activity of buildup neurons to be similar across the SC, before the target was identified, and reduced when the number of possible targets increased. The results of our experiments are consistent with a role for this activity in establishing a motor set. We found, consistent with this interpretation, that the activity of these neurons was predictive of the latency of a saccadic eye movement and not other saccade parameters such as end point or peak velocity.

https://www.jneurosci.org/content/jneuro/18/18/7519.full.pdf

Modulation of neuronal activity in superior colliculus by changes in target probability.

Visual scenes are composed of many elements and although we can appreciate a scene as a whole, we can only move our eyes to one element of the scene at a time. As visual scenes become more complex, the number of potential targets in the scene increases, and the uncertainty that any particular one will be selected for an eye movement also increases. How motor systems accommodate this target uncertainty remains unknown. The activities of neurons in both the cerebral cortex and superior colliculus are modulated by this selection process. We reasoned that activity associated with target uncertainty should be evident in the saccadic motor system at the final stages of neural processing, in the superior colliculus. By systematically changing the number of stimuli from which a selection must be made and recording from superior colliculus neurons, we found that as the target uncertainty increased, the neural activity preceding target selection decreased. These results indicate that neurons within the final common pathway for movement generation are active well in advance of the selection of a particular movement. This early activity varies with the probability that a particular movement will be selected.

Modulation of neuronal activity by target uncertainty

The basal ganglia : An overview of circuits and function

The superior colliculus is one of the most well-studied structures in the brain, and with each new report, its proposed role in behavior seems to increase in complexity. Forty years of evidence show that the colliculus is critical for reorienting an organism toward objects of interest. In monkeys, this involves saccadic eye movements. Recent work in the monkey colliculus and in the homologous optic tectum of the bird extends our understanding of the role of the colliculus in higher mental functions, such as attention and decision making. In this review, we highlight some of these recent results, as well as those capitalizing on circuit-based methodologies using transgenic mice models, to understand the contribution of the colliculus to attention and decision making. The wealth of information we have about the colliculus, together with new tools, provides a unique opportunity to obtain a detailed accounting of the neurons, circuits, and computations that underlie complex behavior.

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Circuits for Action and Cognition: A View from the Superior Colliculus.

Hyperexcitable reflex blinks are a cardinal sign of Parkinson’s disease. The first step in the circuit linking the basal ganglia and brainstem reflex blink circuits is the inhibitory nigrostriatal pathway (Basso et al., 1996). The current study reports the circuits linking the superior colliculus (SC) to trigeminal reflex blink circuits. Microstimulation of the deep layers of the SC suppresses subsequent reflex blinks at a latency of 5.4 msec. This microstimulation does not activate periaqueductal gray antinociceptive circuits. The brainstem structure linking SC to reflex blink circuits must suppress reflex blinks at a shorter latency than the SC and produce the same effect on reflex blink circuits as SC stimulation, and removal of the structure must block SC modulation of reflex blinks. Only the nucleus raphe magnus (NRM) meets these requirements. NRM microstimulation suppresses reflex blinks with a latency of 4.4 msec. Like SC stimulation, NRM microstimulation reduces the responsiveness of the spinal trigeminal nucleus. Finally, blocking the receptors for the NRM transmitter serotonin eliminates SC modulation of reflex blinks, and muscimol inactivation of the NRM transiently prevents SC modulation of reflex blinks. Thus, the circuit through which the basal ganglia modulates reflex blinking is (1) the substantia nigra pars reticulata inhibits SC neurons, (2) the SC excites tonically active NRM neurons, and (3) NRM neurons inhibit spinal trigeminal neurons involved in reflex blink circuits.

https://www.jneurosci.org/content/jneuro/16/22/7318.full.pdf

Michele A. Basso

Papers

Modulation of neuronal activity in superior colliculus by changes in target probability.

Modulation of neuronal activity by target uncertainty

The basal ganglia : An overview of circuits and function

Circuits for Action and Cognition: A View from the Superior Colliculus.

An Explanation for Reflex Blink Hyperexcitability in Parkinson’s Disease. II. Nucleus Raphe Magnus