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In well-differentiated primary cultures of mouse astrocytes, which express no serotonin transporter (SERT), the ‘serotonin-specific reuptake inhibitor’ (SSRI) fluoxetine leads acutely to 5-HT2B receptor-mediated, transactivation-dependent phosphorylation of extracellular regulated kinases 1/2 (ERK1/2) with an EC50 of ~5 μM, and chronically to ERK1/2 phosphorylation-dependent upregulation of mRNA and protein expression of calcium-dependent phospholipase A2 (cPLA2) with ten-fold higher affinity. This affinity is high enough that fluoxetine given therapeutically may activate astrocytic 5-HT2B receptors (Li et al., 2008, 2009). We now confirm the expression of 5-HT2B receptors in astrocytes freshly dissociated from mouse brain and isolated by fluorescence-activated cell sorting (FACS) and investigate in cultured cells if the effects of fluoxetine are shared by all five conventional SSRIs with sufficiently high affinity to be relevant for mechanism(s) of action of SSRIs. Phosphorylated and total ERK1/2 and mRNA and protein expression of cPLA2a were determined by Western blot and reverse transcription polymerase chain reaction (RT-PCR). Paroxetine, which differs widely from fluoxetine in affinity for SERT and for another 5-HT2 receptor, the 5-HT2C receptor, acted acutely and chronically like fluoxetine. One micromolar of paroxetine, fluvoxamine or sertraline increased cPLA2a expression during chronic treatment; citalopram had a similar effect at 0.1–0.5 μM; these are therapeutically relevant concentrations.
Gene expression changes during cell differentiation are thought to be coordinated by histone modifications, but still little is known about the role of specific histone deacetylases (HDACs) in cell fate decisions in vivo. Here we demonstrate that the catalytic function of HDAC2 is required in adult, but not embryonic neurogenesis. While brain development and adult stem cell fate were normal upon conditional deletion of HDAC2 or in mice lacking the catalytic activity of HDAC2, neurons derived from both zones of adult neurogenesis die at a specific maturation stage. This phenotype is correlated with an increase in proliferation and the aberrant maintenance of proteins normally expressed only in progenitors, such as Sox2, also into some differentiating neurons, suggesting that HDAC2 is critically required to silence progenitor transcripts during neuronal differentiation of adult generated neurons. This cell-autonomous function of HDAC2 exclusively in adult neurogenesis reveals clear differences in the molecular mechanisms regulating neurogenesis during development and in adulthood.
The startle response (response to a loud noise, for instance) is a reflex that is wired into the brain at a very basic level. Although everybody has such a reflex, the strength and quickness of the startle response is modified by a subject's underlying psychoneurological state. The nature of this modification, therefore, is now seen as an accurate, objective measure of very deep neurological processes. This book is a comprehensive volume devoted to startle modification and offers a unique overview of the methods, measurement, physiology and psychology of the phenomenon, particularly modification of the human startle eyeblink. Chapters are written by many of the world's leading investigators in the field and include coverage of elicitation and recording of startle blink, issues in measurement and quantification, the neurophysiological basis of the basic startle response and its modification by attentional and affective processes, psychological processes underlying short and long lead interval modification (including prepulse inhibition), applications of startle modification to the study of psychopathology, including schizophrenia, affective disorders, and psychopathy, developmental processes and relationships with ERPs and behavioural measures of information processing.
Memory for the final position of a target is usually displaced in the direction of target motion, a finding referred to as representational momentum. There are several different approaches to explaining representational momentum, and these approaches range from low-level perceptual mechanisms (e.g., oculomotor behavior) to high-level cognitive mechanisms (e.g., internalization of the effects of momentum). These approaches are overviewed, and a classification system involving internalization theories, belief-based theories, neointernalization theories, low-level theories, and network models is proposed. The extent to which each approach is consistent with the wide range of existent empirical data regarding representational momentum is noted, and possible directions of and considerations for a more unified theory of displacement are addressed.
Memory for the final position of a previously viewed target is often displaced in the direction of target motion. This forward displacement has been referred to as representational momentum (Freyd & Finke 1984) and is influenced by numerous variables (Hubbard 1995b, 2005). Although initial studies of representational momentum appeared consistent with the hypothesis that observers internalize or incorporate the principle of momentum into the representation of the target, subsequent studies reported displacement inconsistent with such a literal internalization or incorporation of momentum. For example, variables other than implied momentum such as conceptual knowledge about target identity (Reed & Vinson 1996), expectations regarding future target motion (Verfaillie & d'Ydewalle 1991; Johnston & Jones 2006), attributions about the source of target motion (Hubbard & Ruppel 2002; Hubbard & Favretto 2003), and whether observers visually track the target (Kerzel 2000; Kerzel et al. 2001) influence displacement.
The perceptual stability of visual space becomes fragile in the wake of a saccadic eye movement. Objects flashed shortly before a saccade are mislocalized toward the saccade target. Traditional accounts for this effect have associated the mislocalizations with sluggishness of the efference copy signal, which is important in space perception across eye movements. Recent theories of space perception, however, have emphasized a role for visual memory in the generation of transsaccadic spatial stability. We have investigated the role of visual processes and their interactions with efference copy signals in the perisaccadic compression of space. In our experiments, subjects performed saccades in front of a computer display while visual stimuli were briefly flashed on the screen just before or during the saccade. Subjects had to report the perceived location of the flash. When the saccade target's position was visibly available after the saccade, the perceived location of the flash was compressed toward the target's position. This compression occurred not only along the axis of the saccade but also for parts of visual space along a direction orthogonal to the saccade. When the saccade target was not visibly available after the saccade, the perceived location of the flash showed only a slight shift in saccade direction. In this condition, however, the perceived location of the saccade target was drawn toward the position of the flash. We propose a framework that consists of pre- and postsaccadic processes to explain these findings.
Much work has been described comparing relative timing of different features, mostly motion and color or motion and a flash. Here we study the timing relations of pairs of motion stimuli and pairs of motion and flicker or motion and flashes. In a two-alternative forced choice task we measured thresholds for detecting asynchrony, providing estimates for shifts in subjective simultaneity as well as the window of synchronicity.
Windows of synchronicity varied for different combinations of motion direction. Comparing different velocities or different contrast levels revealed large shifts in subjective synchronicity. Contrast effects were much larger for motion reversals than for luminance flicker, indicating a major influence on motion mechanisms. Our results are compatible with the hypothesis of a flexible, high-level brain program for timing analysis. Temporal resolution of this program is limited. Differences in the processing of separate motion characteristics should be taken into account in cross-feature comparisons involving visual motion information. Results for motion reversals versus luminance flashes did not reveal a clear differential shift in time. Large differences within the motion system and the lack of a differential latency between motion reversals and flashes suggest that the flash-lag effect may be largely caused by instant spatial remapping of positional information for moving objects. We show that spatial extrapolation does not necessarily result in overshoot errors when the motion stops.
In recent years, the study and interpretation of mislocalization phenomena observed with moving objects have caused an intense debate about the processing mechanisms underlying the encoding of position. We use a neurophysiologically plausible recurrent network model to explain visual illusions that occur at the start, midposition, and end of motion trajectories known as the Fröhlich, the flash-lag, and the representational momentum effect, respectively. The model implements the idea that trajectories are internally represented by a traveling activity wave in position space, which is essentially shaped by local feedback loops within pools of neurons. We first use experimentally observed trajectory representations in the primary visual cortex of cat to adjust the spatial ranges of lateral interactions in the model. We then show that the readout of the activity profile at adequate points in time during the build-up, midphase, and decay of the wave qualitatively and quantitatively explain the known dependence of the mislocalization errors on stimulus attributes such as contrast and speed. We conclude that cooperative mechanisms within the network may be responsible for the three illusions, with a possible intervention of top-down influences that modulate the efficacy of the lateral interactions.
Introduction
Localizing an object in the presence of motion is a fundamental ability for many species as a moving object often represents danger or food. In recent years, advances in neurophysiology and psychophysics have substantially increased our understanding of how the visual system calculates the present and future positions of moving objects.
Different features of stimuli are processed in the central nervous system at different speeds. However, such neural time differences do not map directly onto perceptual time differences. How the brain accounts for timing disparities to correctly judge the temporal order of events in the world is the temporal binding problem. I weigh physiological data against new psychophysical findings both within and between modalities. The essence of the paradox is that the timing of neural signals appears, at first blush, too variable for the high accuracy of the psychophysical judgments. I marshal data indicating that ∼80 msec is an important duration in perception and make the novel suggestion that this number is directly mirrored in the physiology. In recordings from several areas of the primate visual system, the difference between the slowest and fastest latencies based on luminance contrast is 80 msec. If the rest of the brain wants to time outside stimuli correctly, it must account for the fact that the earliest stages of the visual system spread signals out in time. I suggest that the brain waits for the slowest information to arrive before committing to a percept. This strategy only applies to visual awareness; in contrast, the motor system may form its reactions based on the first incoming spikes.
Introduction
One goal of modern neuroscience is to relate physiological data to perception (Eagleman 2001). How do spikes recorded from single neurons map onto object recognition, brightness perception, or timing judgments?
In the flash-lag effect (FLE) a stationary flash is usually mislocalized as lagging behind a moving object in spatiotemporal alignment. Nijhawan, who postulated a mechanism of perceptual extrapolation of motion to explain the phenomenon, rediscovered this perceptual effect. The first challenge to the motion extrapolation hypothesis included an attentional shift mechanism as the alternative, which implicitly relied on the spotlight metaphor for visual attention. Other explanations have been forwarded since then, such as those based on differential latencies or perceptual postdiction. In this chapter we aim to scrutinize the role of attention in either modulating or engendering the FLE.
Introduction
To deal with even simple challenges, such as grasping an object or avoiding a collision with either stationary or moving obstacles, everyday life demands from us the ability to localize a visual stimulus, within an acceptable degree of accuracy, in both space and time. Learning how to pin down the location of an object moving along its space–time trajectory in a given task depends on the one hand on the amount and quality of perceptual information provided by the sensory system, and on the other hand on the correctness of the action generated during that task. The behavioral outcome is continuously fed back to the nervous system, therefore constraining and refining, in an adaptive way, the representation of the world both in perception and in action.
However optimized our behavior turns out to be, the underlying perceptual edifice we assemble from the available sensory world is by no means unique.
When observers are asked to localize the initial position of a moving target, they often indicate a position displaced in the direction of motion relative to the true onset position. In this review, the debate between Fröhlich, who discovered this phenomenon, and his contemporaries in the 1920s and 1930s is summarized. Striking misinterpretations of Fröhlich's findings and the anticipation of recent research on the flash-lag effect will be presented. In the second part, current accounts of the Fröhlich effect in terms of attention and metacontrast are evaluated. In the final section, reconciliation between research on the Fröhlich effect and recent reports of an error opposite the direction of motion (the onset repulsion effect) is offered.
Introduction
When asked to localize a moving target entering a window, observers often indicate a position not adjacent to the edge of the window but a position displaced in the direction of motion (see Fig. 19.1(a)). The gap between the edge of a window and the initial perception of the moving target was first discovered by the Norwegian astronomer O. Pihl in 1894, but Fröhlich (1923) was the first to study the effect systematically. Therefore, the illusion has been named the “Fröhlich effect.” Fröhlich's explanation of the illusion in terms of “sensation time” was amply discussed in the 1930s (Fröhlich 1930, 1932; Rubin 1930; G. E. Müller 1931; Metzger 1932; Piéron 1935) but forgotten for the 60 years that followed.
This chapter is concerned with the temporal aspects of visual binding. In particular, it concentrates on findings from studies of perceptual asynchrony between stimulus features and the temporal resolution of feature binding. I review the circumstances in which perceptual asynchronies are apparent versus those in which they are not. I argue that the existing data cannot be accounted for simply by a characteristic latency difference in the processing of different visual attributes (Moutoussis & Zeki 1997a,b) or by a scheme of temporal markers at salient stimulus transitions (Nishida & Johnston 2002). Instead, I outline a potential mechanism based on feedback from higher visual areas to primary visual cortex to account for the dynamics of binding color with orientation and direction of motion.
Introduction
How is the content of our conscious visual experience related to neural processing? Is our visual awareness an online monitor of visual processing, or do interpretative processes intervene to give conscious visual experience a postdictive quality? In the words of William James, “A succession of feelings, in and of itself, is not a feeling of succession. And because, to our successive feelings, a feeling of their own succession is added, that must be treated as an additional fact requiring its own special elucidation” (James 1890). But what is the nature of this “additional fact”? The simplest account would seem to be that the perceived sequence of events is directly related to the amount and duration of neural processing needed to achieve conscious experience (Jeannerod 1992).
The dual-channel differential latency hypothesis (Öğmen et al. 2004) successfully accounts for many aspects of the flash-lag effect (FLE). Here we use the dual-channel differential latency hypothesis to explain an illusion of perceived line length that can be viewed as one component of an illusion reported by Cai and Schlag (2001a). In the phenomenon studied here, a flash is presented collinear with a moving line that is simultaneously changing in length. The moving line is perceived to be misaligned with the flash (the FLE) and the length of the moving line is perceived to differ from its physical length at the instant of the flash. We designate this phenomenon the Cai line-Length Effect (CLE). Our analysis treats a horizontally moving line that also changes its vertical length as composed of two simultaneous motion components: (1) horizontal motion, and (2) vertical expansion or contraction. We measured perceived position misalignment and length misperception in the CLE paradigm, as well as separately for stimuli with the individual motion components of the CLE, as a function of target luminance. Perceived position misalignment and length misperception varied similarly with target luminance, both in the CLE paradigm and when the individual motion components were tested separately. The misperception of stimulus position and length in the CLE reflects an additional processing delay that may be caused by an interaction between the motion components in two directions. […]
When judging the position of a moving object, human observers do not perceive and memorize the moving object's correct position. There are two known phenomena in judged position errors of a moving object, representational momentum (RM) and the flash-lag effect (FLE), both of which we consider here.
RM was originally reported by Freyd and Finke (1984). Freyd and colleagues displayed a series of still frames to imply the rotation of a rectangle (e.g., Freyd & Finke 1984, 1985; Freyd & Johnson 1987). Observers saw three views of a rectangle at different rotations about its center, with 250 msec display duration with 250 msec interstimulus interval. The fourth rectangle was presented as a probe 250 msec after the third frame presentation. The rotation of the probe was selected from possible positions symmetrically distributed around the actual third position of the rectangle. Observers were asked whether the rectangle in the third frame (the last frame of the motion sequence) was the same orientation as the probe. The results showed that their memory for the third orientation tended to be shifted in the direction of rotation. In other words, the orientation of the probe rectangle had to be rotated slightly further to be judged as being in the same position as the third rectangle. To account for the forward shift of the final position of a stimulus undergoing implied motion, some authors postulate that the dynamics of the representational system follow physical laws, such as momentum (representational momentum; Finke & Freyd 1985; Finke et al. 1986; Freyd 1987; Finke & Shyi 1988).
Some basic versions of the flash-lag effect have been known since the early decades of the twentieth century. Intriguingly, neural delays were as central in the early attempts at explaining the effect, as they are in the more recent investigations into its cause. For a changing visual stimulus a delayed registration of the stimulus by the central nervous system (CNS) constitutes an “error” between the instantaneously registered state of the stimulus on the one hand and its physical state on the other. Therefore, for animals to acquire food, mate, and avoid predators, compensation of sensory delays is essential. One may ask which component(s) of the CNS compensate for visual delays. Logically compensation could be carried out either by visual or motor mechanisms, or both. The motion extrapolation account of the flash-lag effect challenged the dominant view that only motor mechanisms compensate for visual delays, suggesting instead that visual mechanisms also contribute. Controversy fueled by empirical observations with unpredictable motion, in particular the flash-initiated and flashterminated conditions of the flash-lag effect, soon followed; prima facie motion extrapolation could not accommodate these results. Armed with these challenging findings (primarily) several alternative accounts of flash-lag were proposed. In light of new developments, this chapter evaluates the motion extrapolation, motion sampling, motion integration, postdiction, differential latency, and attentional cuing accounts of flash-lag.
This chapter is a critical review and discussion of psychophysical studies on perisaccadic visual mislocalization. In particular, it focuses on factors influencing the mislocalization curves. The chapter is organized as follows: first some findings on perisaccadic mislocalization observed in complete darkness are reviewed, followed by empirical and theoretical considerations on eye position signals estimated psychophysically from the mislocalization curves. Next, issues on mislocalization in a lit environment are discussed. Finally, findings on perisaccadic perceptual effects of flickering stimulus are reviewed. Although our understanding of how saccadic eye movements affect visual localization has advanced dramatically in recent years, we probably have only a crude outline of the phenomena and, therefore, further research is needed.
Visual mislocalization in the dark
Basic findings
In a saccade, the projection of the world sweeps across the retina at high speed. Nevertheless, we usually do not notice this visual motion, and the world continues to appear visually stable. This perceptual phenomenon is called “visual stability.”
Although visual stability is preserved during saccades under normal conditions, the perception of the position of objects flashed before, during, or just after a saccade is altered. Examinations into perisaccadic mislocalization were first made in the 1960s by Matin and his colleagues (Matin & Pearce 1965; Matin et al. 1969, 1970). They reported that errors in perceptual localization occurred before the saccade onset and finished slightly after it. Subsequent studies showed essentially the same results (Honda 1989, 1990, 1991; Dassonville et al. 1992, 1995; Sogo & Osaka, 2001).
People shift their gaze more frequently than they realize, sometimes smoothly to track objects in motion, more often abruptly with a saccade to bring a new part of the visual field under closer visual examination. Saccades are typically made three times a second throughout most of our waking life, but they are rarely noticed. Yet they are accompanied by substantial changes in visual function, most notably suppression of visual sensitivity, mislocalization of spatial position, and misjudgments of temporal duration and order of stimuli presented around the time. Here we review briefly these effects and expound a novel theory of their cause. To preserve visual stability, receptive fields undergo a fast but not instantaneous remapping at the time of saccades. If the speed of remapping approaches the physical limit of neural information transfer, it may lead to relativistic-like effects observed psychophysically, namely a compression of spatial relationships and a dilation of time.
Introduction
Saccades are ballistic movements of the eyes made to reposition our gaze. They can be deliberate but normally are automatic and go unnoticed. Not only do the actual eye movements escape notice, but so do the image motion they cause and the fact that gaze itself has been repositioned. This problem has gained the attention of most visual scientists, including von Helmholtz (1866), Sperry (1950), Alhazen (1083), and Howard (1996). A general conclusion to emerge from a variety of studies was that saccades were accompanied by a “corollary discharge” (Sperry 1950) or an “efference copy” (von Holst & Mittelstädt 1954) of the motor signal that corrected for the eye movement (for general review, see Ross et al. 2001).
Visual information is crucial for goal-directed reaching. Recently a number of studies have shown that motion in particular is an important source of information for the visuomotor system. For example, when reaching for a stationary object, nearby visual movement, even when irrelevant to the object or task, can influence the trajectory of the hand. Although it is clear that various kinds of visual motion can influence goal-directed reaching movements, it is less clear how or why they do so. In this chapter, we consider whether the influence of motion on reaching is unique compared to its influence on other forms of visually guided behavior. We also address how motion is coded by the visuomotor system and whether there is one motion processing system that underlies both perception and visually guided reaching. Ultimately, visual motion may operate on a number of levels, influencing goal-directed reaching through more than one mechanism, some of which may actually be beneficial for accurate behavior.
Introduction
Visual motion is constantly produced as we move our eyes and head and as objects move in the world. The visuomotor system, therefore, faces a serious challenge in that it must register target as well as background motion and then segment these different sources of motion in order to direct actions to objects. Over the last three decades, a broad and expanding literature has examined how the visuomotor system processes and uses visual motion in goal-directed behavior.