Passive exposure to visual motion leads to short-term changes in the optomotor response of aging zebrafish.

Numerous studies have shown that prior visual experiences play an important role in sensory processing and adapting behavior in a dynamic environment. A repeated and passive presentation of visual stimulus is one of the simplest procedures to manipulate acquired experiences. Using this approach, we aimed to investigate exposure-based visual learning of aging zebrafish and how cholinergic intervention is involved in exposure-induced changes. Our measurements included younger and older wild-type zebrafish and achesb55/+ mutants with decreased acetylcholinesterase activity. We examined both within-session and across-day changes in the zebrafish optomotor responses to repeated and passive exposure to visual motion. Our findings revealed short-term (within-session) changes in the magnitude of optomotor response (i.e., the amount of position shift by fish as a response to visual motion) rather than long-term and persistent effects across days. Moreover, the observed short-term changes were age- and genotype-dependent. Compared to the initial presentations of motion within a session, the magnitude of optomotor response to terminal presentations decreased in the older zebrafish. There was a similar robust decrease specific to achesb55/+ mutants. Taken together, these results point to short-term (within-session) alterations in the motion detection of adult zebrafish and suggest differential effects of neural aging and cholinergic system on the observed changes. These findings further provide important insights into adult zebrafish optomotor response to visual motion and contribute to understanding this reflexive behavior in the short- and long-term stimulation profiles.

Long-Term Acetylcholinesterase Depletion Alters the Levels of Key Synaptic Proteins while Maintaining Neuronal Markers in the Aging Zebrafish (Danio rerio) Brain.

INTRODUCTION: Interventions targeting cholinergic neurotransmission like acetylcholinesterase (AChE) inhibition distinguish potential mechanisms to delay age-related impairments and attenuate deficits related to neurodegenerative diseases. However, the chronic effects of these interventions are not well described. METHODS: In the current study, global levels of cholinergic, cellular, synaptic, and inflammation-mediating proteins were assessed within the context of aging and chronic reduction of AChE activity. Long-term depletion of AChE activity was induced by using a mutant zebrafish line, and they were compared with the wildtype group at young and old ages. RESULTS: Results demonstrated that AChE activity was lower in both young and old mutants, and this decrease coincided with a reduction in ACh content. Additionally, an overall age-related reduction in AChE activity and the AChE/ACh ratio was observed, and this decline was more prominent in wildtype groups. The levels of an immature neuronal marker were upregulated in mutants, while a glial marker showed an overall reduction. Mutants had preserved levels of inhibitory and presynaptic elements with aging, whereas glutamate receptor subunit levels declined. CONCLUSION: Long-term AChE activity depletion induces synaptic and cellular alterations. These data provide further insights into molecular targets and adaptive responses following the long-term reduction of AChE activity that was also targeted pharmacologically to treat neurodegenerative diseases in human subjects.

Zebrafish optomotor response to second-order motion illustrates that age-related changes in motion detection depend on the activated motion system.

Various aspects of visual functioning, including motion perception, change with age. Yet, there is a lack of comprehensive understanding of age-related alterations at different stages of motion processing and in each motion system. To understand the effects of aging on second-order motion processing, we investigated optomotor responses (OMR) in younger and older wild-type (AB-strain) and acetylcholinesterase (achesb55/+) mutant zebrafish. The mutant fish with decreased levels of acetylcholinesterase have been shown to have delayed age-related cognitive decline. Compared to previous results on first-order motion, we found distinct changes in OMR to second-order motion. The polarity of OMR was dependent on age, such that second-order stimulation led to mainly negative OMR in the younger group while older zebrafish had positive responses. Hence, these findings revealed an overall aging effect on the detection of second-order motion. Moreover, neither the genotype of zebrafish nor the spatial frequency of motion significantly changed the response magnitude. Our findings support the view that age-related changes in motion detection depend on the activated motion system.

A comparison of equivalent noise methods in investigating local and global form and motion integration.

Static and dynamic cues within certain spatiotemporal proximity are used to evoke respective global percepts of form and motion. The limiting factors in this process are, first, internal noise, which indexes local orientation/direction detection, and, second, sampling efficiency, which relates to the processing and the representation of global orientation/direction. These parameters are quantified using the equivalent noise (EN) paradigm. EN has been implemented with just two levels: high and low noise. However, when using this simplified version, one must assume the shape of the overall noise dependence, as the intermediate points are missing. Here, we investigated whether two distinct EN methods, the 8-point and the simplified 2-point version, reveal comparable parameter estimates. This was performed for three different types of stimuli: random dot kinematograms, and static and dynamic translational Glass patterns, to investigate how constant internal noise estimates are, and how sampling efficiency might vary over tasks. The results indicated substantial compatibility between estimates over a wide range of external noise levels sampled with eight data points, and a simplified version producing two highly informative data points. Our findings support the use of a simplified procedure to estimate essential form-motion integration parameters, paving the way for rapid and critical applications to populations that cannot tolerate protracted measurements.

Attentional modulations of audiovisual interactions in apparent motion: Temporal ventriloquism effects on perceived visual speed.

The timing of brief stationary sounds has been shown to alter different aspects of visual motion, such as speed estimation. These effects of auditory timing have been explained by temporal ventriloquism and auditory dominance over visual information in the temporal domain. Although previous studies provide unprecedented evidence for the multisensory nature of speed estimation, how attention is involved in these audiovisual interactions remains unclear. Here, we aimed to understand the effects of spatial attention on these audiovisual interactions in time. We utilized a set of audiovisual stimuli that elicit temporal ventriloquism in visual apparent motion and asked participants to perform a speed comparison task. We manipulated attention either in the visual or auditory domain and systematically changed the number of moving objects in the visual field. When attention was diverted to a stationary object in the visual field via a secondary task, the temporal ventriloquism effects on perceived speed decreased. On the other hand, focusing attention on the auditory stimuli facilitated these effects consistently across different difficulty levels of secondary auditory task. Moreover, the effects of auditory timing on perceived speed did not change with the number of moving objects and existed in all the experimental conditions. Taken together, our findings revealed differential effects of allocating attentional resources in the visual and auditory domains. These behavioral results also demonstrate that reliable temporal ventriloquism effects on visual motion can be induced even in the presence of multiple moving objects in the visual field and under different perceptual load conditions.

Motion processing impaired by transient spatial attention: Potential implications for the magnocellular pathway.

Spatial cues presented prior to the presentation of a static stimulus usually improve its perception. However, previous research has also shown that transient exogenous cues to direct spatial attention to the location of a forthcoming stimulus can lead to reduced performance. In the present study, we investigated the effects of transient exogenous cues on the perception of briefly presented drifting Gabor patches. The spatial and temporal frequencies of the drifting Gabors were chosen to mainly engage the magnocellular pathway. We found better performance in the motion direction discrimination task when neutral cues were presented before the drifting target compared to a valid spatial cue. The behavioral results support the hypothesis that transient attention prolongs the internal response to the attended stimulus, thus reducing the temporal segregation of visual events. These results were complemented by applying a recently developed model for perceptual decisions to rule out a speed-accuracy trade-off and to further assess cueing effects on visual performance. In a model-based assessment, we found that valid cues initially enhanced processing but overall resulted in less efficient processing compared to neutral cues, possibly caused by reduced temporal segregation of visual events.

Behavioral and ERP evidence that object-based attention utilizes fine-grained spatial mechanisms.

Valdes-Sosa, Cobo, and Pinilla (1998) introduced a transparent-motion design that provided evidence of object-based attention whereby attention embraces all features of an attentionally cued perceptual object including new unpredictable features such as a brief translation. Subsequent studies using variants of that design appeared to provide further behavioral, electrophysiological, and brain imaging evidence of object-based attention. Stoner and Blanc (2010) observed, however, that these previous results could potentially be explained by feature-based competition/normalization models of attention. To distinguish between the object-based and feature-based accounts, they introduced "feature swaps" into a delayed-onset variant of the transparent-motion design (Reynolds, Alborzian, & Stoner, 2003). Whereas the object-based attention account predicted that the effect of cueing would survive these feature swaps, the motion-competition account predicted that the effect of cueing would be reversed by these feature swaps. The behavioral results of Stoner and Blanc (2010) supported the object-based account, and in doing so, provided evidence that the attentional advantage in this design is spatially selective at the scale of the intermixed texture elements (i.e., dots) of the overlapping and moving dot fields. In the present study, we used the design of Stoner and Blanc (2010) to investigate both psychophysical performance and evoked activities under different cueing and feature swapping conditions. We confirmed that the behavioral effects of attentional cueing survived feature swaps and found event-related potential (ERP) correlates of those effects in the N1 component range over occipital and parieto-occipital scalp sites. These modulations of the neural activity were, moreover, significantly associated with variation in behavioral performance values across the different conditions. Our findings thus provide the first evidence of the role of the N1 component in object-based attention in this transparent-motion design under conditions that rule out feature-based mechanisms and that reveal selective processing at a fine spatial scale.

Neural correlates of metacontrast masking across different contrast polarities.

Metacontrast masking is a powerful illusion to investigate the dynamics of perceptual processing and to control conscious visual perception. However, the neural mechanisms underlying this fundamental investigative tool are still debated. In the present study, we examined metacontrast masking across different contrast polarities by employing a contour discrimination task combined with EEG (Electroencephalography). When the target and mask had the same contrast polarity, a typical U-shaped metacontrast function was observed. A change in mask polarity (i.e., opposite mask polarity) shifted this masking function to a monotonic increasing function such that the target visibility was strongly suppressed at stimulus onset asynchronies less than 50 ms. This transition in metacontrast function has been typically interpreted as an increase in intrachannel inhibition of the sustained activities functionally linked to object visibility and identity. Our EEG analyses revealed an early (160-300 ms) and a late (300-550 ms) spatiotemporal cluster associated with this effect of polarity. The early cluster was mainly over occipital and parieto-occipital scalp sites. On the other hand, the later modulations of the evoked activities were centered over parietal and centro-parietal sites. Since both of these clusters were beyond 160 ms, the EEG results point to late recurrent inhibitory mechanisms. Although the findings here do not directly preclude other proposed mechanisms for metacontrast, they highlight the involvement of recurrent intrachannel inhibition in metacontrast masking.

Audiovisual interactions in speeded discrimination of a visual event.

The integration of information from different senses is central to our perception of the external world. Audiovisual interactions have been particularly well studied in this context and various illusions have been developed to demonstrate strong influences of these interactions on the final percept. Using audiovisual paradigms, previous studies have shown that even task-irrelevant information provided by a secondary modality can change the detection and discrimination of a primary target. These modulations have been found to be significantly dependent on the relative timing between auditory and visual stimuli. Although these interactions in time have been commonly reported, we have still limited understanding of the relationship between the modulations of event-related potentials (ERPs) and final behavioral performance. Here, we aimed to shed light on this important issue by using a speeded discrimination paradigm combined with electroencephalogram (EEG). During the experimental sessions, the timing between an auditory click and a visual flash was varied over a wide range of stimulus onset asynchronies and observers were engaged in speeded discrimination of flash location. Behavioral reaction times were significantly changed by click timing. Furthermore, the modulations of evoked activities over medial parietal/parieto-occipital electrodes were associated with this effect. These modulations were within the 126-176 ms time range and more importantly, they were also correlated with the changes in reaction times. These results provide an important functional link between audiovisual interactions at early stages of sensory processing and reaction times. Together with previous research, they further suggest that early crossmodal interactions play a critical role in perceptual performance.

The optomotor response of aging zebrafish reveals a complex relationship between visual motion characteristics and cholinergic system.

Understanding the principles underlying age-related changes in motion perception is paramount for improving the quality of life and health of older adults. However, the mechanisms underlying age-related alterations in this aspect of vision, which is essential for survival in a dynamic world, still remain unclear. Using optomotor responses to drifting gratings, we investigated age-related changes in motion detection of adult zebrafish (wild-type/AB-strain and achesb55/+ mutants with decreased levels of acetylcholinesterase). Our results pointed out negative optomotor responses that significantly depend on the spatial frequency and contrast level of stimulation, providing supporting evidence for the visual motion-driven aspect of this behavior mainly exhibited by adult zebrafish. Although there were no significant main effects of age and genotype, we found a significant three-way interaction between contrast level, age, and genotype. In the contrast domain, the changes in optomotor responses and thus in the detection of motion direction were age- and genotype-specific. Accordingly, these behavioral findings suggest a strong but complicated relationship between visual motion characteristics and the cholinergic system during neural aging.

Dietary and Pharmacological Interventions That Inhibit Mammalian Target of Rapamycin Activity Alter the Brain Expression Levels of Neurogenic and Glial Markers in an Age-and Treatment-Dependent Manner.

Intermittent fasting (IF) and its mimetic, rapamycin extend lifespan and healthspan through mechanisms that are not fully understood. We investigated different short-term durations of IF and rapamycin on cellular and molecular changes in the brains of young (6-10 months) and old (26-31 months) zebrafish. Interestingly, our results showed that IF significantly lowered glucose levels while increasing DCAMKL1 in both young and old animals. This proliferative effect of IF was supported by the upregulation of foxm1 transcript in old animals. Rapamycin did not change glucose levels in young and old animals but had differential effects depending on age. In young zebrafish, proliferating cell nuclear antigen and the LC3-II/LC3-I ratio was decreased, whereas glial fibrillary acidic protein and gephyrin were decreased in old animals. The changes in proliferative markers and a marker of autophagic flux suggest an age-dependent interplay between autophagy and cell proliferation. Additionally, changes in glia and inhibitory tone suggest a suppressive effect on neuroinflammation but may push the brain toward a more excitable state. Mammalian target of rapamycin (mTOR) activity in the brain following the IF and rapamycin treatment was differentially regulated by age. Interestingly, rapamycin inhibited mTOR more potently in young animals than IF. Principal component analysis supported our conclusion that the regulatory effects of IF and rapamycin were age-specific, since we observed different patterns in the expression levels and clustering of young and old animals. Taken together, our results suggest that even a short-term duration of IF and rapamycin have significant effects in the brain at young and old ages, and that these are age and treatment dependent.

Short- and long-term forms of neural adaptation: An ERP investigation of dynamic motion aftereffects.

Adaptation is essential to interact with a dynamic and changing environment, and can be observed on different timescales. Previous studies on a motion paradigm called dynamic motion aftereffect (dMAE) showed that neural adaptation can establish even in very short timescales. However, the neural mechanisms underlying such rapid form of neural plasticity is still debated. In the present study, short- and long-term forms of neural plasticity were investigated using dynamic motion aftereffect combined with EEG (Electroencephalogram). Participants were adapted to directional drifting gratings for either short (640 msec) or long (6.4 sec) durations. Both adaptation durations led to motion aftereffects on the perceived direction of a dynamic and directionally ambiguous test pattern, but the long adaptation produced stronger dMAE. In line with behavioral results, we found robust changes in the event-related potentials elicited by the dynamic test pattern within 64-112 msec time range. These changes were mainly clustered over occipital and parieto-occipital scalp sites. Within this time range, the aftereffects induced by long adaptation were stronger than those by short adaptation. Moreover, the aftereffects by each adaptation duration were in the opposite direction. Overall, these EEG findings suggest that dMAEs reflect changes in cortical areas mediating low- and mid-level visual motion processing. They further provide evidence that short- and long-term forms of motion adaptation lead to distinct changes in neural activity, and hence support the view that adaptation is an active time-dependent process which involves different neural mechanisms.

Cortical processes underlying the effects of static sound timing on perceived visual speed.

It is well known that the timing of brief static sounds can alter different aspects of visual motion perception. For instance, previous studies have shown that time intervals demarcated by brief sounds can modulate perceived visual speed such that apparent motions with short auditory time intervals are typically perceived as faster than those with long time intervals. Yet, little is known about the principles and cortical processes underlying such effects of auditory timing. Using a speed judgment paradigm combined with EEG recording, we aimed to identify when and where in the cortex auditory timing takes place for motion processing. Our results indicated significant effects of auditory timing over the medial parieto-occipital and parietal, right centro-parietal, and frontal scalp sites. In addition, these effects were not restricted to a single ERP component and we observed both significant changes in early and late components. Therefore, our findings here suggest that auditory timing may take place at both early and late stages of motion processing and its influences on motion perception may be the outcome of the dynamic interplay between different cortical regions. Together with accumulating evidence, these findings also support the notion that audiovisual integration is a multistage process and it may be achieved through more diversified processes than previously thought.

Auditory modulation of spiking activity and local field potentials in area MT does not appear to underlie an audiovisual temporal illusion.

The timing of brief stationary sounds has been shown to alter the perceived speed of visual apparent motion (AM), presumably by altering the perceived timing of the individual frames of the AM stimuli and/or the duration of the interstimulus intervals (ISIs) between those frames. To investigate the neural correlates of this "temporal ventriloquism" illusion, we recorded spiking and local field potential (LFP) activity from the middle temporal area (area MT) in awake, fixating macaques. We found that the spiking activity of most MT neurons (but not the LFP) was tuned for the ISI/speed (these parameters covaried) of our AM stimuli but that auditory timing had no effect on that tuning. We next asked whether the predicted changes in perceived timing were reflected in the timing of neuronal responses to the individual frames of the AM stimuli. Although spiking dynamics were significantly, if weakly, affected by auditory timing in a minority of neurons, the timing of spike responses did not systematically mirror the predicted perception of stimuli. Conversely, the duration of LFP responses in ß- and γ-frequency bands was qualitatively consistent with human perceptual reports. We discovered, however, that LFP responses to auditory stimuli presented alone were robust and that responses to audiovisual stimuli were predicted by the linear sum of responses to auditory and visual stimuli presented individually. In conclusion, we find evidence of auditory input into area MT but not of the nonlinear audiovisual interactions we had hypothesized to underlie the illusion. NEW & NOTEWORTHY We utilized a set of audiovisual stimuli that elicit an illusion demonstrating "temporal ventriloquism" in visual motion and that have spatiotemporal intervals for which neurons within the middle temporal area are selective. We found evidence of auditory input into the middle temporal area but not of the nonlinear audiovisual interactions underlying this illusion. Our findings suggest that either the illusion was absent in our nonhuman primate subjects or the neuronal correlates of this illusion lie within other areas.

Temporal ventriloquism along the path of apparent motion: speed perception under different spatial grouping principles.

The coordination of intramodal perceptual grouping and crossmodal interactions plays a critical role in constructing coherent multisensory percepts. However, the basic principles underlying such coordinating mechanisms still remain unclear. By taking advantage of an illusion called temporal ventriloquism and its influences on perceived speed, we investigated how audiovisual interactions in time are modulated by the spatial grouping principles of vision. In our experiments, we manipulated the spatial grouping principles of proximity, uniform connectedness, and similarity/common fate in apparent motion displays. Observers compared the speed of apparent motions across different sound timing conditions. Our results revealed that the effects of sound timing (i.e., temporal ventriloquism effects) on perceived speed also existed in visual displays containing more than one object and were modulated by different spatial grouping principles. In particular, uniform connectedness was found to modulate these audiovisual interactions in time. The effect of sound timing on perceived speed was smaller when horizontal connecting bars were introduced along the path of apparent motion. When the objects in each apparent motion frame were not connected or connected with vertical bars, the sound timing was more influential compared to the horizontal bar conditions. Overall, our findings here suggest that the effects of sound timing on perceived speed exist in different spatial configurations and can be modulated by certain intramodal spatial grouping principles such as uniform connectedness.

The involvement of centralized and distributed processes in sub-second time interval adaptation: an ERP investigation of apparent motion.

Accumulating evidence suggests that the timing of brief stationary sounds affects visual motion perception. Recent studies have shown that auditory time interval can alter apparent motion perception not only through concurrent stimulation but also through brief adaptation. The adaptation after-effects for auditory time intervals was found to be similar to those for visual time intervals, suggesting the involvement of a central timing mechanism. To understand the nature of cortical processes underlying such after-effects, we adapted observers to different time intervals using either brief sounds or visual flashes and examined the evoked activity to the subsequently presented visual apparent motion. Both auditory and visual time interval adaptation led to significant changes in the ERPs elicited by the apparent motion. However, the changes induced by each modality were in the opposite direction. Also, they mainly occurred in different time windows and clustered over distinct scalp sites. The effects of auditory time interval adaptation were centred over parietal and parieto-central electrodes while the visual adaptation effects were mostly over occipital and parieto-occipital regions. Moreover, the changes were much more salient when sounds were used during the adaptation phase. Taken together, our findings within the context of visual motion point to auditory dominance in the temporal domain and highlight the distinct nature of the sensory processes involved in auditory and visual time interval adaptation.

Rapid Motion Adaptation Reveals the Temporal Dynamics of Spatiotemporal Correlation between ON and OFF Pathways.

At the early stages of visual processing, information is processed by two major thalamic pathways encoding brightness increments (ON) and decrements (OFF). Accumulating evidence suggests that these pathways interact and merge as early as in primary visual cortex. Using regular and reverse-phi motion in a rapid adaptation paradigm, we investigated the temporal dynamics of within and across pathway mechanisms for motion processing. When the adaptation duration was short (188 ms), reverse-phi and regular motion led to similar adaptation effects, suggesting that the information from the two pathways are combined efficiently at early-stages of motion processing. However, as the adaption duration was increased to 752 ms, reverse-phi and regular motion showed distinct adaptation effects depending on the test pattern used, either engaging spatiotemporal correlation between the same or opposite contrast polarities. Overall, these findings indicate that spatiotemporal correlation within and across ON-OFF pathways for motion processing can be selectively adapted, and support those models that integrate within and across pathway mechanisms for motion processing.

Audiovisual associations alter the perception of low-level visual motion.

Motion perception is a pervasive nature of vision and is affected by both immediate pattern of sensory inputs and prior experiences acquired through associations. Recently, several studies reported that an association can be established quickly between directions of visual motion and static sounds of distinct frequencies. After the association is formed, sounds are able to change the perceived direction of visual motion. To determine whether such rapidly acquired audiovisual associations and their subsequent influences on visual motion perception are dependent on the involvement of higher-order attentive tracking mechanisms, we designed psychophysical experiments using regular and reverse-phi random dot motions isolating low-level pre-attentive motion processing. Our results show that an association between the directions of low-level visual motion and static sounds can be formed and this audiovisual association alters the subsequent perception of low-level visual motion. These findings support the view that audiovisual associations are not restricted to high-level attention based motion system and early-level visual motion processing has some potential role.