Mechanisms Of Target Selection Research Articles

Abstract 88: Novel cell-based bioassays enable preclinical animal studies during immuno-oncology drug development

Abstract Translation of immuno-oncology research into novel therapies relies on animal models to advise target selection and portray mechanism of action (MoA) and pharmacokinetics of lead candidates. Mouse, monkey, and more recently, canine models of human cancers are being utilized to this end. However, one major challenge in developing and utilizing these models is the lack of technology to characterize non-human analogs of therapeutic antibodies. Herein, we report the development of novel cell-based bioassays for mouse, monkey, and canine targets to enable immuno-oncology preclinical studies. Antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) are important MoAs for antibody-based cancer immunotherapies. We have developed a suite of cell-based bioassays, each expressing a corresponding animal Fcγ receptor (FcγR) and a luciferase reporter that responds to FcγR activation. These assays exhibit sensitive and quantitative luciferase readouts of FcγR activation. Animal models are further used to provide insight into the potential efficacy of immune checkpoint (IC) inhibitors. Programmed cell death protein 1 (PD-1) is an IC receptor that negatively regulates T cell function. Blockade of PD-1 has demonstrated clinical efficacy, but there remains a significant fraction of patients unresponsive to this therapy. Combination of PD-1 inhibitors with other interventions has been a significant focus for many programs. However, tools for functional validation of non-human PD-1 inhibitors are lacking. We report here the development of two new bioassays for functional characterization of PD-1/PD-L1 inhibitors for mouse and canine targets. Each of these assays consists of two engineered cell lines: a T effector cell line that express a luciferase reporter driven by specific promoter/response elements responding to the intracellular signals mediated by the T cell receptor (TCR), with modulation from PD-1, and an artificial antigen presenting cell line (aAPC). The bioassays are sensitive, quantitative, and have demonstrated characteristics required for potency assays for validation of antibodies in preclinical combination studies. Citation Format: Jun Wang, Denise Garvin, Aileen Paguio, Elizabeth Perrin, Jim Hartnett, Mei Cong, Jamison Grailer. Novel cell-based bioassays enable preclinical animal studies during immuno-oncology drug development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 88.

Development Status and Influencing Factors of Competitive Basketball Management System under the Background of Deep Learning.

Competitive basketball is one of the most popular sports in the world. With the development of China's sports power strategy, the national movement has strengthened the status of basketball in sports. However, China's competitive basketball ranking is not high in the world, and the analysis of the reasons should start with the management system. Therefore, this paper aims to explore the development status and influencing factors of China's competitive basketball management system under the background of deep learning. For the background of deep learning, this paper describes the application of deep learning algorithms in basketball strategy. It adopts the expert interview method for the competitive basketball management system and elaborates in detail on five aspects: target mechanism, competition mechanism, selection mechanism, market mechanism, and incentive mechanism. The experimental results of the article believe that, based on the suggestions of 10 experts, the current Chinese competitive basketball selection mechanism is the most influential factor, with a weight of 16.1%, and the smallest impact is the level of athletes, accounting for 11.4%.

EEG evidence for enhanced attentional performance during moderate-intensity exercise.

Research on attentional control within real-world contexts has become substantially more feasible and thus frequent over the past decade. However, relatively little is known regarding how these processes may be influenced by common naturalistic behaviors such as engaging in physical activity, which is thought to modulate the availability of neurometabolic resources. Here, we used an event-related potential (ERP) approach to determine whether various intensities of aerobic exercise might affect the concurrent performance of attentional control mechanisms. Participants performed an additional-singleton visual search task across three levels of aerobic activity while seated on a stationary bicycle: at rest, during moderate-intensity exercise, and during vigorous-intensity exercise. In addition to behavioral measures, attentional processing was assessed via lateralized ERPs referencing target selection (PCN) and distractor suppression (PD ) mechanisms. Whereas engaging in exercise resulted in speeded response times overall, moderate-intensity exercise was found to uniquely eliminate the expression of distractor interference by the PCN while also giving rise to an unanticipated distractor-elicited Ppc. These findings demonstrate workload-specific and object-selective influences of aerobic exercise on attentional processing, providing insights not only for approaching attention in real-world contexts but also for understanding how attentional resources are used overall.

Membrane Protein Quality Control Mechanisms in the Endo-Lysosome System.

Protein quality control (PQC) machineries play a critical role in selective identification and removal of mistargeted, misfolded, and aberrant proteins. This task is extremely complicated due to the enormous diversity of the proteome. It also requires nuanced and careful differentiation between 'normal' and 'folding intermediates' from 'abnormal' and 'misfolded' protein states. Multiple genetic and proteomic approaches have started to delineate the molecular underpinnings of how these machineries recognize their target and how their activity is regulated. In this review, we summarize our understanding of the various E3 ubiquitin ligases and associated machinery that mediate PQC in the endo-lysosome system in yeast and humans, how they are regulated, and mechanisms of target selection, with the intent of guiding future research in this area.

Theory of visual attention (TVA) in action: Assessing premotor attention in simultaneous eye-hand movements

Attention shifts that precede goal-directed eye and hand movements are regarded as markers of motor target selection. Whether effectors compete for a single, shared attentional resource during simultaneous eye-hand movements or whether attentional resources can be allocated independently towards multiple target locations is controversially debated. Independent, effector-specific target selection mechanisms underlying parallel allocation of visuospatial attention to saccade and reach targets would predict an increase of the overall attention capacity with the number of active effectors. We test this hypothesis in a modified Theory of Visual Attention (TVA; Bundesen, 1990) paradigm. Participants reported briefly presented letters during eye, hand, or combined eye-hand movement preparation to centrally cued locations. Modeling the data according to TVA allowed us to assess both the overall attention capacity and the deployment of visual attention to individual locations in the visual work space. In two experiments, we show that attention is predominantly allocated to the motor targets–without pronounced competition between effectors. The parallel benefits at eye and hand targets, however, have concomitant costs at non-motor locations, and the overall attention capacity does not increase by the simultaneous recruitment of both effector systems. Moreover, premotor shifts of attention dominate over voluntary deployment of processing resources, yielding severe impairments of voluntary attention allocation. We conclude that attention shifts to multiple effector targets without mutual competition given that sufficient processing resources can be withdrawn from movement-irrelevant locations.

Integrated transcriptome and phosphoproteome analyses reveal that fads2 is critical for maintaining body LC-PUFA homeostasis

Fatty acid desaturate 2 (Fads2) is associated with many chronic diseases. Nevertheless, comprehensive researches on its role have not been performed. We here conducted an integrated analysis of long-chain polyunsaturated fatty acid (LC-PUFA) metabolism of fads2-deletion zebrafish (fads2−/−) by transcriptomics, proteomics and phosphoproteomics. Compared with wild type zebrafish (WT), fads2−/− showed significantly higher contents of hepatic linoleic acid (all-cis-9,12-C18:2), α-linolenic acid (all-cis-9,12,15-C18:3) and docosapetaenoic acid (all-cis-7,10,13,16,19-C22:5), and lower contents of γ-linolenic acid (all-cis-6,9,12-C18:3), stearidonic acid (all-cis-6,9,12,15-C18:4) and docosahexaenoic acid (all-cis-4,7,10,13,16,19-C22:6), accompanied by an increased n-6/n-3 PUFA level. In total, we identified 1608 differentially expressed genes (DEGs), 209 differentially expressed proteins (DEPs) and 153 differentially expressed phosphorylated proteins (DEPPs) with 190 sites between fads2−/− and WT. Transcriptome and proteome analysis simultaneously aggregated these DEGs and DEPs into LC-PUFA synthesis and PPAR signaling pathways. Further interaction network analysis of the DEPPs showed that spliceosome and protein processing in endoplasmic reticulum pathway were critical groups. Additionally, we determined seven highly phosphorylated kinases and a highly expressed phosphatase in fads2−/− zebrafish. These results give insights into the mechanism by which fads2 affects metabolic disease occurrence, and provide datasets for target selections for human disease treatment. SignificanceBalanced LC-PUFA composition was deeply associated with body health, while changes of LC-PUFAs usually induced serious diseases such as cardiovascular disease, type 2 diabetes and inflammatory disease. Fatty acid desaturase 2 (Fads2), subordinating to the fatty acid desaturase protein family, catalyzes the first desaturation reaction in LC-PUFA synthesis. Although Fads2 is associated with many chronic diseases including metabolic abnormalities, type 2 diabetes and obesity, comprehensive researches on its role have not been performed.On the basis of the integrated transcriptome, proteome and phosphoproteome analysis, we identified that fads2 was critical for maintaining body LC-PUFA homeostasis. Moreover, the crucial pathways including PPAR signaling pathway, spliceosome and protein processing in endoplasmic reticulum pathway, and candidate kinase targets associated with LC-PUFA metabolism were determined. These findings will contribute to the revealing of the mechanism and supply possible datasets for target selection for human disease treatment.

Electrophysiological correlates of attentional selection in tactile search tasks: The impact of singleton distractors on target selection.

Recent event-related potential (ERP) studies have suggested that the N140cc component reflects target selection mechanisms in tactile search tasks in which the target is presented simultaneously with homogeneous distractors. To investigate if and how the attentional selection of the tactile target is affected by the presence of a singleton distractor, we presented a four-item search array (two stimuli to the middle and index fingers of the left and right hand) which included a singleton distractor in addition to the target and two other homogenous distractors. Participants had to localize the target (top or bottom finger on either hand), while ignoring all distractors. Behavioral results revealed that the target localization was hindered by the presence of the singleton distractor as demonstrated by distractor-presence costs for both speed and accuracy. ERP results confirmed that attention was directed to the singleton distractor when this was the only singleton item in the array as suggested by the presence of a distractor-related N140cc component on distractor only trials. Furthermore, when target and singleton distractor were presented to opposite hands (contralateral distractor trials) the target-related N140cc amplitude was reduced as compared to target only trials, suggesting reduced attentional resources to the target. However, when target and singleton distractor were presented to the same hand (ipsilateral distractor trials), the N140cc amplitude was comparable to that observed on target only trials. These findings suggest that the N140cc reflects the attentional selection of the target side rather than the competition between stimuli presented to the same hand.

Decision support system design of higher education scholarship recipients with android-based

The purpose of this study is to present the design of Decision Support System (DSS) to analyse the college scholarship recipients on the android-based. The design methodology for selecting scholarship recipients is used Fuzzy Multiple Attribute Decision Making (Fuzzy MADM). Fuzzy MADM is an algorithm that used to find the optimal result of a number of alternatives with certain criteria. This method is chosen because the calculation of this method uses multiplication to correlate the attribute rating and only yields the largest value that will be selected as an alternative scholarship recipient. The object set in this research is UIN Sunan Gunung Djati Bandung student. The design system is made based on android with hardware in the form of smart phone. The design results have a level of compliance with regulatory standards that have been established. The results also indicate the logical and appropriate target selection mechanism for scholarship recipients for the most eligible students who received scholarship assistance.

Autonomous Robotic Exploration by Incremental Road Map Construction

In this paper, we propose a novel path planning framework for autonomous exploration in unknown environments using a mobile robot. A graph structure is incrementally constructed along with the exploration process. The structure is the road map that represents the topology of the explored environment. To construct the road map, we design a sampling strategy to get random points in the explored environment uniformly. A global path from the current location of the robot to the target area can be found on this road map efficiently. We utilize a lazy collision checking method that only checks the feasibility of the generated global path to improve the planning efficiency. The feasible global path is further optimized with our proposed trajectory optimization method considering the motion constraints of the robot. This mechanism can facilitate the path cost evaluation for the next best view selection. In order to select the next best target region, we propose a utility function that takes into account both the path cost and the information gain of a candidate target region. Moreover, we present a target reselection mechanism to evaluate the target region and reduce the extra path cost. The efficiency and effectiveness of our approach are demonstrated using a mobile robot in both simulation and real experimental studies. Note to Practitioners —This paper is motivated by the efficient exploration problem, which plays a key role in various areas such as the information gathering and environment monitoring. In these applications, the mission length and executing time are often restricted by the battery capacity of the robot. In this paper, an efficient path planning framework is introduced to reduce the path length and exploration time. The robot keeps a road map of the environment to facilitate the path planning. The proposed target selection mechanism helps the robot determine the next best target to explore. Furthermore, the proposed trajectory optimization algorithm helps in reducing the path cost. Overall, this framework enables efficiently and autonomously exploration with a novel path planning framework.

An Energy-Aware Transmission Target Selection Mechanism for UAV Networking

An Energy-Aware Transmission Target Selection Mechanism for UAV Networking

Early and late selection processes have separable influences on the neural substrates of attention

To improve our understanding of the mechanisms of target selection, we examined how the spatial separation of salient items and their similarity to a pre-defined target interact using lateralised electrophysiological correlates of visual spatial attention (N2pc component) and visual short-term memory (VSTM; SPCN component). Using these features of target selection, we sought to expand on previous work proposing a model of early and late selection, where the N2pc is suggested to reflect the selection probability of visual stimuli (Aubin and Jolicoeur, 2016). The authors suggested that early-selection processes could be enhanced when items are adjacent. In the present work, the stimuli were short oriented lines, all of which were grey except for two that were blue and hence salient. A decrease in N2pc amplitude with decreasing spatial separation between salient items was observed. The N2pc increased in amplitude with increasing similarity of salient distractors to the target template, but only in target-absent trials. There was no interaction between these two factors, suggesting that separable attentional mechanisms influenced the N2pc. The findings suggest that selection is initially based on easily-distinguished attributes (i.e., both blue items) followed by a later identification-based process (if necessary), which depends on feature similarity to a target template. For the SPCN component, the results were in line with previous work: for target-present trials, an increase in similarity of salient distractors was associated with an increase in SPCN amplitude, suggesting more information was maintained in VSTM. In sum, results suggest there is a need for further inspection of salient distractors when they are similar to the target, increasing the need for focal attention, demonstrated by an increase in N2pc amplitude, followed by a higher probability of transfer to VSTM, demonstrated by an increase in SPCN amplitude.

Reference frames in the decisions of hand choice.

For the brain to decide on a reaching movement, it needs to select which hand to use. A number of body-centered factors affect this decision, such as the anticipated movement costs of each arm, recent choice success, handedness, and task demands. While the position of each hand relative to the target is also known to be an important spatial factor, it is unclear which reference frames coordinate the spatial aspects in the decisions of hand choice. Here we tested the role of gaze- and head-centered reference frames in a hand selection task. With their head and gaze oriented in different directions, we measured hand choice of 19 right-handed subjects instructed to make unimanual reaching movements to targets at various directions relative to their body. Using an adaptive procedure, we determined the target angle that led to equiprobable right/left hand choices. When gaze remained fixed relative to the body this balanced target angle shifted systematically with head orientation, and when head orientation remained fixed this choice measure shifted with gaze. These results suggest that a mixture of head- and gaze-centered reference frames is involved in the spatially guided decisions of hand choice, perhaps to flexibly bind this process to the mechanisms of target selection. NEW & NOTEWORTHY Decisions of target and hand choice are fundamental aspects of human reaching movements. While the reference frames involved in target choice have been identified, it is unclear which reference frames are involved in hand selection. We tested the role of gaze- and head-centered reference frames in a hand selection task. Findings emphasize the role of both spatial reference frames in the decisions of hand choice, in addition to known body-centered computations such anticipated movement costs and handedness.

CRISPR Cas9 Mediated DNA Unwinding Detected using Site-Directed Spin Labeling

The RNA-guided CRISPR–Cas9 nuclease has revolutionized genome engineering, yet its mechanism for DNA target selection is not fully understood. A crucial step in Cas9 target recognition involves unwinding of the DNA duplex to form a three-stranded R-loop structure. Work reported here demonstrates direct detection of Cas9-mediated DNA unwinding by a combination of site-directed spin labeling and molecular dynamics simulations. The results support a model in which the unwound nontarget strand is stabilized by a positively charged patch located between the two nuclease domains of Cas9 and reveal uneven increases in flexibility along the unwound nontarget strand upon scissions of the DNA backbone. This work establishes the synergistic combination of spin-labeling and molecular dynamics to directly monitor Cas9-mediated DNA conformational changes and yields information on the target DNA in different stages of Cas9 function, thus advancing mechanistic understanding of CRISPR–Cas9 and aiding future technological ...

CRISPR-Cas9 Mediated DNA Unwinding Detected Using Site-Directed Spin Labeling.

The RNA-guided CRISPR-Cas9 nuclease has revolutionized genome engineering, yet its mechanism for DNA target selection is not fully understood. A crucial step in Cas9 target recognition involves unwinding of the DNA duplex to form a three-stranded R-loop structure. Work reported here demonstrates direct detection of Cas9-mediated DNA unwinding by a combination of site-directed spin labeling and molecular dynamics simulations. The results support a model in which the unwound nontarget strand is stabilized by a positively charged patch located between the two nuclease domains of Cas9 and reveal uneven increases in flexibility along the unwound nontarget strand upon scissions of the DNA backbone. This work establishes the synergistic combination of spin-labeling and molecular dynamics to directly monitor Cas9-mediated DNA conformational changes and yields information on the target DNA in different stages of Cas9 function, thus advancing mechanistic understanding of CRISPR-Cas9 and aiding future technological development.

Rapid Parallel Attentional Selection Can Be Controlled by Shape and Alphanumerical Category.

Previous research has shown that when two color-defined target objects appear in rapid succession at different locations, attention is deployed independently and in parallel to both targets. This study investigated whether this rapid simultaneous attentional target selection mechanism can also be employed in tasks where targets are defined by a different visual feature (shape) or when alphanumerical category is the target selection attribute. Two displays that both contained a target and a nontarget object on opposite sides were presented successively, and the SOA between the two displays was 100, 50, 20, or 10 msec in different blocks. N2pc components were recorded to both targets as a temporal marker of their attentional selection. When observers searched for shape-defined targets (Experiment 1), N2pc components to the two targets were equal in size and overlapped in time when the SOA between the two displays was short, reflecting two parallel shape-guided target selection processes with their own independent time course. Essentially the same temporal pattern of N2pc components was observed when alphanumerical category was the target-defining attribute (Experiment 2), demonstrating that the rapid parallel attentional selection of multiple target objects is not restricted to situations where the deployment of attention can be guided by elementary visual features but that these processes can even be employed in category-based attentional selection tasks. These findings have important implications for our understanding of the cognitive and neural basis of top-down attentional control.

The visual properties of proximal and remote distractors differentially influence reaching planning times: evidence from pro- and antipointing tasks.

The saccade literature has consistently reported that the presentation of a distractor remote to a target increases reaction time (i.e., the remote distractor effect: RDE). As well, some studies have shown that a proximal distractor facilitates saccade reaction time. The lateral inhibition hypothesis attributes the aforementioned findings to the inhibition/facilitation of target selection mechanisms operating in the intermediate layers of the superior colliculus(SC). Although the impact of remote and proximal distractors has been extensively examined in the saccade literature, a paucity of work has examined whether such findings generalize to reaching responses, and to our knowledge, no work has directly contrasted reaching RTs for remote and proximal distractors. To that end, the present investigation had participants complete reaches in target only trials (i.e., TO) and when distractors were presented at "remote" (i.e., the opposite visual field) and "proximal" (i.e., the same visual field) locations along the same horizontal meridian as the target. As well, participants reached to the target's veridical (i.e., propointing) and mirror-symmetrical (i.e., antipointing) location. The basis for contrasting pro- and antipointing was to determine whether the distractor's visual- or motor-related activity influence reaching RTs. Results demonstrated that remote and proximal distractors, respectively, increased and decreased reaching RTs and the effect was consistent for pro- and antipointing. Accordingly, results evince that the RDE and the facilitatory effects of a proximal distractor are effector independent and provide behavioral support for the contention that the SC serves as a general target selection mechanism. As well, the comparable distractor-related effects for pro- and antipointing trials indicate that the visual properties of remote and proximal distractors respectively inhibit and facilitate target selection.

Causal Inference for Cross-Modal Action Selection: A Computational Study in a Decision Making Framework

Animals try to make sense of sensory information from multiple modalities by categorizing them into perceptions of individual or multiple external objects or internal concepts. For example, the brain constructs sensory, spatial representations of the locations of visual and auditory stimuli in the visual and auditory cortices based on retinal and cochlear stimulations. Currently, it is not known how the brain compares the temporal and spatial features of these sensory representations to decide whether they originate from the same or separate sources in space. Here, we propose a computational model of how the brain might solve such a task. We reduce the visual and auditory information to time-varying, finite-dimensional signals. We introduce controlled, leaky integrators as working memory that retains the sensory information for the limited time-course of task implementation. We propose our model within an evidence-based, decision-making framework, where the alternative plan units are saliency maps of space. A spatiotemporal similarity measure, computed directly from the unimodal signals, is suggested as the criterion to infer common or separate causes. We provide simulations that (1) validate our model against behavioral, experimental results in tasks where the participants were asked to report common or separate causes for cross-modal stimuli presented with arbitrary spatial and temporal disparities. (2) Predict the behavior in novel experiments where stimuli have different combinations of spatial, temporal, and reliability features. (3) Illustrate the dynamics of the proposed internal system. These results confirm our spatiotemporal similarity measure as a viable criterion for causal inference, and our decision-making framework as a viable mechanism for target selection, which may be used by the brain in cross-modal situations. Further, we suggest that a similar approach can be extended to other cognitive problems where working memory is a limiting factor, such as target selection among higher numbers of stimuli and selections among other modality combinations.

Decisions in motion: vestibular contributions to saccadic target selection.

The natural world continuously presents us with many opportunities for action, and thus a process of target selection must precede action execution. While there has been considerable progress in understanding target selection in stationary environments, little is known about target selection when we are in motion. Here we investigated the effect of self-motion signals on saccadic target selection in a dynamic environment. Human subjects were sinusoidally translated (f = 0.6 Hz, 30-cm peak-to-peak displacement) along an interaural axis with a vestibular sled. During the motion two visual targets were presented asynchronously but equidistantly on either side of fixation. Subjects had to look at one of these targets as quickly as possible. With an adaptive approach, the time delay between these targets was adjusted until the subject selected both targets equally often. We determined this balanced time delay for different phases of the motion in order to distinguish the effects of body acceleration and velocity on saccadic target selection. Results show that acceleration (or position, as these are indistinguishable during sinusoidal motion), but not velocity, affects target selection for saccades. Subjects preferred to look at targets in the direction of the acceleration-the leftward target was preferred when the sled accelerated to the left, and vice versa. Saccadic reaction times mimicked this selection bias by being reliably shorter to targets in the direction of acceleration. Our results provide evidence that saccade target selection mechanisms are modulated by self-motion signals, which could be derived directly from the otolith system.

Corticothalamic Axons Are Essential for Retinal Ganglion Cell Axon Targeting to the Mouse Dorsal Lateral Geniculate Nucleus.

Retinal ganglion cells (RGCs) relay information about the outside world to multiple subcortical targets within the brain. This information is either used to dictate reflexive behaviors or relayed to the visual cortex for further processing. Many subcortical visual nuclei also receive descending inputs from projection neurons in the visual cortex. Most areas receive inputs from layer 5 cortical neurons in the visual cortex but one exception is the dorsal lateral geniculate nucleus (dLGN), which receives layer 6 inputs and is also the only RGC target that sends direct projections to the cortex. Here we ask how visual system development and function changes in mice that develop without a cortex. We find that the development of a cortex is essential for RGC axons to terminate in the dLGN, but is not required for targeting RGC axons to other subcortical nuclei. RGC axons also fail to target to the dLGN in mice that specifically lack cortical layer 6 projections to the dLGN. Finally, we show that when mice develop without a cortex they can still perform a number of vision-dependent tasks. The dorsal lateral geniculate nucleus (dLGN) is a sensory thalamic relay area that receives feedforward inputs from retinal ganglion cells (RGCs) in the retina, and feed back inputs from layer 6 neurons in the visual cortex. In this study we examined genetically manipulated mice that develop without a cortex or without cortical layer 6 axonal projections, and find that RGC axons fail to project to the dLGN. Other RGC recipient areas, such as the superior colliculus and suprachiasmatic nucleus, are targeted normally. These results provide support for a new mechanism of target selection that may be specific to the thalamus, whereby descending cortical axons provide an activity that promotes feedforward targeting of RGC axons to the dLGN.

Perceptual task induces saccadic adaptation by target selection.

Adaptation of saccades can be induced by different error signals, such as retinal position errors, prediction errors, or reinforcement learning. Recently, we showed that a shift in the spatial goal of a perceptual task can induce saccadic adaptation, in the absence of a bottom-up position error. Here, we investigated whether this top-down effect is mediated by the visibility of the task-relevant object, by reinforcement due to the feedback about the perceptual judgment or by a target selection mechanism. Participants were asked to discriminate visual stimuli arranged in a vertical compound. To induce adaptation, the discrimination target was presented at eccentric locations in the compound. In the first experiment, we compared adaptation with an easy and difficult discrimination. In the second experiment, we compared adaptation when feedback about the perceptual task was valid and when feedback was provided but was unrelated to performance. In the third experiment, we compared adaptation with instructions to fixate one of the elements in the compound—target selection—to the perceptual task condition—target selection and discrimination. To control for a bottom-up stimulus effect, we ran a fourth experiment in which the only instruction was to look at the compound. The saccade amplitude data were fitted by a two-state model distinguishing between an immediate and a gradual error correction process. We replicated our finding that a perceptual task can drive adaptation of saccades. Adaptation showed no effect of feedback reliability, nor an effect of the perceptual task beyond target selection. Adaptation was induced by a top-down signal since it was absent when there was no target selection instruction and no perceptual task. The immediate error correction was larger for the difficult than for the easy condition, suggesting that task difficulty affects mainly voluntary saccade targeting. In addition, the repetition of experiments one week later increased the magnitude of the gradual error correction. The results dissociate two distinct components of adaptation: an immediate and a gradual error correction. We conclude that perceptual-task induced adaptation is most likely due to top-down target selection within a larger object.