Age-related reduction of hemispheric asymmetry by pigeons: A behavioral and FDG-PET imaging investigation of visual discrimination.

Pigeons are long-lived and slowly aging animals that present a distinct opportunity to further our understanding of age-related brain changes. Generally, for pigeons, the left hemisphere contributes to discrimination of local information, whereas the right contributes to processing of global information. The function of each hemisphere may be examined by covering one eye, as the optic nerves decussate almost completely in birds, directing the majority of visual information to the contralateral hemisphere. Using this eye-capping technique, we investigated pigeons' ability to select grains from among grit while under binocular and monocular viewing conditions, across three different age groups. Prior to the grit-grain discrimination task, pigeons were injected with a radioactive tracer, which was taken up by the brain as the pigeons performed the task. Upon completion of the discrimination task, the pigeons' brains were imaged via [18F] fluorodeoxyglucose positron emission tomography (FDG-PET) scans. This process allowed us to compare hemispheric activity during the discrimination task for each individual within each age group. The Very Old subjects showed significantly worse discrimination performance compared to the Adult and Old subjects, particularly when needing to search primarily with their right hemisphere. Furthermore, the Very Old subjects did not show differences in hemispheric activation when performing the task, whereas the left hemisphere was most active for the Adult and Old groups. To our knowledge, this is the first study to use FDG-PET imaging to evaluate whether the pigeon brain shows evidence of age-related reduction in hemispheric asymmetry during a visual discrimination task.

Measuring response inhibition with a continuous inhibitory-control task.

Inhibitory control enables subjects to quickly react to unexpected changes in external demands. In humans, this kind of behavioral flexibility is often used as an indicator of an individual's executive functions, and more and more research has emerged to investigate this link in nonhuman animals as well. Here we explored the value of a recently developed continuous inhibitory-control task in assessing inhibitory-control capacities in animals. Pigeons completed a response-inhibition task that required them to adjust their movement in space in pursuit of a reward across changing target locations. Inhibition was measured in terms of movement trajectory (path taken toward the correct location for trials in which the target location did and did not change) and velocity (both before and after correcting the trajectory toward the changed location). Although the observed velocities did not follow any of our predictions in a clear way, the pigeons' movement trajectories did prove to be a good indicator of inhibitory control, showing that pigeons, though limited in their capacities relative to the sophisticated control strategies expressed by humans, are capable of exerting some forms of inhibitory control. These results strengthen the role of this paradigm as a valuable tool for evaluating inhibitory-control abilities across the animal kingdom.

A novel continuous inhibitory-control task: variation in individual performance by young pheasants (Phasianus colchicus).

Inhibitory control enables subjects to quickly react to unexpectedly changing external demands. We assessed the ability of young (8 weeks old) pheasants Phasianus colchicus to exert inhibitory control in a novel response-inhibition task that required subjects to adjust their movement in space in pursuit of a reward across changing target locations. The difference in latencies between trials in which the target location did and did not change, the distance travelled towards the initially indicated location after a change occurred, and the change-signal reaction time provided a consistent measure that could be indicative of a pheasant's inhibitory control. Between individuals, there was a great variability in these measures; these differences were not correlated with motivation either to access the reward or participate in the test. However, individuals that were slower to reach rewards in trials when the target did not change exhibited evidence of stronger inhibitory control, as did males and small individuals. This novel test paradigm offers a potential assay of inhibitory control that utilises a natural feature of an animal's behavioural repertoire, likely common to a wide range of species, specifically their ability to rapidly alter their trajectory when reward locations switch.

Targeted inhibition of protein synthesis renders cancer cells vulnerable to apoptosis by unfolded protein response.

Cellular stress responses including the unfolded protein response (UPR) decide over the fate of an individual cell to ensure survival of the entire organism. During physiologic UPR counter-regulation, protective proteins are upregulated to prevent cell death. A similar strategy induces resistance to UPR in cancer. Therefore, we hypothesized that blocking protein synthesis following induction of UPR substantially enhances drug-induced apoptosis of malignant cells. In line, upregulation of the chaperone BiP was prevented by simultaneous arrest of protein synthesis in B cell malignancies. Cytotoxicity by immunotoxins-approved inhibitors of protein synthesis-was synergistically enhanced in combination with UPR-inducers in seven distinct hematologic and three solid tumor entities in vitro. Synergistic cell death depended on mitochondrial outer membrane permeabilization via BAK/BAX, which correlated with synergistic, IRE1α-dependent reduction of BID, accompanied by an additive fall of MCL-1. The strong synergy was reproduced in vivo against xenograft mouse models of mantle cell lymphoma, Burkitt's lymphoma, and patient-derived acute lymphoblastic leukemia. In contrast, synergy was absent in blood cells of healthy donors suggesting a tumor-specific vulnerability. Together, these data support clinical evaluation of blocking stress response counter-regulation using inhibitors of protein synthesis as a novel therapeutic strategy.

Location as a feature in pigeons' recognition of visual objects.

A number of different phenomena in pigeon visual cognition suggest that pigeons do not immediately recognize two identical objects in different locations as being "the same." To examine this question directly, pigeons were trained in an absolute go/no-go discrimination between arbitrary selections from sets of 16 images of paintings by Claude Monet. Of the eight positive stimuli, four always appeared in the same location, whereas the other four appeared equally often in each of two locations; the same was true of the negative stimuli. There was a consistent tendency for stimuli that appeared in a single position to be better discriminated than those that appeared in two positions, although by the end of training this effect was confined to negative stimuli. This result suggests that, for a pigeon, an image's location is one of the bundle of features that define it, and that pigeons need to learn to abstract from that feature rather than doing so automatically. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Age affects pigeons' (Columba livia) memory capacity but not representation of serial order during a locomotor sequential-learning task.

Aging affects individuals of every species, with sometimes detrimental effects on memory and cognition. The simultaneous-chaining task, a sequential-learning task, requires subjects to select items in a predetermined sequence, putting demands on memory and cognitive processing capacity. It is thus a useful tool to investigate age-related differences in these domains. Pigeons of three age groups (young, adult and aged) completed a locomotor adaptation of the task, learning a list of four items. Training began by presenting only the first item; additional items were added, one at a time, once previous items were reliably selected in their correct order. Although memory capacity declined noticeably with age, not all aged pigeons showed impairments compared to younger pigeons, suggesting that inter-individual variability emerged with age. During a subsequent free-recall memory test in the absence of reinforcement, when all trained items were presented alongside novel distractor items, most pigeons did not reproduce the trained sequence. During a further forced-choice test, when pigeons were given a choice between only two of the trained items, all three age groups showed evidence of an understanding of the ordinal relationship between items by choosing the earlier item, indicating that complex cognitive processing, unlike memory capacity, remained unaffected by age.

Pigeons' performance in a tracking change-signal procedure is consistent with the independent horse-race model.

In many cognitive tasks where humans are thought to rely on executive functioning, pigeons' behavior can be explained by associative processes. A key form of executive functioning is inhibiting prepotent responses, often investigated in humans by means of "Stop-Signal" or "Change-Signal" procedures. In these procedures, execution of a well-practiced ("Go") response to a stimulus is occasionally interrupted by a signal to withhold or alter the practiced response. Performance in such tasks is usually described by the "independent horse horse-race model." This model assumes that the processes that cause the Go and inhibitory responses occur independently; the process that finishes first determines the response observed. We further tested this model by training pigeons to track the circular movement of a colored patch around a touchscreen by pecking it; the spot occasionally deviated from its normal path (the Change signal). The pigeons had to inhibit the habitual movement of their heads to land a peck on the spot in its unexpected position. The key predictions of the independent horse-race model were confirmed in the pigeons' latency data. Thus, the independent race model can also successfully describe Stop-change performance of subjects that do not rely on executive control. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Pigeons in control of their actions: Learning and performance in stop-signal and change-signal tasks.

In human participants, 2 paradigms commonly assumed to measure the executive-control processes involved in response inhibition are the stop-signal and change-signal tasks. There is, however, also considerable evidence that performance in these tasks can be mediated by associative processes. To assess which components of inhibitory response control might be associative, we developed analogues of these tasks for pigeons. We trained pigeons to peck quickly at 1 of 2 keys of different colors to obtain a food reward. On some trials, the rewarded key was replaced (after a varying interval) by a signal of a different color. For some birds, this was a change signal: pecking the signal had no effect, but pecking the usually unrewarded alternative key led to a reward, so the response had to be changed. For other birds, the change in color was a stop signal: pecking the alternative key remained ineffective, but pecking the signal now led to a timeout instead of the usual reward, so responses had to be withheld. Pigeons succeeded in both tasks, but performance declined with increasing signal delay. The details of performance in both tasks were consistent with the independent horse-race model of inhibitory control often applied to studies of human participants. This outcome further suggests that stop-signal tasks of the kind used here might not necessarily be suitable for assessing top-down executive-control processes in humans. (PsycINFO Database Record

Multiple feature use in pigeons' category discrimination: The influence of stimulus set structure and the salience of stimulus differences.

Two experiments investigated what makes it more likely that pigeons' behavior will come under the control of multiple relevant visual stimulus dimensions. Experiment 1 investigated the effect of stimulus set structure, using a conditional discrimination between circles that differed in both hue and diameter. Two training conditions differed in whether hue and diameter were correlated in the same way within positive and negative stimulus sets as between sets. Transfer tests showed that all pigeons came under the control of both dimensions, regardless of stimulus set structure. Experiment 2 investigated the effect of the relative salience of the stimulus differences on three visual dimensions. Pigeons learned a multiple simultaneous discrimination between circular patches of sinusoidal gratings that differed in hue, orientation, and spatial frequency. In initial training, each stimulus only included one positive or negative feature, and the stimulus differences on the three dimensions were adjusted so that the rates of learning about the three dimensions were kept approximately equal. Transfer tests showed that all three dimensions acquired control over behavior, with no single dimension dominating consistently across pigeons. Subsequently the pigeons were trained in a polymorphous category discrimination using all three dimensions, and the level of control by the three dimensions tended to become more equal as polymorphous training continued. We conclude that the salience of the stimulus differences on different dimensions is an important factor in whether pigeons will come under the control of multiple dimensions of visual stimuli. (PsycINFO Database Record

Task-switching in pigeons: Associative learning or executive control?

Human performance in task-switching paradigms is seen as a hallmark of executive-control processes: switching between tasks induces switch costs (such that performance when changing from Task A to Task B is worse than on trials where the task repeats), which is generally attributed to executive control suppressing one task-set and activating the other. However, even in cases where task-sets are not employed, as well as in computational modeling of task switching, switch costs can still be found. This observation has led to the hypothesis that associative-learning processes might be responsible for all or part of the switch costs in task-switching paradigms. To test which cognitive processes contribute to the presence of task-switch costs, pigeons performed two different tasks on the same set of stimuli in rapid alternation. The pigeons showed no sign of switch costs, even though performance on Trial N was influenced by Trial N - 1, showing that they were sensitive to sequential effects. Using Pearce's (1987) model for stimulus generalization, we conclude that they learned the task associatively-in particular, a form of Pavlovian-conditioned approach was involved-and that this was responsible for the lack of any detectable switch costs. Pearce's model also allows us to make interferences about the common occurrence of switch costs in the absence of task-sets in human participants and in computational models, in that they are likely due to instrumental learning and the establishment of an equivalence between cues signaling the same task.

A stimulus-location effect in contingency-governed, but not rule-based, discrimination learning.

We tested pigeons' acquisition of a conditional discrimination task between colored grating stimuli that included choosing 1 of 2 response keys, which either appeared as white keys to the left and right of the discriminative stimulus, or were replicas of the stimulus. Pigeons failed to acquire the discrimination when the response keys were white disks but succeeded when directly responding to a replica of the stimulus. These results highlight how conditioning processes shape learning in pigeons: The results can be accounted for by supposing that, when pigeons were allowed to respond directly toward the stimulus, learning was guided by classical conditioning, but that responding to white keys demanded instrumental learning, which impaired task acquisition for pigeons. In contrast, humans completing the same paradigm showed no differential learning success depending on whether figure or position indicated the correct key. However, only participants who could state the underlying discrimination rule acquired the task, which implies that human performance in this situation relied on the deduction and application of task rules instead of associative processes.

Pigeons can learn to make visual category discriminations using either low or high spatial frequency information.

Pigeons were trained to discriminate photographs of cat faces from dog faces, using either high- or low-pass spatial frequency filtered stimuli. Each pigeon was trained with multiple exemplars of the categories, but only with either high-pass or low-pass filtered stimuli. Not all pigeons reached the discrimination criterion. Successful pigeons were exposed in probe trials to test stimuli: cat and dog faces that had been subjected to the opposite kind of filtering from their training stimuli; the unfiltered original stimuli from which their training stimuli had been derived; and new exemplars of the cat- and dog-face categories, with the same filtering as was used in training. There was no transfer of discrimination to the stimuli with the opposite filtering from those used in training. Discrimination transferred, with some decrement, to the original unfiltered stimuli and to new exemplars with the same type of filtering as used in training. These results provide further evidence that both high and low spatial frequency information can be sufficient for pigeons to make category discriminations, and that there is no clear advantage for high spatial frequency information. They also confirm that high-pass and low-pass spatial frequency filtering produce images that have effectively no information in common. This article is part of a Special Issue entitled: Tribute to Tom Zentall.

Pigeons use low rather than high spatial frequency information to make visual category discriminations.

Pigeons were trained to discriminate photographs of cat faces from dog faces. They were then presented with test stimuli involving high- and low-pass spatial frequency filtering. Discrimination was maintained with both types of filtered stimuli, though it was increasingly impaired the more information was filtered out, and high-pass filtering impaired discrimination more than low-pass filtering. The pigeons were then exposed to hybrid stimuli in which high-pass filtered dog faces were combined with low-pass filtered cat faces, and vice versa. Response to hybrid stimuli was determined more by the low spatial frequency content than by the high-frequency content, whereas humans viewing the same stimuli at corresponding viewing distance respond more strongly to the high-frequency content. These results are unexpected given that, compared with humans, pigeons' behavior tends to be controlled by the local details of visual stimuli rather than their global appearance.