Motor System-Dependent Effects of Amygdala and Ventral Striatum Lesions on Explore-Exploit Behaviors.

Deciding whether to forego immediate rewards or explore new opportunities is a key component of flexible behavior and is critical for the survival of the species. Although previous studies have shown that different cortical and subcortical areas, including the amygdala and ventral striatum (VS), are implicated in representing the immediate (exploitative) and future (explorative) value of choices, the effect of the motor system used to make choices has not been examined. Here, we tested male rhesus macaques with amygdala or VS lesions on two versions of a three-arm bandit task where choices were registered with either a saccade or an arm movement. In both tasks we presented the monkeys with explore-exploit tradeoffs by periodically replacing familiar options with novel options that had unknown reward probabilities. We found that monkeys explored more with saccades but showed better learning with arm movements. VS lesions caused the monkeys to be more explorative with arm movements and less explorative with saccades, although this may have been due to an overall decrease in performance. VS lesions affected the monkeys' ability to learn novel stimulus-reward associations in both tasks, while after amygdala lesions this effect was stronger when choices were made with saccades. Further, on average, VS and amygdala lesions reduced the monkeys' ability to choose better options only when choices were made with a saccade. These results show that learning reward value associations to manage explore-exploit behaviors is motor system dependent and they further define the contributions of amygdala and VS to reinforcement learning.

Reevaluating the role of the hippocampus in memory: A meta-analysis of neurotoxic lesion studies in nonhuman primates.

The hippocampus and perirhinal cortex are both broadly implicated in memory; nevertheless, their relative contributions to visual item recognition and location memory remain disputed. Neuropsychological studies in nonhuman primates that examine memory function after selective damage to medial temporal lobe structures report various levels of memory impairment-ranging from minor deficits to profound amnesia. The discrepancies in published findings have complicated efforts to determine the exact magnitude of visual item recognition and location memory impairments following damage to the hippocampus and/or perirhinal cortex. To provide the most accurate estimate to date of the overall effect size, we use meta-analytic techniques on data aggregated from 26 publications that assessed visual item recognition and/or location memory in nonhuman primates with and without selective neurotoxic lesions of the hippocampus or perirhinal cortex. We estimated the overall effect size, evaluated the relation between lesion extent and effect size, and investigated factors that may account for between-study variation. Grouping studies by lesion target and testing method, separate meta-analyses were conducted. One meta-analysis indicated that impairments on tests of visual item recognition were larger after lesions of perirhinal cortex than after lesions of the hippocampus. A separate meta-analysis showed that performance on tests of location memory was severely impaired by lesions of the hippocampus. For the most part, meta-regressions indicated that greater impairment corresponds with greater lesion extent; paradoxically, however, more extensive hippocampal lesions predicted smaller impairments on tests of visual item recognition. We conclude the perirhinal cortex makes a larger contribution than the hippocampus to visual item recognition, and the hippocampus predominately contributes to spatial navigation.

The anterior cingulate cortex is necessary for forming prosocial preferences from vicarious reinforcement in monkeys.

A key feature of most social relationships is that we like seeing good things happen to others. Research has implicated the anterior cingulate cortex (ACC) in attaching value to social outcomes. For example, single neurons in macaque ACC selectively code reward delivery to the self, a partner, both monkeys, or neither monkey. Here, we assessed whether the ACC's contribution to social cognition is causal by testing rhesus monkeys (Macaca mulatta) on a vicarious reinforcement task before and after they sustained ACC lesions. Prior to surgery, actors learned that 3 different visual cues mapped onto 3 distinct reward outcomes: to self ("Self"), to the other monkey ("Other"), or to neither monkey ("Neither"). On each trial, actors saw a cue that predicted one of the 3 juice offers and could accept the offer by making a saccade to a peripheral target or reject the offer by breaking fixation. Preoperatively, all 6 actors displayed prosocial preferences, indicated by their greater tendency to give reward to Other relative to Neither. Half then received selective, bilateral, excitotoxic lesions of the ACC, and the other half served as unoperated controls. After surgery, all monkeys retained the social preferences they had demonstrated with the preoperatively learned cues, but this preference was reduced in the monkeys with ACC lesions. Critically, none of the monkeys in the ACC lesion group acquired social preferences with a new set of cues introduced after surgery. These data indicate that the primate ACC is necessary for acquisition of prosocial preferences from vicarious reinforcement.

Effects of Amygdala Lesions on Object-Based Versus Action-Based Learning in Macaques.

The neural systems that underlie reinforcement learning (RL) allow animals to adapt to changes in their environment. In the present study, we examined the hypothesis that the amygdala would have a preferential role in learning the values of visual objects. We compared a group of monkeys (Macaca mulatta) with amygdala lesions to a group of unoperated controls on a two-armed bandit reversal learning task. The task had two conditions. In the What condition, the animals had to learn to select a visual object, independent of its location. And in the Where condition, the animals had to learn to saccade to a location, independent of the object at the location. In both conditions choice-outcome mappings reversed in the middle of the block. We found that monkeys with amygdala lesions had learning deficits in both conditions. Monkeys with amygdala lesions did not have deficits in learning to reverse choice-outcome mappings. Rather, amygdala lesions caused the monkeys to become overly sensitive to negative feedback which impaired their ability to consistently select the more highly valued action or object. These results imply that the amygdala is generally necessary for RL.

Amygdala lesions eliminate viewing preferences for faces in rhesus monkeys.

In free-viewing experiments, primates orient preferentially toward faces and face-like stimuli. To investigate the neural basis of this behavior, we measured the spontaneous viewing preferences of monkeys with selective bilateral amygdala lesions. The results revealed that when faces and nonface objects were presented simultaneously, monkeys with amygdala lesions had no viewing preference for either conspecific faces or illusory facial features in everyday objects. Instead of directing eye movements toward socially relevant features in natural images, we found that, after amygdala loss, monkeys are biased toward features with increased low-level salience. We conclude that the amygdala has a role in our earliest specialized response to faces, a behavior thought to be a precursor for efficient social communication and essential for the development of face-selective cortex.

Nonnavigational spatial memory performance is unaffected by hippocampal damage in monkeys.

Evidence that the hippocampus is critical for spatial memory in nonnavigational tests is mixed. A recent study reported that temporary hippocampal inactivation impaired spatial memory in the nonnavigational Hamilton Search Task in monkeys. However, several studies have documented no impairment on other nonnavigational spatial memory tests following permanent hippocampal lesions. It was hypothesized that transient, but not permanent, hippocampal disruption produces deficits because monkeys undergoing transient inactivation continue to try to use a hippocampal-dependent strategy, whereas monkeys with permanent lesions use a nonhippocampal-dependent strategy. We evaluated this hypothesis by testing five rhesus monkeys with hippocampal lesions and five controls on a computerized analogue of the Hamilton Search Task. On each trial, monkeys saw an array of squares on a touchscreen, each of which "hid" one reward. Retrieving a reward depleted that location and monkeys continued selecting squares until they found all rewards. The optimal strategy is to remember chosen locations and choose each square once. Unlike the inactivation study, monkeys with hippocampal damage were as accurate as controls regardless of retention interval. Critically, we found no evidence that the groups used different strategies, as measured by learning rates, spatial search biases, perseverative win-stay errors, or inter-choice distance. This discrepancy between the effect of inactivations and lesions may result from off-target effects of inactivations or as-yet-unidentified differences between the physical and computerized tasks. Combined with previous evidence that hippocampal damage impairs navigational memory in monkeys, this evidence constrains the role of the hippocampus in spatial memory as being critical for navigational tests that likely involve allocentric spatial memory but not nonnavigational tests that likely involve egocentric spatial memory.

Hippocampal damage attenuates habituation to videos in monkeys.

Monkeys with selective damage to the hippocampus are often unimpaired in matching-to-sample tests but are reportedly impaired in visual paired comparison. While both tests assess recognition of previously seen images, delayed matching-to-sample may engage active memory maintenance whereas visual paired comparison may not. Passive memory tests that are not rewarded with food and that do not require extensive training may provide more sensitive measures of hippocampal function. To test this hypothesis, we assessed memory in monkeys with hippocampal damage and matched controls by providing them the opportunity to repeatedly view small sets of videos. Monkeys pressed a button to play each video. The same 10 videos were used for six consecutive days, after which 10 new videos were introduced in each of seven cycles of testing. Our measure of memory was the extent to which monkeys habituated with repeated presentations, watching fewer videos per session over time. Monkeys with hippocampal lesions habituated more slowly than did control monkeys, indicating poorer memory for previous viewings. Both groups dishabituated each time new videos were introduced. These results, like those from preferential viewing, suggest that the hippocampus may be especially important for memory of incidentally encoded events.

Dissociation of memory signals for metamemory in rhesus monkeys (Macaca mulatta).

Some nonhuman species demonstrate metamemory, the ability to monitor and control memory. Here, we identify memory signals that control metamemory judgments in rhesus monkeys by directly comparing performance in two metamemory paradigms while holding the availability of one memory signal constant and manipulating another. Monkeys performed a four-choice match-to-sample memory task. In Experiment 1, monkeys could decline memory tests on some trials for a small, guaranteed reward. In Experiment 2, monkeys could review the sample on some trials. In both experiments, monkeys improved accuracy by selectively declining tests or reviewing samples when memory was poor. To assess the degree to which different memory signals made independent contributions to the metamemory judgement, we made the decline-test or review-sample response available either prospectively, before the test, or concurrently with test stimuli. Prospective metamemory judgements are likely controlled by the current contents of working memory, whereas concurrent metamemory judgements may also be controlled by additional relative familiarity signals evoked by the sight of the test stimuli. In both paradigms, metacognitive responding enhanced accuracy more on concurrent than on prospective tests, suggesting additive contributions of working memory and stimulus-evoked familiarity. Consistent with the hypothesis that working memory and stimulus-evoked familiarity both control metamemory judgments when available, metacognitive choice latencies were longer in the concurrent condition, when both were available. Together, these data demonstrate that multiple memory signals can additively control metacognitive judgements in monkeys and provide a framework for mapping the interaction of explicit memory signals in primate memory.

Two-item same/different discrimination in rhesus monkeys (Macaca mulatta).

Almost all nonhuman animals can recognize when one item is the same as another item. It is less clear whether nonhuman animals possess abstract concepts of "same" and "different" that can be divorced from perceptual similarity. Pigeons and monkeys show inconsistent performance, and often surprising difficulty, in laboratory tests of same/different learning that involve only two items. Previous results from tests using multi-item arrays suggest that nonhumans compute sameness along a continuous scale of perceptual variability, which would explain the difficulty of making two-item same/different judgments. Here, we provide evidence that rhesus monkeys can learn a two-item same/different discrimination similar to those on which monkeys and pigeons have previously failed. Monkeys' performance transferred to novel stimuli and was not affected by perceptual variations in stimulus size, rotation, view, or luminance. Success without the use of multi-item arrays, and the lack of effect of perceptual variability, suggests a computation of sameness that is more categorical, and perhaps more abstract, than previously thought.

Dissociation of visual localization and visual detection in rhesus monkeys (Macaca mulatta).

Conscious and unconscious cognitive processes contribute independently to human behavior and can be dissociated. For example, humans report failing to see objects clearly in the periphery while simultaneously being able to grasp those objects accurately (Milner in Proc R Soc B Biol Sci 279:2289-2298, 2012). Knowing whether similar dissociations are present in nonverbal species is critical to our understanding of comparative psychology and the evolution of brains. However, such dissociations are difficult to detect in nonhumans because verbal reports of experience are the main way we discriminate putative conscious from unconscious processing. We trained monkeys in a localization task in which they responded to the location where a target appeared, and a matched detection task in which they reported the presence or absence of the same target. We used masking to manipulate the visibility of targets. Accuracy was high in both tasks when stimuli were unmasked and was attenuated by visual masking. At the strongest level of masking, performance in the detection task was at chance, while localization remained significantly above chance. Critically, errors in the detection task were predominantly misses, indicating that the monkeys' behavior remained under stimulus control, but that the monkeys did not detect the target despite above-chance localization. While these results cannot establish the existence of phenomenal vision in monkeys, the dissociation of visually guided action from detection parallels the dissociation of conscious and unconscious vision seen in humans.

Recognition errors suggest fast familiarity and slow recollection in rhesus monkeys.

One influential model of recognition posits two underlying memory processes: recollection, which is detailed but relatively slow, and familiarity, which is quick but lacks detail. Most of the evidence for this dual-process model in nonhumans has come from analyses of receiver operating characteristic (ROC) curves in rats, but whether ROC analyses can demonstrate dual processes has been repeatedly challenged. Here, we present independent converging evidence for the dual-process model from analyses of recognition errors made by rhesus monkeys. Recognition choices were made in three different ways depending on processing duration. Short-latency errors were disproportionately false alarms to familiar lures, suggesting control by familiarity. Medium-latency responses were less likely to be false alarms and were more accurate, suggesting onset of a recollective process that could correctly reject familiar lures. Long-latency responses were guesses. A response deadline increased false alarms, suggesting that limiting processing time weakened the contribution of recollection and strengthened the contribution of familiarity. Together, these findings suggest fast familiarity and slow recollection in monkeys, that monkeys use a "recollect to reject" strategy to countermand false familiarity, and that primate recognition performance is well-characterized by a dual-process model consisting of recollection and familiarity.

What does preferential viewing tell us about the neurobiology of recognition memory?

The two tests most widely used in nonhuman primates to assess the neurobiology of recognition memory produce conflicting results. Preferential viewing tests (e.g., visual paired comparison) produce robust impairments following hippocampal lesions, whereas matching tests (e.g., delayed nonmatching-to-sample) often show complete sparing. Here, we review the data, the proposed explanations for this discrepancy, and then critically evaluate those explanations. The most likely explanation is that preferential viewing tests are not a process-pure assessment of recognition memory, but also test elements of novelty-seeking, habituation, and motivation. These confounds likely explain the conflicting results. Thus, we propose that memory researchers should prefer explicit matching tests and readers interested in the neural substrates of recognition memory should give explicit matching tests greater interpretive weight.

Automated cognitive testing of monkeys in social groups yields results comparable to individual laboratory-based testing.

Cognitive abilities likely evolved in response to specific environmental and social challenges and are therefore expected to be specialized for the life history of each species. Specialized cognitive abilities may be most readily engaged under conditions that approximate the natural environment of the species being studied. While naturalistic environments might therefore have advantages over laboratory settings for cognitive research, it is difficult to conduct certain types of cognitive tests in these settings. We implemented methods for automated cognitive testing of monkeys (Macaca mulatta) in large social groups (Field station) and compared the performance to that of laboratory-housed monkeys (Laboratory). The Field station animals shared access to four touch-screen computers in a large naturalistic social group. Each Field station subject had an RFID chip implanted in each arm for computerized identification and individualized assignment of cognitive tests. The Laboratory group was housed and tested in a typical laboratory setting, with individual access to testing computers in their home cages. Monkeys in both groups voluntarily participated at their own pace for food rewards. We evaluated performance in two visual psychophysics tests, a perceptual classification test, a transitive inference test, and a delayed matching-to-sample memory test. Despite the differences in housing, social environment, age, and sex, monkeys in the two groups performed similarly in all tests. Semi-free ranging monkeys living in complex social environments are therefore viable subjects for cognitive testing designed to take advantage of the unique affordances of naturalistic testing environments.

Interspecific differences in the effects of masking and distraction on anti-predator behavior in suburban anthropogenic noise.

Predation is a common threat to animal survival. The detection of predators or anti-predator communication signals can be disrupted by anthropogenic noise; however, the mechanism by which responses are affected is unclear. Masking and distraction are the two hypotheses that have emerged as likely explanations for changes in behavior in noise. Masking occurs when the signal and noise fall within the same sensory domain; noise overlapping the energy in the signal reduces signal detection. Distraction can occur when noise in any sensory domain contributes to a greater cognitive load, thereby reducing signal detection. Here, we used a repeated measures field experiment to determine the relative contributions of masking and distraction in mediating reduced anti-predator responses in noise. We recorded the approaches and vocalizations of black-capped chickadees (Poecile atricapillus), tufted titmice (Baeolophus bicolor), and white-breasted nuthatches (Sitta carolinensis) to both visual and acoustic cues of predator presence, either with or without simultaneous exposure to anthropogenic noise. Titmice increased their calling to both visual and acoustic cues of predator presence. However, there was no significant effect of noise on the calling responses of titmice regardless of stimulus modality. Noise appeared to produce a distraction effect in chickadees; however, this effect was small, suggesting that chickadees may be relatively unaffected by low levels of anthropogenic noise in suburban environments. White-breasted nuthatch calling behavior was affected by the interaction of the modality of the predator stimulus and the noise condition. Nuthatches had a delayed response to the predator presentations, with a greater calling rate following the presentation of the acoustic stimulus in quiet compared to the presentation of the acoustic stimulus in noise. However, there was no difference in calling rate between the quiet and noise conditions for the visual stimulus. Together this suggests that even moderate levels of noise have some masking effect for white-breasted nuthatches. We suggest that the mechanisms through which noise influences anti-predator behavior may depend on the social roles, foraging ecology and auditory capabilities of each species.

The amygdala is not necessary for the familiarity aspect of recognition memory.

Dual-process accounts of item recognition posit two memory processes: slow but detailed recollection, and quick but vague familiarity. It has been proposed, based on prior rodent work, that the amygdala is critical for the familiarity aspect of item recognition. Here, we evaluated this proposal in male rhesus monkeys (Macaca mulatta) with selective bilateral excitotoxic amygdala damage. We used four established visual memory tests designed to assess different aspects of familiarity, all administered on touchscreen computers. Specifically, we assessed monkeys' tendencies to make low-latency false alarms, to make false alarms to recently seen lures, to produce curvilinear ROC curves, and to discriminate stimuli based on repetition across days. Three of the four tests showed no familiarity impairment and the fourth was explained by a deficit in reward processing. Consistent with this, amygdala damage did produce an anticipated deficit in reward processing in a three-arm-bandit gambling task, verifying the effectiveness of the lesions. Together, these results contradict prior rodent work and suggest that the amygdala is not critical for the familiarity aspect of item recognition.

No evidence that monkeys attribute mental states to animated shapes in the Heider-Simmel videos.

Human Theory of Mind (ToM) is so automatic and pervasive that we spontaneously attribute mental states to animated abstract shapes, as evidenced by the classic Heider-Simmel findings. The extent to which this represents a fundamental characteristic of primate social cognition is debated. Prior research suggests that monkeys spontaneously predict behavior and attribute basic goals to conspecifics, but it remains unclear whether, like humans, they spontaneously ascribe mental states to animated shapes. Here, we address this question by analyzing rhesus monkeys' viewing patterns of the classic Heider-Simmel animations. We hypothesized that if rhesus monkeys also spontaneously attribute mental states to animated shapes, then, like humans, they would have the longest fixation durations for theory of mind animations, medium duration fixation for goal-directed animations, and shortest fixations for animations with random motion. In contrast, if attributing mental states to animations is specific to humans and perhaps other apes, then we predict no differences in looking time across animation categories. Unlike humans, monkeys did not fixate longer on ToM videos. Critically, monkeys' viewing patterns did not correlate with humans' viewing patterns or intentionality ratings from previously published research. The only major difference in viewing patterns between animation categories tracked differences in low-level visual motion. Thus, monkeys do not view the classic Heider-Simmel animations like humans do and we found no evidence that they spontaneously attribute mental states to animated shapes.

Autonomic arousal tracks outcome salience not valence in monkeys making social decisions.

The evolutionary and neural underpinnings of human prosociality are still being identified. A growing body of evidence suggests that some species find the sight of another individual receiving a reward reinforcing, called vicarious reinforcement, and that this capacity is supported by a network of brain areas including the anterior cingulate cortex (ACC) and the amygdala. At the same time, analyses of autonomic arousal have been increasingly used to contextualize and guide neural research, especially for studies of reward processing. Here, we characterized the autonomic pupil response of eight monkeys across two laboratories in two different versions of a vicarious reinforcement paradigm. Monkeys were cued as to whether an upcoming reward would be delivered to them, another monkey, or nobody and could accept or decline the offer. As expected, all monkeys in both laboratories showed a marked preference for juice to the self, together with a reliable prosocial preference for juice to a social partner compared to juice to nobody. However, contrary to our expectations, we found that pupils were widest in anticipation of juice to the self, moderately sized in anticipation of juice to nobody, and narrowest in anticipation of juice to a social partner. This effect was seen across both laboratories and regardless of specific task parameters. The seemingly paradoxical pupil effect can be explained by a model in which pupil size tracks outcome salience, prosocial tendencies track outcome valence, and the relation between salience and valence is U-shaped. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Preserved visual memory and relational cognition performance in monkeys with selective hippocampal lesions.

The theory that the hippocampus is critical for visual memory and relational cognition has been challenged by discovery of more spared hippocampal tissue than previously reported in H.M., previously unreported extra-hippocampal damage in developmental amnesiacs, and findings that the hippocampus is unnecessary for object-in-context memory in monkeys. These challenges highlight the need for causal tests of hippocampal function in nonhuman primate models. Here, we tested rhesus monkeys on a battery of cognitive tasks including transitive inference, temporal order memory, shape recall, source memory, and image recognition. Contrary to predictions, we observed no robust impairments in memory or relational cognition either within- or between-groups following hippocampal damage. These results caution against over-generalizing from human correlational studies or rodent experimental studies, compel a new generation of nonhuman primate studies, and indicate that we should reassess the relative contributions of the hippocampus proper compared to other regions in visual memory and relational cognition.

An assessment of memory awareness in tufted capuchin monkeys (Cebus apella).

Humans, apes, and rhesus monkeys demonstrate memory awareness by collecting information when ignorant and acting immediately when informed. In this study, five capuchin monkeys searched for food after either watching the experimenter bait one of four opaque tubes (seen trials), or not watching (unseen trials). Monkeys with memory awareness should look into the tubes before making a selection only on unseen trials because on seen trials they already know the location of the food. In Experiment 1, one of the five capuchins looked significantly more often on unseen trials. In Experiment 2, we ensured that the monkeys attended to the baiting by interleaving training and test sessions. Three of the five monkeys looked more often on unseen trials. Because monkeys looked more often than not on both trial types, potentially creating a ceiling effect, we increased the effort required to look in Experiment 3, and predicted a larger difference in the probability of looking between seen and unseen trials. None of the five monkeys looked more often on unseen trials. These findings provide equivocal evidence for memory awareness in capuchin monkeys using tests that have yielded clear evidence in humans, apes, and rhesus monkeys.

Dissociation of item and source memory in rhesus monkeys.

Source memory, or memory for the context in which a memory was formed, is a defining characteristic of human episodic memory and source memory errors are a debilitating symptom of memory dysfunction. Evidence for source memory in nonhuman primates is sparse despite considerable evidence for other types of sophisticated memory and the practical need for good models of episodic memory in nonhuman primates. A previous study showed that rhesus monkeys confused the identity of a monkey they saw with a monkey they heard, but only after an extended memory delay. This suggests that they initially remembered the source - visual or auditory - of the information but forgot the source as time passed. Here, we present a monkey model of source memory that is based on this previous study. In each trial, monkeys studied two images, one that they simply viewed and touched and the other that they classified as a bird, fish, flower, or person. In a subsequent memory test, they were required to select the image from one source but avoid the other. With training, monkeys learned to suppress responding to images from the to-be-avoided source. After longer memory intervals, monkeys continued to show reliable item memory, discriminating studied images from distractors, but made many source memory errors. Monkeys discriminated source based on study method, not study order, providing preliminary evidence that our manipulation of retention interval caused errors due to source forgetting instead of source confusion. Finally, some monkeys learned to select remembered images from either source on cue, showing that they did indeed remember both items and both sources. This paradigm potentially provides a new model to study a critical aspect of episodic memory in nonhuman primates.