Where Actions Meet Outcomes: Medial Prefrontal Cortex, Central Thalamus, and the Basal Ganglia.

Medial prefrontal cortex (mPFC) interacts with distributed networks that give rise to goal-directed behavior through afferent and efferent connections with multiple thalamic nuclei and recurrent basal ganglia-thalamocortical circuits. Recent studies have revealed individual roles for different thalamic nuclei: mediodorsal (MD) regulation of signaling properties in mPFC neurons, intralaminar control of cortico-basal ganglia networks, ventral medial facilitation of integrative motor function, and hippocampal functions supported by ventral midline and anterior nuclei. Large scale mapping studies have identified functionally distinct cortico-basal ganglia-thalamocortical subnetworks that provide a structural basis for understanding information processing and functional heterogeneity within the basal ganglia. Behavioral analyses comparing functional deficits produced by lesions or inactivation of specific thalamic nuclei or subregions of mPFC or the basal ganglia have elucidated the interdependent roles of these areas in adaptive goal-directed behavior. Electrophysiological recordings of mPFC neurons in rats performing delayed non-matching-to position (DNMTP) and other complex decision making tasks have revealed populations of neurons with activity related to actions and outcomes that underlie these behaviors. These include responses related to motor preparation, instrumental actions, movement, anticipation and delivery of action outcomes, memory delay, and spatial context. Comparison of results for mPFC, MD, and ventral pallidum (VP) suggest critical roles for mPFC in prospective processes that precede actions, MD for reinforcing task-relevant responses in mPFC, and VP for providing feedback about action outcomes. Synthesis of electrophysiological and behavioral results indicates that different networks connecting mPFC with thalamus and the basal ganglia are organized to support distinct functions that allow organisms to act efficiently to obtain intended outcomes.

Adaptive specialization for spatial memory does not improve route efficiency: Comparing the ability of Clark's nutcrackers (Nucifraga columbiana) and pigeons (Columba livia) to solve traveling salesperson problems.

An important question in comparative cognition is whether animals are capable of planning ahead. Todd and Hills (Current Directions in Psychological Science, 29(3), 309-315, 2020) recently suggested that the ability to plan and choose internally may have scaffolded upon the cognitive mechanisms required by animals to search among patchy resources in their external environment. The traveling salesperson problem (TSP) is a spatial optimization problem in which a traveler is faced with the task of finding the best route from a start location to two or more destinations or targets. The Clark's nutcracker (Nucifraga columbiana) is a food-storing corvid with a highly specialized spatial memory. Spatial memory would appear to be deeply rooted in the cognitive mechanisms required for choosing efficiently among multiple alternative routes during a TSP. If so, then species like nutcrackers that are more dependent upon spatial memory for survival may have a greater ability to plan ahead or choose more efficiently among different route options than species that have less selective pressure for remembering the location of food, like pigeons. We examined the ability of nutcrackers to solve TSPs using the same procedures and target configurations as in our past research (Gibson, Wilkerson, & Kelly, Animal Cognition, 15, 379-391, 2012) to explore if nutcrackers can efficiently solve TSPs and how their route solutions compare with those of pigeons. Nutcrackers did not display an advantage in route efficiency and performed comparably to pigeons. Both species tended to prefer a nearest-neighbor strategy to more globally efficient routes. Having a more robust spatial memory may not improve the ability of animals to determine routes to multiple locations.

Central Thalamic-Medial Prefrontal Control of Adaptive Responding in the Rat: Many Players in the Chamber.

The medial prefrontal cortex (mPFC) has robust afferent and efferent connections with multiple nuclei clustered in the central thalamus. These nuclei are elements in large-scale networks linking mPFC with the hippocampus, basal ganglia, amygdala, other cortical areas, and visceral and arousal systems in the brainstem that give rise to adaptive goal-directed behavior. Lesions of the mediodorsal nucleus (MD), the main source of thalamic input to middle layers of PFC, have limited effects on delayed conditional discriminations, like DMTP and DNMTP, that depend on mPFC. Recent evidence suggests that MD sustains and amplifies neuronal responses in mPFC that represent salient task-related information and is important for detecting and encoding contingencies between actions and their consequences. Lesions of rostral intralaminar (rIL) and ventromedial (VM) nuclei produce delay-independent impairments of egocentric DMTP and DNMTP that resemble effects of mPFC lesions on response speed and accuracy: results consistent with projections of rIL to striatum and VM to motor cortices. The ventral midline and anterior thalamic nuclei affect allocentric spatial cognition and memory consistent with their connections to mPFC and hippocampus. The dorsal midline nuclei spare DMTP and DNMTP. They have been implicated in behavioral-state control and response to salient stimuli in associative learning. mPFC functions are served during DNMTP by discrete populations of neurons with responses related to motor preparation, movements, lever press responses, reinforcement anticipation, reinforcement delivery, and memory delay. Population analyses show that different responses are timed so that they effectively tile the temporal interval from when DNMTP trials are initiated until the end. Event-related responses of MD neurons during DNMTP are predominantly related to movement and reinforcement, information important for DNMTP choice. These responses closely mirror the activity of mPFC neurons with similar responses. Pharmacological inactivation of MD and adjacent rIL affects the expression of diverse action- and outcome-related responses of mPFC neurons. Lesions of MD before training are associated with a shift away from movement-related responses in mPFC important for DNMTP choice. These results suggest that MD has short-term effects on the expression of event-related activity in mPFC and long-term effects that tune mPFC neurons to respond to task-specific information.

Clark's nutcrackers (Nucifraga columbiana) use a visual barrier for cache protection.

Previous work with corvids such as scrub jays (Aphelocoma californica) and ravens (Corvus corax) suggests that many social corvids alter their caching behavior when observed by conspecifics to protect their caches. We examined whether the Clark's nutcracker (Nucifraga columbiana), an asocial corvid, can utilize a barrier to conceal its caching activities from a conspecific observer. Nutcrackers were allowed to cache nuts in a visible or concealed location in either the presence or absence of an observer. Nutcrackers were also given experience of having their caches pilfered. The nutcrackers cached significantly more nuts in the concealed compared to a visible location when observed. Importantly, nutcrackers also recovered a larger percentage of their nuts 24 hr later from a visible cache location but when the observer was no longer present. The results extend recent work suggesting that relatively nonsocial corvids, similar to their more social relatives, also engage in multiple forms of cache protection. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Central thalamic inactivation impairs the expression of action- and outcome-related responses of medial prefrontal cortex neurons in the rat.

The mediodorsal (MD) and adjacent intralaminar (IL) and midline nuclei provide the main thalamic input to the medial prefrontal cortex (mPFC) and are critical for associative learning and decision-making. MD neurons exhibit activity related to actions and outcomes that mirror responses of mPFC neurons in rats during dynamic delayed non-match to position (dDNMTP), a variation of DNMTP where start location is varied randomly within an open octagonal arena to avoid confounding behavioral events with spatial location. To test whether the thalamus affects the expression of these responses in mPFC, we inhibited the central thalamus unilaterally by microinjecting muscimol at doses and sites found to affect decision-making when applied bilaterally. Unilateral inactivation reduced normalized task-related responses in the ipsilateral mPFC without disrupting behavior needed to characterize event-related neuronal activity. Our results extend earlier findings that focused on delay-related activity by showing that central thalamic inactivation interferes with responses related to actions and outcomes that occur outside the period of memory delay. These findings are consistent with the broad effects of central thalamic lesions on behavioral measures of reinforcement-guided responding. Most (7/8) of the prefrontal response types affected by thalamic inactivation have also been observed in MD during dDNMTP. These results support the hypothesis that MD and IL act as transthalamic gates: monitoring prefrontal activity through corticothalamic inputs; integrating this information with signals from motivational and sensorimotor systems that converge in thalamus; and acting through thalamocortical projections to enhance expression of neuronal responses in the PFC that support adaptive goal-directed behavior.

Mediodorsal Thalamic Neurons Mirror the Activity of Medial Prefrontal Neurons Responding to Movement and Reinforcement during a Dynamic DNMTP Task.

The mediodorsal nucleus (MD) interacts with medial prefrontal cortex (mPFC) to support learning and adaptive decision-making. MD receives driver (layer 5) and modulatory (layer 6) projections from PFC and is the main source of driver thalamic projections to middle cortical layers of PFC. Little is known about the activity of MD neurons and their influence on PFC during decision-making. We recorded MD neurons in rats performing a dynamic delayed nonmatching to position (dDNMTP) task and compared results to a previous study of mPFC with the same task (Onos et al., 2016). Criterion event-related responses were observed for 22% (254/1179) of neurons recorded in MD, 237 (93%) of which exhibited activity consistent with mPFC response types. More MD than mPFC neurons exhibited responses related to movement (45% vs. 29%) and reinforcement (51% vs. 27%). MD had few responses related to lever presses, and none related to preparation or memory delay, which constituted 43% of event-related activity in mPFC. Comparison of averaged normalized population activity and population response times confirmed the broad similarity of common response types in MD and mPFC and revealed differences in the onset and offset of some response types. Our results show that MD represents information about actions and outcomes essential for decision-making during dDNMTP, consistent with evidence from lesion studies that MD supports reward-based learning and action-selection. These findings support the hypothesis that MD reinforces task-relevant neural activity in PFC that gives rise to adaptive behavior.

Prefrontal Neurons Encode Actions and Outcomes in Conjunction with Spatial Location in Rats Performing a Dynamic Delayed Non-Match to Position Task.

To respond adaptively to change organisms must utilize information about recent events and environmental context to select actions that are likely to produce favorable outcomes. We developed a dynamic delayed nonmatching to position task to study the influence of spatial context on event-related activity of medial prefrontal cortex neurons during reinforcement-guided decision-making. We found neurons with responses related to preparation, movement, lever press responses, reinforcement, and memory delays. Combined event-related and video tracking analyses revealed variability in spatial tuning of neurons with similar event-related activity. While all correlated neurons exhibited spatial tuning broadly consistent with relevant task events, for instance reinforcement-related activity concentrated in locations where reinforcement was delivered, some had elevated activity in more specific locations, for instance reinforcement-related activity in one of several locations where reinforcement was delivered. Timing analyses revealed a limited set of distinct response types with activity time-locked to critical behavioral events that represent the temporal organization of dDNMTP trials. Our results suggest that reinforcement-guided decision-making emerges from discrete populations of medial prefrontal neurons that encode information related to planned or ongoing movements and actions and anticipated or actual action-outcomes in conjunction with information about spatial context.

A pathway for spatial memory encoding.

The medial prefrontal cortex has been shown to play a role for rodents in successful completion of tasks that require spatial memory, but the pathways responsible for the transmission of spatial information to the mPFC, and the nature and timing of such information, are unknown. Recently, Spellman, Rigotti, Ahmari, Fusi, Gogos, and Gordon (Nature, 522, 309-314, 2015) addressed these questions in an eloquent and ingenious series of experiments, which we review in the broader context of the neurobiology of spatial memory.

Clark's nutcrackers (Nucifraga columbiana) are sensitive to distance, but not lighting when caching in the presence of a conspecific.

We examined the caching behavior of the Clark's nutcracker (Nucifraga columbiana), a relatively asocial corvid bird, during social and non-social conditions with conspecifics. Past work by Dally et al., (2004, 2005a) has found that the related but more social scrub jay (Aphelocoma californica) caches food in locations that are far away or that are more dimly illuminated when in the presence of an observer. Here, we used procedures comparable to those of Dally's group to examine if the less social nutcracker is also sensitive to these same factors when caching in the presence of a conspecific. We found that nutcrackers cached nuts farther away, but showed no preference for caching in a dimly compared to a brightly illuminated area when in the presence of a conspecific observer. When comparing the measures of cache protection used in the past work with scrub jays the results are consistent with the social organization of these birds; that is, the less social nutcracker engaged in fewer cache protection behaviors than the more social scrub jays, However, we explore other possible explanations for our findings given the wider body of literature on corvid cache protection suggesting that nutcrackers and scrub jays may be more comparable.

Spatial context learning in pigeons (Columba livia).

In a seminal paper in the cognitive sciences, Chun and Jiang (1998) described the contextual cueing paradigm in which they used artificial stimuli and showed that people became faster to locate a target when the background predicted the location of a target compared to when it did not. Here we examined contextual cueing in pigeons for the first time using artificial stimuli and procedures similar to those of Chun and Jiang. In the first test, we had pigeons search for a target among a display of seven distractors; during one condition, the position of the distractors predicted the location of the target, and in the second condition, there was no relationship between the two. In a second test, we presented the pigeons with the predictive displays from Test 1 and a second set of displays that also predicted the location of a target to see if learning about one set of predictive backgrounds disrupted learning about a second set. The pigeons were quick to acquire context-based knowledge and retain that information when faced with additional contexts. The results suggest that contextual cueing can occur for a variety of stimuli in nonhuman animals and that it may be a common mechanism for processing visual information across a wide variety of species.

The neurobiology of thalamic amnesia: Contributions of medial thalamus and prefrontal cortex to delayed conditional discrimination.

Although medial thalamus is well established as a site of pathology associated with global amnesia, there is uncertainty about which structures are critical and how they affect memory function. Evidence from human and animal research suggests that damage to the mammillothalamic tract and the anterior, mediodorsal (MD), midline (M), and intralaminar (IL) nuclei contribute to different signs of thalamic amnesia. Here we focus on MD and the adjacent M and IL nuclei, structures identified in animal studies as critical nodes in prefrontal cortex (PFC)-related pathways that are necessary for delayed conditional discrimination. Recordings of PFC neurons in rats performing a dynamic delayed non-matching-to position (DNMTP) task revealed discrete populations encoding information related to planning, execution, and outcome of DNMTP-related actions and delay-related activity signaling previous reinforcement. Parallel studies recording the activity of MD and IL neurons and examining the effects of unilateral thalamic inactivation on the responses of PFC neurons demonstrated a close coupling of central thalamic and PFC neurons responding to diverse aspects of DNMTP and provide evidence that thalamus interacts with PFC neurons to give rise to complex goal-directed behavior exemplified by the DNMTP task.

Surgeon-rated visualization in shoulder arthroscopy: a randomized blinded controlled trial comparing irrigation fluid with and without epinephrine.

PURPOSE: The objective of the current study was to compare surgeon-rated visualization in shoulder arthroscopy using irrigation fluid with and without epinephrine. METHODS: Eighty-three patients were randomized to receive irrigation fluid with (44 patients) or without (39 patients) epinephrine during their arthroscopic shoulder procedures. After each procedure, the blinded senior author (G.F.C.) evaluated visualization based on a visual analog scale (VAS), and all clinically important procedure variables were recorded. RESULTS: Eighty-three arthroscopic shoulder procedures were included in the study. Fifty-four of these procedures were arthroscopic rotator cuff repairs, allowing a subset analysis of this specific procedure. There was a significant difference, with improved visualization in the epinephrine group versus the group without epinephrine when comparing all procedures (P < .0001) and when comparing only rotator cuff repairs (P < .0001). However, there was no statistical difference in other clinically important variables, including operative time and amount of irrigation fluid used. CONCLUSIONS: The addition of epinephrine to irrigation fluid significantly improves surgeon-rated visualization in shoulder arthroscopy. Without an observed significant difference in operative time or volume of irrigation fluid used, the clinical significance of this improved visualization is unclear, and the use of irrigation fluid without epinephrine remains a viable option in the hands of an experienced surgeon. LEVEL OF EVIDENCE: Level I, high-quality randomized controlled trial with statistically significant difference.

An investigation of quantity discrimination in Clark's nutcrackers (Nucifraga columbiana).

We examined quantity discrimination in the Clark's nutcracker (Nucifraga columbiana), a corvid bird with a strong dependence upon caching and recovering nuts. We presented 2 sets of nuts simultaneously, in 21 different conditions, to see if the nutcrackers could choose the larger of the 2 quantities. The nutcrackers displayed a strong ability to discriminate quantities of nuts. Like other animals tested previously, the nutcrackers' performance decreased as the ratio of the 2 quantities approached 1. Interestingly, at constant distances, the nutcrackers did not have more difficulty with contrasts containing larger quantities. Thus, nutcrackers have a fine sensitivity for discriminating between 2 quantities. We review the relevant literature and explore the possibility that nutcrackers, like some other birds, may have developed a keen ability to discriminate quantities. This ability may have developed as an adaptive specialization to cope with their scatter-hoarding ecology, though the evidence for such a conclusion is mixed.

Rats average entire vectors when navigating toward a hidden goal: a test of the vector sum model in rodents.

Cheng and colleagues (Cheng, 1988, 1989, 1990; Cheng and Sherry, 1992; Spetch et al., 1992) have shown that birds use vector information from landmarks to return to hidden goal locations. Cheng (1994) subsequently showed that pigeons average the distance and directional components of landmark-to-goal vectors separately, rather than as a single entity (distance-averaging model). Cheng reasoned that other animals might also average the distance and directional components of landmark-to-goal vectors separately, in part, given commonalities in the neural architecture of visual systems. We used procedures developed by Cheng (1994) to examine how rats utilize landmark-to-goal vectors. In contrast to the results with pigeons, we found evidence indicating that rats average whole vectors rather than their separate scalars (vector-averaging). The ways that pigeons and rats use vectors may be related to evolved differences in the visual systems between these two species. This article is part of a Special Issue entitled: CO3 2013.

The head-direction signal is critical for navigation requiring a cognitive map but not for learning a spatial habit.

Head-direction (HD) cells fire as a function of an animal's directional heading in the horizontal plane during two-dimensional navigational tasks [1]. The information from HD cells is used with place and grid cells to form a spatial representation (cognitive map) of the environment [2, 3]. Previous studies have shown that when rats are inverted (upside down), they have difficulty learning a task that requires them to find an escape hole from one of four entry points but that they can learn it when released from one or two start points [4]. Previous reports also indicate that the HD signal is disrupted when a rat is oriented upside down [5, 6]. Here we monitored HD cell activity in the two-entry-point version of the inverted task and when the rats were released from a novel start point. We found that despite the absence of direction-specific firing in HD cells when inverted, rats could successfully navigate to the escape hole when released from one of two familiar locations by using a habit-associated directional strategy. In the continued absence of normal HD cell activity, inverted rats failed to find the escape hole when started from a novel release point. The results suggest that the HD signal is critical for accurate navigation in situations that require a flexible allocentric cognitive mapping strategy, but not for situations that utilize habit-like associative spatial learning.

Tests of inferential reasoning by exclusion in Clark's nutcrackers (Nucifraga columbiana).

We examined inferential reasoning by exclusion in the Clark's nutcracker (Nucifraga columbiana) using two-way object-choice procedures. While other social scatter-hoarding corvids appear capable of engaging in inferential reasoning, it remains unclear if the relatively less social nutcracker is able to do so. In an initial experiment, food was hidden in one of two opaque containers. All of the birds immediately selected the baited container when shown only the empty container during testing. We subsequently examined the nutcrackers in two follow-up experiments using a task that may have been less likely to be solved by associative processes. The birds were trained that two distinctive objects were always found hidden in opaque containers that were always positioned at the same two locations. During testing, one of the two objects was found in a transparent "trash bin" and was unavailable. The birds were required to infer that if one of the objects was in the "trash," then the other object should still be available in its hidden location. Five out of six birds were unable to make this inference, suggesting that associative mechanisms likely accounted for our earlier results. However, one bird consistently chose the object that was not seen in the "trash," demonstrating that nutcrackers may have the ability to use inferential reasoning by exclusion to solve inference tasks. The role of scatter hoarding and social organization is discussed as factors in the ability of corvid birds to reason.

Let the pigeon drive the bus: pigeons can plan future routes in a room.

The task of determining an optimal route to several locations is called the traveling salesperson problem (TSP). The TSP has been used recently to examine spatial cognition in humans and non-human animals. It remains unclear whether or not the decision process of animals other than non-human primates utilizes rigid rule-based heuristics, or whether non-human animals are able to flexibly 'plan' future routes/behavior based on their knowledge of multiple locations. We presented pigeons in a One-way and Round-Trip group with TSPs that included two or three destinations (feeders) in a laboratory environment. The pigeons departed a start location, traveled to each feeder once before returning to a final destination. Pigeons weighed the proximity of the next location heavily, but appeared to plan ahead multiple steps when the travel costs for inefficient behavior appeared to increase. The results provide clear and strong evidence that animals other than primates are capable of planning sophisticated travel routes.

Qualitative similarities in the visual short-term memory of pigeons and people.

Visual short-term memory plays a key role in guiding behavior, and individual differences in visual short-term memory capacity are strongly predictive of higher cognitive abilities. To provide a broader evolutionary context for understanding this memory system, we directly compared the behavior of pigeons and humans on a change detection task. Although pigeons had a lower storage capacity and a higher lapse rate than humans, both species stored multiple items in short-term memory and conformed to the same basic performance model. Thus, despite their very different evolutionary histories and neural architectures, pigeons and humans have functionally similar visual short-term memory systems, suggesting that the functional properties of visual short-term memory are subject to similar selective pressures across these distant species.

Clark's nutcrackers (Nucifraga columbiana) use gestures to identify the location of hidden food.

Heterospecific cues, such as gaze direction and body position, may be an important source of information that an animal can use to infer the location of resources like food. The use of heterospecific cues has been largely investigated using primates, dogs, and other mammals; less is known about whether birds can also use heterospecific gestures. We tested six Clark's nutcrackers in a two-way object-choice task using touch, point, and gaze cues to investigate whether these birds can use human gestures to find food. Most of the birds were able to use a touch gesture during the first trial of testing and were able to learn to use point and gaze (eyes and head alternation) cues after a limited number of trials. This study is the first to test a non-social corvid on the object-choice task. The performance of non-social nutcrackers is similar to that of more social and related corvids, suggesting that species with different evolutionary histories can utilize gestural information.

The synthetic approach to the study of spatial memory: have we properly addressed Tinbergen's "four questions"?

In 1963, Niko Tinbergen suggested that to truly understand the behavior of an animal, the ultimate causes (e.g., adaptive value, evolutionary history) as well as the proximate mechanisms (e.g., neurobiology, development) that result in the production of the behavior must be understood in an integrated framework. We examine whether the study of spatial memory in food storing birds has adequately addressed Tinbergen's questions and highlight the work of Sara Shettleworth, who has made a tremendous contribution to this area of study, and whom this issue honors. Our conclusion is that while the study of food caching and spatial memory in birds has been a very good model of a program of research that has addressed Tinbergen's questions, additional work remains.