Assessing Human Spatial Navigation in a Virtual Space and its Sensitivity to Exercise.

Spatial navigation (SN) is the ability to locomote through the environment, which requires an understanding of where one is located in time and space. This capacity is known to rely on the sequential firing of place cells within the hippocampus. SN is an important behavior to investigate as this process deteriorates with age, especially in neurodegenerative disorders. However, the investigation of SN is limited by the lack of sophisticated behavioral techniques to assess this hippocampal-dependent task. Therefore, the goal of this protocol was to develop a novel, real-world approach to studying SN in humans. Specifically, an active virtual SN task was developed using a cross-platform game engine. During the encoding phase, participants navigated their way through a virtual city to locate landmarks. During the remembering phase, participants remembered where these reward locations were and delivered items to these locations. Time to find each location was captured and episodic memory was assessed by a free recall phase, including aspects of place, order, item, and association. Movement behavior (x, y, and z coordinates) was assessed through an asset available in the game engine. Importantly, results from this task demonstrate that it accurately captures both spatial learning and memory abilities as well as episodic memory. Further, findings indicate that this task is sensitive to exercise, which improves hippocampal functioning. Overall, the findings suggest a novel way to track human hippocampal functioning over the course of time, with this behavior being sensitive to physical activity training paradigms.

Dispositional mindfulness and its relationship to exercise motivation and experience.

Mindfulness is the psychological state of staying attuned to the present moment, without ruminating on past or future events, and allowing thoughts, feelings, or sensations to arise without judgment or attachment. Previous work has shown that heightened dispositional mindfulness is associated with the awareness of the importance of exercise, exercise self-efficacy, exercise motivation, and self-reported exercise level. However, more methodologically rigorous studies are needed to understand the relationship between mindfulness and the psychological mechanisms related to exercise motivation, including the identification of why individuals are motivated to engage in exercise, the subjective experience of exercise, and the propensity for exercise dependence and addiction. In this cross-sectional investigation, we utilized the framework of the Self-Determination Theory to examine the hypothesis that heightened dispositional mindfulness (as measured by the Mindful Attention Awareness Scale) would be associated with increased levels of exercise motivation that were derived by higher levels of autonomous self-regulation. Individuals were recruited from urban areas who self-reported either low (exercising 2 or fewer times per week for 20 min or less; n = 78) or moderate (exercising 1 or 2 times per week for 20 min or more; n = 127) levels of exercise engagement. As hypothesized, heightened dispositional mindfulness was significantly associated with heightened levels of exercise self-determination as measured by the Behavioral Regulations in Exercise Questionnaire, with this effect being driven by negative associations with amotivation, external regulation, and introjected regulation. Additionally, we found that heightened dispositional mindfulness was associated with lower levels of psychological distress upon exercise and decreased exercise dependence/addiction. Overall, increased dispositional mindfulness may support a healthy relationship with exercise. These findings have implications for the utility of mindfulness interventions to support the regulation of exercise behaviors in service of enhancing exercise motivation and engagement.

Examining the Effect of Increased Aerobic Exercise in Moderately Fit Adults on Psychological State and Cognitive Function.

Regular physical exercise can decrease the risk for obesity, diabetes, and cardiovascular disease, increase life expectancy, and promote psychological health and neurocognitive functioning. Cross-sectional studies show that cardiorespiratory fitness level (VO2 max) is associated with enhanced brain health, including improved mood state and heightened cognitive performance. Interventional studies are consistent with these cross-sectional studies, but most have focused on low-fit populations. Few such studies have asked if increasing levels of physical activity in moderately fit people can significantly enhance mood, motivation, and cognition. Therefore, the current study investigated the effects of increasing aerobic exercise in moderately fit individuals on psychological state and cognitive performance. We randomly assigned moderately fit healthy adults, 25-59 years of age, who were engaged in one or two aerobic exercise sessions per week to either maintain their exercise regimen (n = 41) or increase their exercise regimen (i.e., 4-7 aerobic workouts per week; n = 39) for a duration of 3 months. Both before and after the intervention, we assessed aerobic capacity using a modified cardiorespiratory fitness test, and hippocampal functioning via various neuropsychological assessments including a spatial navigation task and the Mnemonic Similarity Task as well as self-reported measures including the Positive and Negative Affect Scale, Beck Anxiety Inventory, State-Trait Anxiety Inventory, Perceived Stress Scale, Rumination Scale, Eating Disorders Examination, Eating Attitudes Test, Body Attitudes Test, and Behavioral Regulation of Exercise Questionnaire. Consistent with our initial working hypotheses, we found that increasing exercise significantly decreased measures of negative affect, including fear, sadness, guilt, and hostility, as well as improved body image. Further, we found that the total number of workouts was significantly associated with improved spatial navigation abilities and body image as well as reduced anxiety, general negative affect, fear, sadness, hostility, rumination, and disordered eating. In addition, increases in fitness levels were significantly associated with improved episodic memory and exercise motivation as well as decreased stress and disordered eating. Our findings are some of the first to indicate that in middle-aged moderately-fit adults, continuing to increase exercise levels in an already ongoing fitness regimen is associated with additional benefits for both psychological and cognitive health.

Neural evidence for recognition of naturalistic videos in monkey hippocampus.

The role of the hippocampus in recognition memory has long been a source of debate. Tasks used to study recognition that typically require an explicit probe, where the participant must make a response to prove they remember, yield mixed results on hippocampal involvement. Here, we tasked monkeys to freely view naturalistic videos, and only tested their memory via looking times for two separate novel versus repeat video conditions on each trial. Notably, a large proportion (>30%) of hippocampal neurons differentiated these videos via changes in firing rates time-locked to the duration of their presentation on screen, and not during the delay period between them as would be expected for working memory. Many of these single neurons (>15%) contributed to both retrieval conditions, and differentiated novel from repeat videos across trials with trial-unique content, suggesting they detect familiarity. The majority of neurons contributing to the classifier showed an enhancement in firing rate on repeat compared with novel videos, a pattern which has not previously been shown in hippocampus. These results suggest the hippocampus contributes to recognition memory via familiarity during free-viewing.

The contributions of entorhinal cortex and hippocampus to error driven learning.

Computational models proposed that the medial temporal lobe (MTL) contributes importantly to error-driven learning, though little direct in-vivo evidence for this hypothesis exists. To test this, we recorded in the entorhinal cortex (EC) and hippocampus (HPC) as macaques performed an associative learning task using an error-driven learning strategy, defined as better performance after error relative to correct trials. Error-detection signals were more prominent in the EC relative to HPC. Early in learning hippocampal but not EC neurons signaled error-driven learning by increasing their population stimulus-selectivity following error trials. This same pattern was not seen in another task where error-driven learning was not used. After learning, different populations of cells in both the EC and HPC signaled long-term memory of newly learned associations with enhanced stimulus-selective responses. These results suggest prominent but differential contributions of EC and HPC to learning from errors and a particularly important role of the EC in error-detection.

A neural signature of pattern separation in the monkey hippocampus.

The CA3 and dentate gyrus (DG) regions of the hippocampus are considered key for disambiguating sensory inputs from similar experiences in memory, a process termed pattern separation. The neural mechanisms underlying pattern separation, however, have been difficult to compare across species: rodents offer robust recording methods with less human-centric tasks, while humans provide complex behavior with less recording potential. To overcome these limitations, we trained monkeys to perform a visual pattern separation task similar to those used in humans while recording activity from single CA3/DG neurons. We find that, when animals discriminate recently seen novel images from similar (lure) images, behavior indicative of pattern separation, CA3/DG neurons respond to lure images more like novel than repeat images. Using a population of these neurons, we are able to classify novel, lure, and repeat images from each other using this pattern of firing rates. Notably, one subpopulation of these neurons is more responsible for distinguishing lures and repeats-the key discrimination indicative of pattern separation.

Brief, daily meditation enhances attention, memory, mood, and emotional regulation in non-experienced meditators.

Meditation is an ancient practice that cultivates a calm yet focused mind; however, little is known about how short, practical meditation practices affect cognitive functioning in meditation-naïve populations. To address this question, we randomized subjects (ages of 18-45) who were non-experienced meditators into either a 13-min daily guided meditation session or a 13-min daily podcast listening session (control group) for a total duration of 8 weeks. We examined the effects of the daily meditation practice relative to podcast listening on mood, prefrontal and hippocampal functioning, baseline cortisol levels, and emotional regulation using the Trier Social Stress Test (TSST). Compared to our control group, we found that 8 but not 4 weeks of brief, daily meditation decreased negative mood state and enhanced attention, working memory, and recognition memory as well as decreased state anxiety scores on the TSST. Furthermore, we report that meditation-induced changes in emotional regulation are more strongly linked to improved affective state than improved cognition. This study not only suggests a lower limit for the duration of brief daily meditation needed to see significant benefits in non-experienced meditators, but suggests that even relatively short daily meditation practice can have similar behavioral effects as longer duration and higher-intensity mediation practices.

Dialogues: The Science and Power of Storytelling.

Skillful storytelling helps listeners understand the essence of complex concepts and ideas in meaningful and often personal ways. For this reason, storytelling is being embraced by scientists who not only want to connect more authentically with their audiences, but also want to understand how the brain processes this powerful form of communication. Here we present part of a conversation between a group of scientists actively engaged with the practice and/or the science of storytelling. We highlight the brain networks involved in the telling and hearing of stories and show how storytelling is being used well beyond the realm of public communication to add a deeper dimension to communication with our students and colleagues, as well as helping to make our profession more inclusive.

Contributions of primate prefrontal cortex and medial temporal lobe to temporal-order memory.

Neuropsychological and neurophysiological studies have emphasized the role of the prefrontal cortex (PFC) in maintaining information about the temporal order of events or items for upcoming actions. However, the medial temporal lobe (MTL) has also been considered critical to bind individual events or items to their temporal context in episodic memory. Here we characterize the contributions of these brain areas by comparing single-unit activity in the dorsal and ventral regions of macaque lateral PFC (d-PFC and v-PFC) with activity in MTL areas including the hippocampus (HPC), entorhinal cortex, and perirhinal cortex (PRC) as well as in area TE during the encoding phase of a temporal-order memory task. The v-PFC cells signaled specific items at particular time periods of the task. By contrast, MTL cortical cells signaled specific items across multiple time periods and discriminated the items between time periods by modulating their firing rates. Analysis of the temporal dynamics of these signals showed that the conjunctive signal of item and temporal-order information in PRC developed earlier than that seen in v-PFC. During the delay interval between the two cue stimuli, while v-PFC provided prominent stimulus-selective delay activity, MTL areas did not. Both regions of PFC and HPC exhibited an incremental timing signal that appeared to represent the continuous passage of time during the encoding phase. However, the incremental timing signal in HPC was more prominent than that observed in PFC. These results suggest that PFC and MTL contribute to the encoding of the integration of item and timing information in distinct ways.

The Effects of Acute Exercise on Mood, Cognition, Neurophysiology, and Neurochemical Pathways: A Review.

A significant body of work has investigated the effects of acute exercise, defined as a single bout of physical activity, on mood and cognitive functions in humans. Several excellent recent reviews have summarized these findings; however, the neurobiological basis of these results has received less attention. In this review, we will first briefly summarize the cognitive and behavioral changes that occur with acute exercise in humans. We will then review the results from both human and animal model studies documenting the wide range of neurophysiological and neurochemical alterations that occur after a single bout of exercise. Finally, we will discuss the strengths, weaknesses, and missing elements in the current literature, as well as offer an acute exercise standardization protocol and provide possible goals for future research.

How Body Affects Brain.

Studies show that physical exercise can affect a range of brain and cognitive functions. However, little is known about the peripheral signals that initiate these central changes. Moon et al. (2016) provide exciting new evidence that a novel myokine, cathepsin B (CTSB), released with exercise is associated with improved memory.

Acute Exercise Improves Prefrontal Cortex but not Hippocampal Function in Healthy Adults.

The effects of acute aerobic exercise on cognitive functions in humans have been the subject of much investigation; however, these studies are limited by several factors, including a lack of randomized controlled designs, focus on only a single cognitive function, and testing during or shortly after exercise. Using a randomized controlled design, the present study asked how a single bout of aerobic exercise affects a range of frontal- and medial temporal lobe-dependent cognitive functions and how long these effects last. We randomly assigned 85 subjects to either a vigorous intensity acute aerobic exercise group or a video watching control group. All subjects completed a battery of cognitive tasks both before and 30, 60, 90, or 120 min after the intervention. This battery included the Hopkins Verbal Learning Test-Revised, the Modified Benton Visual Retention Test, the Stroop Color and Word Test, the Symbol Digit Modalities Test, the Digit Span Test, the Trail Making Test, and the Controlled Oral Word Association Test. Based on these measures, composite scores were formed to independently assess prefrontal cortex- and hippocampal-dependent cognition. A three-way mixed Analysis of Variance was used to determine whether differences existed between groups in the change in cognitive function from pre- to post-intervention testing. Acute exercise improved prefrontal cortex- but not hippocampal-dependent functioning, with no differences found between delay groups. Vigorous acute aerobic exercise has beneficial effects on prefrontal cortex-dependent cognition and these effects can last for up to 2 hr after exercise.

Measuring the signal-to-noise ratio of a neuron.

The signal-to-noise ratio (SNR), a commonly used measure of fidelity in physical systems, is defined as the ratio of the squared amplitude or variance of a signal relative to the variance of the noise. This definition is not appropriate for neural systems in which spiking activity is more accurately represented as point processes. We show that the SNR estimates a ratio of expected prediction errors and extend the standard definition to one appropriate for single neurons by representing neural spiking activity using point process generalized linear models (PP-GLM). We estimate the prediction errors using the residual deviances from the PP-GLM fits. Because the deviance is an approximate χ(2) random variable, we compute a bias-corrected SNR estimate appropriate for single-neuron analysis and use the bootstrap to assess its uncertainty. In the analyses of four systems neuroscience experiments, we show that the SNRs are -10 dB to -3 dB for guinea pig auditory cortex neurons, -18 dB to -7 dB for rat thalamic neurons, -28 dB to -14 dB for monkey hippocampal neurons, and -29 dB to -20 dB for human subthalamic neurons. The new SNR definition makes explicit in the measure commonly used for physical systems the often-quoted observation that single neurons have low SNRs. The neuron's spiking history is frequently a more informative covariate for predicting spiking propensity than the applied stimulus. Our new SNR definition extends to any GLM system in which the factors modulating the response can be expressed as separate components of a likelihood function.

Context-dependent incremental timing cells in the primate hippocampus.

We examined timing-related signals in primate hippocampal cells as animals performed an object-place (OP) associative learning task. We found hippocampal cells with firing rates that incrementally increased or decreased across the memory delay interval of the task, which we refer to as incremental timing cells (ITCs). Three distinct categories of ITCs were identified. Agnostic ITCs did not distinguish between different trial types. The remaining two categories of cells signaled time and trial context together: One category of cells tracked time depending on the behavioral action required for a correct response (i.e., early vs. late release), whereas the other category of cells tracked time only for those trials cued with a specific OP combination. The context-sensitive ITCs were observed more often during sessions where behavioral learning was observed and exhibited reduced incremental firing on incorrect trials. Thus, single primate hippocampal cells signal information about trial timing, which can be linked with trial type/context in a learning-dependent manner.

The perirhinal cortex.

Anatomically, the perirhinal cortex sits at the boundary between the medial temporal lobe and the ventral visual pathway. It has prominent interconnections not only with both these systems, but also with a wide range of unimodal and polymodal association areas. Consistent with these diverse projections, neurophysiological studies reveal a multidimensional set of mnemonic signals that include stimulus familiarity, within- and between-domain associations, associative recall, and delay-based persistence. This wide range of perirhinal memory signals not only includes signals that are largely unique to the perirhinal cortex (i.e., object familiarity), consistent with dual-process theories, but also includes a range of signals (i.e., associative flexibility and recall) that are strongly associated with the hippocampus, consistent with single-process theories. These neurophysiological findings have important implications for bridging the gap between single-process and dual-process models of medial temporal lobe function.

Conserved fMRI and LFP signals during new associative learning in the human and macaque monkey medial temporal lobe.

We measured local field potential (LFP) and blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in the medial temporal lobes of monkeys and humans, respectively, as they performed the same conditional motor associative learning task. Parallel analyses were used to examine both data sets. Despite significantly faster learning in humans relative to monkeys, we found equivalent neural signals differentiating new versus highly familiar stimuli, first stimulus presentation, trial outcome, and learning strength in the entorhinal cortex and hippocampus of both species. Thus, the use of parallel behavioral tasks and analyses in monkeys and humans revealed conserved patterns of neural activity across the medial temporal lobe during an associative learning task.

Integrating what and when across the primate medial temporal lobe.

Episodic memory or memory for the detailed events in our lives is critically dependent on structures of the medial temporal lobe (MTL). A fundamental component of episodic memory is memory for the temporal order of items within an episode. To understand the contribution of individual MTL structures to temporal-order memory, we recorded single-unit activity and local field potential from three MTL areas (hippocampus and entorhinal and perirhinal cortex) and visual area TE as monkeys performed a temporal-order memory task. Hippocampus provided incremental timing signals from one item presentation to the next, whereas perirhinal cortex signaled the conjunction of items and their relative temporal order. Thus, perirhinal cortex appeared to integrate timing information from hippocampus with item information from visual sensory area TE.

Rhesus monkeys (Macaca mulatta) rapidly learn to select dominant individuals in videos of artificial social interactions between unfamiliar conspecifics.

Social animals, such as primates, must behave appropriately in complex social situations such as dominance interactions. Learning dominance information through trial and error would be dangerous; therefore, cognitive mechanisms for rapid learning of dominance information by observation would be adaptive. We used a set of digitally edited artificial social interactions to examine whether rhesus monkeys (Macaca mulatta) can learn dominance relationships between unfamiliar conspecifics through observation. Our method allowed random assignment of stimulus monkeys to ranks in an artificial hierarchy, controlling for nonbehavioral cues that could indicate dominance. Subject monkeys watched videos depicting 1 stimulus monkey behaving dominantly toward another and were rewarded for selecting the dominant individual. Monkeys rapidly learned this discrimination across 5 behavior types in Experiment 1 and transferred performance to novel videos of new individuals in Experiment 2. In addition, subjects selected the dominant individual more often than expected by chance in probe videos containing no behavioral dominance information, indicating some retention of the relative dominance status of stimulus monkeys from training. Together, our results suggest that monkeys can learn dominance hierarchies through observation of third-party social interactions.

Untangling memory from perception in the medial temporal lobe.

An active debate in the learning and memory literature centers on the question of whether the perirhinal cortex, part of the medial temporal lobe (MTL), plays its major role in declarative/relational learning and memory or if it also makes an important contribution to high- level perception, similar to the functions of the adjacent visual area TE. Here I consider evidence from neuroanatomical and neurophysiological studies and argue that the perirhinal cortex has distinct and dissociable structure and function from area TE, making its major contribution to declarative/relational learning and memory. I propose additional neurophysiological studies that could help differentiate between these two debated roles of the perirhinal cortex: memory alone or memory plus high- level perception.