Integrating Visual Information into the Auditory Cortex Promotes Sound Discrimination through Choice-Related Multisensory Integration.

An increasing number of studies have shown that cross-modal interaction can occur in early sensory cortices. Yet, how neurons in sensory cortices integrate multisensory cues in perceptual tasks and to what extent this influences behavior is largely unclear. To investigate, we examined visual modulation of auditory responses in the primary auditory cortex (A1) in a two-alternative forced-choice task. During the task, male rats were required to make a behavioral choice based on the pure tone frequency (low vs high) of the self-triggered stimulus to get a water reward. The result showed that the presence of a noninformative visual cue did not uniformly influence auditory response, with frequently enhancing just one of them. Closely correlated with behavioral choice, the visual cue mainly enhanced responsiveness to the auditory cue indicating a movement direction contralateral to A1 being recorded. Operating in this fashion provided A1 neurons a superior capability to discriminate sound during multisensory trials. Concomitantly, behavioral data and decoding analysis revealed that visual cue presence could speed the process of sound discrimination. We also observed this differential multisensory integration effect in well-trained rats when tested with passive stimulation and under anesthesia, albeit to a much lesser extent. We did not see this differentially integrative effect while recording in A1 in another similar group of rats performing a free-choice task. These data suggest that auditory cortex can engage in meaningful audiovisual processing, and perceptual learning can modify its multisensory integration mechanism to meet task requirements.SIGNIFICANCE STATEMENT In the natural environment, visual stimuli are frequently accompanied by auditory cues. Although multisensory integration has traditionally been seen as a feature of associational cortices, recent studies have shown that cross-modal inputs can also influence neuronal activity in primary sensory cortices. However, exactly how neurons in sensory cortices integrate multisensory cues to guide behavioral choice is still unclear. Here, we describe a novel model of multisensory integration used by A1 neurons to shape auditory representations when rats performed a cue-guided task. We found that a task-irrelevant visual cue could specifically enhance the response of neurons in sound guiding to the contralateral choice. This differentially integrative model facilitated sound discrimination and behavioral choice. This result indicates that task engagement can modulate multisensory integration.

Temporal Alterations to Central Auditory Processing without Synaptopathy after Lifetime Exposure to Environmental Noise.

People are increasingly exposed to environmental noise through the cumulation of occupational and recreational activities, which is considered harmless to the auditory system, if the sound intensity remains <80 dB. However, recent evidence of noise-induced peripheral synaptic damage and central reorganizations in the auditory cortex, despite normal audiometry results, has cast doubt on the innocuousness of lifetime exposure to environmental noise. We addressed this issue by exposing adult rats to realistic and nontraumatic environmental noise, within the daily permissible noise exposure limit for humans (80 dB sound pressure level, 8 h/day) for between 3 and 18 months. We found that temporary hearing loss could be detected after 6 months of daily exposure, without leading to permanent hearing loss or to missing synaptic ribbons in cochlear hair cells. The degraded temporal representation of sounds in the auditory cortex after 18 months of exposure was very different from the effects observed after only 3 months of exposure, suggesting that modifications to the neural code continue throughout a lifetime of exposure to noise.

Reliability of the empathy selection task, a novel behavioral measure of empathy avoidance.

The empathy selection task is a novel behavioral paradigm designed to assess an individual's willingness to engage in empathy. Work with this task has demonstrated that people prefer to avoid empathy when some other activity is available, though individual differences that might predict performance on this task have been largely unexamined. Here, we assess the suitability of the empathy selection task for use in individual difference and experimental research by examining its reliability within and across testing sessions. We compare the reliability of summary scores on the empathy selection task (i.e., proportion of empathy choices) as an individual difference metric to that of two commonly used experimental tasks, the Stroop error rate and go/no-go commission rate. Next, we assess systematic changes at the item/trial level using generalized multilevel modeling which considers participants' individual performance variation. Across two samples (N = 89), we find that the empathy selection task is stable between testing sessions and has good/substantial test-retest reliability (ICCs = .65 and .67), suggesting that it is comparable or superior to other commonly used experimental tasks with respect to its ability to consistently rank individuals.

Behavioral paradigms for studying pro-environmental behavior: A systematic review.

In view of global environmental deterioration and climate change, researchers from multiple fields of the behavioral sciences examine the determinants of pro-environmental behavior. Research on pro-environmental behavior is dominated by the use of self-report measures, which relates to critical validity problems. Some of these problems can be addressed by studying consequential behavior in behavioral paradigms (i.e., systematically arranged situations of actual environmental relevance). However, pro-environmental behavior paradigms have been scattered across disciplines, and many researchers may not be aware of the wealth of available paradigms. The present review aims to acquaint researchers across disciplinary borders with the behavioral paradigms developed to study pro-environmental behavior in different domains. A systematic literature search revealed 99 ad hoc paradigms and five validated paradigms of pro-environmental behavior. I review how different authors have succeeded in implementing the consequences of pro-environmental behavior in standardized field, laboratory, or online situations, point to caveats in the use of behavioral paradigms, and illustrate how researchers can select a paradigm for their own research.

Are all pain tolerance tasks the same? Convergent validity of four behavioral pain tolerance tasks, self-reported capability for suicide, and lifetime self-injurious behaviors.

OBJECTIVES: Discrepancies persist regarding the extent to which different pain measures provide similar information and relate to capability for suicide and self-injurious behaviors. This study examined pain threshold, tolerance, and persistence across four modalities (cold, heat, pressure, shock) and assessed associations with self-reported capability for suicide, non-suicidal self-injury (NSSI), and suicide attempts. METHODS: A sample of 211 students who reported lifetime suicidal ideation completed four behavioral pain tasks and self-reported on capability for suicide, NSSI, and self-injurious behaviors. RESULTS: All pain thresholds, tolerances, and persistences were positively correlated across the four tasks. Pain facets were related to self-reported capability for suicide with small effect sizes but generally did not differ across suicide attempt or NSSI histories. CONCLUSIONS: Pain thresholds, tolerances, and persistences demonstrated convergent validity across the four modalities, suggesting that these tasks provide similar information. Although the relation between pain and self-injurious behaviors remains unclear, these tasks can generally be used interchangeably.

A spike analysis method for characterizing neurons based on phase locking and scaling to the interval between two behavioral events.

Standard analysis of neuronal functions assesses the temporal correlation between animal behaviors and neuronal activity by aligning spike trains with the timing of a specific behavioral event, e.g., visual cue. However, spike activity is often involved in information processing dependent on a relative phase between two consecutive events rather than a single event. Nevertheless, less attention has so far been paid to such temporal features of spike activity in relation to two behavioral events. Here, we propose "Phase-Scaling analysis" to simultaneously evaluate the phase locking and scaling to the interval between two events in task-related spike activity of individual neurons. This analysis method can discriminate conceptual "scaled"-type neurons from "nonscaled"-type neurons using an activity variation map that combines phase locking with scaling to the interval. Its robustness was validated by spike simulation using different spike properties. Furthermore, we applied it to analyzing actual spike data from task-related neurons in the primary visual cortex (V1), posterior parietal cortex (PPC), primary motor cortex (M1), and secondary motor cortex (M2) of behaving rats. After hierarchical clustering of all neurons using their activity variation maps, we divided them objectively into four clusters corresponding to nonscaled-type sensory and motor neurons and scaled-type neurons including sustained and ramping activities, etc. Cluster/subcluster compositions for V1 differed from those of PPC, M1, and M2. The V1 neurons showed the fastest functional activities among those areas. Our method was also applicable to determine temporal "forms" and the latency of spike activity changes. These findings demonstrate its utility for characterizing neurons.NEW & NOTEWORTHY Phase-Scaling analysis is a novel technique to unbiasedly characterize the temporal dependency of functional neuron activity on two behavioral events and objectively determine the latency and form of the activity change. This powerful analysis can uncover several classes of latently functioning neurons that have thus far been overlooked, which may participate differently in intermediate processes of a brain function. The Phase-Scaling analysis will yield profound insights into neural mechanisms for processing internal information.

The development of a cognitive rehabilitation task for mice.

Obesity, neurodegenerative diseases, and injury can all lead to cognitive deficits, which can be improved clinically with the implementation of cognitive rehabilitation. Due to a lack of effective cognitive rehabilitation tools in mice, we re-designed a cognitive task utilized to detect problem-solving deficits, to develop a cognitive rehabilitation paradigm for mice. In this study, we developed a modified the Puzzle Box task by exposing B6 mice to a variety of obstacles and assessing the escape latencies. We then combined obstacles in order to create a "complex obstacle" for the problem-solving task. We determined that our task was reproducible in different cohorts of mice. Furthermore, with repetition the mice display an improvement in the performance, evident by a shorter escape latency and the ability to maintain this improvement in performance, indicative of long-term memory. Given that this approach is new, we validated whether this task could successfully detect deficits in a mouse model of cognitive impairment, the high-fat diet mouse. We demonstrate that high-fat diet mice have longer escape latencies when exposed to the complex obstacle compared to standard diet control mice. Taken together, these data suggest that the Puzzle Box is a valid task for cognitive rehabilitation in mice.

The globus pallidus pars interna in goal-oriented and routine behaviors: Resolving a long-standing paradox.

BACKGROUND: There is an apparent contradiction between experimental data showing that the basal ganglia are involved in goal-oriented and routine behaviors and clinical observations. Lesion or disruption by deep brain stimulation of the globus pallidus interna has been used for various therapeutic purposes ranging from the improvement of dystonia to the treatment of Tourette's syndrome. None of these approaches has reported any severe impairment in goal-oriented or automatic movement. METHOD: To solve this conundrum, we trained 2 monkeys to perform a variant of a 2-armed bandit-task (with different reward contingencies). In the latter we alternated blocks of trials with choices between familiar rewarded targets that elicit routine behavior and blocks with novel pairs of targets that require an intentional learning process. RESULTS: Bilateral inactivation of the globus pallidus interna, by injection of muscimol, prevents animals from learning new contingencies while performance remains intact, although slower for the familiar stimuli. We replicate in silico these data by adding lateral competition and Hebbian learning in the cortical layer of the theoretical model of the cortex-basal ganglia loop that provided the framework of our experimental approach. CONCLUSION: The basal ganglia play a critical role in the deliberative process that underlies learning but are not necessary for the expression of routine movements. Our approach predicts that after pallidotomy or during stimulation, patients should have difficulty with complex decision-making processes or learning new goal-oriented behaviors. © 2016 Movement Disorder Society.

Contribution of the subthalamic nucleus to motor, cognitive and limbic processes: an electrophysiological and stimulation study in monkeys.

Deep brain stimulation of the subthalamic nucleus (STN) has become the gold standard surgical treatment for Parkinson's disease and is being investigated for obsessive compulsive disorders. Even if the role of the STN in the behavior is well documented, its organization and especially its division into several functional territories is still debated. A better characterization of these territories and a better knowledge of the impact of stimulation would address this issue. We aimed to find specific electrophysiological markers of motor, cognitive and limbic functions within the STN and to specifically modulate these components. Two healthy non-human primates (Macaca fascicularis) performed a behavioral task allowing the assessment of motor, cognitive and limbic reward-related behavioral components. During the task, four contacts in the STN allowed recordings and stimulations, using low frequency stimulation (LFS) and high frequency stimulation (HFS). Specific electrophysiological functional markers were found in the STN with beta band activity for the motor component of behavior, theta band activity for the cognitive component, and, gamma and theta activity bands for the limbic component. For both monkeys, dorsolateral HFS and LFS of the STN significantly modulated motor performances, whereas only ventromedial HFS modulated cognitive performances. Our results validated the functional overlap of dorsal motor and ventral cognitive subthalamic territories, and, provide information that tends toward a diffuse limbic territory sensitive to the reward within the STN.

Activation of primate frontal eye fields with a CMUT phased array system.

BACKGROUND: There are pushes toward non-invasive stimulation of neural tissues to prevent issues that arise from invasive brain recordings and stimulation. Transcranial Focused Ultrasound (TFUS) has been examined as a way to stimulate non-invasively, but previous studies have limitations in the application of TFUS. As a result, refinement is needed to improve stimulation results. NEW METHOD: We utilized a custom-built capacitive micromachined ultrasonic transducer (CMUT) that would send ultrasonic waves through skin and skull to targets located in the Frontal Eye Fields (FEF) region triangulated from co-registered MRI and CT scans while a non-human primate subject was performing a discrimination behavioral task. RESULTS: We observed that the stimulation immediately caused changes in the local field potential (LFP) signal that continued until stimulation ended, at which point there was higher voltage upon the cue for the animal to saccade. This co-incided with increases in activity in the alpha band during stimulation. The activity rebounded mid-way through our electrode-shank, indicating a specific point of stimulation along the shank. We observed different LFP signals for different stimulation targets, indicating the ability to"steer" the stimulation through the transducer. We also observed a bias in first saccades towards the opposite direction. CONCLUSIONS: In conclusion, we provide a new approach for non-invasive stimulation during performance of a behavioral task. With the ability to steer stimulation patterns and target using a large amount of transducers, the ability to provide non-invasive stimulation will be greatly improved for future clinical and research applications.

A robot-rodent interaction arena with adjustable spatial complexity for ethologically relevant behavioral studies.

Outside of the laboratory, animals behave in spaces where they can transition between open areas and coverage as they interact with others. Replicating these conditions in the laboratory can be difficult to control and record. This has led to a dominance of relatively simple, static behavioral paradigms that reduce the ethological relevance of behaviors and may alter the engagement of cognitive processes such as planning and decision-making. Therefore, we developed a method for controllable, repeatable interactions with others in a reconfigurable space. Mice navigate a large honeycomb lattice of adjustable obstacles as they interact with an autonomous robot coupled to their actions. We illustrate the system using the robot as a pseudo-predator, delivering airpuffs to the mice. The combination of obstacles and a mobile threat elicits a diverse set of behaviors, such as increased path diversity, peeking, and baiting, providing a method to explore ethologically relevant behaviors in the laboratory.

Developing and Validating a Facial Emotion Recognition Task With Graded Intensity.

Facial emotion recognition (FER) tasks are often digitally altered to vary expression intensity; however, such tasks have unknown psychometric properties. In these studies, an FER task was developed and validated-the Graded Emotional Face Task (GEFT)-which provided an opportunity to examine the psychometric properties of such tasks. Facial expressions were altered to produce five intensity levels for six emotions (e.g., 40% anger). In Study 1, 224 undergraduates viewed subsets of these faces and labeled the expressions. An item selection algorithm was used to maximize internal consistency and balance gender and ethnicity. In Study 2, 219 undergraduates completed the final GEFT and a multimethod battery of validity measures. Finally, in Study 3, 407 undergraduates oversampled for borderline personality disorder (BPD) completed the GEFT and a self-report BPD measure. Broad FER scales (e.g., overall anger) demonstrated evidence of reliability and validity; however, more specific subscales (e.g., 40% anger) had more variable psychometric properties. Notably, ceiling/floor effects appeared to decrease both internal consistency and limit external validity correlations. The findings are discussed from the perspective of measurement issues in the social cognition literature.

Developmental Manipulation-Induced Changes in Cognitive Functioning.

Schizophrenia is a complex neurodevelopmental disorder with as-yet no identified cause. The use of animals has been critical to teasing apart the potential individual and intersecting roles of genetic and environmental risk factors in the development of schizophrenia. One way to recreate in animals the cognitive impairments seen in people with schizophrenia is to disrupt the prenatal or neonatal environment of laboratory rodent offspring. This approach can result in congruent perturbations in brain physiology, learning, memory, attention, and sensorimotor domains. Experimental designs utilizing such animal models have led to a greatly improved understanding of the biological mechanisms that could underlie the etiology and symptomology of schizophrenia, although there is still more to be discovered. The implementation of the Research and Domain Criterion (RDoC) has been critical in taking a more comprehensive approach to determining neural mechanisms underlying abnormal behavior in people with schizophrenia through its transdiagnostic approach toward targeting mechanisms rather than focusing on symptoms. Here, we describe several neurodevelopmental animal models of schizophrenia using an RDoC perspective approach. The implementation of animal models, combined with an RDoC framework, will bolster schizophrenia research leading to more targeted and likely effective therapeutic interventions resulting in better patient outcomes.

Eating disorder symptoms and control-seeking behavior.

OBJECTIVE: Eating disorders (EDs) are a heterogenous group of disorders characterized by disturbed eating patterns. Links have been made between ED symptoms and control-seeking behaviors, which may cause relief from distress. However, whether direct behavioral measures of control-seeking behavior correlate with ED symptoms has not been directly tested. Additionally, existing paradigms may conflate control-seeking behavior with uncertainty-reducing behavior. METHOD: A general population sample of 183 participants completed part in an online behavioral task, in which participants rolled a die in order to obtain/avoid a set of numbers. Prior to each roll, participants could choose to change arbitrary features of the task (such as the color of their die) or view additional information (such as the current trial number). Selecting these Control Options could cost participants points or not (Cost/No-Cost conditions). Each participant completed all four conditions, each with 15 trials, followed by a series of questionnaires, including the Eating Attitudes Test-26 (EAT-26), the Intolerance of Uncertainty Scale, and the Obsessive-Compulsive Inventory-Revised (OCI-R). RESULTS: A Spearman's rank test indicated no significant correlation between total EAT-26 score and total number of Control Options selected, with only elevated scores on a measure of obsessions and compulsivity (OCI-R) correlating with the total number of Control Options selected (rs  = .155, p = .036). DISCUSSION: In our novel paradigm, we find no relationship between EAT-26 score and control-seeking. However, we do find some evidence that this behavior may be present in other disorders that often coincide with ED diagnosis, which may indicate that transdiagnostic factors such as compulsivity are important to control-seeking.

Object recognition tasks in rats: Does sex matter?

Novelty recognition tasks based on object exploration are frequently used for the evaluation of cognitive abilities and investigation of neurobiological and molecular aspects of memory in rodents. This is an interesting approach because variations of the object recognition tasks focus on different aspects of the memory events such as novelty, location, context, and combinations of these elements. Nevertheless, as in most animal neuroscience research, female subjects are underrepresented in object recognition studies. When studies include females, the particularities of this sex are not always considered. For example, appropriate controls for manipulations conducted exclusively in females (such as estrous cycle verification) are not included. In addition, interpretation of data is often based on standardizations conducted with male subjects. Despite that, females are frequently reported as deficient and unable to adequately perform some memory tests. Thus, our study aims to review studies that describe similarities and differences between male and female performances in the different variations of object recognition tasks. In summary, although females are commonly described with deficits and the articles emphasize sex differences, most published data reveal similar performances when sexes are compared.

Application of Real and Virtual Radial Arm Maze Task in Human.

Virtual Reality (VR) emerges as a promising technology capable of creating different scenarios in which the body, environment, and brain are closely related, proving enhancements in the diagnosis and treatment of several spatial memory deficits. In recent years, human spatial navigation has increasingly been studied in interactive virtual environments. However, navigational tasks are still not completely adapted in immersive 3D VR systems. We stipulate that an immersive Radial Arm Maze (RAM) is an excellent instrument, allowing the participants to be physically active within the maze exactly as in the walking RAM version in reality modality. RAM is a behavioral ecological task that allows the analyses of different facets of spatial memory, distinguishing declarative components from procedural ones. In addition to describing the characteristics of RAM, we will also analyze studies in which RAM has been used in virtual modality to provide suggestions into RAM building in immersive modality.

Assessment of motion and model bias on the detection of dopamine response to behavioral challenge.

Compartmental modeling analysis of 11C-raclopride (RAC) PET data can be used to measure the dopaminergic response to intra-scan behavioral tasks. Bias in estimates of binding potential (BPND) and its dynamic changes (ΔBPND) can arise both when head motion is present and when the compartmental model used for parameter estimation deviates from the underlying biology. The purpose of this study was to characterize the effects of motion and model bias within the context of a behavioral task challenge, examining the impacts of different mitigation strategies. Seventy healthy adults were administered bolus plus constant infusion RAC during a simultaneous PET/magnetic resonance (MR) scan with a reward task experiment. BPND and ΔBPND were estimated using an extension of the Multilinear Reference Tissue Model (E-MRTM2) and a new method (DE-MRTM2) was proposed to selectively discount the contribution of the initial uptake period. Motion was effectively corrected with a standard frame-based approach, which performed equivalently to a more complex reconstruction-based approach. DE-MRTM2 produced estimates of ΔBPND in putamen and nucleus accumbens that were significantly different from those estimated from E-MRTM2, while also decoupling ΔBPND values from first-pass k2' estimation and removing skew in the spatial bias distribution of parametric ΔBPND estimates within the striatum.

Research advances on how metformin improves memory impairment in "chemobrain".

Cognitive impairment caused by chemotherapy, referred to as "chemobrain," is observed in approximately 70% of cancer survivors. However, it is not completely understood how chemotherapy induces cognitive dysfunction, and clinical treatment strategies for this problem are lacking. Metformin, used as a first-line treatment for type 2 diabetes mellitus, is reported to reduce the effects of chemobrain. Recently, several studies have examined the effect of metformin in rescuing chemobrain. This review discusses recent clinical/preclinical studies that addressed some mechanisms of chemobrain and evaluates the effect of metformin in rescuing chemobrain and its potential mechanisms of action.

Sustained MK-801 induced deficit in a novel probabilistic reversal learning task.

Cognitive flexibility, the ability to adapt to unexpected changes, is critical for healthy environmental and social interactions, and thus to everyday functioning. In neuropsychiatric diseases, cognitive flexibility is often impaired and treatment options are lacking. Probabilistic reversal learning (PRL) is commonly used to measure cognitive flexibility in rodents and humans. In PRL tasks, subjects must sample choice options and, from probabilistic feedback, find the current best choice which then changes without warning. However, in rodents, pharmacological models of human cognitive impairment tend to disrupt only the first (or few) of several contingency reversals, making quantitative assessment of behavioral effects difficult. To address this limitation, we developed a novel rat PRL where reversals occur at relatively long intervals in time that demonstrates increased sensitivity to the non-competitive NMDA receptor antagonist MK-801. Here, we quantitively compare behavior in time-based PRL with a widely used task where reversals occur based on choice behavior. In time-based PRL, MK-801 induced sustained reversal learning deficits both in time and across reversal blocks but, at the same dose, only transient weak effects in performance-based PRL. Moreover, time-based PRL yielded better estimates of behavior and reinforcement learning model parameters, which opens meaningful pharmacological windows to efficiently test and develop novel drugs preclinically with the goal of improving cognitive impairment in human patients.

Behavioral Tasks Evaluating Schizophrenia-like Symptoms in Animal Models: A Recent Update.

BACKGROUND: Schizophrenia is a serious mental illness that affects more than 21 million people worldwide. Both genetics and the environment play a role in its etiology and pathogenesis. Symptoms of schizophrenia are mainly categorized into positive, negative, and cognitive. One major approach to identify and understand these diverse symptoms in humans has been to study behavioral phenotypes in a range of animal models of schizophrenia. OBJECTIVE: We aimed to provide a comprehensive review of the behavioral tasks commonly used for measuring schizophrenia-like behaviors in rodents together with an update of the recent study findings. METHODS: Articles describing phenotypes of schizophrenia-like behaviors in various animal models were collected through a literature search in Google Scholar, PubMed, Web of Science, and Scopus, with a focus on advances over the last 10 years. RESULTS: Numerous studies have used a range of animal models and behavioral paradigms of schizophrenia to develop antipsychotic drugs for improved therapeutics. In establishing animal models of schizophrenia, the candidate models were evaluated for schizophrenia-like behaviors using several behavioral tasks for positive, negative, and cognitive symptoms designed to verify human symptoms of schizophrenia. Such validated animal models were provided as rapid preclinical avenues for drug testing and mechanistic studies. CONCLUSION: Based on the most recent advances in the field, it is apparent that a myriad of behavior tests are needed to confirm and evaluate the congruency of animal models with the numerous behaviors and clinical signs exhibited by patients with schizophrenia.