Behavioral Relevance Research Articles

Large-scale coupling of prefrontal activity patterns as a mechanism for cognitive control in health and disease: evidence from rodent models.

Cognitive control of behavior is crucial for well-being, as allows subject to adapt to changing environments in a goal-directed way. Changes in cognitive control of behavior is observed during cognitive decline in elderly and in pathological mental conditions. Therefore, the recovery of cognitive control may provide a reliable preventive and therapeutic strategy. However, its neural basis is not completely understood. Cognitive control is supported by the prefrontal cortex, structure that integrates relevant information for the appropriate organization of behavior. At neurophysiological level, it is suggested that cognitive control is supported by local and large-scale synchronization of oscillatory activity patterns and neural spiking activity between the prefrontal cortex and distributed neural networks. In this review, we focus mainly on rodent models approaching the neuronal origin of these prefrontal patterns, and the cognitive and behavioral relevance of its coordination with distributed brain systems. We also examine the relationship between cognitive control and neural activity patterns in the prefrontal cortex, and its role in normal cognitive decline and pathological mental conditions. Finally, based on these body of evidence, we propose a common mechanism that may underlie the impaired cognitive control of behavior.

Tactile processing in mouse cortex depends on action context

The brain receives constant tactile input, but only a subset guides ongoing behavior. Actions associated with tactile stimuli thus endow them with behavioral relevance. It remains unclear how the relevance of tactile stimuli affects processing in the somatosensory (S1) cortex. We developed a cross-modal selection task in which head-fixed mice switched between responding to tactile stimuli in the presence of visual distractors or to visual stimuli in the presence of tactile distractors using licking movements to the left or right side in different blocks of trials. S1 spiking encoded tactile stimuli, licking actions, and direction of licking in response to tactile but not visual stimuli. Bidirectional optogenetic manipulations showed that sensory-motor activity in S1 guided behavior when touch but not vision was relevant. Our results show that S1 activity and its impact on behavior depend on the actions associated with a tactile stimulus.

Mouse hippocampal CA1 VIP interneurons detect novelty in the environment and support recognition memory

In the CA1 hippocampus, vasoactive intestinal polypeptide-expressing interneurons (VIP-INs) play a prominent role in disinhibitory circuit motifs. However, the specific behavioral conditions that lead to circuit disinhibition remain uncertain. To investigate the behavioral relevance of VIP-IN activity, we employed wireless technologies allowing us to monitor and manipulate their function in freely behaving mice. Our findings reveal that, during spatial exploration in new environments, VIP-INs in the CA1 hippocampal region become highly active, facilitating the rapid encoding of novel spatial information. Remarkably, both VIP-INs and pyramidal neurons (PNs) exhibit increased activity when encountering novel changes in the environment, including context- and object-related alterations. Concurrently, somatostatin- and parvalbumin-expressing inhibitory populations show an inverse relationship with VIP-IN and PN activity, revealing circuit disinhibition that occurs on a timescale of seconds. Thus, VIP-IN-mediated disinhibition may constitute a crucial element in the rapid encoding of novelty and the acquisition of recognition memory.

Learner engagement with instructor‐generated video

AbstractEffective video resources are assumed to promote learner engagement, but the extent to which this occurs is unclear. This study examines learners' engagement with instructor‐generated video. It contributes an analytical synthesis of qualitative and quantitative data that provides the basis for investigating the extent to which, and how, learners engage with video resources provided in their courses. Specifically, three dimensions of learner engagement with video are studied: behavioural, cognitive and affective. The study contributes to educational technology research by identifying distinctive patterns of learner control over the use of video which diverges from instructors' assumptions. It shows the complex and nuanced features of cognitive and affective engagement. Videos can have positive effects, but inappropriate use of technical features results in learner disengagement. This study contributes a novel use of signalling theory, suggesting the importance of instructor signals concerning relevance, focus and utility as a feature of video generation, as a prerequisite of cognitive engagement. A research and theory development agenda is developed, locating video‐based learning in student contexts as a basis for explaining both engagement and disengagement with video technology affordances. Practitioner notesWhat is already known about this topic Higher education tutors are increasingly expected to generate video content as a feature of their course delivery. Although effective video resources are assumed to promote learner engagement, the extent to which this occurs is unclear. Video technology affordances rarely feature in academic professional development programmes leaving tutors ill‐equipped to understand how and in what ways students engage with video resources as a part of their courses. What this paper adds A novel use of signalling theory to explain different patterns of learner engagement and disengagement. Learner agency and control results in video technology affordances being fitted and ‘flexed’ around factors that instructors rarely consider in the video generation process. A new model to describe factors that affect student engagement with instructor‐generated video. Implications for practice and/or policy Raise awareness for instructors about patterns of student engagement with video technology affordances that affect learning experience and outcomes. Implement professional development programmes to equip instructors to design and generate video content that takes account of patterns of behavioural, cognitive and affective engagement and signals relevance, focus and utility. Develop clear policies regarding technical features of video generation to avoid learner disengagement.

When temporal attention interacts with expectation

Temporal attention is voluntarily deployed at specific moments, whereas temporal expectation is deployed according to timing probabilities. When the target appears at an expected moment in a sequence, temporal attention improves performance at the attended moments, but the timing and the precision of the attentional window remain unknown. Here we independently and concurrently manipulated temporal attention–via behavioral relevance–and temporal expectation–via session-wise precision and trial-wise hazard rate–to investigate whether and how these mechanisms interact to improve perception. Our results reveal that temporal attention interacts with temporal expectation–the higher the precision, the stronger the attention benefit, but surprisingly this benefit decreased with delayed onset despite the increasing probability of stimulus appearance. When attention was suboptimally deployed to earlier than expected moments, it could not be reoriented to a later time point. These findings provide evidence that temporal attention and temporal expectation are different mechanisms, and highlight their interplay in optimizing visual performance.

Neural Correlates of Early-Life Urbanization and Their Spatial Relationships with Gene Expression, Neurotransmitter, and Behavioral Domain Atlases.

Previous neuroimaging research has established associations between urban exposure during early life and alterations in brain function and structure. However, the molecular mechanisms and behavioral relevance of these associations remain largely unknown. Here, we aimed to address this question using a combined analysis of multimodal data. Initially, we calculated amplitude of low-frequency fluctuations (ALFF) and gray matter volume (GMV) using resting-state functional and structural MRI to investigate their associations with early-life urbanization in a large sample of 511 healthy young adults. Then, we examined the spatial relationships of the identified neural correlates of early-life urbanization with gene expression, neurotransmitter, and behavioral domain atlases. Results showed that higher early-life urbanization scores were correlated with increased ALFF of the right fusiform gyrus and decreased GMV of the left dorsal medial prefrontal cortex and left precuneus. Remarkably, the identified neural correlates of early-life urbanization were spatially correlated with expression of gene categories primarily involving immune system process, signal transduction, and cellular metabolic process. Concurrently, there were significant associations between the neural correlates and specific neurotransmitter systems including dopamine, acetylcholine, and serotonin. Finally, we found that the ALFF correlates were associated with behavioral terms including "perception," "sensory," "cognitive control," and "reasoning." Apart from expanding existing knowledge of early-life urban environmental risk for mental disorders and health in general, our findings may contribute to an emerging framework for integrating social science, neuroscience, genetics, and public policy to respond to the major health challenge of world urbanization.

Involvement of superior colliculus in complex figure detection of mice.

Object detection is an essential function of the visual system. Although the visual cortex plays an important role in object detection, the superior colliculus can support detection when the visual cortex is ablated or silenced. Moreover, it has been shown that superficial layers of mouse SC (sSC) encode visual features of complex objects, and that this code is not inherited from the primary visual cortex. This suggests that mouse sSC may provide a significant contribution to complex object vision. Here, we use optogenetics to show that mouse sSC is involved in figure detection based on differences in figure contrast, orientation, and phase. Additionally, our neural recordings show that in mouse sSC, image elements that belong to a figure elicit stronger activity than those same elements when they are part of the background. The discriminability of this neural code is higher for correct trials than for incorrect trials. Our results provide new insight into the behavioral relevance of the visual processing that takes place in sSC.

Deviance Detection to Natural Stimuli in Population Responses of the Brainstem of Bats.

Deviance detection describes an increase of neural response strength caused by a stimulus with a low probability of occurrence. This ubiquitous phenomenon has been reported for humans and multiple other species, from subthalamic areas to the auditory cortex. Cortical deviance detection has been well characterized by a range of studies using a variety of different stimuli, from artificial to natural, with and without a behavioral relevance. This allowed the identification of a broad variety of regularity deviations that are detected by the cortex. Moreover, subcortical deviance detection has been studied with simple stimuli that are not meaningful to the subject. Here, we aim to bridge this gap by using noninvasively recorded auditory brainstem responses (ABRs) to investigate deviance detection at population level in the lower stations of the auditory system of a highly vocal species: the bat Carollia perspicillata (of either sex). Our present approach uses behaviorally relevant vocalization stimuli that are similar to the animals' natural soundscape. We show that deviance detection in ABRs is significantly stronger for echolocation pulses than for social communication calls or artificial sounds, indicating that subthalamic deviance detection depends on the behavioral meaning of a stimulus. Additionally, complex physical sound features like frequency- and amplitude modulation affected the strength of deviance detection in the ABR. In summary, our results suggest that the brain can detect different types of deviants already in the brainstem, showing that subthalamic brain structures exhibit more advanced forms of deviance detection than previously known.

Dissociation of Reliability, Heritability, and Predictivity inCoarse- and Fine-Scale Functional Connectomes duringDevelopment.

The functional connectome supports information transmission through the brain at various spatial scales, from exchange between broad cortical regions to finer-scale, vertex-wise connections that underlie specific information processing mechanisms. In adults, while both the coarse- and fine-scale functional connectomes predict cognition, the fine scale can predict up to twice the variance as the coarse-scale functional connectome. Yet, past brain-wide association studies, particularly using large developmental samples, focus on the coarse connectome to understand the neural underpinnings of individual differences in cognition. Using a large cohort of children (age 9-10 years; n = 1,115 individuals; both sexes; 50% female, including 170 monozygotic and 219 dizygotic twin pairs and 337 unrelated individuals), we examine the reliability, heritability, and behavioral relevance of resting-state functional connectivity computed at different spatial scales. We use connectivity hyperalignment to improve access to reliable fine-scale (vertex-wise) connectivity information and compare the fine-scale connectome with the traditional parcel-wise (coarse scale) functional connectomes. Though individual differences in the fine-scale connectome are more reliable than those in the coarse-scale, they are less heritable. Further, the alignment and scale of connectomes influence their ability to predict behavior, whereby some cognitive traits are equally well predicted by both connectome scales, but other, less heritable cognitive traits are better predicted by the fine-scale connectome. Together, our findings suggest there are dissociable individual differences in information processing represented at different scales of the functional connectome which, in turn, have distinct implications for heritability and cognition.

Ethanol’s interaction with BK channel α subunit residue K361 does not mediate behavioral responses to alcohol in mice

Large conductance potassium (BK) channels are among the most sensitive molecular targets of ethanol and genetic variations in the channel-forming α subunit have been nominally associated with alcohol use disorders. However, whether the action of ethanol at BK α influences the motivation to drink alcohol remains to be determined. To address this question, we first tested the effect of systemically administered BK channel modulators on voluntary alcohol consumption in C57BL/6J males. Penitrem A (blocker) exerted dose-dependent effects on moderate alcohol intake, while paxilline (blocker) and BMS-204352 (opener) were ineffective. Because pharmacological manipulations are inherently limited by non-specific effects, we then sought to investigate the behavioral relevance of ethanol’s direct interaction with BK α by introducing in the mouse genome a point mutation known to render BK channels insensitive to ethanol while preserving their physiological function. The BK α K361N substitution prevented ethanol from reducing spike threshold in medial habenula neurons. However, it did not alter acute responses to ethanol in vivo, including ataxia, sedation, hypothermia, analgesia, and conditioned place preference. Furthermore, the mutation did not have reproducible effects on alcohol consumption in limited, continuous, or intermittent access home cage two-bottle choice paradigms conducted in both males and females. Notably, in contrast to previous observations made in mice missing BK channel auxiliary β subunits, the BK α K361N substitution had no significant impact on ethanol intake escalation induced by chronic intermittent alcohol vapor inhalation. It also did not affect the metabolic and locomotor consequences of chronic alcohol exposure. Altogether, these data suggest that the direct interaction of ethanol with BK α does not mediate the alcohol-related phenotypes examined here in mice.

Afferents to Action: Cortical Proprioceptive Processing Assessed with Corticokinematic Coherence Specifically Relates to Gross Motor Skills.

Voluntary motor control is thought to be predicated on the ability to efficiently integrate and process somatosensory afferent information. However, current approaches in the field of motor control have not factored in objective markers of how the brain tracks incoming somatosensory information. Here, we asked whether motor performance relates to such markers obtained with an analysis of the coupling between peripheral kinematics and cortical oscillations during continuous movements, best known as corticokinematic coherence (CKC). Motor performance was evaluated by measuring both gross and fine motor skills using the Box and Blocks Test (BBT) and the Purdue Pegboard Test (PPT), respectively, and with a biomechanics measure of coordination. A total of 61 participants completed the BBT, while equipped with electroencephalography and electromyography, and the PPT. We evaluated CKC, from the signals collected during the BBT, as the coherence between movement rhythmicity and brain activity, and coordination as the cross-correlation between muscle activity. CKC at movements' first harmonic was positively associated with BBT scores (r = 0.41, p = 0.001), and alone showed no relationship with PPT scores (r = 0.07, p = 0.60), but in synergy with BBT scores, participants with lower PPT scores had higher CKC than expected based on their BBT score. Coordination was not associated with motor performance or CKC (p > 0.05). These findings demonstrate that cortical somatosensory processing in the form of strengthened brain-peripheral coupling is specifically associated with better gross motor skills and thus may be considered as a valuable addition to classical tests of proprioception acuity.

Auditory Corticofugal Neurons Transmit Auditory and Non-auditory Information During Behavior.

Layer 5 pyramidal neurons of sensory cortices project "corticofugal" axons to myriad sub-cortical targets, thereby broadcasting high-level signals important for perception and learning. Recent studies suggest dendritic Ca2+ spikes as key biophysical mechanisms supporting corticofugal neuron function: these long-lasting events drive burst firing, thereby initiating uniquely powerful signals to modulate sub-cortical representations and trigger learning-related plasticity. However, the behavioral relevance of corticofugal dendritic spikes is poorly understood. We shed light on this issue using 2-photon Ca2+ imaging of auditory corticofugal dendrites as mice of either sex engage in a GO/NO-GO sound-discrimination task. Unexpectedly, only a minority of dendritic spikes were triggered by behaviorally relevant sounds under our conditions. Task related dendritic activity instead mostly followed sound cue termination and co-occurred with mice's instrumental licking during the answer period of behavioral trials, irrespective of reward consumption. Temporally selective, optogenetic silencing of corticofugal neurons during the trial answer period impaired auditory discrimination learning. Thus, auditory corticofugal systems' contribution to learning and plasticity may be partially nonsensory in nature.

Synaptic plasticity through a naturalistic lens.

From the myriad of studies on neuronal plasticity, investigating its underlying molecular mechanisms up to its behavioral relevance, a very complex landscape has emerged. Recent efforts have been achieved toward more naturalistic investigations as an attempt to better capture the synaptic plasticity underpinning of learning and memory, which has been fostered by the development of in vivo electrophysiological and imaging tools. In this review, we examine these naturalistic investigations, by devoting a first part to synaptic plasticity rules issued from naturalistic in vivo-like activity patterns. We next give an overview of the novel tools, which enable an increased spatio-temporal specificity for detecting and manipulating plasticity expressed at individual spines up to neuronal circuit level during behavior. Finally, we put particular emphasis on works considering brain-body communication loops and macroscale contributors to synaptic plasticity, such as body internal states and brain energy metabolism.

Holistic bursting cells store long-term memory in auditory cortex

The sensory neocortex has been suggested to be a substrate for long-term memory storage, yet which exact single cells could be specific candidates underlying such long-term memory storage remained neither known nor visible for over a century. Here, using a combination of day-by-day two-photon Ca2+ imaging and targeted single-cell loose-patch recording in an auditory associative learning paradigm with composite sounds in male mice, we reveal sparsely distributed neurons in layer 2/3 of auditory cortex emerged step-wise from quiescence into bursting mode, which then invariably expressed holistic information of the learned composite sounds, referred to as holistic bursting (HB) cells. Notably, it was not shuffled populations but the same sparse HB cells that embodied the behavioral relevance of the learned composite sounds, pinpointing HB cells as physiologically-defined single-cell candidates of an engram underlying long-term memory storage in auditory cortex.

Behavioural relevance of redundant and synergistic stimulus information between functionally connected neurons in mouse auditory cortex

Measures of functional connectivity have played a central role in advancing our understanding of how information is transmitted and processed within the brain. Traditionally, these studies have focused on identifying redundant functional connectivity, which involves determining when activity is similar across different sites or neurons. However, recent research has highlighted the importance of also identifying synergistic connectivity—that is, connectivity that gives rise to information not contained in either site or neuron alone. Here, we measured redundant and synergistic functional connectivity between neurons in the mouse primary auditory cortex during a sound discrimination task. Specifically, we measured directed functional connectivity between neurons simultaneously recorded with calcium imaging. We used Granger Causality as a functional connectivity measure. We then used Partial Information Decomposition to quantify the amount of redundant and synergistic information about the presented sound that is carried by functionally connected or functionally unconnected pairs of neurons. We found that functionally connected pairs present proportionally more redundant information and proportionally less synergistic information about sound than unconnected pairs, suggesting that their functional connectivity is primarily redundant. Further, synergy and redundancy coexisted both when mice made correct or incorrect perceptual discriminations. However, redundancy was much higher (both in absolute terms and in proportion to the total information available in neuron pairs) in correct behavioural choices compared to incorrect ones, whereas synergy was higher in absolute terms but lower in relative terms in correct than in incorrect behavioural choices. Moreover, the proportion of redundancy reliably predicted perceptual discriminations, with the proportion of synergy adding no extra predictive power. These results suggest a crucial contribution of redundancy to correct perceptual discriminations, possibly due to the advantage it offers for information propagation, and also suggest a role of synergy in enhancing information level during correct discriminations.

Transcriptionally defined amygdala subpopulations play distinct roles in innate social behaviors

Social behaviors are innate and supported by dedicated neural circuits, but the molecular identities of these circuits and how they are established developmentally and shaped by experience remain unclear. Here we show that medial amygdala (MeA) cells originating from two embryonically parcellated developmental lineages have distinct response patterns and functions in social behavior in male mice. MeA cells expressing the transcription factor Foxp2 (MeAFoxp2) are specialized for processing male conspecific cues and are essential for adult inter-male aggression. By contrast, MeA cells derived from the Dbx1 lineage (MeADbx1) respond broadly to social cues, respond strongly during ejaculation and are not essential for male aggression. Furthermore, MeAFoxp2 and MeADbx1 cells show differential anatomical and functional connectivity. Altogether, our results suggest a developmentally hardwired aggression circuit at the MeA level and a lineage-based circuit organization by which a cell’s embryonic transcription factor profile determines its social information representation and behavioral relevance during adulthood.

Tax amnesties and the insurance effect: An experimental study

Many countries grant exemption from legal prosecution under certain conditions, allowing for voluntary disclosures regarding tax evasion. Empirically, tax amnesties appear most successful when accompanied by an increase in enforcement efforts as they help evaders to adjust to the new circumstances. Time-limited amnesties are frequently repeated and, in some countries, even made permanent. Anticipated tax amnesties can, however, serve as an insurance against a rise in the detection probability, potentially leading to less and not more tax compliance. We test the behavioral relevance of this insurance effect in an experimental tax game and find that it indeed decreases overall tax compliance by about 9-10 percent, highlighting its relevance for the design of tax policies. A high predictability of amnesties may work to their detriment.

Novelty detection in an auditory oddball task on freely moving rats

The relative importance or saliency of sensory inputs depend on the animal’s environmental context and the behavioural responses to these same inputs can vary over time. Here we show how freely moving rats, trained to discriminate between deviant tones embedded in a regular pattern of repeating stimuli and different variations of the classic oddball paradigm, can detect deviant tones, and this discriminability resembles the properties that are typical of neuronal adaptation described in previous studies. Moreover, the auditory brainstem response (ABR) latency decreases after training, a finding consistent with the notion that animals develop a type of plasticity to auditory stimuli. Our study suggests the existence of a form of long-term memory that may modulate the level of neuronal adaptation according to its behavioural relevance, and sets the ground for future experiments that will help to disentangle the functional mechanisms that govern behavioural habituation and its relation to neuronal adaptation.

Visual feature tuning properties of stimulus-driven saccadic inhibition in macaque monkeys.

Saccadic inhibition refers to a short-latency transient cessation of saccade generation after visual sensory transients. This oculomotor phenomenon occurs with a latency that is consistent with a rapid influence of sensory responses, such as stimulus-induced visual bursts, on oculomotor control circuitry. However, the neural mechanisms underlying saccadic inhibition are not well understood. Here, we exploited the fact that macaque monkeys experience robust saccadic inhibition to test the hypothesis that inhibition time and strength exhibit systematic visual feature tuning properties to a multitude of visual feature dimensions commonly used in vision science. We measured saccades in three monkeys actively controlling their gaze on a target, and we presented visual onset events at random times. Across seven experiments, the visual onsets tested size, spatial frequency, contrast, orientation, motion direction, and motion speed dependencies of saccadic inhibition. We also investigated how inhibition might depend on the behavioral relevance of the appearing stimuli. We found that saccadic inhibition starts earlier, and is stronger, for large stimuli of low spatial frequencies and high contrasts. Moreover, saccadic inhibition timing depends on motion direction and orientation, with earlier inhibition systematically occurring for horizontally drifting vertical gratings. On the other hand, saccadic inhibition is stronger for faster motions and when the appearing stimuli are subsequently foveated. Besides documenting a range of feature tuning dimensions of saccadic inhibition to the properties of exogenous visual stimuli, our results establish macaque monkeys as an ideal model system for unraveling the neural mechanisms underlying a ubiquitous oculomotor phenomenon in visual neuroscience.NEW & NOTEWORTHY Visual onsets dramatically reduce saccade generation likelihood with very short latencies. Such latencies suggest that stimulus-induced visual responses, normally jump-starting perceptual and scene analysis processes, can also directly impact the decision of whether to generate saccades or not, causing saccadic inhibition. Consistent with this, we found that changing the appearance of the visual onsets systematically alters the properties of saccadic inhibition. These results constrain neurally inspired models of coordination between saccade generation and exogenous sensory stimulation.

Quantitative susceptibility mapping of brain iron in healthy aging and cognition

Quantitative susceptibility mapping (QSM) is a magnetic resonance imaging (MRI) technique that can assess the magnetic properties of cerebral iron in vivo. Although brain iron is necessary for basic neurobiological functions, excess iron content disrupts homeostasis, leads to oxidative stress, and ultimately contributes to neurodegenerative disease. However, some degree of elevated brain iron is present even among healthy older adults. To better understand the topographical pattern of iron accumulation and its relation to cognitive aging, we conducted an integrative review of 47 QSM studies of healthy aging, with a focus on five distinct themes. The first two themes focused on age-related increases in iron accumulation in deep gray matter nuclei versus the cortex. The overall level of iron is higher in deep gray matter nuclei than in cortical regions. Deep gray matter nuclei vary with regard to age-related effects, which are most prominent in the putamen, and age-related deposition of iron is also observed in frontal, temporal, and parietal cortical regions during healthy aging. The third theme focused on the behavioral relevance of iron content and indicated that higher iron in both deep gray matter and cortical regions was related to decline in fluid (speed-dependent) cognition. A handful of multimodal studies, reviewed in the fourth theme, suggest that iron interacts with imaging measures of brain function, white matter degradation, and the accumulation of neuropathologies. The final theme concerning modifiers of brain iron pointed to potential roles of cardiovascular, dietary, and genetic factors. Although QSM is a relatively recent tool for assessing cerebral iron accumulation, it has significant promise for contributing new insights into healthy neurocognitive aging.