Recent Behavioral Data Research Articles

Estradiol and Mu opioid-mediated reward: The role of estrogen receptors in opioid use

Opioid use and opioid use disorder are characterized by sex and gender differences, and some of these differences may be mediated by differences in the hormonal milieu within and across individuals. This review focuses on the role of ovarian hormones, and particularly estradiol, on the endogenous mu opioid receptor system. There is an abundance of data indicating that estradiol influences the activity of endogenous mu opioid peptides, the activation of mu opioid receptors, and the internalization and desensitization of mu opioid receptors. These effects have functional consequences on behaviors mediated by endogenous mu opioid receptor activity and on sensitivity to mu opioid agonists and antagonists. Recent behavioral data suggest these consequences extend to mu opioid reward, and preclinical studies report that estradiol decreases self-administration of mu opioid receptor agonists across a range of experimental conditions. Data collected in human laboratory studies suggest that estradiol may have functionally similar effects in clinical populations, and thus estrogen receptors may be a potential target in the development of novel therapeutics. This review summarizes data from cellular assays to clinical trials to explore how estradiol influences mu opioid receptor activity, as well as potential ways in which estrogen receptors may be targeted to address the problems of opioid use.

Working memory prioritization impacts neural recovery from distraction

The ability to protect goal-relevant information from disruption over short intervals is a hallmark of working memory. Recent behavioral data suggest that high-priority items in working memory are more vulnerable to disruption. We used functional magnetic resonance imaging to evaluate the hypothesis that prioritization of working memories might impact the recovery of their neural representation(s) after distraction. A delay-period retrospective cue informed participants which of two memory items (a face or a scene) to prioritize during a first delay period. Consistent with prior work, and confirming successful prioritization, multivoxel pattern classifier evidence in perceptual brain regions was higher for cued versus uncued memory items. A distraction task was then imposed before a second retrospective cue informed participants to either “stay” remembering the previously cued item or “switch” to the previously uncued item. This allowed for the evaluation of recovery for high-priority items (on stay trials) and also low-priority items (on switch trials). Classifiers showed successful reinstatement of both high- and low-priority items after distraction, but only low-priority items recovered to their pre-distraction representational levels. Moreover, the degree of prioritization before distraction predicted the amount of disruption for high-priority items after distraction, suggesting that the more a participant prioritized the cued item, the greater the impact of distraction. Our data provide neural evidence that prioritizing working memory information in perceptual regions makes that information more vulnerable to disruption.

The Contribution of the Descending Pain Modulatory Pathway in Opioid Tolerance.

Opioids remain among the most effective pain-relieving therapeutics. However, their long-term use is limited due to the development of tolerance and potential for addiction. For many years, researchers have explored the underlying mechanisms that lead to this decreased effectiveness of opioids after repeated use, and numerous theories have been proposed to explain these changes. The most widely studied theories involve alterations in receptor trafficking and intracellular signaling. Other possible mechanisms include the recruitment of new structural neuronal and microglia networks. While many of these theories have been developed using molecular and cellular techniques, more recent behavioral data also supports these findings. In this review, we focus on the mechanisms that underlie tolerance within the descending pain modulatory pathway, including alterations in intracellular signaling, neural-glial interactions, and neurotransmission following opioid exposure. Developing a better understanding of the relationship between these various mechanisms, within different parts of this pathway, is vital for the identification of more efficacious, novel therapeutics to treat chronic pain.

The Functional Role of Large-scale Brain Network Coordination in Placebo-induced Anxiolysis.

Anxiety reduction through mere expectation of anxiolytic treatment effects (placebo anxiolysis) has enormous clinical importance. Recent behavioral and electrophysiological data suggest that placebo anxiolysis involves reduced vigilance and enhanced internalization of attention; however, the underlying neurobiological mechanisms are not yet clear. Given the fundamental function of intrinsic connectivity networks (ICNs) in basic cognitive processes, we investigated ICN activity patterns associated with externally and internally directed mental states under the influence of an anxiolytic placebo medication. Based on recent findings, we specifically analyzed the functional role of the rostral anterior cingulate cortex (rACC) in coordinating placebo-dependent cue-related (phasic) and cue-unrelated (sustained) network activity. Under placebo, we observed a down-regulation of the entire salience network (SN), particularly in response to threatening cues. The rACC exhibited enhanced cue-unrelated functional connectivity (FC) with the SN, which correlated with reductions in tonic arousal and anxiety. Hence, apart from the frequently reported modulation of aversive cue responses, the rACC appears to be crucially involved in exerting a tonically dampening control over salience-responsive structures. In line with a more internally directed mental state, we also found enhanced FC within the default mode network (DMN), again predicting reductions in anxiety under placebo.

Deep Brain Stimulation of the Subthalamic Nucleus Does Not Affect the Decrease of Decision Threshold during the Choice Process When There Is No Conflict, Time Pressure, or Reward.

During a decision process, the evidence supporting alternative options is integrated over time, and the choice is made when the accumulated evidence for one of the options reaches a decision threshold. Humans and animals have an ability to control the decision threshold, that is, the amount of evidence that needs to be gathered to commit to a choice, and it has been proposed that the subthalamic nucleus (STN) is important for this control. Recent behavioral and neurophysiological data suggest that, in some circumstances, the decision threshold decreases with time during choice trials, allowing overcoming of indecision during difficult choices. Here we asked whether this within-trial decrease of the decision threshold is mediated by the STN and if it is affected by disrupting information processing in the STN through deep brain stimulation (DBS). We assessed 13 patients with Parkinson disease receiving bilateral STN DBS six or more months after the surgery, 11 age-matched controls, and 12 young healthy controls. All participants completed a series of decision trials, in which the evidence was presented in discrete time points, which allowed more direct estimation of the decision threshold. The participants differed widely in the slope of their decision threshold, ranging from constant threshold within a trial to steeply decreasing. However, the slope of the decision threshold did not depend on whether STN DBS was switched on or off and did not differ between the patients and controls. Furthermore, there was no difference in accuracy and RT between the patients in the on and off stimulation conditions and healthy controls. Previous studies that have reported modulation of the decision threshold by STN DBS or unilateral subthalamotomy in Parkinson disease have involved either fast decision-making under conflict or time pressure or in anticipation of high reward. Our findings suggest that, in the absence of reward, decision conflict, or time pressure for decision-making, the STN does not play a critical role in modulating the within-trial decrease of decision thresholds during the choice process.

Structural Plasticity, Effectual Connectivity, and Memory in Cortex.

Learning and memory is commonly attributed to the modification of synaptic strengths in neuronal networks. More recent experiments have also revealed a major role of structural plasticity including elimination and regeneration of synapses, growth and retraction of dendritic spines, and remodeling of axons and dendrites. Here we work out the idea that one likely function of structural plasticity is to increase “effectual connectivity” in order to improve the capacity of sparsely connected networks to store Hebbian cell assemblies that are supposed to represent memories. For this we define effectual connectivity as the fraction of synaptically linked neuron pairs within a cell assembly representing a memory. We show by theory and numerical simulation the close links between effectual connectivity and both information storage capacity of neural networks and effective connectivity as commonly employed in functional brain imaging and connectome analysis. Then, by applying our model to a recently proposed memory model, we can give improved estimates on the number of cell assemblies that can be stored in a cortical macrocolumn assuming realistic connectivity. Finally, we derive a simplified model of structural plasticity to enable large scale simulation of memory phenomena, and apply our model to link ongoing adult structural plasticity to recent behavioral data on the spacing effect of learning.

Brain processing of a configural vs elemental odor mixture in the newborn rabbit.

Organisms are surrounded throughout life by chemically complex odors. How individuals process an odorant within a mixture or a mixture as a whole is a key question in neuroethology and chemical senses. This question is addressed here by using newborn rabbits, which can be rapidly conditioned to a new stimulus by single association with the mammary pheromone. After conditioning to ethyl maltol (odorant B), pups behaviorally respond to B and an A'B' mixture (68/32 ratio) but not to ethyl isobutyrate (odorant A) or an AB mixture (30/70 ratio). This suggests elemental and configural perception of A'B' and AB, respectively. We then explored the neural substrates underlying the processing of these mixtures with the hypothesis that processing varies according to perception. Pups were pseudoconditioned or conditioned to B on postnatal day 3 before exposure to B, A'B' or AB on day 4. Fos expression was not similar between groups (mainly in the olfactory bulb and posterior piriform cortex) suggesting a differential processing of the stimuli that might reflect either stimulus complexity or conditioning effect. Thus, the ratio of components in A'B' vs AB leads to differential activation of the olfactory system which may contribute to elemental and configural percepts of these mixtures. In addition, together with recent behavioral data, this highlights that configural perception occurs even in relatively immature animals, emphasizing the value of the newborn rabbit for exploration of odor mixture processing from molecules to brain and behavior.

Effects of musically cued gait training in Parkinson's disease: beyond a motor benefit.

Auditory stimulation via rhythmic cues can be used successfully in the rehabilitation of motor function in patients with motor disorders. A prototypical example is provided by dysfunctional gait in patients with idiopathic Parkinson's disease (PD). Coupling steps to external rhythmic cues (the beat of music or the sounds of a metronome) leads to long-term motor improvements, such as increased walking speed and greater stride length. These effects are likely to be underpinned by compensatory brain mechanisms involving cerebellar-thalamocortical networks. Because these areas are also involved in perceptual and motor timing, parallel improvement in timing tasks is expected in PD beyond purely motor benefits. In keeping with this idea, we report here recent behavioral data showing beneficial effects of musically cued gait training (MCGT) on gait performance (i.e., increased stride length and speed), perceptual timing (e.g., discriminating stimulus durations), and sensorimotor timing abilities (i.e., in paced tapping tasks) in PD patients. Particular attention is paid to individual differences in timing abilities in PD, thus paving the ground for an individualized MCGT-based therapy.

Re-evaluating the extractive foraging hypothesis

Abstract In his seminal 1992 paper, Dunbar examined three hypotheses advanced to explain primate intelligence, arguing that whereas his social group size hypothesis was supported, neither of two ecological hypotheses, the extractive foraging and frugivory hypotheses, were supported. Following this, and Dunbar's subsequently elaborated argument, many investigators concluded that primate intelligence arose as social rather than ecological adaptations. This paper questions Dunbar's characterization of extractive foraging and social intelligence as alternative hypotheses, raises sampling issues about Dunbar's brain data, species choice, and measurement of extractive foraging. It summarizes the extractive foraging hypothesis, and counters its critics. It reexamines the hypothesis in light of recent behavioral and brain data, new methodology for quantifying extractive foraging, and a new phylogeny of primate intelligence. It concludes that the extractive foraging hypothesis is now supported by several converging lines of evidence.

Face processing in the brains of pre-school aged children measured with MEG

There are two competing theories concerning the development of face perception: a late maturation account and an early maturation account. Magnetoencephalography (MEG) neuroimaging holds promise for adjudicating between the two opposing accounts by providing objective neurophysiological measures of face processing, with sufficient temporal resolution to isolate face-specific brain responses from those associated with other sensory, cognitive and motor processes. The current study used a customized child MEG system to measure M100 and M170 brain responses in 15 children aged three to six years while they viewed faces, cars and their phase-scrambled counterparts. Compared to adults tested using the same stimuli in a conventional MEG system, children showed significantly larger and later M100 responses. Children's M170 responses, derived by subtracting the responses to phase-scrambled images from the corresponding images (faces or cars) were delayed in latency but otherwise resembled the adult M170. This component has not been obtained in previous studies of young children tested using conventional adult MEG systems. However children did show a markedly reduced M170 response to cars in comparison to adults. This may reflect children's lack of expertise with cars relative to faces. Taken together, these data are in accord with recent behavioural and neuroimaging data that support early maturation of the basic face processing functions.

Sex in a lifetime: Sexual behaviors in the United States by lifetime number of sex partners, 2006-2010.

Using data from the 2006-2010 National Survey of Family Growth, we found that lifetime number of vaginal sex partners is positively associated with the number of sex partners in the past 12 months and negatively associated with age at first vaginal intercourse among 15- to 44-year-old male and female respondents.

Demonstration of an Ebbinghaus Illusion at a Memory Level

Based on recent behavioral and neuroimaging data suggesting that memory and perception are partially based on the same sensorimotor system, the theoretical aim of the present study was to show that it is difficult to dissociate memory mechanisms from perceptual mechanisms other than on the basis of the presence (perceptual processing) or absence (memory processing) of the characteristics of the objects involved in the processing. In line with this assumption, two experiments using an adaptation of the Ebbinghaus illusion paradigm revealed similar effects irrespective of whether the size difference between the inner circles and the surrounding circles was manipulated perceptually (the size difference was perceptually present, Experiment 1) or merely reactivated in memory (the difference was perceptually absent, Experiment 2).

Suppression of the auditory N1-component for heartbeat-related sounds reflects interoceptive predictive coding

Although many studies have elucidated the neurocognitive mechanisms supporting the processing of externally generated sensory signals, less is known about the processing of interoceptive signals related to the viscera. Drawing a parallel with research on agency and the perception of self-generated action effects, in the present EEG study we report a reduced auditory N1 component when participants listened to heartbeat-related sounds compared to externally generated sounds. The auditory suppression for heartbeat sounds was robust and persisted after controlling for ECG-related artifacts, the number of trials involved and the phase of the cardiac cycle. In addition, the auditory N1 suppression for heartbeat-related sounds had a comparable scalp distribution as the N1 suppression observed for actively generated sounds. This finding indicates that the brain automatically differentiates between heartbeat-related and externally generated sounds through a process of sensory suppression, suggesting that a comparable predictive mechanism may underlie the processing of heartbeat and action-related information. Extending recent behavioral data about cardio-visual integration, the present cardio-auditory EEG data reveal that the processing of sounds in auditory cortex is systematically modulated by an interoceptive cardiac signal. The findings are discussed with respect to theories of interoceptive awareness, emotion, predictive coding, and their relevance to bodily self-consciousness.

Does the greater involvement of executive control in memory with age act as a compensatory mechanism?

Recent behavioural and imaging data have shown that memory functioning seems to rely more on executive functions and on the prefrontal cortex (PFC) in older than in young adults. Using a behavioural approach, our objective was to confirm the hypothesis that young and older adults present different patterns of correlation between episodic memory performance and executive functioning. We report three studies comparing the correlations of young and older adults in a broad range of episodic memory and executive function tasks. The results indicated that memory and executive performance were consistently and significantly correlated in older but not in younger adults. Regression analyses confirmed that age-related differences in episodic memory performance could be explained by individual differences in executive functioning. The results are consistent with the view that memory functioning in aging is accompanied by a shift from automatic to controlled forms of processing. They also generalise the executive hypothesis of episodic memory aging and are in line with the idea that executive functions act as a compensatory mechanism against age-related memory decline.

Critical role of peripheral sensory systems in mediating the neural effects of nicotine following its acute and repeated exposure

It is well established that the reinforcing properties of nicotine (NIC) depend on its action on nicotinic acetylcholine receptors expressed by brain neurons. However, when administered systemically, NIC first phasically activates nicotinic receptors located on the afferents of sensory nerves at the sites of drug administration before reaching the brain and directly interacting with central neurons. While this peripheral action of NIC has been known for years, it is usually neglected in any consideration of the drug's reinforcing properties and experience-dependent changes of its behavioral and physiological effects. The goal of this work was to review our recent behavioral, electrophysiological, and physiological data suggesting the critical importance of peripheral actions of NIC in mediating its neural effects following acute drug exposure and their involvement in alterations of NIC effects consistently occurring following repeated drug exposure. Because NIC, by acting peripherally, produces a rapid sensory signal to the central nervous system that is followed by slower, more prolonged direct drug actions in the brain, these two pharmacological actions interact in the central nervous system during repeated drug use with the development of Pavlovian conditioned association. This within-drug conditioning mechanism could explain the experience-dependent changes in the physiological, behavioral, and human psychoemotional effects of NIC, which, in drug-experienced individuals, always represent a combination of pharmacological and learning variables.

Learning Representations of Animated Motion Sequences—A Neural Model

AbstractThe detection and categorization of animate motions is a crucial task underlying social interaction and perceptual decision making. Neural representations of perceived animate objects are partially located in the primate cortical region STS, which is a region that receives convergent input from intermediate‐level form and motion representations. Populations of STS cells exist which are selectively responsive to specific animated motion sequences, such as walkers. It is still unclear how and to what extent form and motion information contribute to the generation of such representations and what kind of mechanisms are involved in the learning processes. The article develops a cortical model architecture for the unsupervised learning of animated motion sequence representations. We demonstrate how the model automatically selects significant motion patterns as well as meaningful static form prototypes characterized by a high degree of articulation. Such key poses are selectively reinforced during learning through a cross talk between the motion and form processing streams. Furthermore, we show how sequence‐selective representations are learned in STS by fusing static form and motion input from the segregated bottom‐up driving input streams. Cells in STS, in turn, feed their activities recurrently to their input sites along top‐down signal pathways. We show how such learned feedback connections enable predictions about future input as anticipation generated by sequence‐selective STS cells. Network simulations demonstrate the computational capacity of the proposed model by reproducing several experimental findings from neurosciences and by accounting for recent behavioral data.

The extended features of mirror neurons and the voluntary control of vocalization in the pathway to language

AbstractIn this book it has been proposed that the mirror system can be a scaffold for building a language-ready brain, because of its property of matching action observation with action execution, a feature that can correspond to the “parity” requirement for communication. In this commentary we will first emphasize two properties of mirror neurons and motor cortex that may have contributed to language: the generalization of the property of understanding action goals and the capacity to decode the goal of action sequences. Then we will propose, based on recent behavioural and neurophysiological data in monkeys, that the vocalization in non-human primates could have reached a partial voluntary control, thus contributing to the emergence of a communicative system relying on the coordination of gestures and utterances.

Peripheral Visual Perception During Exercise

Peripheral visual perception may be relevant to performance in sports. Peripheral visual perception seems to be impaired during strenuous exercise. The hypothesis proposed is that a decrease in cerebral oxygenation is associated with impairment in peripheral visual perception during strenuous exercise. Recent behavioral and physiological data are presented to support the hypothesis.

Lifelong Bilingualism Maintains Neural Efficiency for Cognitive Control in Aging

Recent behavioral data have shown that lifelong bilingualism can maintain youthful cognitive control abilities in aging. Here, we provide the first direct evidence of a neural basis for the bilingual cognitive control boost in aging. Two experiments were conducted, using a perceptual task-switching paradigm, including a total of 110 participants. In Experiment 1, older adult bilinguals showed better perceptual switching performance than their monolingual peers. In Experiment 2, younger and older adult monolinguals and bilinguals completed the same perceptual task-switching experiment while functional magnetic resonance imaging (fMRI) was performed. Typical age-related performance reductions and fMRI activation increases were observed. However, like younger adults, bilingual older adults outperformed their monolingual peers while displaying decreased activation in left lateral frontal cortex and cingulate cortex. Critically, this attenuation of age-related over-recruitment associated with bilingualism was directly correlated with better task-switching performance. In addition, the lower blood oxygenation level-dependent response in frontal regions accounted for 82% of the variance in the bilingual task-switching reaction time advantage. These results suggest that lifelong bilingualism offsets age-related declines in the neural efficiency for cognitive control processes.

A Parieto-Medial Temporal Pathway for the Strategic Control over Working Memory Biases in Human Visual Attention

The contents of working memory (WM) can both aid and disrupt the goal-directed allocation of visual attention. WM benefits attention when its contents overlap with goal-relevant stimulus features, but WM leads attention astray when its contents match features of currently irrelevant stimuli. Recent behavioral data have documented that WM biases of attention may be subject to strategic cognitive control processes whereby subjects are able to either enhance or inhibit the influence of WM contents on attention. However, the neural mechanisms supporting cognitive control over WM biases on attention are presently unknown. Here, we characterize these mechanisms by combining human functional magnetic resonance imaging with a task that independently manipulates the relationship between WM cues and attention targets during visual search (with WM contents matching either search targets or distracters), as well as the predictability of this relationship (100 vs 50% predictability) to assess participants' ability to strategically enhance or inhibit WM biases on attention when WM contents reliably matched targets or distracter stimuli, respectively. We show that cues signaling predictable (> unpredictable) WM-attention relations reliably enhanced search performance, and that this strategic modulation of the interplay between WM contents and visual attention was mediated by a neuroanatomical network involving the posterior parietal cortex, the posterior cingulate, and medial temporal lobe structures, with responses in the hippocampus proper correlating with behavioral measures of strategic control of WM biases. Thus, we delineate a novel parieto-medial temporal pathway implementing cognitive control over WM biases to optimize goal-directed selection.