Novelty Exploration Research Articles

Large-Scale and Multiscale Networks in the Rodent Brain during Novelty Exploration.

Neural activity is coordinated across multiple spatial and temporal scales, and these patterns of coordination are implicated in both healthy and impaired cognitive operations. However, empirical cross-scale investigations are relatively infrequent, because of limited data availability and to the difficulty of analyzing rich multivariate datasets. Here, we applied frequency-resolved multivariate source-separation analyses to characterize a large-scale dataset comprising spiking and local field potential (LFP) activity recorded simultaneously in three brain regions (prefrontal cortex, parietal cortex, hippocampus) in freely-moving mice. We identified a constellation of multidimensional, inter-regional networks across a range of frequencies (2–200 Hz). These networks were reproducible within animals across different recording sessions, but varied across different animals, suggesting individual variability in network architecture. The theta band (∼4–10 Hz) networks had several prominent features, including roughly equal contribution from all regions and strong inter-network synchronization. Overall, these findings demonstrate a multidimensional landscape of large-scale functional activations of cortical networks operating across multiple spatial, spectral, and temporal scales during open-field exploration.

Effects of active exploration on novelty-related declarative memory enhancement

Exploration of novel environments has reliably been shown to enhance learning in rodents. More recently, these effects have been replicated in humans using virtual reality: Memory is enhanced after exploration of novel compared to familiar virtual environments. However, exploration of a novel versus familiar environment differs in another aspect. Navigating familiar territory can rely more on habits, while navigating new territory requires active decision-making. This difference in choices could contribute to the positive effects of novelty exploration on memory. In this study, we aimed to investigate this possibility. Participants familiarized with a virtual environment (day 1) and were exposed to this environment again (day 2 or 3) and to a novel environment (day 2 or 3). Participants either actively explored the environments or were passively exposed to the exploration behavior of another participant in virtual reality. After exposure to the environment, participants performed a word-learning task and filled out questionnaires regarding virtual presence and the novelty seeking personality trait. Mixed models suggested that memory performance was higher after participants actively explored versus were passively exposed to a novel environment, while these effects were reversed for a familiar environment. Bayesian statistics provided further weak evidence that memory performance was influenced by the interaction between novelty and exposure type. Taken together, our findings suggest that active exploration may contribute to novelty-induced memory benefits, but future studies need to confirm this finding.

Human complex exploration strategies are enriched by noradrenaline-modulated heuristics.

An exploration-exploitation trade-off, the arbitration between sampling a lesser-known against a known rich option, is thought to be solved using computationally demanding exploration algorithms. Given known limitations in human cognitive resources, we hypothesised the presence of additional cheaper strategies. We examined for such heuristics in choice behaviour where we show this involves a value-free random exploration, that ignores all prior knowledge, and a novelty exploration that targets novel options alone. In a double-blind, placebo-controlled drug study, assessing contributions of dopamine (400 mg amisulpride) and noradrenaline (40 mg propranolol), we show that value-free random exploration is attenuated under the influence of propranolol, but not under amisulpride. Our findings demonstrate that humans deploy distinct computationally cheap exploration strategies and that value-free random exploration is under noradrenergic control.

Locomotion in virtual environments predicts cardiovascular responsiveness to subsequent stressful challenges

Individuals differ in their physiological responsiveness to stressful challenges, and stress potentiates the development of many diseases. Heart rate variability (HRV), a measure of cardiac vagal break, is emerging as a strong index of physiological stress vulnerability. Thus, it is important to develop tools that identify predictive markers of individual differences in HRV responsiveness without exposing subjects to high stress. Here, using machine learning approaches, we show the strong predictive power of high-dimensional locomotor responses during novelty exploration to predict HRV responsiveness during stress exposure. Locomotor responses are collected in two ecologically valid virtual reality scenarios inspired by the animal literature and stress is elicited and measured in a third threatening virtual scenario. Our model’s predictions generalize to other stressful challenges and outperforms other stress prediction instruments, such as anxiety questionnaires. Our study paves the way for the development of behavioral digital phenotyping tools for early detection of stress-vulnerable individuals.

Altered behaviour, dopamine and norepinephrine regulation in stressed mice heterozygous in TPH2 gene

Gene-environment interaction (GxE) determines the vulnerability of an individual to a spectrum of stress-related neuropsychiatric disorders. Increased impulsivity, excessive aggression, and other behavioural characteristics are associated with variants within the tryptophan hydroxylase-2 (Tph2) gene, a key enzyme in brain serotonin synthesis. This phenotype is recapitulated in naïve mice with complete, but not with partial Tph2 inactivation. Tph2 haploinsufficiency in animals reflects allelic variation of Tph2 facilitating the elucidation of respective GxE mechanisms. Recently, we showed excessive aggression and altered serotonin brain metabolism in heterozygous Tph2-deficient male mice (Tph2+/−) after predator stress exposure. Here, we sought to extend these studies by investigating aggressive and anxiety-like behaviours, sociability, and the brain metabolism of dopamine and noradrenaline. Separately, Tph2+/− mice were examined for exploration activity in a novel environment and for the potentiation of helplessness in the modified swim test (ModFST). Predation stress procedure increased measures of aggression, dominancy, and suppressed sociability in Tph2+/− mice, which was the opposite of that observed in control mice. Anxiety-like behaviour was unaltered in the mutants and elevated in controls. Tph2+/− mice exposed to environmental novelty or to the ModFST exhibited increased novelty exploration and no increase in floating behaviour compared to controls, which is suggestive of resilience to stress and despair. High-performance liquid chromatography (HPLC) revealed significant genotype-dependent differences in the metabolism of dopamine, and norepinephrine within the brain tissue. In conclusion, environmentally challenged Tph2+/− mice exhibit behaviours that resemble the behaviour of non-stressed null mutants, which reveals how GxE interaction studies can unmask latent genetically determined predispositions.

Forebrain overexpression of type 1 adenylyl cyclase promotes molecular stability and behavioral resilience to physical stress

The ability to cope with stress is essential for emotional stability and mental health. It is also hypothesized that factors promoting resilience to stress may offer treatment strategies for maladaptive disorders such as anxiety and depression. Here, we find that physical restraint reduces the expression of type 1 adenylyl cyclase (Adcy1), a neurospecific synaptic enzyme that positively regulates the cAMP signaling cascade. Conversely, an increase of forebrain Adcy1 expression in transgenic mouse (i.e., Adcy1tg mouse) predisposes individuals to molecular stability and behavioral resilience. Transgenic overexpression of Adcy1 prevents the physical restraint-induced down-regulation of brain-derived neurotrophic factor (BDNF) and neuropeptide Y (NPY). Further, Adcy1tg mice maintain regular locomotive activity in novelty exploration and voluntary wheel running following physical restraint. Adcy1tg mice show higher corticosterone and lower basal glucocorticoid receptor (GR) expression, along with a higher MR (mineralocorticoid receptor) to GR ratio in the hippocampus. Further, Adcy1tg mice show reduced immobility under acute physical stress conditions in the forced swimming test and are more sensitive to the antidepressant desipramine. Our results demonstrate a novel function of Adcy1 in stress coping and suggest Adcy1 as a potential target to antagonize stress vulnerability and promote antidepressant efficacy.

Preference for vigorous exercise versus sedentary sucrose drinking: an animal model of anergia induced by dopamine receptor antagonism.

Motivation has activational and directional components. Mesolimbic dopamine is critical for the regulation of behavioral activation and effort-related processes in motivated behaviors. Impairing mesolimbic dopamine function leads to fatigue and anergia, but leaves intact other aspects of reinforce seeking behaviors, such as the consummatory or hedonic component. In male Swiss mice, we characterized the impact of dopamine antagonism on the selection of concurrently presented stimuli that have different vigor requirements. We analyzed running wheel activity versus sucrose solution intake, typically used as a measure of anhedonia. Results are compared with data from nonconcurrent presentation to those stimuli. In the concurrent presentation experiment, control mice preferred to spend time running compared to sucrose intake. Dopamine antagonism shifted relative reinforcer preference, reducing time spent on the running wheel, but actually increasing time-consuming sucrose. Mice increased frequency of bouts for both reinforcers, suggesting that there was fatigue in the running wheel rather than aversion. Moreover, satiation or habituation by preexposing animals to both reinforcers did not shift preferences. In the nonconcurrent experiments, haloperidol reduced running wheel but had no impact on sucrose consumption. Dopamine antagonism did not change preference for sucrose or total volume consumed. Additional correlational analyses indicated that baseline differences in sucrose consumption were independent of baseline running or novelty exploration. Thus, dopamine antagonism seems to have anergic rather than anhedonic effects, and the concurrent presentation in this setting could be useful for assessing preferences based on effort requirements.

The temporal effect of hippocampal Arc in the working memory paradigm during novelty exploration

Arc (activity-regulated cytoskeleton-associated protein) is one of the neuronal Immediate Early Genes (IEG), which is involved in the consolidation of memory and is an essential factor in the induction of Long-term Potentiation (LTP), Long-term Depression (LTD) and homeostatic synaptic plasticity. It has also been implicated in the increased familiarization of novel environments during reference memory paradigms. However, the Arc associated temporal effects in a working memory paradigm during novelty exploration are not well studied. Therefore, in the present study, we used spontaneous alternation behavior (SAB) test along with the expression analysis of Arc to study its temporal effects on the working memory paradigms. Using a modified SAB test, we found that the increase in the duration of exposure to a novel environment in the short time-scale (<min) increases the alternations showing that short-term habituation increases the alternation rate. Additionally, during repeated exposure to a novel environment, the alternation rates decrease after shorter inter-session interval. Parallelly, we observed the upregulation of Arc mRNA and protein level 30 min after the SAB test in the cortex and hippocampus of mice, which returns to near-basal level after two hours. The novel experience, associated with the enhanced expression of Arc, helps in the decrease of alternations in subsequent sessions. This change in alternations was absent if the environment was familiar. Further, the role of Arc during these SAB test was confirmed by the inhibition of hippocampal Arc protein through the stereotaxic infusion of Arc antisense oligodeoxynucleotides. We observed that the Arc is involved in the temporal decrease of spontaneous alternations during a series of exposures to a novel environment. Finally, the significance of these results has been discussed in the light of Wagner’s Sometimes Opponent Processes model, where we suggest that Arc reduces the ability for short-term habituation during repeated exposures in the working memory paradigm, and the loss of this ability is more prominent when subjected to a novel environment.

Early postnatal allopregnanolone levels alteration and adult behavioral disruption in rats: Implication for drug abuse

Several studies have highlighted the role that early postnatal levels of allopregnanolone play in the development of the CNS and adult behavior. Changes in allopregnanolone levels related to stress have been observed during early postnatal periods, and perinatal stress has been linked to neuropsychiatric disorders. The alteration of early postnatal allopregnanolone levels in the first weeks of life has been proven to affect adult behaviors, such as anxiety-related behaviors and the processing of sensory inputs. This review focuses on the first studies about the possible relationship between the early postnatal allopregnanolone levels and the vulnerability to abuse of drugs such as alcohol in adulthood, given that (1) changes in neonatal allopregnanolone levels affect novelty exploration and novelty seeking has been linked to vulnerability to drug abuse; (2) early postnatal administration of progesterone, the main allopregnanolone precursor, affects the maturation of dopaminergic meso-striatal systems, which have been related to novelty seeking and drug abuse; and (3) alcohol consumption increases plasma and brain allopregnanolone levels in animals and humans. Manipulating neonatal allopregnanolone by administering finasteride, an inhibitor of the 5α-reductase enzyme that participates in allopregnanolone synthesis, increases alcohol consumption and decreases the locomotor stimulant effects of low alcohol doses. At a molecular level, finasteride decreases dopamine and serotonin in ventral striatum and dopamine release in nucleus accumbens. Preliminary results suggest that serotonin 5HT3 receptors could also be affected. Although an in-depth study is necessary, evidence suggests that there is a relation between early postnatal allopregnanolone and vulnerability to drug use/abuse.

Serotonin transporter deficiency alters socioemotional ultrasonic communication in rats

It has been widely established that serotonin plays important role in the regulation of emotional and social behaviour. Rodents with a genetic deletion of the serotonin reuptake transporter (SERT) are used as a model to study lifelong consequences of increased extracellular 5‐HT levels due to its impaired reuptake. SERT knock-out (SERT-KO) mice and rats consistently showed anxiety-like symptoms and social deficits. Nevertheless, the impact of SERT deletion on socioemotional ultrasonic communication has not been addressed. Here we investigated the impact of lifelong serotonin abundance on ultrasonic vocalisation accompanying social interactions and open field exploration in rats. SERT-KO rats displayed reduced overall duration of social contacts, but increased time spent on following the conspecific. The altered pattern of social behaviour in SERT-KO rats was accompanied by the structural changes in ultrasonic vocalisations, as they differed from their controls in distribution of call categories. Moreover, SERT deletion resulted in anxiety-like behaviours assessed in the open field test. Their anxious phenotype resulted in a lower tendency to emit appetitive 50-kHz calls during novelty exploration. The present study demonstrates that genetic deletion of SERT not only leads to the deficits in social interaction and increased anxiety but also affects ultrasonic communication.

Pre-plaque Aß-Mediated Impairment of Synaptic Depotentiation in a Transgenic Rat Model of Alzheimer's Disease Amyloidosis.

How endogenously produced soluble amyloid ß-protein (Aß) affects synaptic plasticity in vulnerable circuits should provide insight into early Alzheimer’s disease pathophysiology. McGill-R-Thy1-APP transgenic rats, modeling Alzheimer’s disease amyloidosis, exhibit an age-dependent soluble Aß-mediated impairment of the induction of long-term potentiation (LTP) by 200 Hz conditioning stimulation at apical CA3-to-CA1 synapses. Here, we investigated if synaptic weakening at these synapses in the form of activity-dependent persistent reversal (depotentiation) of LTP is also altered in pre-plaque rats in vivo. In freely behaving transgenic rats strong, 400 Hz, conditioning stimulation induced stable LTP that was NMDA receptor- and voltage-gated Ca2+ channel-dependent. Surprisingly, the ability of novelty exploration to induce depotentiation of 400 Hz-induced LTP was impaired in an Aß-dependent manner in the freely behaving transgenic rats. Moreover, at apical synapses, low frequency conditioning stimulation (1 Hz) did not trigger depotentiation in anaesthetized transgenic rats, with an age-dependence similar to the LTP deficit. In contrast, at basal synapses neither LTP, induced by 100 or 200 Hz, nor novelty exploration-induced depotentiation was impaired in the freely behaving transgenic rats. These findings indicate that activity-dependent weakening, as well as strengthening, is impaired in a synapse- and age-dependent manner in this model of early Alzheimer’s disease amyloidosis.

Predicting Search Intent Based on In-Search Context for Exploratory Search

Modern information systems are expected to assist users with diverse goals, via exploiting the topical dimension (‘what' the user is searching for) of information needs. However, the intent dimension (‘why' the user is searching) has preferred relatively lesser for the same intention. Traditionally, the intent is an ‘immediate reason, purpose, or goal' that motivates the user search, and captured in search contexts (Pre-search, In-search, Pro-Search), an ideal information system would be able to use. This article proposes a novel intent estimation strategy; based on the intuition that captured intent, and proactively extracts likely results. The captured ‘Pre-search' context adapts query term proximities within matched results beside document-term statistics and pseudo-relevance feedback with user-relevance feedback for In-search. The assessment asserts the superior performance of the proposed strategy over the equivalent on tradeoffs, e.g., novelty, diversity (coverage, topicality), retrieval (precision, recall, F-measure) and exploitation vs exploration.

Methanol stem bark extract of Adansonia digitata ameliorates chronic unpredictable mild stress-induced depression-like behavior: Involvement of the HPA axis, BDNF, and stress biomarkers pathways.

Background Adansonia digitata L. (Malvaceae) is used locally in the management of depressive illnesses, and its antidepressant-like effect has been previously reported. The present study was aimed at determining the effect of the methanol extract of the stem bark of A. digitata (MEAD) on chronic unpredictable mild stress (CUMS) and the possible mechanism responsible for its antidepressant activity. Methods Acute toxicity of MEAD was determined using the OECD guideline 420. The CUMS model was used to induce depression, and behavioral tests such as sucrose preference test (SPT), open field test (OFT), novel-object recognition test (NORT), and tail suspension test (TST) were carried out in mice. The concentrations of plasma cortisol and brain-derived neurotrophic factor (BDNF) protein in the brain were assessed using enzyme-linked immunosorbent assay kits. The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were assessed using colorimetric methods. Results The LD50 was established to be ≥5000 mg/kg. On CUMS-induced depression, MEAD significantly (p ≤ 0.05) and dose dependently reversed the weight loss, increased the line-crossing activity in OFT, increased sucrose consumption in SPT, decreased the duration of immobility in TST, and increased the novelty exploration time in NORT. The MEAD extract significantly (p ≤ 0.05) and dose dependently increased the levels of BDNF, decreased the levels of plasma cortisol, increased the levels of total SOD activity, and decreased the levels of plasma MDA. Conclusion Our findings show that MEAD ameliorates CUMS-induced depressive-like behavior and its effect is possibly mediated via the neuroendocrine, neurotrophic, and oxidative stress pathways.

Memory Susceptibility to Retroactive Interference Is Developmentally Regulated by NMDA Receptors

Retroactive interference (RI) occurs when new incoming information impairs an existing memory, which is one of the primary sources of forgetting. Although long-term potentiation (LTP) reversal shows promise as the underlying neural correlate, the key molecules that control the sensitivity of memory circuits to RI are unknown, and the developmental trajectory of RI effects is unclear. Here we found that depotentiation in the hippocampal dentate gyrus (DG) depends on GluN2A-containing NMDA receptors (NMDARs). The susceptibility of LTP to disruption progressively increases with the rise in the GluN2A/GluN2B ratio during development. The vulnerability of hippocampus-dependent memory to interference from post-learning novelty exploration is subject to similar developmental regulation by NMDARs. Both GluN2A overexpression andGluN2B downregulation in the DG promote RI-induced forgetting. Altogether, our results suggest that a switch in GluN2 subunit predominance may confer age-related differences to depotentiation and underlie the developmental decline in memory resistance to RI.

Rats selectively bred for showing divergent behavioral traits in response to stress or novelty or spontaneous yawning with a divergent frequency show similar changes in sexual behavior: the role of dopamine.

Sexual behavior plays a fundamental role for reproduction in mammals and other animal species. It is characterized by an anticipatory and a consummatory phase, and several copulatory parameters have been identified in each phase, mainly in rats. Sexual behavior varies significantly across rats even when they are of the same strain and reared under identical conditions. This review shows that rats of the same strain selectively bred for showing a divergent behavioral trait when exposed to stress or novelty (i.e. Roman high and low avoidance rats, bred for their different avoidance response to the shuttle box, and high and low novelty exploration responders rats, bred for their different exploratory response to a novel environment) or a spontaneous behavior with divergent frequency (i.e. low and high yawning frequency rats, bred for their divergent yawning frequency) show similar differences in sexual behavior, mainly in copulatory pattern, but also in sexual motivation. As shown by behavioral pharmacology and intracerebral microdialysis experiments carried out mainly in Roman rats, these sexual differences may be due to a more robust dopaminergic tone present in the mesocorticolimbic dopaminergic system of one of the two sub-lines (e.g. high avoidance, high novelty exploration, and low yawning rat sub-lines). Thus, differences in genotype and/or in prenatal/postnatal environment lead not only to individual differences in temperament and environmental/emotional reactivity but also in sexual behavior. Because of the highly conserved mechanisms controlling reproduction in mammals, this may occur not only in rats but also in humans.

Feeling the Shape: Active Exploration Behaviors for Object Recognition With a Robotic Hand

Autonomous exploration in robotics is a crucial feature to achieve robust and safe systems capable to interact with and recognize their surrounding environment. In this paper, we present a method for object recognition using a three-fingered robotic hand actively exploring interesting object locations to reduce uncertainty. We present a novel probabilistic perception approach with a Bayesian formulation to iteratively accumulate evidence from robot touch. Exploration of better locations for perception is performed by familiarity and novelty exploration behaviors, which intelligently control the robot hand to move toward locations with low and high levels of interestingness, respectively. These are active behaviors that, similar to the exploratory procedures observed in humans, allow robots to autonomously explore locations they believe that contain interesting information for recognition. Active behaviors are validated with object recognition experiments in both offline and real-time modes. Furthermore, the effects of inhibiting the active behaviors are analyzed with a passive exploration strategy. The results from the experiments demonstrate the accuracy of our proposed methods, but also their benefits for active robot control to intelligently explore and interact with the environment.

Developmental neurotoxicity in the progeny after maternal gavage with chlorpyrifos

Today, developmental intellectual disorders affect one out of six children in industrialised countries. Intensively used in agriculture, the neurotoxicant pesticide chlorpyrifos (CPF) is known for its environmental persistence and bioaccumulation. Its role has not yet been established in the aetiology of intellectual impairments. Here we assessed whether maternal ingestion of low CPF dose in rats could impair the cerebral function of their progeny.Rat dams received daily CPF exposures (1 mg/kg, per os) during gestation and lactation. Behaviours relevant to mental retardation were measured in the surface righting, negative geotaxis and grip strength at post-natal days (PND) 3 and 7. Open field tests were performed at PND 16, 18 and 20. Fear conditioning was assessed at PND 34. Startle inhibition was tested at PND 31 and 60.According to the results, the progeny of CPF-treated dams showed slower negative geotaxis as neonates, lower novelty exploration as juveniles and faster startle reflex as adolescents and adults.This data suggests that developmental CPF relevant to human exposure may impair novelty-related activity and sensori-motor functions, thus adaptability to the environment. This data supports the hypothesis that CPF may contribute to behavioural disorders including acquisition retardation and consequences as an adult.

Objective assessment of exploratory behaviour in schizophrenia using wireless motion capture

Motivation deficits are a prominent feature of schizophrenia and have substantial consequences for functional outcome. The impact of amotivation on exploratory behaviour has not been extensively assessed by entirely objective means. This study evaluated deficits in exploratory behaviour in an open-field setting using wireless motion capture. Twenty-one stable adult outpatients with schizophrenia and twenty matched healthy controls completed the Novelty Exploration Task, in which participants explored a novel environment containing familiar and uncommon objects. Objective motion data were used to index participants' locomotor activity and tendency for visual and tactile object exploration. Clinical assessments of positive and negative symptoms, apathy, cognition, depression, medication side-effects, and community functioning were also administered. Relationships between task performance and clinical measures were evaluated using Spearman correlations, and group differences were evaluated using multivariate analysis of covariance tests. Although locomotor activity and tactile exploration were similar between the schizophrenia and healthy control groups, schizophrenia participants exhibited reduced visual object exploration (F(2,35)=3.40, p=0.045). Further, schizophrenia participants' geometric pattern of locomotion, visual exploration, and tactile exploration were correlated with overall negative symptoms (|ρ|=0.46–0.64, p<=0.039) and apathy (|ρ|=0.49–0.62, p<=0.028), and both visual and tactile exploration were also correlated with community functioning (|ρ|=0.46–0.48, p<=0.043). The Novelty Exploration Task may be a valuable tool to quantify exploratory behaviour beyond what is captured through standard clinical instruments and human observer ratings. Findings from this initial study suggest that locomotor activity and object interaction tendencies are impacted by motivation, and reveal deficits specifically in visual exploration in schizophrenia.

Mismatch novelty exploration training enhances hippocampal synaptic plasticity: A tool for cognitive stimulation?

Memory formation relies on experience-dependent changes in synaptic strength such as long-term potentiation (LTP) or long-term depression (LTD) of synaptic activity, that in turn depend on previous learning experiences through metaplasticity. Novelty detection is a particularly important cognitive stimulus in this respect, and mismatch novelty has been associated with the activation of the hippocampal CA1 area in human studies. A single exposure to a new location of known objects in a familiar environment, a behavioural mismatch novelty paradigm, is known to favour the expression of LTD in hippocampal CA3 to CA1 synaptic transmission in vivo, through short-term metaplasticity. Aiming to shape hippocampal responsiveness to synaptic plasticity phenomena we developed a training program based on exploration of a known environment containing familiar objects, everyday presented in a new location. Repeated exposure to this new location of objects for two weeks caused a mild long-lasting decrease in synaptic efficacy. Furthermore, it enhanced both LTP evoked by theta-burst stimulation and depotentiation evoked by low-frequency stimulation of CA3 to CA1hippocampal synaptic transmission in juvenile rats. This suggests that training programs using these behavioural tasks involving mismatch novelty can be used to reshape brain circuits and promote cognitive recovery in pathologies where LTP/LTD imbalance occurs, such as epilepsy, aging or Down’s syndrome, an approach that requires further investigation at the behavioural level.

Handling newborn monkeys alters later exploratory, cognitive, and social behaviors

Touch is one of the first senses to develop and one of the earliest modalities for infant-caregiver communication. While studies have explored the benefits of infant touch in terms of physical health and growth, the effects of social touch on infant behavior are relatively unexplored. Here, we investigated the influence of neonatal handling on a variety of domains, including memory, novelty seeking, and social interest, in infant monkeys (Macaca mulatta; n = 48) from 2 to 12 weeks of age. Neonates were randomly assigned to receive extra holding, with or without accompanying face-to-face interactions. Extra-handled infants, compared to standard-reared infants, exhibited less stress-related behavior and more locomotion around a novel environment, faster approach of novel objects, better working memory, and less fear towards a novel social partner. In sum, infants who received more tactile stimulation in the neonatal period subsequently demonstrated more advanced motor, social, and cognitive skills—particularly in contexts involving exploration of novelty—in the first three months of life. These data suggest that social touch may support behavioral development, offering promising possibilities for designing future early interventions, particularly for infants who are at heightened risk for social disorders.