Jocelyne Bachevalier

• Emory University

Socially guided visual attention, such as gaze following and joint attention, represents the building block of higher-level social cognition in primates, although their neurodevelopmental processes are still poorly understood. Atypical development of these social skills has served as early marker of autism spectrum disorder and Williams syndrome. I...

Human episodic memory is not functionally evident until about 2 years of age and continues to develop into the school years. Behavioral studies have elucidated this developmental timeline and its constituent processes. In tandem, lesion and neurophysiological studies in non-human primates and rodents have identified key neural substrates and circui...

This study examined the role of male pubertal maturation on physical growth and development of neurocircuits that regulate stress, emotional and cognitive control using a translational nonhuman primate model. We collected longitudinal data from male macaques between pre- and peri-puberty, including measures of physical growth, pubertal maturation (...

Differences in looking at the eyes of others are one of the earliest behavioral markers for social difficulties in neurodevelopmental disabilities, including autism. However, it is unknown how early visuo-social experiences relate to the maturation of infant brain networks that process visual social stimuli. We investigated functional connectivity...

Exposure to early life adversity has long term consequences on cognitive function. Most research has focused on understanding components of early life adversities that contribute to later risk, including poverty, trauma, maltreatment, and neglect. Whereas these factors, in the aggregate, explain a significant proportion of emotional and cognitive p...

The hippocampus is important for long-term memory storage, but also plays a role in regulating the hypothalamic-pituitary-adrenal (HPA) axis and emotional behaviors. We previously reported that early hippocampal damage in monkeys result in increased anxious expression and blunted HPA responses to an acute stressor. Here, we further probe their resp...

Sensory-motor gating, the process of filtering sensory stimuli to modulate motor responses, is impaired in many psychiatric diseases but especially schizophrenia. Sensory-motor gating assessed with the prepulse inhibition paradigm (PPI) measures startle in response to preceding acoustic stimuli. PPI studies in rodents have consistently found that n...

The amygdala and orbitofrontal cortex (OFC) are interconnected regions that serve as key nodes in brain circuits supporting social and affective behaviors. An important question that has come into focus is whether these regions also play a fundamental role in responding to novelty. One possibility is that these regions are important for discriminat...

With the ultimate goal of developing a more representative animal model of Alzheimer's disease (AD), two female amyloid-β-(Aβ) precursor protein-transgenic (APPtg) rhesus monkeys were generated by lentiviral transduction of the APP gene into rhesus oocytes, followed by in vitro fertilization and embryo transfer. The APP-transgene included the AD-as...

Nonhuman primates and especially rhesus macaques (Macaca mulatta) have been indispensable animal models for studies of various aspects of neurobiology, developmental psychology, and other aspects of neuroscience. While remarkable progress has been made in our understanding of influences on atypical human social behavior, such as that observed in au...

Primates form strong social bonds and depend on social relationships and networks that provide shared resources and protection critical for survival. Social deficits such as those present in autism spectrum disorder (ASD) and other psychiatric disorders hinder the individual’s functioning in communities. Given that early diagnosis and intervention...

This study mapped the developmental trajectories of cortical regions in comparison to overall brain growth in typically developing, socially-housed infant macaques. Volumetric changes of cortical brain regions were examined longitudinally between 2–24 weeks of age (equivalent to the first 2 years in humans) in 21 male rhesus macaques. Growth of the...

The dorsolateral prefrontal cortex (DLPFC) and ventral lateral prefrontal cortex (VLPFC) play critical but different roles in working memory (WM) processes. Resting-state functional MRI (rs-fMRI) was employed to investigate the effects of neonatal hippocampal lesions on the functional connectivity (FC) between the hippocampus (H) and the DLPFC and...

An earlier study in monkeys indicated that lesions to the mid-portion of the ventral orbitofrontal cortex (OFC), including Walker’s areas 11 and 13 (OFC11/13), altered the spontaneous scanning of still pictures of primate faces (neutral and emotional) and the modulation of arousal. Yet, these conclusions were limited by several shortcomings, includ...

Inflammation has been linked to the development of nonmotor symptoms in Parkinson's disease (PD), which greatly impact patients' quality of life and can often precede motor symptoms. Suitable animal models are critical for our understanding of the mechanisms underlying disease and the associated prodromal disturbances. The neurotoxin 1-methyl-4-phe...

Primates form strong social bonds and depend on social relationships and networks that provide shared resources and protection critical for survival. Social deficits such as those present in autism spectrum disorder (ASD) and other psychiatric disorders hinder the individual’s functioning in communities. Given that early diagnosis and intervention...

The typical developmental trajectory of brain structure among nonhuman primates (NHPs) remains poorly understood. In this study, we characterized the normative trajectory of developmental change among a cohort of rhesus monkeys (n = 28), ranging in age from 2 to 22 months, using structural MRI datasets that were longitudinally acquired every 3-4 mo...

The amygdala plays an essential role in evaluating social information, threat detection, and learning fear associations. Yet, most of that knowledge comes from studies in adult humans and animals with a fully developed amygdala. Given the considerable protracted postnatal development of the amygdala, it is important to understand how early damage t...

Impairments in social interaction in Autism Spectrum Disorder (ASD) differ greatly across individuals and vary throughout an individual’s lifetime. Yet, an important marker of ASD in infancy is deviations in social-visual engagement, such as the reliably detectable early deviations in attention to the eyes or to biological movement (Klin et al., 20...

To further assess orbitofrontal cortex (OFC) contribution to the processing of socioemotional signals, spontaneous scanning patterns and pupil diameter variations were measured while adult rhesus macaques with either bilateral lesions of OFC areas 11 and 13 (Group O-asp) or sham-operations (Group C) freely viewed pictures of neutral and expressive...

Inflammation has been linked to the development of nonmotor symptoms in Parkinson’s disease (PD), which greatly impact patients’ quality of life and can often precede motor symptoms. Suitable animal models are critical for our understanding of the mechanisms underlying disease and the associated prodromal disturbances. The neurotoxin 1- methyl-4-ph...

Nonhuman primates provide highly valuable animal models that have significantly advanced our understanding of numerous behavioral and biological phenomena in humans. Here, we reviewed a series of developmental neuropsychological studies that informed us on the timing of development of the hippocampus and of hippocampal-dependent cognitive functions...

Perceiving, integrating, and interpreting multimodal signals are essential for social success, but the neural substrates mediating these functions are not fully understood. This study examined the role of the amygdala in processing bimodal species-specific vocalizations using eye tracking in rhesus macaques. Looking behavior of 6 adult rhesus monke...

Previous research indicated that monkeys with neonatal perirhinal lesions (Neo-PRh) were impaired on working memory (WM) tasks that generated proactive interference, but performed normally on WM tasks devoid of interference (Weiss et al., 2016). This finding suggested that the early lesions disrupted cognitive processes important for resolving proa...

This study examined whether selective neonatal hippocampal lesions in monkeys ( Macaca mulatta ), which left the surrounding cortical areas (parahippocampal cortex) intact, affect contextual learning and memory compared with controls. Monkeys were tested with an automated touch-screen apparatus so that stimuli and contextual cues could be manipulat...

Objective: Although a large body of research has identified discrete neuroanatomical regions involved in social cognition and behavior (the 'social brain'), the existing findings are based largely on studies of specific brain structures defined within the context of particular tasks or for specific types of social behavior. The objective of the cu...

Early social interactions shape the development of social behavior, although the critical periods or the underlying neurodevelopmental processes are not completely understood. Here, we studied the developmental changes in neural pathways underlying visual social engagement in the translational rhesus monkey model. Changes in functional connectivity...

To investigate the effects of neonatal hippocampal lesions on the microstructural integrity of the corpus callosum (CC) in adulthood, macaque monkeys (n = 5) with neonatal bilateral neurotoxic hippocampal lesion (Neo-Hibo) and sham-operated controls (Neo-C, n = 5) were scanned using magnetic resonance diffusion tensor imaging (DTI) technique at 8-1...

Due to its incidental nature, the visual paired comparison (VPC) task has been the task of choice to study recognition memory development and its neural substrate in primates. In this chapter, we review a series of studies in adult monkeys that are shading light on the role of the medial temporal lobe structures in object and spatial recognition me...

Our understanding of human amnesia has been greatly advanced through the use of animal models. Although animals and humans differ greatly in many ways, the basic principles of brain organization and function are homologous. The use of selective methods of lesion production has enabled neuroscientists to examine in rats and monkeys the contribution...

Transgenic Huntington’s disease monkey (HD monkey) model provides great opportunity for studying disease progression that could lead to new insight for developing biomarker, early intervention and novel therapeutics. Whole brain white matter integrity of HD-monkeys was examined longitudinally from 6 to 48 months using diffusion tensor imaging (DTI)...

The medial temporal lobe (MTL) is a collection of brain regions best known for their role in perception, memory, and emotional behavior. Within the MTL, the perirhinal cortex (PRh) plays a critical role in perceptual representation and recognition memory, although its contribution to emotional regulation is still debated. Here, rhesus monkeys with...

The perirhinal cortex is known to support high-level perceptual abilities as well as familiarity judgments that may affect recognition memory. We tested whether poor perceptual abilities or a loss of familiarity judgment contributed to the recognition memory impairments reported earlier in monkeys with PRh lesions received in infancy (Neo-PRh) (Wei...

This study provides the first characterization of early developmental trajectories of corpus callosum (CC) segments in rhesus macaques using noninvasive MRI techniques and assesses long-term effects of neonatal amygdala or hippocampal lesions on CC morphometry. In Experiment 1, 10 monkeys (5 males) were scanned at 1 week-2 years of age; eight addit...

The use of Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) in neuroscience has rapidly expanded in rodent studies, but has lagged behind in nonhuman primate (NHP) experiments, slowing the development of this method for therapeutic use in humans. One reason for the slow adoption of DREADD technology in primates is that the pharm...

The present study tested whether relational memory processes, as measured by the transverse patterning problem, are late-developing in nonhuman primates as they are in humans. Eighteen macaques ranging from 3-36 months of age, were trained to solve a set of visual discriminations that formed the transverse patterning problem. Subjects were trained...

The hippocampus is most notably known for its role in cognition and spatial memory; however it also plays an essential role in emotional behaviors and neuroendocrine responses. The current study investigated the long-term effects of neonatal hippocampal lesions (Neo-Hibo) on emotional and hypothalamic-pituitary-adrenal (HPA) axis functioning. Durin...

Developmental amnesia is a selective episodic memory disorder associated with hypoxia-induced bilateral hippocampal atrophy of early onset. Despite the systemic impact of hypoxia-ischaemia, the resulting brain damage was previously reported to be largely limited to the hippocampus. However, the thalamus and the mammillary bodies are parts of the hi...

Neonatal hippocampal lesions in monkeys impairs normal performance on both relational and working memory tasks, suggesting that the early lesions have impacted the normal development of prefrontal-hippocampal functional interactions necessary for normal performance on these tasks. Given that working memory processes engage distributed neuronal netw...

The contribution of the perirhinal cortex (PRh) to recognition memory is well characterized in adults, yet the same lesions have limited effect on recognition of spatial locations. Here, we assessed whether the same outcomes will follow when perirhinal lesions are performed in infancy. Monkeys with neonatal perirhinal (Neo-PRh) lesions and control...

The lateral prefrontal cortex is known for its contribution to working memory (WM) processes in both humans and animals. Yet, recent studies indicate that the prefrontal cortex is part of a broader network of interconnected brain areas involved in WM. Within the medial temporal lobe (MTL) structures, the perirhinal cortex, which has extensive direc...

One of the roadblocks to developing effective therapeutics for Huntington disease (HD) is the lack of animal models that develop progressive clinical traits comparable to those seen in patients. Here we report a longitudinal study that encompasses cognitive and motor assessment, and neuroimaging of a group of transgenic HD and control monkeys from...

Studies investigating the development of memory processes and their neural substrates have flourished over the past two decades. The review by Jabès and Nelson (2015) adds an important piece to our understanding of the maturation of different elements and circuits within the hippocampal system and their association with the progressive development...

Social context influences the timing of puberty in both humans and nonhuman primates, such as delayed first ovulation in low-ranking rhesus macaques, but the brain region(s) mediating the effects of social context on pubertal timing are unknown. The amygdala is important for responding to social information and thus, is a potential brain region med...

The current study examined the effects of neonatal amygdala lesions on mother-infant interactions in rhesus monkeys reared in large species-typical social groups. Focal observations of mother-infant interactions were collected in their social group for the first 12 months postpartum on infants that had received amygdala lesions (Neo-A) at 24-25 day...

Attachment to the caregiver, typically the biological mother, is crucial to young mammals' socio-emotional development. Although studies in nonprimate species suggest that the amygdala regulates social preference and attachment development, its role in primate filial attachment development has been little investigated and has produced mixed results...

Unlike adult damage, neonatal damage to the inferior prefrontal convexity (IC) in monkeys spares learning and performance on the delayed nonmatching-to-sample (DNMS) task ( Málková et al. 2000). We investigated whether this sparing was due to compensation by undamaged orbital frontal cortex (O), an area also critical for DNMS, by comparing combined...

Neuropsychological and brain imaging studies have demonstrated persistent deficits in memory functions and structural changes after neonatal neurotoxic hippocampal lesion in monkeys. However, the relevant microstructural changes in the white matter of affected brain regions following this early insult remain unknown. This study assessed white matte...

The current study examined the long-term effects of neonatal amygdala (Neo-A) lesions on brain corticotropin-releasing factor (CRF) systems and hypothalamic-pituitary-adrenal (HPA) axis function of male and female prepubertal rhesus monkeys. At 12-months-old, CSF levels of CRF were measured and HPA axis activity was characterized by examining diurn...

This study further investigated the specific contributions of the medial temporal lobe structures to contextual recognition memory. Monkeys (Macaca mulatta) with either neurotoxic lesions of the hippocampus, aspiration lesions of the perirhinal cortex and parahippocampal areas TH/TF, or sham operations were tested on five conditions of a visual-pai...

To investigate the role of the perirhinal cortex on the development of recognition measured by the visual paired-comparison (VPC) task, infant monkeys with neonatal perirhinal lesions and sham-operated controls were tested at 1.5, 6, 18, and 48 months of age on the VPC task with color stimuli and intermixed delays of 10 s, 30 s, 60 s, and 120 s. Mo...

Background: Patients with developmental amnesia (DA) experi-ence a profound yet selective episodic memory loss. We previ-ously showed that this impairment is related to severe bilateral hippocampal atrophy (of ~30% and above) sustained during an early episode of hypoxia-ischaemia (Isaacs et al., PNAS, 2003). Milder deficits in memory function and/o...

Recent studies in monkeys have demonstrated that damage to the lateral subfields of orbital frontal cortex (OFC areas 11/13) yields profound changes in flexible modulation of goal-directed behaviors and deficits in fear regulation. Yet, little consideration has been placed on its role in emotional and social development throughout life. The current...

A two-year longitudinal study composed of morphometric MRI measures and cognitive behavioral evaluation was performed on a transgenic Huntington's disease (HD) monkey. rHD1, a transgenic HD monkey expressing exon 1 of the human gene encoding huntingtin (HTT) with 29 CAG repeats regulated by a human polyubiquitin C promoter was used together with fo...

The human brain develops rapidly over the first few years of life, allowing the nearly helpless infant to perceive, organize thought, and respond adaptively to internal and environmental cues. The story of brain development from infancy through adolescence occupies the first part of Chapter 43, Cognitive Development and Aging, followed by a conside...

Crossmodal integration of audio/visual information is vital for recognition, interpretation and appropriate reaction to social signals. Here we examined how rhesus macaques process bimodal species-specific vocalizations by eye tracking, using an unconstrained preferential looking paradigm. Six adult rhesus monkeys (3M, 3F) were presented two side-b...

This chapter begins with a brief review of the existence of multiple memory systems. Then, a description of the anatomical organization of the medial temporal lobe (MTL) structures and their participation in declarative memory processes provides basic knowledge that led to the development of animal models for assessing the brain systems associated...

In a recent longitudinal study to assess the development of incidental recognition memory processes in monkeys, we showed that the effects of neonatal hippocampal lesions did alter incidental recognition memory only when the animals reached the juvenile period (Zeamer et al., 2010). The current follow-up study tested whether this incidental memory...

The amygdala is known to be a key neural structure in many neuropsychiatric disorders. Primarily known for its involvement in fear regulation, the amygdala also plays a critical role in appetitive flexible decision-making. Yet, its contribution to the development of flexible goal-directed behavior has not been thoroughly examined. The current study...

This study traces the development of spatial memory abilities in monkeys and reports the effects of selective neonatal hippocampal lesions on performance across development. Two different versions of the visual paired-comparison (VPC) task were used. The VPC-Spatial-Location task tested memory for object-locations that could be solved using an egoc...

Amygdala dysfunction and abnormal fear and stress reactivity are common features of several developmental neuropsychiatric disorders. Yet, little is known about the exact role the amygdala plays in the development of threat detection and emotional modulation. The current study examined the effects of neonatal amygdala lesions on defensive, emotiona...

This study describes a novel spatial memory paradigm for monkeys and reports the effects of neonatal damage to the hippocampus on performance in adulthood. Monkeys were trained to forage in eight boxes hung on the walls of a large enclosure. Each box contained a different food item that varied in its intrinsic reward value, as determined from food...

We examined the role of the hippocampus in list-memory processing. Three rhesus monkeys that had extensive experience in this task and had demonstrated full abstract-concept learning and excellent list memory performance (Katz et al., 2002; Wright et al., 2003) received bilateral neurotoxic hippocampal lesions and were re-tested in the serial list...

The amygdala is mostly thought to exert an excitatory influence on the hypothalamic-pituitary-adrenal (HPA) axis, although its role regulating HPA basal tone is less clear, particularly during primate development. The current study examined the effects of neonatal amygdala lesions on basal HPA function and the postnatal testosterone (T) surge of rh...

The current study examined the long-term effects of neonatal amygdala lesions on emotional and hypothalamic-pituitary-adrenal (HPA) axis reactivity to an acute stressor in rhesus monkeys. Rhesus monkeys received either bilateral MRI-guided ibotenic acid amygdala (Neo-Aibo; n=6) or sham (Neo-C; n=7) lesions between 7 and 14 days of age. Emotional re...

A previous study in this laboratory demonstrated, for the first time, that neonatal lesions of the hippocampus impair monitoring working memory, as measured by a self-order task, but spare recency memory, as measured by the session-unique delayed nonmatching task. To substantiate and extend this novel finding, we assessed working memory in these sa...

Rationale : Rodent studies indicate that the orbital and medial prefrontal cortex have an inhibitory control on the hypothalamic–pituitary–adrenal (HPA) axis, by restraining the acute stress response and facilitating negative feedback inhibition, which can also affect its basal tone of activity. Similarly in humans, extent of damage to the medial p...

Fear conditioning studies have demonstrated the critical role played by the amygdala in emotion processing. Although all lesion studies until now investigated the effect of adult-onset damage on fear conditioning, the current study assessed fear-learning abilities, as measured by fear-potentiated startle, in adult monkeys that had received neonatal...

Neither lesions of orbital frontal (OFC) areas 11/13 nor selective amygdala lesions alter the ability to learn stimulus-reinforcer association and reversal discriminations in adult monkeys. Here, we investigated whether the same conclusion will hold true when the same lesions occur in infancy. Infant rhesus monkeys received sham-operations, neuroto...

A variety of behavioral instruments are available for assessing important aspects of cognition in both animals and humans and, in many cases, the same instruments can be used in both. While nonhuman primates are phylogenetically closest to humans, rodents, pigeons and other animals also offer behaviors worthy of note. Delay Discounting procedures a...

The orbital frontal cortex (OFC) has been implicated in a number of psychiatric disorders, including depression, anxiety, phobia, and obsessive-compulsive disorder. Thus, a better understanding of its functions will likely provide critical information to understand the specific behavioral and cognitive processes affected in these human disorders. I...

The oddity task (e.g., A-, A-, B+) is classified as a conjunctive or relational task in which accurate performance depends upon learning to attend to stimulus relationships, not stimulus identity, and has no retention component as stimuli are presented simultaneously. It has been suggested that the hippocampus may play a particular role in learning...

Neonatal hippocampal damage in rodents impairs medial prefrontal working memory functions. To examine whether similar impairment will follow the same damage in primates, adult monkeys with neonatal hippocampal lesions and sham-operated controls were trained on two working memory tasks. The session-unique delayed nonmatch-to-sample (SU-DNMS) task me...

The purpose of the present investigation was to characterize the relations of specific social communication behaviors, including joint attention, gestures, and verbalization, with surface area of midsagittal corpus callosum (CC) subregions in children who sustained traumatic brain injury (TBI) before 7 years of age. Participants sustained mild (n=1...

Background: Investigation of the social skills of non-human primates in the wild and in the laboratory have revealed that monkeys, like humans, live in social groups characterized by complex and dynamic social organization through a variety of specific, long-term relationships between group members. This inherently social behavior has a neural basi...

A dysregulated fear response is one of the hallmark clinical presentations of patients suffering from posttraumatic stress disorder (PTSD). These patients show over-generalization of fear and in tandem an inability to inhibit fear responses in the presence of safety. Here, we summarize our recent findings using a conditional discrimination paradigm...

Earlier studies in monkeys have reported mild impairment in recognition memory after nonselective neonatal hippocampal lesions. To assess whether the memory impairment could have resulted from damage to cortical areas adjacent to the hippocampus, we tested adult monkeys with neonatal focal hippocampal lesions and sham-operated controls in three rec...

Recognition memory impairment after selective hippocampal lesions in monkeys is more profound when measured with visual paired-comparison (VPC) than with delayed nonmatching-to-sample (DNMS). To clarify this issue, we assessed the impact of stimuli similarity and encoding duration on the VPC performance in monkeys with hippocampal lesions and sham-...

Socioemotional abnormalities, including decreased social interactions and increased self-directed activity, were reported when rhesus monkeys with neonatal ablations of either the medial temporal lobe (AH) or the inferior temporal cortex (TE) were paired with unoperated peers at two and six months of age, though these abnormalities were more severe...

Many studies have shown that the direction of gaze of a face covertly facilitates the response to a target presented in the matching direction. In this study we seek to determine whether there exist separate reflexive and voluntary forms of such covert social orienting and how they interact with each other. We measured the effect of the predictive...

Malformations of the hippocampal formation and amygdala have been implicated in several neurodevelopmental disorders; yet relatively little is known about their normal structural development. The purpose of this study was to characterize the early developmental trajectories of the hippocampus and amygdala in the rhesus macaques (Macaca mulatta) usi...

To examine the developmental trajectory of object recognition memory and its neural substrate, 10-12-d-old monkeys (Macaca mulatta) received sham operations or neurotoxic hippocampal lesions and were tested at the ages of 1.5, 6, and 18 months on the visual paired-comparison task using delays of 10, 30, 60, and 120 s. In sham-operated controls, inc...

Background: Autism is a neurodevelopmental disorder characterized by social-cognitive differences affecting many areas of functioning. Autism is also highly heterogeneous with a complex genetic and neural basis. Medial temporal lobe structures including amygdala and hippocampus have been identified by imaging, histopathologic, neurologic and neurop...

This article provides a survey of sex dimorphism in behaviors and cognitive abilities, its expression across the life span and across different primate species, and its relation to brain anatomy and function. Gonadal hormones organize the brain pre- and perinatally and result in sexually dimorphic behaviors related to reproductive functions and cog...

The medial temporal lobe plays a critical role in recognition memory but, within the medial temporal lobe, the precise neural structures underlying recognition memory remain equivocal. In this study, visual paired comparison (VPC) was used to investigate recognition memory in a human patient (YR), who had a discrete lesion of the hippocampus, and a...

Damage to the orbital frontal cortex (OFC) has long been associated with reversal learning deficits in several species. In monkeys, this impairment follows lesions that include several OFC subfields. However, the different connectional patterns of OFC subfields together with neuroimaging data in humans have suggested that specific OFC areas play di...

The authors measured the effects of bilateral amygdaloid, orbital frontal, or hippocampal lesions on emotional reactivity and passive avoidance in rhesus monkeys (Macaca mulatta). Animals were presented with 8 neutral or 8 aversive objects, each paired with a highly preferred food reward. Sham-operated control animals displayed heightened defensive...