Which hand knows the "right" word? What hand selection reveals about vocabulary in pre-and school-aged children.

Research has shown that infants with increased right-hand selection for their first gestures perform better at an array of language tasks when they are tested later as toddlers. There is a smaller body of literature which focuses on preschoolers and how their right-handed movements relate to their speech and vocabulary development. Some research has established a connection between right-hand preference for grasping and speech production ability in preschool children, but the link to gestures is relatively unexplored in this age group. We investigated if lateralized gestures (pointing) are related to measures of language development (vocabulary) in a preschool-age sample. Specifically, typically developing children (aged 3-6) completed the Peabody Picture Vocabulary Test (PPVT) to assess receptive language. We recorded their hand preference for pointing during the PPVT and the incidence of mistakes (pointing to the wrong picture). Despite the length of the test, children were more likely to select a correct response with their right hand. This result suggests a relationship between lateralized communicative gestures (pointing) and receptive language. This study provides evidence for an intimate relationship between right-handed manual movement and language development. Implications of this finding include developing simple fine-motor tasks to detect and/or ameliorate delayed language development.

The association between sedentary behavior and cognitive ability in older adults.

Executive functions (EF) are a grouping of cognitive abilities essential for daily life. Previous research has shown that physical activity (PA) may in fact preserve EF in older adults, but the link between sedentary behavior (SB) and cognitive ability has been less explored. The purpose of this study was to examine the relationship between SB and cognition (executive function and memory) in older adults. Seventy five older adults (74.6 ± 9 years) self-reported their sedentary time (ST) and PA, as well as EF ability (paper-based measure of EF). Participants also completed several performance-based measures of EF and a memory task. Older adults who were less sedentary had superior EF and memory (e.g., Stroop time was significantly faster in less sedentary adults (34.7 s ± 1.9) compared to more sedentary adults (39.6 s ± 1.8), p = .02). Regression analysis showed that total ST was associated with several measures of EF after adjusting for age, and physical activity (e.g., Stroop time ß = .005 (.002, .009). Less cognitively demanding SB (TV viewing and napping) was associated with worse performance on most EF and in the memory task. Performing a hobby was also associated with lower levels of EF and memory. For example, the building times for the Lego task were positively related to napping (r2 = .34), watching TV (r2 = .27), and performing a hobby (r2 = .46). Associations of ST with cognitive abilities were more pronounced in older adults who engaged in less PA. These results suggest that SB may play an important role in cognitive abilities of older adults. Longitudinal studies using performance-based assessments of EF are needed. Lara Coelho and Kayla Hauck contributed equally to the manuscript.

Development of ultrasonic calls in rat pups follows similar patterns regardless of isolation distress.

Ultrasonic vocalizations (USVs) emitted by rat pups have been extensively studied in the context of isolation from their mother and littermates. The heightened call rate of isolation-induced USVs indicates increased anxiety, whereas other acoustic parameters, such as frequency and call duration, are thought to be useful in reflecting developmental changes, which by weaning have developed into their adult form. However, it is possible that stress can affect the quality as well as the quantity of calls, and that as the pups become more mobile, the effects of the stress may change. Therefore, in the present study rats were tested in a test arena either in isolation or with littermates, so as to assess the effects of isolation stress on the developmental changes reported in the literature. Rat pups of both sexes were tested on multiple days from postnatal day (PND) 7 to weaning. Overall, the main changes in the frequency, duration, and types of calls were accounted for by age. The effects of isolation were minor, as were sex differences. This study indicates that the development of USVs in infant rats is a robust process and seemingly resistant to the effects of isolation-induced stress.

Principles of plasticity in the developing brain.

The developing brain is especially sensitive to a wide range of experiences, showing a remarkable capacity for plastic changes that influence behavioural outcomes throughout the lifetime. We review the principles that regulate this plasticity in development and consider the factors that modulate the developing brain. These include early sensory, motor, and language experience, early stress, caregiver interactions, peer interactions, psychoactive drugs, diet, microbiome, and the immune system. Emphasis is given to changes in behaviour, epigenetics, and neuronal morphology. WHAT THIS PAPER ADDS: A discussion of the surprising range of factors influencing brain development Life experiences interact resulting in a phenomenon called metaplasticity.

Effects of prenatal exposure to valproic acid on the development of juvenile-typical social play in rats.

Autism is a severe neurodevelopmental disorder characterized by qualitative impairments in social behavior, communication, and aberrant repetitive behaviors. A major focus of animal models of autism has been to mimic the social deficits of the disorder. The present study assessed whether rats exposed prenatally to valproic acid (VPA) show deficits in social play as juveniles that are consistent with the social deficits observed in autism. Dams were exposed to an acute dose of VPA on gestational day 12.5. Later, the playful interactions and associated ultrasonic vocalizations of the juveniles were examined. It was predicted that VPA-treated rats should play less than the controls. Characteristic of neurobehavioral insult at this early age, the VPA-treated juveniles showed significant increases in the frequency of body shakes and sexual mounting, but played at the same frequency as the controls. However, when playing, they were less likely to use tactics that facilitated bodily contact and vocalized less. These data suggest that prenatal VPA exposure disrupts some aspects of being able to communicate effectively and engage partners in dynamic interactions - deficits that are consistent with those observed in autism.

Experience and the developing prefrontal cortex.

The prefrontal cortex (PFC) receives input from all other cortical regions and functions to plan and direct motor, cognitive, affective, and social behavior across time. It has a prolonged development, which allows the acquisition of complex cognitive abilities through experience but makes it susceptible to factors that can lead to abnormal functioning, which is often manifested in neuropsychiatric disorders. When the PFC is exposed to different environmental events during development, such as sensory stimuli, stress, drugs, hormones, and social experiences (including both parental and peer interactions), the developing PFC may develop in different ways. The goal of the current review is to illustrate how the circuitry of the developing PFC can be sculpted by a wide range of pre- and postnatal factors. We begin with an overview of prefrontal functioning and development, and we conclude with a consideration of how early experiences influence prefrontal development and behavior.

Brain development, experience, and behavior.

Brain development progresses through a series of stages beginning with neurogenesis and progressing to neural migration, maturation, synaptogenesis, pruning, and myelin formation. This review examines the literature on how early experiences alter brain development, including environmental events such as sensory stimuli, early stress, psychoactive drugs, parent-child relationships, peer relationships, intestinal flora, diet, and radiation. This sensitivity of the brain to early experiences has important implications for understanding neurodevelopmental disorders as well as the effect of medical interventions in children.

Tactile stimulation facilitates functional recovery and dendritic change following neonatal hemidecortication in rats.

After large neocortical lesions, such as hemidecortication, children can show significant motor and cognitive impairments. It thus is of considerable interest to identify treatments that might enhance long-term functional outcome. We have previously shown that tactile stimulation enhances recovery from perinatal focal cortical lesions in rats, so the goal of the present experiment was to explore the effectiveness of postlesion tactile stimulation in reducing functional deficits associated with neonatal hemidecortication. Rats were given hemidecortications on postnatal day 10 (P10). Half of the group was then exposed to a daily tactile stimulation treatment for 15 min, three times a day for eleven days following the surgery. All groups were then tested on a number of behavioural tasks (Morris water task, skilled reaching, forelimb placing during spontaneous vertical exploration, and a sunflower seed opening task) beginning at P 120. The brains of the male animals were prepared for Golgi-Cox staining and subsequent analysis of dendritic arborisation and spine density. There were two main findings in this experiment: 1) Tactile stimulation improved cognitive ability and some motor performance after P 10 hemidecortication; and, 2) Tactile stimulation altered cortical organization after P10 hemidecortication. Tactile stimulation may provide an important noninvasive therapy after hemispherectomy in children.

Comparison of motor recovery after neonatal and adult hemidecortication.

Hemidecortication produces a wide range of cognitive and motor symptoms in both children and lab animals that are generally far greater than smaller bilateral focal lesions of cerebral cortex. Although there have been many studies of motor functions after hemidecortication, the analyses largely have been of general motor functions rather than of more skilled motor functions such as forelimb reaching. The objective of the present experiment was to analyze the sensorimotor forelimb function of rats after infant or adult hemidecortication by utilizing multiple motor analyses. Rats were given hemidecortications either on postnatal day 10 (P10) or day 90 (P90). Both groups were then tested on a number of behavioural tasks (two tests of skilled reaching, forelimb placing during spontaneous vertical exploration, and a sunflower seed opening task) beginning at P 120. In a portion of the P10 female animals, topographic movement representations were derived in the hemisphere contralateral to lesion using Intracortical Microstimulation (ICMS). The brains of the male animals were prepared for Golgi-Cox staining and subsequent analysis of dendritic arborisation and spine density. There were three main findings. 1) Both groups of hemidecorticate animals were impaired when tested on the motor tasks, but the impairments were qualitatively different in the neonatal and adult operates. For example, the P 10 hemidecorticate animals displayed simultaneous bilateral forelimb movement, or "mirror movements." 2) Hemidecortication at P90 but not P10, led to increased dendritic arborisation of Layer III pyramidal cells in the intact parietal cortex but whereas P90 animals showed a decrease in cortical thickness in the intact hemisphere, the P10 animals do not, even though there are no callosal connections. 3) P10 hemidecortication altered the details of the ICMS-delineated motor maps in a small group of female hemidecorticates that were studied. In conclusion, there was postinjury compensation for motor impairments in both P10 and P90 rats but the mechanisms were different. Furthermore, comparisons of postinjury behavioral and anatomical compensation in rats with focal cortical injuries at those ages in our previous studies showed marked differences. These results suggest that there is a fundamental difference in the way that the brain compensates from hemidecortication and focal injury in development.

Embryonic pretreatment with bromodeoxyuridine blocks regeneration and functional recovery from perinatal medial frontal lesions in rats.

Removal of the midline frontal cortex on postnatal day 10 is followed by apparent regeneration of the part of the lost cortex, correlated with substantial recovery of function in adulthood. The spontaneous regrowth of the medial frontal cortex after midline frontal lesions on postnatal day 10 was blocked by pretreatment with bromodeoxyuridine (BrdU) on embryonic days 11, 12, 13, 15, or 17. BrdU pretreatment on embryonic day 21 or postnatal day 10 did not block either functional recovery or cortical regrowth. These results demonstrate a teratological effect of BrdU and are consistent with the claim that functional recovery after midline frontal removal on postnatal day 10 is supported by the generation of new midline frontal tissue.

Prenatal stress alters dendritic morphology and synaptic connectivity in the prefrontal cortex and hippocampus of developing offspring.

The current study used stereological techniques in combination with Golg-Cox methods to examine the neuroanatomical alterations in the prefrontal cortex and hippocampus of developing offspring exposed to gestational stress. Morphological changes in dendritic branching, length, and spine density, were examined at weaning along with changes in actual numbers of neurons. Using this information we generated a gross estimation of synaptic connectivity. The results showed region-specific and sex-dependent alterations to neuroanatomy in response to prenatal stress. The two regions of the prefrontal cortex, medial prefrontal, and orbital prefrontal cortices, exhibited sexually dimorphic, opposite changes, in synaptic connectivity in response to the same experience. Both male and female offspring demonstrated a loss of neuron number and estimated synapse number in the hippocampus despite exhibiting increased spine density. The results from this study suggest that prenatal stress alters normal development and the organization of neuronal circuits in both neocortex and hippocampus early in development and thus likely influences the course of later experience-dependent synaptic changes.

Prenatal nicotine exposure alters neuroanatomical organization of the developing brain.

Although there has been considerable research conducted regarding the long-term effects of prenatal exposure to nicotine, there has been little examination of how this experience influences brain development. This study was designed to examine if there are morphological changes (dendritic branching, dendritic length, and spine density) in medial prefrontal cortex, orbital frontal cortex, parietal cortex, and nucleus accumbens associated with exposure to nicotine during gestation. Nicotine or saline was administered to pregnant Long Evans dams for the duration of pregnancy. Golgi-Cox techniques were used to examine neuroanatomy of offspring at postnatal day 21. The dendritic changes identified in rats exposed to nicotine prenatally resembled neuroanatomical changes that are identified in rats administered with nicotine in adulthood. Of the 18 anatomical parameters measured, 11 exhibited significant modification, with two parameters apical and basilar spine density in parietal cortex demonstrating sex-dependent modification. These early changes in anatomy and behavior have important implications for later plasticity and long-term well-being.

Distinct sex-dependent effects of maternal preconception nicotine and enrichment on the early development of rat offspring brain and behavior.

Developmental nicotine exposure is harmful to offspring. Whereas much is known about the consequences of prenatal nicotine exposure, relatively little is understood about how maternal preconception nicotine impacts the next generation. Positive experiences, such as environmental enrichment/complexity, have considerable potential to improve developmental outcomes and even treat and prevent drug addiction. Therefore, the current study sought to identify how maternal exposure to moderate levels of nicotine prior to conception impacts offspring development, and if the presumably negative consequence of nicotine could be reversed by concurrent exposure to an enriched environment. We treated female Long Evans rats with nicotine in their drinking water (15 mg nicotine salt/L) for seven weeks while residing in either standard or enriched conditions. Both experiences occurred exclusively prior to mating. Nicotine exposure reduced dam fertility by ~20% (p = .06). Females reared their own litters, and offspring were tested in two assessments of early development: negative geotaxis and open field. Offspring were euthanized at weaning (P21), and their brains were processed with Golgi-Cox solution to allow quantification of dendritic spine density. Results indicate that neither maternal nicotine or enrichment had an impact on maternal care, but male offspring were impaired at negative geotaxis due to maternal nicotine, female offspring showed altered open field exploration due to maternal enrichment, and offspring of both sexes had increased spine density in OFC due to maternal enrichment. Therefore, this experiment provides novel insights into the unique, sex-dependent consequences of maternal preconception nicotine and enrichment on the early development of rat behavior and brain.

Maternal stress prior to conception impairs memory and decreases right dorsal hippocampal volume and basilar spine density in the prefrontal cortex of adult male offspring.

Chronic parental stress impacts offspring functioning throughout life. Chronic variable stress prior to conception impairs offspring development in terms of behavior, neuroanatomy, and neurobiology. Previously, our lab demonstrated that even a consistent stressor experienced by the sire or the dam shapes offspring development beginning in early life. Here, we show how consistent maternal stress prior to conception influences the brain and behavior of offspring in adolescence and adulthood. Female Long-Evans rats were exposed to elevated platform stress twice daily for 27 consecutive days immediately prior to mating with non-stressed males. Male and female offspring were assessed in the open field and elevated plus maze in adolescence, and open field, elevated plus maze, Whishaw tray reaching, and Morris water task in adulthood. Offspring were then euthanized, and their brains were stained with Golgi-Cox solution and then examined for dendritic spine density and hippocampal volume. Major findings include deficits in spatial memory, decreased medial prefrontal cortex spine density, and reduced right dorsal hippocampal volume in male offspring only. This work illustrates that the effects of consistent maternal stress prior to conception are lifelong and highly sexually dimorphic.

Acute gut inflammation reduces neural activity and spine maturity in hippocampus but not basolateral amygdala.

Gastrointestinal tract (gut) inflammation increases stress and threat-coping behaviors, which are associated with altered activity in fear-related neural circuits, such as the basolateral amygdala and hippocampus. It remains to be determined whether inflammation from the gut affects neural activity by altering dendritic spines. We hypothesized that acute inflammation alters dendritic spines in a brain region-specific manner. Here we show that acute gut inflammation (colitis) evoked by dextran sodium sulfate (DSS) did not affect the overall spine density in the CA1 region of hippocampus, but increased the relative proportion of immature spines to mature spines on basal dendrites of pyramidal neurons. In contrast, in animals with colitis, no changes in spine density or composition on dendrites of pyramidal cells was observed in the basolateral amygdala. Rather, we observed decreased spine density on dendrites of stellate neurons, but not the relative proportions of mature vs immature spines. We used cFos expression evoked by the forced swim task as a measure of neural activity during stress and found no effect of DSS on the density of cFos immunoreactive neurons in basolateral amygdala. In contrast, fewer CA1 neurons expressed cFos in mice with colitis, relative to controls. Furthermore, CA1 cFos expression negatively correlated with active stress-coping in the swim task and was negatively correlated with gut inflammation. These data reveal that the effects of acute gut inflammation on synaptic remodeling depend on brain region, neuronal phenotype, and dendrite location. In the hippocampus, a shift to immature spines and hypoactivity are more strongly related to colitis-evoked behavioral changes than is remodeling in basolateral amygdala.

Prenatal stress produces sexually dimorphic and regionally specific changes in gene expression in hippocampus and frontal cortex of developing rat offspring.

Prenatal stress has been known to induce structural changes in the brain and lead to negative psychological well-being. To further understanding of the mechanisms that underlie these effects, whole genome microarray analysis was used to analyze gene expression changes in the developing brain. Epigenetic changes in the hippocampus and frontal cortex of offspring exposed to stress during gestation were investigated. Biological process ontology and pathway analysis was used to increase understanding of the changes produced in response to prenatal stress. The study identified over 700 genes in the frontal cortex and hippocampus that are differentially expressed following prenatal stress. The epigenetic changes demonstrate sex-dependent and region-specific profiles, exhibiting very little overlap between sexes and brain area. Frontal cortex changes were largely related to neurotransmitter function, whereas hippocampal changes were more prominent in females and concentrated around growth factors. These findings have important implications for generalized intervention strategies using a single methodology for all individuals.

Prenatal bystander stress alters brain, behavior, and the epigenome of developing rat offspring.

The prenatal environment, including prenatal stress, has been extensively studied in laboratory animals and humans. However, studies of the prenatal environment usually directly stress pregnant females, but stress may come 'indirectly', through stress to a cage-mate. The current study used indirect prenatal bystander stress and investigated the effects on the gross morphology, pre-weaning behavior, and epigenome of rat offspring. Pregnant Long-Evans rats were housed with another female rat that underwent elevated platform stress from gestational days 12 to 16. We found that ultrasonic vocalizations of female cage-mates were disrupted following the stress procedure. After birth, offspring were tested on two behavioral tasks and sacrificed at postnatal day 21 (p21). Frontal cortex and hippocampal tissue was used to measure global DNA methylation and gene expression changes. At p21, bystander-stressed female offspring exhibited increased body weight. Offspring behavior on the negative geotaxis task was altered by prenatal bystander stress, and locomotor behavior was reduced in female offspring. Global DNA methylation increased in the frontal cortex and hippocampus of bystander-stressed offspring. Microarray analysis revealed significant gene expression level changes in 558 different genes, of which only 10 exhibited overlap between males and females or brain areas. These alterations in gene expression were associated with overrepresentation of 36 biological processes and 34 canonical pathways. Prenatal stress thus does not have to be experienced by the mother herself to influence offspring brain development. Furthermore, this type of 'indirect' prenatal stress alters offspring DNA methylation patterns, gene expression profiles, and behavior.

Brain plasticity and recovery from early cortical injury.

Neocortical development represents more than a simple unfolding of a genetic blueprint: rather, it represents a complex dance of genetic and environmental events that interact to adapt the brain to fit a particular environmental context. Most cortical regions are sensitive to a wide range of experiential factors during development and later in life, but the injured cortex appears to be unusually sensitive to perinatal experiences. This paper reviews the factors that influence how normal and injured brains (both focal and ischemic injuries) develop and adapt into adulthood. Such factors include prenatal experiences in utero as well as postnatal experiences throughout life. Examples include the effects of sensory and motor stimulation, psychoactive drugs (including illicit and prescription drugs), maternal and postnatal stress, neurotrophic factors, and pre- and postnatal diet. All these factors influence cerebral development and influence recovery from brain injury during development.

A Neural Network Reveals Motoric Effects of Maternal Preconception Exposure to Nicotine on Rat Pup Behavior: A New Approach for Movement Disorders Diagnosis.

Neurodevelopmental disorders can stem from pharmacological, genetic, or environmental causes and early diagnosis is often a key to successful treatment. To improve early detection of neurological motor impairments, we developed a deep neural network for data-driven analyses. The network was applied to study the effect of maternal nicotine exposure prior to conception on 10-day-old rat pup motor behavior in an open field task. Female Long-Evans rats were administered nicotine (15 mg/L) in sweetened drinking water (1% sucralose) for seven consecutive weeks immediately prior to mating. The neural network outperformed human expert designed animal locomotion measures in distinguishing rat pups born to nicotine exposed dams vs. control dams (87 vs. 64% classification accuracy). Notably, the network discovered novel movement alterations in posture, movement initiation and a stereotypy in "warm-up" behavior (repeated movements along specific body dimensions) that were predictive of nicotine exposure. The results suggest novel findings that maternal preconception nicotine exposure delays and alters offspring motor development. Similar behavioral symptoms are associated with drug-related causes of disorders such as autism spectrum disorder and attention-deficit/hyperactivity disorder in human children. Thus, the identification of motor impairments in at-risk offspring here shows how neuronal networks can guide the development of more accurate behavioral tests to earlier diagnose symptoms of neurodevelopmental disorders in infants and children.

Promoting Executive Function Skills in Preschoolers Using a Play-Based Program.

In recent years, play has been shown to be a powerful means to enhance learning and brain development. It is also known that through play children enhance their executive function (EF) skills. Furthermore, well-developed EF in preschoolers has been shown to be an important predictor for later academic and life success. Armed with this information a program, Building Brains and Futures (BBF), for developing EF through play was designed for 3-5-year-old. The program consisted of 10 simple, fun, and interactive games selected to enhance various facets of EF. The 10 games included were: dimensional change card sort, lips and ears, block building, musical freeze, opposites, pretend play, red light/green light, shared project, Simon says, and wait for it. The program was implemented with a group of children shown to have challenges with respect to kindergarten readiness. The approach was first, to build adult capability by sharing knowledge of brain development, EF, and the importance of play with educators, caregivers, and parents. Second, to build skills in delivering the program in the school setting. Children engaged with the program of games for a minimum of 6 weeks. Their performance on a battery of direct measures of EF, language, and motor skills, were recorded before and after the program. The results showed improvement in all three domains. In addition, adopters of the BBF program reported it was easily and successfully integrated into their existing preschool curricula. The importance of intentional adult directed play in building developmental learning, including EF, is discussed.