Structural and functional magnetic resonance imaging (MRI) are increasingly common research methods among investigators interested in typically and atypically developing populations. However, the effective use of these tools requires an understanding of the basis of the magnetic resonance signal, as well as some of the additional experimental complications that arise when collecting MRI data from developmental populations. This primer provides a foundation for investigators who wish to utilize MRI methods in their research and whose primary interest involves typically and atypically developing populations. The basic concepts of MRI physics are introduced, as well as the typical MRI scanner components and their role in MRI data acquisition. In addition, a variety of scan types (structural, functional, diffusion tensor) are discussed, along with a number of important experimental design factors that can impact the quality and utility of the data collected. Special consideration is given to working with pediatric and special populations.

The psychological construct of empathy refers to an intersubjective induction process by which positive and negative emotions are shared, without losing sight of whose feelings belong to whom. Empathy can lead to personal distress or to empathic concern (sympathy). The goal of this paper is to address the underlying cognitive processes and their neural underpinnings that constitute empathy within a developmental neuroscience perspective. In addition, we focus on how these processes go awry in developmental disorders marked by impairments in social cognition, such as autism spectrum disorder, and conduct disorder. We argue that empathy involves both bottom-up and top-down information processing, underpinned by specific and interacting neural systems. We discuss data from developmental psychology as well as cognitive neuroscience in support of such a model, and highlight the impact of neural dysfunctions on social cognitive developmental behavior. Altogether, bridging developmental science and cognitive neuroscience helps approach a more complete understanding of social cognition. Synthesizing these two domains also contributes to a better characterization of developmental psychopathologies that impacts the development of effective treatment strategies.

We describe recent progress in our program of research that aims to use functional magnetic resonance imaging (fMRI) to identify and delineate the brain systems involved in social perception and to chart the development of those systems and their roles as mechanisms supporting the development of social cognition in children, adolescents, and adults with and without autism. This research program was initiated with the intention of further specifying the role of the posterior superior temporal sulcus (STS) region in the network of neuroanatomical structures comprising the social brain. Initially, this work focused on evaluating STS function when typically developing adults were engaged in the visual analysis of other people's actions and intentions. We concluded that that the STS region plays an important role in social perception via its involvement in representing and predicting the actions and social intentions of other people from an analysis of biological–motion cues. These studies of typically developing people provided a set of core findings and a methodological approach that informed a set of fMRI studies of social perception dysfunction in autism. The work has established that dysfunction in the STS region, as well as reduced connectivity between this region and other social brain structures including the fusiform gyrus and amygdala, play a role in the pathophysiology of social perception deficits in autism. Most recently, this research program has incorporated a developmental perspective in beginning to chart the development of the STS region in children with and without autism.

Autism is a neurodevelopmental disorder characterized by social and communication deficits, and repetitive behavior. Studies investigating the integrity of brain systems in autism suggest a wide range of gray and white matter abnormalities that are present early in life and change with development. These abnormalities predominantly affect association areas and undermine functional integration. Executive function, which has a protracted development into adolescence and reflects the integration of complex widely distributed brain function, is also affected in autism. Evidence from studies probing response inhibition and working memory indicate impairments in these core components of executive function, as well as compensatory mechanisms that permit normative function in autism. Studies also demonstrate age-related improvements in executive function from childhood to adolescence in autism, indicating the presence of plasticity and suggesting a prolonged window for effective treatment. Despite developmental gains, mature executive functioning is limited in autism, reflecting abnormalities in wide-spread brain networks that may lead to impaired processing of complex information across all domains.

This paper discusses how converging methods may form a powerful tool in unraveling the neurobiology of attention-deficit/hyperactivity disorder (ADHD). Integrating findings from multiple disciplines can inform us on how different neurobiological and cognitive mechanisms tie together in both typical and atypical development. Examples are discussed of this approach: combining family and genetic approaches with anatomical neuroimaging illustrates how mapping familial effects can bring us closer to understanding the neurobiology of ADHD. Functional neuroimaging has convincingly linked cognitive problems in this disorder with frontostriatal functioning, but also shows that other systems may be involved in some of the symptoms of ADHD. Combining these findings has suggested new avenues for investigation, such as the role of frontocerebellar networks. Furthermore, findings may have practical applications: this paper discusses an example of how converging evidence of striatal dysregulation in ADHD suggests possible directions for treatment that are now being explored in functional imaging studies.

The recent development of low-risk imaging technologies, such as functional magnetic resonance imaging (fMRI), have had a significant impact on the investigation of psychopathologies in children and adolescents. This review considers what we can infer from fMRI work regarding the development of conduct disorder (CD) and oppositional defiant disorder (ODD). We make two central assumptions that are grounded in the empirical literature. First, the diagnoses of CD and ODD identify individuals with heterogeneous pathologies; that is, different developmental pathologies can receive a CDD or ODD diagnosis. This is indicated by the comorbidities associated with CD/ODD, some of which appear to be mutually exclusive at the biological level (e.g., posttraumatic stress disorder [PTSD] and psychopathic tendencies). Second, two populations of antisocial individuals can be identified: those that show an increased risk for only reactive aggression and those that show an increased risk for both reactive and instrumental aggression. We review the fMRI data indicating that particular comorbidities of CD/ODD (i.e., mood and anxiety conditions such as childhood bipolar disorder and PTSD) are associated with either increased responsiveness of neural regions implicated in the basic response to threat (e.g., the amygdala) or decreased responsiveness in regions of frontal cortex (e.g., ventromedial frontal cortex) that are implicated in the regulation of the basic threat response. We suggest why such pathology would increase the risk for reactive aggression and, in turn, lead to the association with a CD/ODD diagnosis. We also review the literature on psychopathic tendencies, a condition where the individual is at significantly elevated risk for both reactive and instrumental aggression. We show that in individuals with psychopathic tendencies, the functioning of the amygdala in stimulus-reinforcement learning and of the ventromedial frontal cortex in the representation of reinforcement expectancies is impaired. We suggest why such pathology would increase the risk for reactive and instrumental aggression and thus also lead to the association with a CD/ODD diagnosis.

Human brain development is created through continuing complex interactions of genetic and environmental influences. The challenge of linking specific genetic or environmental risk factors to typical or atypical behaviors has led to interest in using brain structural features as an intermediate phenotype. Twin studies in adults have found that many aspects of brain anatomy are highly heritable, demonstrating that genetic factors provide a significant contribution to variation in brain structures. Less is known about the relative impact of genes and environment while the brain is actively developing. We summarize results from the ongoing National Institute of Mental Health child and adolescent twin study that suggest that heritability of different brain areas changes over the course of development in a regionally specific fashion. Areas associated with more complex reasoning abilities become increasingly heritable with maturation. The potential mechanisms by which gene–environment interactions may affect heritability values during development is discussed.

Chronic elevations of endogenous cortisol levels have been shown to alter medial temporal cortical structures and to be accompanied by declarative memory impairments and depressive symptoms in human adults. These effects of elevated endogenous levels of cortisol have not been directly studied in adolescents. Because adolescents with Cushing syndrome show endogenous elevations in cortisol, they represent a unique natural model to study the effects of prolonged hypercortisolemia on brain function, and memory and affective processes during this developmental stage. Using functional magnetic resonance imaging (fMRI), we compared 12 adolescents with Cushing syndrome with 22 healthy control adolescents on amygdala and anterior hippocampus activation during an emotional faces encoding task. None of these adolescents manifested depressive symptoms. Encoding success was assessed using a memory recognition test performed after the scan. The fMRI analyses followed an event-related design and were conducted using the SPM99 platform. Compared to healthy adolescents, patients with Cushing syndrome showed greater left amygdala and right anterior hippocampus activation during successful face encoding. Memory performance for faces recognition did not differ between groups. This first study of cerebral function in adolescents with chronic endogeneous hypercortisolemia due to Cushing syndrome demonstrates the presence of functional alterations in amygdala and hippocampus, which are not associated with affective or memory impairments. Such findings need to be followed by work examining the role of age and related brain maturational stage on these effects, as well as the identification of possible protective factors conferring resilience to affective and cognitive consequences in this disease and/or during this stage of cerebral development.

The pursuit of rewarding experiences motivates everyday human behavior, and can prove beneficial when pleasurable, positive consequences result (e.g., satisfying hunger, earning a paycheck). However, reward seeking may also be maladaptive and lead to risky decisions with potentially negative long-term consequences (e.g., unprotected sex, drug use). Such risky decision making is often observed during adolescence, a time in which important structural and functional refinements occur in the brain's reward circuitry. Although much of the brain develops before adolescence, critical centers for goal-directed behavior, such as frontal corticobasal ganglia networks, continue to mature. These ongoing changes may underlie the increases in risk-taking behavior often observed during adolescence. Further, typical development of these circuits is vital to our ability to make well-informed decisions; atypical development of the human reward circuitry can have severe implications, as is the case in certain clinical and developmental conditions (e.g., attention-deficit/hyperactivity disorder). This review focuses on current research probing the neural correlates of reward-related processing across human development supporting the current research hypothesis that immature or atypical corticostriatal circuitry may underlie maladaptive behaviors observed in adolescence.

Despite the assumed prevalence of risk-taking behavior in adolescence, the laboratory evidence of risk taking remains scarce, and the individual variation poorly understood. Drawing from neuroscience studies, we tested whether risk and reward orientation are influenced by the perspective that adolescents take when making risky decisions. Perspective taking was manipulated by cuing participants prior to each choice whether the decision was made for “self,” or from the perspective of an “other” (the experimenter in Experiment 1; a hypothetical peer in Experiment 2). In Experiment 1, we show a developmental decrease in risk-taking behavior across different stages of adolescence. In addition, all age groups made fewer risky choices for the experimenter, but the difference between self and other was larger in early adolescence. In Experiment 2, we show that high sensation-seeking (SS) adolescents make more risky choices than low SS adolescents, but both groups make a similar differentiation for other individuals (low risk-taking or high risk-taking peers). Together, the results show that younger adolescents and high SS adolescents make more risky choices for themselves, but can appreciate that others may make fewer risky choices. The developmental change toward more rational decisions versus emotional, impulsive decisions may reflect, in part, more efficient integration of others’ perspectives into one's decision making. These developmental results are discussed regarding brain systems important for risk taking and perspective taking.

Disturbances in the detection of, response to, and interpretation of emotion are common in many forms of psychopathology. The amygdala, striatum, and structures within the prefrontal cortex are highly involved in mediating these stages of emotion processing, and evidence indicates that these regions show structural and functional alterations in different types of psychopathology, including anxiety, depression, and autism spectrum disorders. However, we do not know how genes and the environment interact to alter development of these brain regions in ways that give rise to emotion-related psychopathology. This review discusses the current understanding of brain regions that are involved in emotional functioning, how they develop, and how they are altered in three forms of psychopathology: anxiety, depression, and autism spectrum disorders. Following this, a framework is described that may facilitate the integration of investigations of genetic variation and brain function with symptom and diagnostic measures. The framework involves three components: (a) a greater emphasis on simultaneously analyzing multiple levels (genes, brain function, behavior, symptoms, and diagnoses); (b) further integration of developmental considerations, including timing of environmental events, adaptations (or maladaptations), and disorder-related trajectories that guide some children toward atypical experiences; and (c) greater cross-talk between animal and human investigations to take advantage of biological measures that cannot be acquired in humans.

Functional imaging studies have reported with remarkable consistency hyperactivity in the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), and caudate nucleus of patients with obsessive–compulsive disorder (OCD). These findings have often been interpreted as evidence that abnormalities in cortico–basal ganglia–thalamo–cortical loops involving the OFC and ACC are causally related to OCD. This interpretation remains controversial, however, because such hyperactivity may represent either a cause or a consequence of the symptoms. This article analyzes the evidence for a causal role of these loops in producing OCD in children and adults. The article first reviews the strong evidence for anatomical abnormalities in these loops in patients with OCD. These findings are not sufficient to establish causality, however, because anatomical alterations may themselves be a consequence rather than a cause of the symptoms. The article then reviews three lines of evidence that, despite their own limitations, permit stronger causal inferences: the development of OCD following brain injury, pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection, and neurosurgical lesions that attenuate OCD. Converging evidence from these various lines of research supports a causal role for the cortico–basal ganglia–thalamo–cortical loops that involve the OFC and ACC in the pathogenesis of OCD in children and adults.

The amygdala has received great interest as a possible neurophysiological substrate of bipolar disorder (BD). This review summarizes information about the structure and function of the amygdala with attention to its role in experienced emotion and mood. We review the evidence for amygdala pathology in psychiatric conditions and discuss the role of the amygdala in BD during development. There appear to be consistent findings in the neuroimaging literature that suggest an etiological model for BD that involves abnormalities in the structure and function of the amygdala, but also depends on the failure of prefrontal cortical regions to modulate amygdala activity. In addition, evidence is accumulating to suggest that this model has flexible outcomes, depending on factors intrinsic and extrinsic to BD, and may follow several possible paths across the course of maturational development.

Schizophrenia has been thought of as a disorder of reduced functional and structural connectivity. Recent advances in neuroimaging techniques such as functional magnetic resonance imaging, structural magnetic resonance imaging, diffusion tensor imaging, and small animal imaging have advanced our ability to investigate this hypothesis. Moreover, the power of longitudinal designs possible with these noninvasive techniques enable the study of not just how connectivity is disrupted in schizophrenia, but when this disruption emerges during development. This article reviews genetic and neurodevelopmental influences on structural and functional connectivity in human populations with or at risk for schizophrenia and in animal models of the disorder. We conclude that the weight of evidence across these diverse lines of inquiry points to a developmental disruption of neural connectivity in schizophrenia and that this disrupted connectivity likely involves susceptibility genes that affect processes involved in establishing intra- and interregional connectivity.

Extraordinary progress in functional brain imaging, primarily advances in functional magnetic resonance imaging, now allows scientists to understand the neural systems serving reading and how these systems differ in dyslexic readers. Scientists now speak of the neural signature of dyslexia, a singular achievement that for the first time has made what was previously a hidden disability, now visible. Paralleling this achievement in understanding the neurobiology of dyslexia, progress in the identification and treatment of dyslexia now offers the hope of identifying children at risk for dyslexia at a very young age and providing evidence-based, effective interventions. Despite these advances, for many dyslexic readers, becoming a skilled, automatic reader remains elusive, in great part because though children with dyslexia can be taught to decode words, teaching children to read fluently and automatically represents the next frontier in research on dyslexia. We suggest that to break through this “fluency” barrier, investigators will need to reexamine the more than 20-year-old central dogma in reading research: the generation of the phonological code from print is modular, that is, automatic and not attention demanding, and not requiring any other cognitive process. Recent findings now present a competing view: other cognitive processes are involved in reading, particularly attentional mechanisms, and that disruption of these attentional mechanisms play a causal role in reading difficulties. Recognition of the role of attentional mechanisms in reading now offer potentially new strategies for interventions in dyslexia. In particular, the use of pharmacotherapeutic agents affecting attentional mechanisms not only may provide a window into the neurochemical mechanisms underlying dyslexia but also may offer a potential adjunct treatment for teaching dyslexic readers to read fluently and automatically. Preliminary studies suggest that agents traditionally used to treat disorders of attention, particularly attention-deficit/hyperactivity disorder, may prove to be an effective adjunct to improving reading in dyslexic students.

The purpose of this study was to evaluate whether children with a history of disorganized attachment in infancy were more likely than children without a history of disorganized attachment to exhibit symptoms of posttraumatic stress disorder (PTSD) at school age following trauma exposure. The sample consisted of 78 8.5-year-old children from a larger, ongoing prospective study evaluating the effects of intrauterine cocaine exposure (IUCE) on children's growth and development from birth to adolescence. At the 12-month visit, children's attachment status was scored from videotapes of infant–caregiver dyads in Ainsworth's strange situation. At the 8.5-year visit, children were administered the Violence Exposure Scale—Revised, a child-report trauma exposure inventory, and the Diagnostic Interview for Children and Adolescents by an experienced clinical psychologist masked to children's attachment status and IUCE status. Sixteen of the 78 children (21%) were classified as insecure–disorganized/insecure–other at 12 months. Poisson regressions covarying IUCE, gender, and continuity of maternal care indicated that disorganized attachment status at 12 months, compared with nondisorganized attachment status, significantly predicted both higher avoidance cluster PTSD symptoms and higher reexperiencing cluster PTSD symptoms. These findings suggest that the quality of early dyadic relationships may be linked to differences in children's later development of posttraumatic stress symptoms following a traumatic event.