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  3. Functional Neuroimaging in Child Psychiatry
  • Cited by 11
Publisher:
Cambridge University Press
Online publication date:
January 2010
Print publication year:
2000
Online ISBN:
9780511470998
DOI:
https://doi.org/10.1017/CBO9780511470998
Subjects:
Psychiatry and Clinical Psychology, Neurology and Clinical Neuroscience, Medicine, Psychiatry
Information

Book description

This 2000 publication reviews the rapid development of functional neuroimaging techniques and their implications for child psychiatry. It is unusual in its focus on children, and in integrating brain mapping with genetics and behavioural testing. This reference will help clinicians and investigators to:Understand through imaging the mechanisms of childhood psychiatric disordersDecide which technique is most appropriate for their purposes, with respect to technology, experimental design, data analysis and ethical considerationsAppreciate the role of molecular genetics and neuropsychology in planning brain imaging studiesCoverage includes description of brain imaging strategies and the application to children of imaging techniques used in adults, set against an overview of normal behavioural and cognitive development. Linking the latest findings from neuroimaging to neurophysiological models, this is an essential resource for researchers and clinicians concerned with neurodevelopmental disorders.

Reviews

Review of the hardback:‘This book will be of great use to doctors, researchers and teachers and as it is known the brain does not reach maturity until about the age of 20 it implies a maturing concept … This very clear, current and rigourous work brings psychiatry and neurology to its origins.’

Dr J. M. Sala Source: European Journal of Psychiatry

Review of the hardback:'Every professional and novice in functional neuroimaging will benefit from these authors' insightful reflections on the caveats and dangers involved in interpreting functional neruoimaging … Functional Neuroimaging in Child Psychiatry is an interesting, informative and comprehensive textbook on the subject; worthwhile reading for the lay reader, the novice and the expert.'

Source: Cognitive Neuropsychiatry

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Contents

Page 1 of 2

Contents
  • 1 - Functional brain imaging with PET and SPECT
    pp 3-26
  • View abstract

    Summary

    Two nuclear medicine-based approaches to functional brain imaging can be used to study the pediatric population, positron emission tomography (PET) and single-photon emission computed tomography (SPECT). This chapter talks about PET instrumentation, positron-emitting radiotracers, and radiotracer modeling. It describes the PET methods used to measure cerebral blood flow (rCBF) and cerebral blood volume (rCBV) and glucose and oxygen metabolism. Measurements of CBF glucose metabolism are widely used as indices of neuronal activity. The radionuclides used in SPECT decay by emitting a single photon or gamma ray from their nucleus; radioactivity distribution is estimated by detection of gamma rays. To interpret changes in PET and SPECT studies, it is necessary to understand the relationships among CBF, metabolism, and local neuronal activity. Radiation exposure in the context of PET and SPECT is an important consideration when they are used for research rather than diagnostic purposes.
  • 2 - Modeling of receptor images in PET and SPECT
    pp 27-44
  • View abstract

    Summary

    Currently, positron emission tomography (PET) and single photon emission computed tomography (SPECT) are the only noninvasive imaging modalities that can be used to image specific receptor molecules and to quantify their kinetics. By formally comparing the output of the model to the experimentally obtained PET or SPECT data, one can estimate values for the kinetic parameters and thus extract information on binding, or any hypothesized process. The simplest of compartmental models applied to receptor-ligand studies postulates two tissue compartments. These two tissue compartments along with a plasma compartment are arranged in series. The partial volume effect is widely recognized as a limiting factor in the ability to quantify the amount of radioactivity in tissue accurately. The pharmacokinetic approach requires the PET or SPECT data to be analyzed using a mathematical model of radioactivity uptake. PET and SPECT brain imaging studies are divided into two groups: receptor-ligand studies and tracer studies.
  • 3 - Functional magnetic resonance imaging
    pp 45-58
  • View abstract

    Summary

    Functional magnetic resonance imaging (fMRI) methods allow rapid and non-invasive determination of brain structure and brain function, characteristics that are of particular importance in studies involving children. The goal of analysis of fMRI time series is to extract the best estimate of neuronal activity from the recorded hemodynamic signal. This process is made difficult by a host of instrumental and physiologic artifacts encountered in fMRI data acquisition and analysis. Structural and functional brain imaging using commercial magnetic resonance (MR) imaging systems has an excellent safety record. fMRI has been employed clinically to study language function in children. One of the most important applications of pediatric fMRI studies lies in clinical studies. Clearly a number of limitations imposed by the MR environment need to be taken into consideration when conducting functional neuroimaging with MRI. The outcome of the statistical analysis is greatly determined by the acquisition parameters and experimental procedures.
  • 4 - MRS in childhood psychiatric disorders
    pp 59-76
  • View abstract

    Summary

    The application of magnetic resonance spectroscopy (MRS) techniques to the study of neuropsychiatric disorders in childhood provides an extraordinary opportunity to advance the understanding of the neurobiological mechanisms underlying these disorders. All MR methods (MRS, magnetic resonance imaging (MRI) and functional MRI, (fMRI)) rely on the same basic principles. MRS offers several advantages over radionuclide neuroimaging techniques (positron emission tomography (PET) and single-photon emission computed tomography (SPECT)) for the study of children and adolescents, in particular its absence of ionizing radiation. The chapter considers evidence for abnormal concentrations of various metabolites detected with MRS in the brains of children with psychiatric disorders. MRS employs standard MRI devices to make measurements of chemical levels within the brain. MRS findings in children with acute or chronic neurologic insults are important because they may clarify the significance of biochemical changes identified in children with psychiatric diagnoses.
  • 5 - Magnetoencephalography
    pp 77-96
  • View abstract

    Summary

    Magnetoencephalography (MEG) provides extremely fine temporal resolution and reasonable spatial resolution within the same recording, which makes it fairly unique among the various imaging strategies. MEG is more comfortable for children than electroencephalography (EEG) since it does not involve scalp abrasion, which is particularly bothersome in studies using high sensor densities. MEG provides high temporal resolution and moderate spatial resolution in a relatively comfortable, nonthreatening environment, characteristics that should make it ideal for use in child psychiatry. This chapter talks about the neurophysiologic and neuroanatomic basis of MEG signals. Instrumentation in MEG has evolved significantly since the early 1980s from single channel neuromagnetometer systems to large, high-density whole-head arrays. The most common data analysis technique in MEG involves signal averaging to improve the signal-to-noise ratios (SNR). The chapter presents the comparison of MEG- and EEG. EEG reflects primarily extracellular current and MEG measures intracellular current.
  • 6 - Ethical issues in neuroimaging research with children
    pp 99-110
  • View abstract

    Summary

    This chapter focuses on the three principles for the protection of human subjects of scientific research, established in the Belmont report. These principles include: respect for persons, beneficence, and justice. The principle of beneficence, with the assessment of benefit-risk ratio, poses the most complex issues. A literature search yielded few systematic studies of the physical or psychologic risks of biological research procedures in general, and none on neuroimaging in children. The risks involved in neuroimaging research in children include those associated with radiation exposure, electromagnetic fields, and psychologic stress. The risk of breach of confidentiality between children and parents needs to be carefully evaluated and is particularly salient in research with adolescents. The chapter considers the possibilities for improving the benefit-risk ratio by increasing benefits, decreasing risk, or both. Current regulations may excessively limit children's opportunities both to contribute altruistic service and to benefit as a group from research.
  • 7 - Brain development and evolution
    pp 113-136
  • View abstract

    Summary

    This chapter reviews the development of the human brain from conception to adult age and its evolution across time and species. The size and the shapes of the various portions of the mature nervous system result from a variety of developmental processes such as cellular proliferation, cellular migration, and cell death, and also from the constraints imposed by the surrounding non-neural tissues. During brain development, neurons are dependent on external factors for guidance and survival. These factors include biochemical influences such as neurotransmitters and steroid hormones. The mechanisms involved are complex and require appropriate spatiotemporal relationships and feedback loops. Human brains appear to be products of evolutionary mechanisms such as selection and genetic variation. During the evolution of the nervous system, certain general trends seem to have occurred. Laterality in the cortex of humans represents a behavioral and morphologic reorganization within the brain.
  • 8 - Cognitive development from a neuropsychologic perspective
    pp 137-154
  • View abstract

    Summary

    This chapter reviews the developmental trajectories of specific cognitive and neuropsychologic functions. Piaget observations regarding children's abilities to think, reason, and perceive their world have had a tremendous impact on the conceptualization of cognitive maturation. Piaget conceptualized cognitive development as consisting of a sequence of stages, although it is important to emphasize that he envisaged a continuity of development over its entire course. Piaget's description of the sensorimotor and preoperational stages provides some insight into the development of attention. The ceilings for maturation of various cognitive functions have been identified to be around the ages of 10 to 12 years, but this may simply reflect the limitations of neuropsychologic tests. Neuroimaging studies have shown that the brain continues to undergo striking reorganization even in the adulthood. Functional neuroimaging holds great promise for mapping the brain maturational changes underlying neuropsychologic development in children and adolescents.
  • 9 - Cognitive and behavioral probes of developmental landmarks for use in functional neuroimaging
    pp 155-168
  • View abstract

    Summary

    Functional magnetic resonance imaging (fMRI) allows neuroscientists to examine the function of the human brain, especially the developing human brain, in a relatively noninvasive manner. The significance of studying functional brain changes in a developmental context becomes more apparent when aspects of brain development are considered. Several neuroimaging studies have examined developing sensorimotor systems in infants and young children. The prefrontal cortex supports representations of information against interference over time or from competing sources. A number of classic developmental studies have demonstrated that memory-related processes develop throughout childhood and adolescence. This chapter addresses the important themes of the development of age-appropriate behavioral paradigms and appropriate task designs in the context of four developmental fMRI studies. These empirical studies revolve around two central themes: maintenance of information in prefrontal cortex over time and suppression of competing responses in prefrontal cortex.
  • 10 - Autism
    pp 171-188
  • View abstract

    Summary

    Studies of glucose metabolism and blood flow have suggested a variety of global and focal brain abnormalities in autism. The accurate diagnosis and careful description of associated features of the subjects are essential criteria for obtaining meaningful functional imaging data. The majority of the functional imaging studies published to date have utilized clinical diagnoses of autism based upon DSM-III-R, DSMIV or ICD-10 criteria. This chapter presents a detailed discussion on functional imaging studies in autistic subjects. It is difficult to scan young children and to obtain appropriate age-matched controls; consequently, the majority of functional imaging studies of autistic subjects have employed adolescents and adults. The chapter discusses the problems that need to be addressed in future studies of autism. It is clear that functional imaging studies in young children, as well as new strategies for the assessment of developmental functional imaging data, are necessary to advance our understanding of autism.
  • 11 - Functional imaging in childhood-onset schizophrenia
    pp 189-204
  • View abstract

    Summary

    This chapter deals with the developmental theories of schizophrenia to provide a foundation for a discussion of functional brain imaging studies of childhood-onset schizophrenia. Neurochemical brain imaging methodologies have permitted testing of the dopamine hypothesis of schizophrenia. Clinical studies have demonstrated prominent premorbid developmental delays in childhood-onset schizophrenia, especially in the areas of speech and language. Neurobiologic studies of the NIMH childhood-onset schizophrenia sample have generally supported neurobiologic continuity between childhood- and adult-onset schizophrenia. Very few functional brain imaging studies have been conducted in patients with childhood-onset schizophrenia. The only study of cerebral glucose metabolism in childhood-onset schizophrenia has been conducted with a subset of the National Institute of Mental Health (NIMH) childhood-onset schizophrenia sample. The finding of cerebellar hypermetabolism in childhood-onset schizophrenia, seen with both data analytic approaches, is notable in light of recent evidence implicating the cerebellum in higher cortical processes.
  • 12 - Pediatric mood disorders and neuroimaging
    pp 205-223
  • View abstract

    Summary

    Functional imaging studies have the potential to provide valuable information about the neurobiologic basis of child and adolescent mood disorders and their development into adult mood disorders. This chapter presents the clinical characteristics of these disorders in children and adolescents. It discusses the epidemiology, signs, symptoms, comorbidity, and natural course of pediatric mood disorder. Children with depression often present to pediatricians or general practitioners with vague somatic complaints including headaches, stomach aches, or other physical symptoms for which the physician can find no cause. The diagnosis of a mood disorder is often obscured by the presence of other comorbid psychiatric diagnoses, as well as by general medical disorders. The developmental course of mood disorders suggests a continuum of pathology from childhood to adulthood. The chapter covers neuroimaging studies in adults, including activation studies using neurobehavioral probes, and the few imaging studies performed in children and adolescents.
  • 13 - Neuroimaging of childhood-onset anxiety disorders
    pp 224-241
  • View abstract

    Summary

    This chapter discusses the use of magnetic resonance spectroscopy (MRS) and functional magnetic resonance imaging (fMRI) techniques in childhood-onset anxiety disorders. It reviews brain imaging studies in various childhood-onset anxiety disorders, including obsessive-compulsive disorder (OCD), generalized anxiety disorder (GAD), panic disorder, social phobia, and post-traumatic stress disorder (PTSD), as well as suggest directions for future investigation. Functional neuroimaging has most consistently identified the caudate nucleus, ventral prefrontal cortex, and anterior cingulate as neural substrates of OCD. These regions have shown abnormal serotonergic and/or glutamatergic function. The brain regions implicated in panic disorder are consistent with the brain networks subserving fear and anxiety. The structural imaging findings suggest that functional dysfunction in the hippocampus is associated with PTSD. The studies highlight that some of the common findings in OCD and PTSD may reflect similarities in symptoms, with both disorders involving repetitive, ritualistic behaviors and intrusive thoughts.
  • 14 - Tourette's syndrome: what are we really imaging?
    pp 242-265
  • View abstract

    Summary

    This chapter discusses the numerous conflicting findings produced by a wide variety of functional imaging studies in Tourette's syndrome (TS) performed by different investigators under different experimental protocols over a large number of years. Superficially, the behavioral phenotypes of TS, obsessive-compulsive disorder (OCD), and attention-deficit hyperactivity disorder (ADHD) differ dramatically: one consists of motor and vocal tics. Another consists of obsessions and compulsions, and yet another consists of inattention, hyperactivity, and impulsivity. The phenomenology of TS introduces numerous potential confounds that can seriously impair our ability to interpret adequately the findings from functional imaging studies. The orbitofrontal cortex is interconnected with the anterior cingulate and other limbic structures. The cingulate cortex is a heterogeneous structure that probably is a component in most of the major cortico-striato-thalamo-cortical (CSTC) pathways: the supplementary motor area, orbitofrontal cortex and temporolimbic circuits.
  • 15 - Dyslexia: conceptual issues and psychiatric comorbidity
    pp 266-277
  • View abstract

    Summary

    Present data acquired by functional neuroimaging in dyslexia suggests a diverse range of neurofunctional deficits. The range of neurobehavioral disorders that have been investigated by computed tomography (CT) and magnetic resonance imaging (MRI) technology has reflected two rather different theoretical perspectives, seldom reconciled. The modular cognitive model postulates that a circumscribed, relatively specific cognitive process is disrupted in relative isolation from other processes. Comorbidity is often considered in psychiatric nosology as a problem that threatens the accuracy and specificity of diagnosis. Subtraction methodology compares a given cognitive activation task with a control condition in an effort to isolate a particular cognitive mechanism that is impaired. Longitudinal studies are possible with fMRI and may allow data to be acquired early enough in childhood to capture the genetic heterogeneity at a time when it is less subtle and more readily demonstrable.
  • 16 - Attention-deficit hyperactivity disorder: neuroimaging and behavioral/cognitive probes
    pp 278-297
  • View abstract

    Summary

    Functional imaging studies of attention-deficit hyperactivity disorder (ADHD) tend to follow a dimensional rather than a categorical approach and focus on a combination of behavioral- and circuit-specific paradigms to elucidate neural abnormalities specific to behavioral subtypes. A much needed approach is the application of methods designed to examine functional interactions between various brain regions such as prefrontal cortex, caudate nuclei, putamen and globus pallidus to delineate more closely the neural circuits underlying the psychopathology. The authors hypothesized that ADHD is a progressive neurodevelopmental disorder in which the initial deficit is at the site of dopaminergic cell bodies. A step in investigating ADHD using neuroimaging involves the use of cognitive/behavioral activation tasks that place demands on the neurobiochemical systems that are putatively dysfunctional in ADHD. Continuous performance tasks (CPTs) are used frequently in research to assess deficits in sustained attention in individuals with ADHD.
  • 17 - Eating disorders
    pp 298-312
  • View abstract

    Summary

    The range of eating disorders in children includes selective eating, food avoidance emotional disorder, functional dysphagia, and pervasive refusal syndrome. This chapter provides background information, including theories of etiology concerning early-onset anorexia nervosa and bulimia nervosa. The majority of physical changes in anorexia nervosa are predominantly related to the effects of starvation and dehydration. Herzog reported that major depressive disorder was the most prevalent comorbid disorder, occurring in 37% of patients with anorexia nervosa. The physical manifestations of bulimia nervosa are initially less dramatic than those of anorexia nervosa because weight is usually maintained within normal range. A number of other eating disorders are identified in children. Other eating disorders include food avoidance emotional disorder, selective eating and pervasive refusal syndrome. A number of computed tomography (CT) and magnetic resonance imaging (MRI) studies in female adult and adolescent patients with anorexia nervosa have shown structural abnormalities in the brain.
  • 18 - Techniques of molecular genetics
    pp 315-327
  • View abstract

    Summary

    This chapter describes the techniques that facilitate new understanding of neuroimaging results by adding a molecular genetic approach to examining neuroimaging phenotypes. It provides Mendelian genetics to highlight the point that variation in a single gene can affect many of the phenotypes measured in neuroimaging. The chapter discusses the expansion of trinucleotide repeat DNA sequences and imprinting, to the characteristics the inheritance and course of a disorder. The genetic analysis of pairs of siblings examines the degree of similarity between affected siblings for a quantitative phenotype. The transmission disequilibrium test (TDT) is based on the fact that a parent donates a single chromosome of each pair and, thus, one allele of any particular genetic marker. The population association method is commonly used but has a serious caveat, which is the association test between two groups of unrelated individuals.
  • 19 - Issues in the genetic study of complex neurobehavioral conditions
    pp 328-334
  • View abstract

    Summary

    This chapter discusses some of the issues that need to be considered in the genetic study of complex phenotypes. First critical issue in any genetic study is the accurate delineation of the inherited phenotype. The issue of phenotypic classification is particularly critical in genetic linkage studies. Second critical issue in the search for genes important for the manifestation of behavior is the assessment of the phenotype. Neuroimaging data could be very helpful in elucidating more quantitative biological aspects of the phenotype. A third issue has to do with methodologic approaches. Until recently, there has been an almost exclusive commitment to one approach. A fourth issue in the study of the genetics of behavior is the relative lack of attention to nongenetic risk factors. The final and fifth issue is the lack of a developmental focus in genetic studies of neurobehavior.
  • 20 - The duplicity of plasticity: a conceptual approach to the study of early lesions and developmental disorders
    pp 335-365
  • View abstract

    Summary

    Neuroimaging studies in patients with early acquired damage will primarily seek to identify enhanced activations in regions outside a structural lesion. By comparison, imaging studies in developmental disorders will typically look for an absence or abnormality of activation that is assumed to reflect a particular cognitive or affective impairment. This chapter deals with evidence indicating vulnerability effects in non-human animals and human patients with early structural lesions. It discusses the interaction of vulnerability and compensatory events in developmental disorders, with exemplary focus on autism, developmental language impairment (DLI), and dyslexia. The chapter presents developmental disorders both in terms of the obvious effects of maturational vulnerability and in terms of the typically more elusive effects of compensatory reorganization. It focuses on autism and Asperger's syndrome. In the discussion presented here on bottom-up and top-down approaches, there are interesting parallels in the debates about developmental disorders of spoken and of written language.

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