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Imaging brain systems in normality and psychopathology

Published online by Cambridge University Press:  07 October 2008

Dante Cicchetti*
Affiliation:
University of Minnesota
Kathleen M. Thomas*
Affiliation:
University of Minnesota
*
Address correspondence and reprint requests to: Dante Cicchetti, 51 East River Road, Institute of Child Development, University of Minnesota, Minneapolis, MN 55455; E-mail: [email protected]; or Kathleen M. Thomas, 51 East River Road, Institute of Child Development, University of Minnesota, Minneapolis, MN 55455; E-mail: [email protected].
Address correspondence and reprint requests to: Dante Cicchetti, 51 East River Road, Institute of Child Development, University of Minnesota, Minneapolis, MN 55455; E-mail: [email protected]; or Kathleen M. Thomas, 51 East River Road, Institute of Child Development, University of Minnesota, Minneapolis, MN 55455; E-mail: [email protected].
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Abstract

Type
Editorial
Copyright
Copyright © Cambridge University Press 2008

Neurobiological development is a complex process that originates at conception and extends throughout the life span (Casey, Tottenham, Liston, & Durston, Reference Casey, Tottenham, Liston and Durston2005; Cicchetti & Cannon, Reference Cicchetti and Cannon1999; Nowakowski, Reference Nowakowski1987; Rakic, Reference Rakic and Lewis1996; Thompson & Nelson, Reference Thompson and Nelson2001). The course of brain development can be altered by a host of factors, ranging from genetic liabilities to psychosocial stressors, and mental disorders are thought to eventuate from etiologic factors that modify the normal progression of brain development.

Perturbations that take place in the developing brain can trigger a cascade of growth and function changes that lead the neural system down a pathway that deviates from that taken in normal neurobiological development (Cicchetti & Tucker, Reference Cicchetti and Tucker1994). Accordingly, abnormal perturbations at one stage of brain development likely impede the creation of some new structures and functions, distort the form of later emerging ones, bring about the construction of structures and functions that would never become manifest, and hinder or limit the elaboration and usage of ones that had appeared earlier (Cicchetti, Reference Cicchetti, Hartup and Weinberg2002; Courchesne, Chisum, & Townsend, Reference Courchesne, Chisum and Townsend1994). Subsequently, abnormal neural network configurations and operations likely develop that may cause aberrant connections to be retained or created (Courchesne et al., Reference Courchesne, Chisum and Townsend1994). Such early developmental abnormalities may eventuate in the development of aberrant neurocircuity, and often compound themselves into enduring forms of psychopathology (Cicchetti & Cannon, Reference Cicchetti and Cannon1999; Nowakowski & Hayes, Reference Nowakowski and Hayes1999).

An outgrowth of systems theorizing in neuroscience has been a growing acceptance that neurobiological development and experience are mutually influencing (Cicchetti & Tucker, Reference Cicchetti and Tucker1994; Eisenberg, Reference Eisenberg1995; Greenough, Black, & Wallace, Reference Greenough, Black and Wallace1987; Kandel, Reference Kandel1998; Nelson & Bloom, Reference Nelson and Bloom1997). Pathological experience may become part of a vicious cycle, as the pathology induced in the brain structure may distort the child's experience, with subsequent alterations in cognition or social interactions causing additional pathological experience and added brain pathology (Black, Jones, Nelson, & Greenough, Reference Black, Jones, Nelson, Greenough, Alessi, Coyle, Harrison and Eth1998). Because experience-expectant and experience-dependent processes may continue to operate during psychopathological states, children who incorporate pathological experience during these processes may add neuropathological connections into their developing brains instead of functional neuronal connections (Black et al., Reference Black, Jones, Nelson, Greenough, Alessi, Coyle, Harrison and Eth1998; Cicchetti & Tucker, Reference Cicchetti and Tucker1994).

Basic research in neuroscience has begun to elucidate the neural events that mediate the relation between experience and behavior. Researchers in the field of developmental psychopathology have begun to use this knowledge base to inform their investigations aimed at uncovering the neural mechanisms that might subserve the dynamic, multiple-level interactions that exist among genes, brain, behavior, and experience (Gottlieb, Reference Gottlieb2002; Gottlieb & Willoughby, Reference Gottlieb, Willoughby, Cicchetti and Cohen2006).

Despite the major influence that embryology exerted upon the leading systematizers in the field of developmental psychology (Fishbein, Reference Fishbein1976; Sameroff, Reference Sameroff and Mussen1983; Waddington, Reference Waddington1957; Weiss, Reference Weiss1961, Reference Weiss, Koestler and Smythies1969), the majority of the classic theories of normal development that were prominent throughout much of the 20th century accorded little attention to neurobiological processes (Cicchetti, Reference Cicchetti, Hartup and Weinberg2002; Goldman-Rakic, Reference Goldman-Rakic1987; Johnson, Reference Johnson, Kuhn and Siegler1998; Nelson, Thomas, & de Haan, Reference Nelson, Thomas and de Haan2006; Segalowitz, Reference Segalowitz, Dawson and Fischer1994). Undoubtedly, the paucity of information that existed about the structural and functional organization of the brain contributed to the relative neglect of neurobiology in the formulation of developmental theorizing on the ontogenesis and epigenesis of behavior (Goldman-Rakic, Reference Goldman-Rakic1987; Johnson, Reference Johnson, Kuhn and Siegler1998; Kandel, Reference Kandel1998, Reference Kandel1999).

Although extant knowledge of the nature of the relations between neurobiology and behavior in both normal and abnormal development across the life span is far from complete, in recent decades a number of technological advances have emerged that have greatly enhanced the ability of neuroscientists and psychopathologists to discover normal and abnormal pathological processes in the brain (Amso & Casey, Reference Amso and Casey2006; Casey, Giedd, & Thomas, Reference Casey, Giedd and Thomas2000; Casey et al., Reference Casey, Tottenham, Liston and Durston2005; Durston et al., Reference Durston, Davidson, Tottenham, Galvan, Spicer and Fossella2006; Johnson, Halit, Grice, & Karmiloff-Smith, Reference Johnson, Halit, Grice and Karmiloff-Smith2002). This rapid growth in the development of sophisticated techniques that permit the anatomical and physiological imaging of the nervous system has enabled researchers to uncover diverse information about the brain, including brain metabolic processes, glucose metabolic rate, the ability to distinguish between cerebrospinal fluid and white and gray matter, the capacity to detect biochemical changes within brain cells, such as changes in neurotransmitter receptors, and the examination of brain connectivity through tracing white matter tracts and detecting brain functional connectivity (Hunt & Thomas, Reference Hunt and Thomas2008; Thomas, Reference Thomas2003).

Because developmental psychopathology and neuroscience share fundamental principles, the connection between neuroscience and developmental psychopathology can provide a compelling framework to support the study of normal and abnormal neurobiological development (Cicchetti & Posner, Reference Cicchetti and Posner2005). For example, one of the central principles of developmental psychopathology, that the study of normality and pathology are mutually informative, is also embraced by developmental neuroscientists (Goldman-Rakic, Reference Goldman-Rakic1987; Johnson, Reference Johnson, Kuhn and Siegler1998). Scientists in each of these disciplines believe that a firm knowledge base of normative developmental processes is essential for understanding both psychopatholgy and resilient functioning (Cicchetti, Reference Cicchetti1993; Sroufe, Reference Sroufe1990). Moreover, scientists in these two fields have long asserted that one can gain valuable information about an organism's normal functioning by investigating its abnormal condition (Cicchetti & Cannon, Reference Cicchetti and Cannon1999; Goldman-Rakic, Reference Goldman-Rakic1987; Johnson, Reference Johnson, Kuhn and Siegler1998; Nelson et al., Reference Nelson, Thomas and de Haan2006).

The theme of this Special Issue, “Imaging Brain Systems in Normality and Psychopathology,” addresses a timely and important topic that has the potential to augment the understanding of the etiology, developmental course, and pathogenesis of high-risk conditions and mental disorders across the life span. Furthermore, in the present era, where interdisciplinary and multiple levels of analysis perspectives are receiving increased attention and emphasis (see, e.g., Cacioppo et al., Reference Cacioppo, Amaral, Blanchard, Cameron, Carter and Crews2007; Cicchetti & Posner, Reference Cicchetti and Posner2005; Gottlieb, Wahlsten, & Lickliter, 2006; Masten, Reference Masten, Romer and Walker2007; Pellmar & Eisenberg, Reference Pellmar and Eisenberg2000), the incorporation of neuroimaging into the research armamentarium of developmental psychopathologists may contribute to an increased comprehension of the mechanisms underlying maladaptive, psychopathological, and resilient adaptation (Cicchetti & Curtis, Reference Cicchetti and Curtis2007). Furthermore, because psychopathology and resilience cannot be understood fully unless all levels of analysis are examined, the integration of neuroimaging into basic multilevel empirical investigations will be critical to suggesting future opportunities for translational research in neuroscience and developmental psychopathology (Cicchetti & Gunnar, Reference Cicchetti and Gunnar2008; Gunnar & Cicchetti, in press).

As illustrated through the contributions to this Special Issue, neuroimaging methods are being used by neuroscientists and developmental psychopathologists to enhance the understanding of normal and abnormal neurobiological development and to augment knowledge concerning the processes and pathways linking neurodevelopment and outcomes, typical and disordered (Casey et al., Reference Casey, Tottenham, Liston and Durston2005; Giedd, Shaw, Wallace, Gogtay, & Lenroot, Reference Giedd, Shaw, Wallace, Gogtay, Lenroot, Cicchetti and Cohen2006; Nelson & Bloom, Reference Nelson and Bloom1997). For example, it is now thought that the increasing cognitive capacities that emerge in childhood may take place concurrently with a gradual loss rather than with the formation of new synapses and a presumed strengthening of the synaptic connections that remain (Casey et al., Reference Casey, Giedd and Thomas2000). Moreover, regions of the brain that are associated with basic functions (e.g., sensory and motor processes) have been shown to mature earliest, followed by maturation of the association regions that are involved in the top-down control of behavior (Casey et al., Reference Casey, Tottenham, Liston and Durston2005). In addition, as cortical systems undergo a fine-tuning, it has been shown that there is a corresponding enhancement of connectivity with cortical and subcortical circuitry (Amso & Casey, Reference Amso and Casey2006). Thus, neuroimaging research has helped the field of cognitive development transcend the questions of what develops and when, to how these transformations in cognition across time may take place (Amso & Casey, 2005; Casey et al., Reference Casey, Giedd and Thomas2000). Furthermore, neuroimaging research has aided in the discovery of the underlying neural mechanisms of a number of psychopathological conditions.

These scientific gains may allow us to develop therapeutic strategies that may lead to advances in the treatment, and even in the prevention of, behavioral and emotional symptoms, as well as coping strategies, that may have been adaptive in their initial context, but proved to be ultimately maladaptive. Through investigating brain structure and function developmentally, we may get closer to specifying etiological pathways or a set of necessary precursors for the development of symptoms associated with various mental disorders. Regional differences in structural brain development or patterns of brain activity may serve as an endophenotype (Gottesman & Gould, Reference Gottesman and Gould2003), providing an alternate means of identifying those individuals who are more likely to respond positively to various treatments, those whose symptoms may be more refractory to intervention, or even those at risk for developing disorder. Moreover, the use of neuroimaging methods may allow for more precise subclassification of behavioral symptoms and syndromes. In addition, examination of the brain systems associated with specific cognitive, emotional, and social behaviors across development may aid in identifying key symptoms that are common among individuals with different behavioral or emotional profiles. Neuroimaging may indicate previously unstudied overlap between seemingly disparate symptoms.

Further investigating the activity of brain systems associated with disrupted behavior or emotion dysregulation can aid in understanding typical individual variability in brain function and organization, and in comprehending processes of risk and resilience. Neuroimaging also provides a unique method for examining the impact of various environmental and experiential factors on brain development and biological instantiations of behavior. In the future, emphasis should be placed on longitudinal data, especially on functional neuroimaging. To truly comprehend the emergence of behavioral and affective symptoms, it is critical for the field to conduct prospective longitudinal investigations. The prohibitive financial cost of neuroimaging research and the vast amount of human effort expended on coding and data analysis have thus far rendered the accumulation of prospective data to be a challenging goal.

Clearly, however, brain imaging technology cannot solve the complex issues inherent to the relation between typical and atypical development alone. Sound theory, in conjunction with experimental paradigms that permit the investigation of cognitive, emotional, and social behavior, has enabled research on neuroimaging to enhance the understanding of the relation between typical and atypical development across multiple levels of analysis. Because individual levels of analysis constrain other levels, researchers conducting their work at each level will need to develop theories that are consistent across all levels. Interdisciplinary research will become increasingly prevalent, necessitating that the challenge of establishing communication between scientists from different fields be confronted and solved (Gunnar & Cicchetti, in press; Pellmar & Eisenberg, Reference Pellmar and Eisenberg2000). This will enable the field of developmental psychopathology to make optimal use of the advances in technology that have occurred. If disciplines function in isolation, then it is likely that the theories they promulgate will ultimately prove to be incorrect because existing vital information from other disciplines will either have been unknown or have been ignored. Just as has been witnessed in the development of the discipline of systems neuroscience (Kandel & Squire, Reference Kandel and Squire2000), it is essential that we strive to develop an integrative framework that incorporates all levels of analysis about complex systems in typical development, as well as the development of psychopathology, and resilience. The sophisticated and comprehensive portrayals of adaptation, maladaptation, and resilience that ensue will serve not only to advance scientific understanding but also to inform efforts to prevent, ameliorate, and ultimately develop cures for mental disorders (Insel & Scolnick, Reference Insel and Scolnick2006).

Footnotes

Our work on this Special Issue was supported by grants from the National Institutes of Health (NS34458 and MH79513 to K.M.T., MH54643 and MH067792-01 to D.C.) and the Spunk Fund (to D.C.).

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