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From Neurons to Neighborhoods: The Science of Early Childhood Development C Technologies for Studying the Developing Human Brain NEUROPSYCHOLOGICAL TOOLS The strategy behind the use of neuropsychological tools is to generate a hypothesis about which area of the brain is involved in a particular behavior and then employ a behavioral test (or tests) to evaluate this hypothesis. Ideally one is able to dissociate one behavior from another (e.g., explicit from implicit memory) using a cluster of tasks or by applying such tasks to both normative and clinical populations. In terms of elucidating brain-behavior relations in normative samples, neuropsychological tools are frequently adopted that have first been used in animal models or in clinical populations of humans. For example, if one is interested in the type of memory subserved by the medial temporal lobe (i.e., episodic memory), one might employ tasks that have been demonstrated in monkeys or in humans in whom the hippocampus has been lesioned through surgery or through injury to result in memory impairments. The use of neuropsychological tools has received extensive study in the developing human. For example, Diamond has employed the Piagetian A-not-B task and its animal analogue, the delayed response task, to study the development of certain functions subserved by the prefrontal cortex (e.g., spatial working memory; see Diamond, 1990; Diamond and Doar, 1989; Diamond and Goldman-Rakic, 1989; Diamond et al., 1989). And Bachevalier (with respect to the monkey) and Nelson (with respect to the human) have utilized a set of tools (e.g., visual paired comparison; the
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From Neurons to Neighborhoods: The Science of Early Childhood Development “oddball” paradigm using event-related potentials) to study the development of explicit memory (see Bachevalier, 1992; Bachevalier et al., 1991, 1993; Nelson, C.A., 1994, 1995, 1996). Finally, Luciana and colleagues (e.g., Luciana and Nelson, 1998) have used an extensive battery of tasks to examine a range of cognitive behaviors. The use of neuropsychological tools have several advantages over the other approaches discussed below: (a) they are completely noninvasive, (b) they can be used across the lifespan, (c) parallel studies can be conducted across species, and (d) they can provide insight into specific behaviors. The neuropsychological approach also has shortcomings: (a) these tools only indirectly couple brain structure and function (i.e., because no direct measures of the brain are taken) and thus may lack precision with regard to this relation; (b) when adopting such tools from the animal literature, it is important to consider whether both species are responding to the tasks the same way; (c) caution must be exercised when generalizing from clinical to normative samples; and (d) when used with the lesion method (i.e., the population under study has experienced a lesion to a particular part of the brain), it is important to be aware that the mapping of specific lesion to specific function may be less than one to one (i.e., a lesion in a particular area could affect the function of surrounding areas as well). METABOLIC PROCEDURES This class of tools depends on the ability to track various metabolic functions as they occur in real time. These include positron emission tomography and functional magnetic resonance imaging, each of which is described below. Positron Emission Tomography Positron emission tomography (PET) scanning typically involves the injection of a natural substance such as oxygen or glucose that has been made radioactive. In so doing one is able to track the metabolism of this substance by those regions of the brain calling for its use. Positrons are emitted as the radioactive substance decays, and these positrons can be measured using a positron detector (i.e., PET scanner). The detector, in turn, computes the point of origin of these positrons, and thus localizes in the brain (within centimeters of resolution) the source of neural activity. A good example of this work comes from studies conducted by Chugani and his colleagues. Here a form of radioactive glucose (FDG) has been used in infants and children to infer the development of synapses (i.e., synapse formation requires energy and thus glucose can be used as an indirect marker for synaptogenesis; see Chugani, 1994; Chugani and Phelps, 1986;
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From Neurons to Neighborhoods: The Science of Early Childhood Development Chugani et al., 1987). The participants in these studies are typically studied under resting conditions (sometimes under sedation); that is, no task is being performed. A number of shortcomings with PET must be acknowledged. First, although the levels of radioactivity used in this work are relatively low, ethical constraints prevent samples of normally developing children from being evaluated; thus, currently all participants in this work require medical cause for doing the scan. Second, the spatial resolution of PET is typically confined to relatively large voxels (cubic centimeters of tissue), and thus it is difficult to pinpoint the locus of neural activity much beyond the centimeter range. Third, PET suffers from poor temporal resolution (i.e., on the order of minutes), and thus little useful information can be obtained about when brain activity is taking place. Finally, because a cyclotron is required to make the radioactive agents, PET studies are an expensive endeavor. Functional Magnetic Resonance Imaging Functional magnetic resonance imaging (fMRI) is a rapidly expanding technology that is increasingly finding a home in studies of development. The technique is based on the concept that deoxygenated hemoglobin is paramagnetic (paramagnetism refers to the ability of a normally nonmagnetic material to become magnetic) and thus can be detected using conventional magnetic resonance technology. When a particular part of the brain is called on to perform some task, that region receives increased blood flow and, as a by-product, increased oxygen. Increases and decreases in oxygen (generally on the order of 2 to 5 percent relative to background) are then monitored. By taking consecutive slices of the brain in various orientations, the MRI scanner is able to reconstruct where in the brain the greatest areas of activation occur. Over the past 10 years, there have been hundreds of studies using fMRI in the adult human. Increasingly, however, developmental investigators have begun to utilize this technique with children. For example, Casey and colleagues (e.g., Casey et al., 1995; Thomas et al., 1999), as well as Nelson and colleagues (e.g., Nelson et al., 2000) have used fMRI to study the development of working memory in normally developing children as young as 6 years. There are multiple advantages to fMRI. For example, it is completely noninvasive, does not require exposure to ionizing radiation, and can be performed in a relatively short period of time. Critically, the spatial resolution of fMRI is comparable to conventional MRI and thus can provide detailed anatomic images along the lines of a few millimeters. There are also a number of limitations that must be acknowledged. For example, participants must sit very still so as to keep motion artifacts to a minimum.
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From Neurons to Neighborhoods: The Science of Early Childhood Development In addition, they must be able to tolerate a somewhat high (e.g., 90 dB) level of noise and a confining environment. In summary, both PET and, in particular, fMRI lend themselves to the study of developing brain function. Unfortunately, neither PET nor fMRI provides much useful information about the chronometry of mental events.
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