Functional MRI (fMRI) permits exploration of structure-function relations across development, allowing identification of where, when, and how cognitive abilities develop in relation to the maturation of anatomical brain systems. Cognitive processes such as language, executive functioning, and emotion regulation are most likely to elicit differences in patterns of brain activations in children compared with adults because association cortices in the brain that are critically important for these higher-order cognitive functions (especially superior temporal and dorsal prefrontal cortices) are those that undergo neuroanatomical changes well into adolescence and beyond.50
Language development is one of the most widely studied brain functions in healthy children.111– 114
It is a fundamental human trait that begins developing early and rapidly, making language a sensitive index of normal brain development. Findings from studies of language comprehension,115
indicate that healthy individuals show age-related increases and decreases in prefrontal and temporal brain areas when engaging these various linguistic functions.114
Functional MRI findings suggest, for example, that age-related increases in activation of language systems in the left frontal and temporal cortices seem to support the normal acquisition of reading and phonological skills during childhood and adolescence,98
consistent with the protracted anatomical thinning of these cortices during development.39,50
Delineating the trajectory of brain activation association with improved reading skills during the course of typical development can serve as a reference that allows us to identify disruptions in developmental processes that may contribute to reading impairments in children with dyslexia. In addition, these normal developmental trajectories may also be used to identify adaptive, developmentally based compensatory systems that support the acquisition of reading skills in children with dyslexia whose deficits in phonological processing typically persist into adulthood.117
Functional MRI studies of the development of normal language functions, for example, have helped to inform our understanding that dyslexia may be a consequence of disruptions in the development of normal functioning of the left hemisphere parietal- and occipital-temporal brain systems.118,119
These systems support reading abilities, including phonological processing, or the linking of sounds to symbols that ultimately enables the rapid perception of words in unimpaired readers. One fMRI study compared age-related changes associated with phonological processing when reading pseudowords across large samples of children and adolescents with dyslexia and normal reading abilities.120
Individuals with dyslexia relied increasingly more on the left posterior medial occipital-temporal areas with increasing age, whereas normal readers relied on a more anterior occipital-temporal region in the left hemisphere. These findings suggest that when children with dyslexia mature, they rely on an alternative posterior neural system that is involved in recognition memory,121
likely supporting their memorization of words to compensate for their deficits in phonological processing when reading. In contrast, with advancing age, normal readers increasingly rely on an anterior temporo-occipital region that has been termed the visual word form area122,123
and that supports phonological processing in normal adult readers. Although future longitudinal studies on individuals who are dyslexic and unimpaired readers are warranted, these findings suggest that developmental dyslexia may arise from an early functional disruption in the visual word form area that in typical readers supports development of adult-level reading skills.
Another important developmental process investigated extensively using fMRI is the ability to control behaviors that conflict with personal and societal norms.124–126
Both cognitive and emotional maturation requires the development of this capacity for “inhibitory control,” making it one of the most centrally defining characteristics of healthy psychological development. Children must learn to engage inhibitory processes to filter and to organize their thoughts, feelings, and behaviors based on social and emotional cues, especially in the face of competing information or distracting stimuli.127
Findings from fMRI studies of healthy individuals suggest that the maturation of these functions is associated with the development of the prefrontal cortex, along with anatomically connected, subcortical brain regions.124–126,128
Many experimental paradigms have been used to study the development of inhibitory control processes. The Stroop, Simon, flanker, go/no-go, and stop-signal reaction time tasks all require participants to suppress a more automatic behavior in favor of a less automatic one in the face of cognitive conflict that arises from the presentation of competing or distracting stimuli. Inhibitory control is necessary to mobilize attentional resources toward the appropriate stimuli and thereby resolve cognitive conflict to modulate the automatic tendency to respond in one way rather than another. Findings from developmental studies reveal that performance on these tasks improves continuously with age during childhood and does not reach adult levels of performance until at least 12 years of age.124–126
The Stroop task is one of the most commonly studied of these paradigms.129
It requires participants to inhibit word reading in favor of a less automatic behavior, naming the color of ink in which the letters of a color-denoting word are written. When the color that a written word denotes matches the color of the ink in which the letters are printed (e.g., “R-E-D” written in red ink), children perform the task easily, as indexed by their rapid responses and infrequent errors. However, cognitive conflict occurs when the color that a word denotes does not match the color of the printed letters (e.g., “R-E-D” written in blue ink), making the task more difficult, as indicated by slower responses and more frequent errors. Imaging studies of brain activity during color naming of the mismatching compared with the matching stimuli have demonstrated activation in large expanses of anterior cingulate, prefrontal, and parietal cortices, as well as the striatum, in both adults 130
A recent fMRI study, for example, identified age-related differences in the brain activity generated by healthy children and adults during performance of the Stroop task.92
Activation of the inferolateral prefrontal cortex and lenticular nucleus increased with age, as did the speed and accuracy of response on the task, indicating that increasing activity in frontostriatal circuits with age supports the age-related improvement in inhibitory control (). These findings are consistent with those from prior developmental imaging studies showing age-related changes in frontostriatal recruitment during performance of other tasks (e.g., Simon, flanker, and go/no-go) that similarly require the resolution of cognitive conflict.124,125,128
The increasing activation of prefrontal cortices during these inhibitory tasks from childhood to adulthood92,132
likely reflects the development of cognitive control processes that typically begin to emerge during adolescence,133
at a time when anatomical studies suggest that cortical gray matter thins39,50
and when DTI studies suggest that frontostriatal fiber tracts are continuing to myelinate.86
Nevertheless, future longitudinal fMRI studies of inhibitory control processes in healthy individuals are required to ensure that these cross-sectional findings represent true developmental changes in inhibitory control functions.65
Fig. 9 Age correlates of cognitive control during performance of the Stroop task. A, Voxelwise correlations of age with Stroop activations. These are transaxial slices positioned superiorly to inferiorly (left to right). B, Group composite t-maps for the percent (more ...)
The protracted anatomical and functional development of the prefrontal cortices and associated subcortical structures that subserve inhibitory control processes may contribute to the development of a variety of psychiatric disorders in which children have difficulty controlling their thoughts, emotions, and behaviors. These disturbances may release from regulatory control, for example, the various underlying impulses or urges that manifest as either the tics of Tourette’s syndrome (TS), the compulsions of obsessive-compulsive disorder, or the impulsive behaviors that characterize ADHD. These neurodevelopmental disorders, particularly when they occur together, are thought to share a common underlying neural basis involving anatomical disturbances in frontostriatal circuits.134,135
Understanding the normal development of inhibitory control functions mediated by these circuits can therefore inform our understanding of the etiology of TS, obsessive-compulsive disorder, and ADHD.
One fMRI study, for example, compared across individuals with and without TS the correlations of age with frontostriatal activations during performance of the Stroop task.136
Behavioral performance on the task improved with increasing age in patients with TS, just as it did in non-TS controls, reflecting the maturation of neural systems that subserve inhibitory control. In contrast to the normal developmental trajectory of behavioral performance on the task, the imaging findings showed that adults with TS rely on exaggerated activation of frontostriatal regions, which was interpreted as a likely compensatory functional response that produces normal performance on the task, despite deficits in neural plasticity and inhibitory reserve in adults with TS.137
Understanding the normal developmental pattern of Stroop-related activations was required to understand how developmental changes in activation of frontostriatal circuits diverge from normal trajectories in people with TS, and how exaggerated activity likely supports normal behavioral performance, even in the presence of an underlying anatomical hypoplasia or in the presence of impaired neural plasticity.
The prefrontal cortex is thought to modulate activity in subcortical structures,138
including limbic areas that likely give rise to the ability to engage inhibitory control over emotions. Emotional changes during adolescence involve the increasing ability to read a wide variety of social and emotional cues, including facial expressions. Thus, fMRI studies involving the perception of (and attention to) facial expressions have been used to study emotional development and the development of emotional control.139–141
For example, a study comparing brain activation across adolescents and adults revealed that adolescents activated the amygdala and prefrontal regions (orbitofrontal and anterior cingulate cortices ) more than adults when viewing fearful faces.139
When instructed to focus on a nonemotionally salient feature of the face, however, only the adults engaged the orbitofrontal cortex. These findings suggested that adults but not adolescents modulate activity in prefrontal cortices in response to attentional demands, thereby engaging control over the emotionally evocative stimuli. Thus, the maturation of neural systems that subserve emotional control processes is protracted during normal development. The evolving capacity for emotional control likely derives primarily from increasing functional maturation of prefrontal cortices during adolescence.
The developmental trajectories of these processes in individuals with mood disorders likely diverge from normal trajectories, thereby contributing to the development of problems with emotional control. Findings from studies of children and adolescents with BD, for example, indicate that when their attention directed to emotional versus nonemotional aspects of faces, children with BD misjudge neutral faces as more threatening than control children. In addition, their misinterpretations of the emotionally salient stimuli were associated with increased engagement of the amygdala.142
Moreover, increased amygdala activation in adolescents with BD relative to controls in response to emotional stimuli coincides with reduced ventrolateral prefrontal activity.143
These findings suggest that the control of affective responses is impaired in both children and adolescents with BD and therefore emerges early in development. The discovery of this developmental delay in prefrontal functioning in BD underscores the importance of studying the normal developmental trajectories of emotional control processes in healthy individuals and in those who may be at risk for psychopathological findings.