Aarthi Padmanabhan

What has fMRI told us about the Development of Cognitive Control through Adolescence

Cognitive control, the ability to voluntarily guide our behavior, continues to improve throughout adolescence. Below we review the literature on age-related changes in brain function related to response inhibition and working memory, which support cognitive control. Findings from studies using functional magnetic resonance imaging (fMRI) indicate that processing errors, sustaining a cognitive control state, and reaching adult levels of precision, persist through adolescence. Developmental changes in patterns of brain function suggest that core regions of the circuitry underlying cognitive control are on-line early in development. However, age-related changes in localized processes across the brain, and in establishing long range connections that support top-down modulation of behavior, more effective neural processing for optimal mature executive function. While great progress has been made in understanding the age-related changes in brain processes underlying cognitive development, there are still important challenges in developmental neuroimaging methods and the interpretation of data that need to be addressed.

Developmental changes in brain function underlying the influence of reward processing on inhibitory control

ABSTRACT Adolescence is a period marked by changes in motivational and cognitive brain systems. However, the development of the interactions between reward and cognitive control processing are just beginning to be understood. Using event-related functional neuroimaging and an incentive modulated antisaccade task, we compared blood-oxygen level dependent activity underlying motivated response inhibition in children, adolescents, and adults. Behaviorally, children and adolescents performed significantly worse than adults during neutral trials. However, children and adolescents showed significant performance increases during reward trials. Adults showed no performance changes across conditions. fMRI results demonstrated that all groups recruited a similar circuitry to support task performance, including regions typically associated with rewards (striatum and orbital frontal cortex), and regions known to be involved in inhibitory control (putative frontal and supplementary eye fields, and posterior parietal cortex, and prefrontal loci). During rewarded trials adolescents showed increased activity in striatal regions, while adults demonstrated heightened activation in the OFC relative to children and adolescents. Children showed greater reliance on prefrontal executive regions that may be related to increased effort in inhibiting responses. Overall, these results indicate that response inhibition is enhanced with reward contingencies over development. Adolescents’ heightened response in striatal regions may be one factor contributing to reward-biased decision making and perhaps risk taking behavior.

Age related changes in striatal resting state functional connectivity in autism

Characterizing the nature of developmental change is critical to understanding the mechanisms that are impaired in complex neurodevelopment disorders such as autism spectrum disorder (ASD) and, pragmatically, may allow us to pinpoint periods of plasticity when interventions are particularly useful. Although aberrant brain development has long been theorized as a characteristic feature of ASD, the neural substrates have been difficult to characterize, in part due to a lack of developmental data and to performance confounds. To address these issues, we examined the development of intrinsic functional connectivity, with resting state fMRI from late childhood to early adulthood (8–36 years), using a seed based functional connectivity method with the striatal regions. Overall, we found that both groups show decreases in cortico-striatal circuits over age. However, when controlling for age, ASD participants showed increased connectivity with parietal cortex and decreased connectivity with prefrontal cortex relative to typically developed (TD) participants. In addition, ASD participants showed aberrant age-related connectivity with anterior aspects of cerebellum, and posterior temporal regions (e.g., fusiform gyrus, inferior and superior temporal gyri). In sum, we found prominent differences in the development of striatal connectivity in ASD, most notably, atypical development of connectivity in striatal networks that may underlie cognitive and social reward processing. Our findings highlight the need to identify the biological mechanisms of perturbations in brain reorganization over development, which may also help clarify discrepant findings in the literature.

Developmental imaging genetics: Linking dopamine function to adolescent behavior

Adolescence is a period of development characterized by numerous neurobiological changes that significantly influence behavior and brain function. Adolescence is of particular interest due to the alarming statistics indicating that mortality rates increase two to three-fold during this time compared to childhood, due largely to a peak in risk-taking behaviors resulting from increased impulsivity and sensation seeking. Furthermore, there exists large unexplained variability in these behaviors that are in part mediated by biological factors. Recent advances in molecular genetics and functional neuroimaging have provided a unique and exciting opportunity to non-invasively study the influence of genetic factors on brain function in humans. While genes do not code for specific behaviors, they do determine the structure and function of proteins that are essential to the neuronal processes that underlie behavior. Therefore, studying the interaction of genotype with measures of brain function over development could shed light on critical time points when biologically mediated individual differences in complex behaviors emerge. Here we review animal and human literature examining the neurobiological basis of adolescent development related to dopamine neurotransmission. Dopamine is of critical importance because of (1) its role in cognitive and affective behaviors, (2) its role in the pathogenesis of major psychopathology, and (3) the protracted development of dopamine signaling pathways over adolescence. We will then focus on current research examining the role of dopamine-related genes on brain function. We propose the use of imaging genetics to examine the influence of genetically mediated dopamine variability on brain function during adolescence, keeping in mind the limitations of this approach.

The Teenage Brain Cognitive Control and Motivation

Adolescence is associated with heightened mortality rates due in large measure to negative consequences from risky behaviors. Theories of adolescent risk taking posit that it is driven by immature cognitive control coupled with heightened reward reactivity, yet surprisingly few empirical studies have examined these neurobiological systems together. In this article, we describe a series of studies from our laboratory aimed at further delineating the maturation of cognitive control through adolescence, as well as how rewards influence a key aspect of cognitive control: response inhibition. Our findings indicate that adolescents can exert adult-like control over their behavior but that they have limitations regarding the consistency with which they can generate optimal responses compared with adults. Moreover, we demonstrate that the brain circuitry supporting mature cognitive (inhibitory) control is still undergoing development. Our work using the rewarded antisaccade task, a paradigm that enables concurrent assessment of rewards and inhibitory control, indicates that adolescents show delayed but heightened responses in key reward regions along with concurrent activation in brain systems that support behaviors leading to reward acquisition. Considered together, our results highlight adolescent-specific differences in the integration of basic brain processes that may underlie decision making and more complex risk taking in adolescence.

The Teenage Brain

Adolescence is associated with heightened mortality rates due in large measure to negative consequences from risky behaviors. Theories of adolescent risk taking posit that it is driven by immature cognitive control coupled with heightened reward reactivity, yet surprisingly few empirical studies have examined these neurobiological systems together. In this article, we describe a series of studies from our laboratory aimed at further delineating the maturation of cognitive control through adolescence, as well as how rewards influence a key aspect of cognitive control: response inhibition. Our findings indicate that adolescents can exert adult-like control over their behavior but that they have limitations regarding the consistency with which they can generate optimal responses compared with adults. Moreover, we demonstrate that the brain circuitry supporting mature cognitive (inhibitory) control is still undergoing development. Our work using the rewarded antisaccade task, a paradigm that enables concurrent assessment of rewards and inhibitory control, indicates that adolescents show delayed but heightened responses in key reward regions along with concurrent activation in brain systems that support behaviors leading to reward acquisition. Considered together, our results highlight adolescent-specific differences in the integration of basic brain processes that may underlie decision making and more complex risk taking in adolescence.

The neural substrates of recognition memory for verbal information: Spanning the divide between short-and long-term memory

One of the classic categorical divisions in the history of memory research is that between short-term and long-term memory. Indeed, because memory for the immediate past (a few seconds) and memory for the relatively more remote past (several seconds and beyond) are assumed to rely on distinct neural systems, more often than not, memory research has focused either on short- (or “working memory”) or on long-term memory. Using an auditory–verbal continuous recognition paradigm designed for fMRI, we examined how the neural signatures of recognition memory change across an interval of time (from 2.5 to 30 sec) that spans this hypothetical division between short- and long-term memory. The results revealed that activity during successful auditory–verbal item recognition in inferior parietal cortex and the posterior superior temporal lobe was maximal for early lags, whereas, conversely, activity in the left inferior frontal gyrus increased as a function of lag. Taken together, the results reveal that as the interval between item repetitions increases, there is a shift in the distribution of memory-related activity that moves from posterior temporo-parietal cortex (lags 1–4) to inferior frontal regions (lags 5–10), indicating that as time advances, the burden of recognition memory is increasingly placed on top–down retrieval mechanisms that are mediated by structures in inferior frontal cortex.

Developmental changes in brain function underlying inhibitory control in autism spectrum disorders.

The development of inhibitory control—the ability to suppress inappropriate actions in order to make goal‐directed responses—is often impaired in autism spectrum disorders (ASD). In the present study, we examined whether the impairments in inhibitory control evident in ASD reflect—in part—differences in the development of the neural substrates of inhibitory control from adolescence into adulthood. We conducted a functional magnetic resonance imaging (fMRI) study on the anti‐saccade task, a probe of inhibitory control, in high‐functioning adolescents and adults with ASD compared to a matched group of typically developing (TD) individuals. The ASD group did not show the age‐related improvements in behavioral performance from adolescence to adulthood evident in the typical group, consistent with previous behavioral work. The fMRI results indicated that much of the circuitry recruited by the ASD group was similar to the TD group. However, the ASD group demonstrated some unique patterns, including: (a) a failure to recruit the frontal eye field during response preparation in adolescence but comparable recruitment in adulthood; (b) greater recruitment of putamen in adolescence and precuneus in adolescence and adulthood than the TD group; and (c) decreased recruitment in the inferior parietal lobule relative to TD groups. Taken together, these results suggest that brain circuitry underlying inhibitory control develops differently from adolescence to adulthood in ASD. Specifically, there may be relative underdevelopment of brain processes underlying inhibitory control in ASD, which may lead to engagement of subcortical compensatory processes. Autism Res 2015, 8: 123–135.

Hippocampal Activation During an Event-related 2-D Navigational Learning Task

355 F-AM Valence-specific frontal hypoactivation during word recognition in Major Depressive Disorder in the context of normal episodic memory performance: Preliminary results from the NESDA-neuroimaging study, M.J. van Tol, L. Melby, N.J. van der Wee, M.M. Nielen, A. Aleman, L.R. Demenescu, M.A. van Buchem, D.J. Veltman, F.G. Zitman, Department of Psychiatry, Leiden University Medical Center, Leiden, Netherlands