Katerina Velanova

Immaturities in Reward Processing and Its Influence on Inhibitory Control in Adolescence

The nature of immature reward processing and the influence of rewards on basic elements of cognitive control during adolescence are currently not well understood. Here, during functional magnetic resonance imaging, healthy adolescents and adults performed a modified antisaccade task in which trial-by-trial reward contingencies were manipulated. The use of a novel fast, event-related design enabled developmental differences in brain function underlying temporally distinct stages of reward processing and response inhibition to be assessed. Reward trials compared with neutral trials resulted in faster correct inhibitory responses across ages and in fewer inhibitory errors in adolescents. During reward trials, the blood oxygen level–dependent signal was attenuated in the ventral striatum in adolescents during cue assessment, then overactive during response preparation, suggesting limitations during adolescence in reward assessment and heightened reactivity in anticipation of reward compared with adults. Importantly, heightened activity in the frontal cortex along the precentral sulcus was also observed in adolescents during reward-trial response preparation, suggesting reward modulation of oculomotor control regions supporting correct inhibitory responding. Collectively, this work characterizes specific immaturities in adolescent brain systems that support reward processing and describes the influence of reward on inhibitory control. In sum, our findings suggest mechanisms that may underlie adolescents’ vulnerability to poor decision-making and risk-taking behavior.

Distinct neural signatures detected for ADHD subtypes after controlling for micro-movements in resting state functional connectivity MRI data

In recent years, there has been growing enthusiasm that functional magnetic resonance imaging (MRI) could achieve clinical utility for a broad range of neuropsychiatric disorders. However, several barriers remain. For example, the acquisition of large-scale datasets capable of clarifying the marked heterogeneity that exists in psychiatric illnesses will need to be realized. In addition, there continues to be a need for the development of image processing and analysis methods capable of separating signal from artifact. As a prototypical hyperkinetic disorder, and movement-related artifact being a significant confound in functional imaging studies, ADHD offers a unique challenge. As part of the ADHD-200 Global Competition and this special edition of Frontiers, the ADHD-200 Consortium demonstrates the utility of an aggregate dataset pooled across five institutions in addressing these challenges. The work aimed to (1) examine the impact of emerging techniques for controlling for “micro-movements,” and (2) provide novel insights into the neural correlates of ADHD subtypes. Using support vector machine (SVM)-based multivariate pattern analysis (MVPA) we show that functional connectivity patterns in individuals are capable of differentiating the two most prominent ADHD subtypes. The application of graph-theory revealed that the Combined (ADHD-C) and Inattentive (ADHD-I) subtypes demonstrated some overlapping (particularly sensorimotor systems), but unique patterns of atypical connectivity. For ADHD-C, atypical connectivity was prominent in midline default network components, as well as insular cortex; in contrast, the ADHD-I group exhibited atypical patterns within the dlPFC regions and cerebellum. Systematic motion-related artifact was noted, and highlighted the need for stringent motion correction. Findings reported were robust to the specific motion correction strategy employed. These data suggest that resting-state functional connectivity MRI (rs-fcMRI) data can be used to characterize individual patients with ADHD and to identify neural distinctions underlying the clinical heterogeneity of ADHD.

Evidence Accumulation and the Moment of Recognition: Dissociating Perceptual Recognition Processes Using fMRI

Decision making can be conceptualized as the culmination of an integrative process in which evidence supporting different response options accumulates gradually over time. We used functional magnetic resonance imaging to investigate brain activity leading up to and during decisions about perceptual object identity. Pictures were revealed gradually and subjects signaled the time of recognition (TR) with a button press. We examined the time course of TR-dependent activity to determine how brain regions tracked the timing of recognition. In several occipital regions, activity increased primarily as stimulus information increased, suggesting a role in lower-level sensory processing. In inferior temporal, frontal, and parietal regions, a gradual buildup in activity peaking in correspondence with TR suggested that these regions participated in the accumulation of evidence supporting object identity. In medial frontal cortex, anterior insula/frontal operculum, and thalamus, activity remained near baseline until TR, suggesting a relation to the moment of recognition or the decision itself. The findings dissociate neural processes that function in concert during perceptual recognition decisions.

Strengthening of top-down frontal cognitive control networks underlying the development of inhibitory control: a functional magnetic resonance imaging effective connectivity study.

The ability to voluntarily inhibit responses to task-irrelevant stimuli, which is a fundamental component of cognitive control, has a protracted development through adolescence. Previous human developmental imaging studies have found immaturities in localized brain activity in children and adolescents. However, little is known about how these regions integrate with age to form the distributed networks known to support cognitive control. In the present study, we used Granger causality analysis to characterize developmental changes in effective connectivity underlying inhibitory control (antisaccade task) compared with reflexive responses (prosaccade task) in human participants. By childhood, few top-down connectivities were evident with increased parietal interconnectivity. By adolescence, connections from prefrontal cortex increased and parietal interconnectivity decreased. From adolescence to adulthood, there was evidence of increased number and strength of frontal connections to cortical regions as well as subcortical regions. Together, results suggest that developmental improvements in inhibitory control may be supported by age-related enhancements in top-down effective connectivity between frontal, oculomotor, and subcortical regions.

Development of eye-movement control

Cognitive control of behavior continues to improve through adolescence in parallel with important brain maturational processes including synaptic pruning and myelination, which allow for efficient neuronal computations and the functional integration of widely distributed circuitries supporting top-down control of behavior. This is also a time when psychiatric disorders, such as schizophrenia and mood disorders, emerge reflecting a particularly vulnerability to impairments in development during adolescence. Oculomotor studies provide a unique neuroscientific approach to make precise associations between cognitive control and brain circuitry during development that can inform us of impaired systems in psychopathology. In this review, we first describe the development of pursuit, fixation, and visually-guided saccadic eye movements, which collectively indicate early maturation of basic sensorimotor processes supporting reflexive, exogenously-driven eye movements. We then describe the literature on the development of the cognitive control of eye movements as reflected in the ability to inhibit a prepotent eye movement in the antisaccade task, as well as making an eye movement guided by on-line spatial information in working memory in the oculomotor delayed response task. Results indicate that the ability to make eye movements in a voluntary fashion driven by endogenous plans shows a protracted development into adolescence. Characterizing the transition through adolescence to adult-level cognitive control of behavior can inform models aimed at understanding the neurodevelopmental basis of psychiatric disorders.

Longitudinal Growth Curves of Brain Function Underlying Inhibitory Control through Adolescence

Neuroimaging studies suggest that developmental improvements in inhibitory control are primarily supported by changes in prefrontal executive function. However, studies are contradictory with respect to how activation in prefrontal regions changes with age, and they have yet to analyze longitudinal data using growth curve modeling, which allows characterization of dynamic processes of developmental change, individual differences in growth trajectories, and variables that predict any interindividual variability in trajectories. In this study, we present growth curves modeled from longitudinal fMRI data collected over 302 visits (across ages 9 to 26 years) from 123 human participants. Brain regions within circuits known to support motor response control, executive control, and error processing (i.e., aspects of inhibitory control) were investigated. Findings revealed distinct developmental trajectories for regions within each circuit and indicated that a hierarchical pattern of maturation of brain activation supports the gradual emergence of adult-like inhibitory control. Mean growth curves of activation in motor response control regions revealed no changes with age, although interindividual variability decreased with development, indicating equifinality with maturity. Activation in certain executive control regions decreased with age until adolescence, and variability was stable across development. Error-processing activation in the dorsal anterior cingulate cortex showed continued increases into adulthood and no significant interindividual variability across development, and was uniquely associated with task performance. These findings provide evidence that continued maturation of error-processing abilities supports the protracted development of inhibitory control over adolescence, while motor response control regions provide early-maturing foundational capacities and suggest that some executive control regions may buttress immature networks as error processing continues to mature.

The Maturation of Task Set-Related Activation Supports Late Developmental Improvements in Inhibitory Control

The ability to voluntarily inhibit a single response is evident early in development, even as the ability to maintain an inhibitory “task set” continues to improve. To date, functional neuroimaging studies have detailed developmental changes in systems supporting inhibitory control exerted at the single-trial level, but changes underlying the ability to maintain an inhibitory task set remain little understood. Here we present findings from a functional magnetic resonance imaging study that characterizes the development of systems supporting both transient (trial-related) and sustained (task set-related) activation during performance of the antisaccade task—an oculomotor test of inhibitory control (Hallett, 1978). Transient activation decreased from childhood to adolescence in regions known to support inhibitory processes and oculomotor control, likely reflecting less effortful response production. In contrast, sustained activation increased to adulthood in regions implicated in control. Our results suggest that development of the ability to maintain a task set is primary to the maturation of inhibitory control and, furthermore, that this ability is still immature in adolescence.

Impact of ADHD and cannabis use on executive functioning in young adults

BACKGROUND Attention-deficit/hyperactivity disorder (ADHD) and cannabis use are each associated with specific cognitive deficits. Few studies have investigated the neurocognitive profile of individuals with both an ADHD history and regular cannabis use. The greatest cognitive impairment is expected among ADHD Cannabis Users compared to those with ADHD-only, Cannabis use-only, or neither. METHODS Young adults (24.2 ± 1.2 years) with a childhood ADHD diagnosis who did (n=42) and did not (n=45) report past year ≥ monthly cannabis use were compared on neuropsychological measures to a local normative comparison group (LNCG) who did (n=20) and did not (n=21) report past year regular cannabis use. Age, gender, IQ, socioeconomic status, and past year alcohol and smoking were statistical covariates. RESULTS The ADHD group performed worse than LNCG on verbal memory, processing speed, cognitive interference, decision-making, working memory, and response inhibition. No significant effects for cannabis use emerged. Interactions between ADHD and cannabis were non-significant. Exploratory analyses revealed that individuals who began using cannabis regularly before age 16 (n=27) may have poorer executive functioning (i.e., decision-making, working memory, and response inhibition), than users who began later (n=32); replication is warranted with a larger sample. CONCLUSIONS A childhood diagnosis of ADHD, but not cannabis use in adulthood, was associated with executive dysfunction. Earlier initiation of cannabis use may be linked to poor cognitive outcomes and a significantly greater proportion of the ADHD group began using cannabis before age 16. Regular cannabis use starting after age 16 may not be sufficient to aggravate longstanding cognitive deficits characteristic of ADHD.

Methodological approaches in developmental neuroimaging studies

Pediatric neuroimaging is increasingly providing insights into the neural basis of cognitive development. Indeed, we have now arrived at a stage where we can begin to identify optimal methodological and statistical approaches to the acquisition and analysis of developmental imaging data. In this article, we describe a number of these approaches and how their selection impacts the ability to examine and interpret developmental effects. We describe preferred approaches to task selection, definition of age groups, selection of fMRI designs, definition of regions of interest (ROI), optimal baseline measures, and treatment of timecourse data. Consideration of these aspects of developmental neuroimaging reveals that unlike single‐group neuroimaging studies, developmental studies pose unique challenges that impact study planning, task design, data analysis, and the interpretation of findings. Hum Brain Mapp , 2010.

Dissociating early and late error signals in perceptual recognition

Decisions about object identity follow a period in which evidence is gathered and analyzed. Evidence can consist of both task-relevant external stimuli and internally generated goals and expectations. How the various pieces of information are gathered and filtered into meaningful evidence by the nervous system is largely unknown. Although object recognition is often highly efficient and accurate, errors are common. Errors may be related to faulty evidence gathering arising from early misinterpretations of incoming stimulus information. In addition, errors in task performance are known to elicit late corrective performance monitoring mechanisms that can optimize or otherwise adjust future behavior. In this study, we used functional magnetic resonance imaging (fMRI) in an extended trial paradigm of object recognition to study whether we could identify performance-based signal modulations prior to and following the moment of recognition. The rationale driving the current report is that early modulations in fMRI activity may reflect faulty evidence gathering, whereas late modulations may reflect the presence of performance monitoring mechanisms. We tested this possibility by comparing fMRI activity on correct and error trials in regions of interest (ROIs) that were selected a priori. We found pre- and postrecognition accuracy-dependent modulation in different sets of a priori ROIs, suggesting the presence of dissociable error signals.