Temporal Dynamics of Functional Brain States Underlie Cognitive Performance.

The functional organization of the human brain adapts dynamically in response to a rapidly changing environment. However, the relation of these rapid changes in functional organization to cognitive functioning is not well understood. This study used a graph-based time-frame modularity analysis approach to identify temporally recurrent functional configuration patterns in neural responses to an n-back working memory task during fMRI. Working memory load was manipulated to investigate the functional relevance of the identified brain states. Four distinct brain states were defined by the predominant patterns of activation in the task-positive, default-mode, sensorimotor, and visual networks. Associated with escalating working memory load, the occurrence of the task-positive state and the probability of transitioning into this state increased. In contrast, the occurrence of the default-mode and sensorimotor states and the probability of these 2 states transitioning away from the task-positive state decreased. The task-positive state occurrence rate and the probability of transitioning from the default-mode state back to the task-positive state explained a significant and unique portion of the variance in task performance. The results demonstrate that dynamic brain activities support successful cognitive functioning and may have heuristic value for understanding abnormal cognitive functioning associated with multiple neuropsychiatric disorders.

Activation of the cognitive control network associated with information uncertainty.

The cognitive control network (CCN) that comprises regions of the frontoparietal network, the cingulo-opercular network, and other sub-cortical regions as core structures is commonly activated by events with an increase in information uncertainty. However, it is not clear whether this CCN activation is associated with both information entropy that represents the information conveyed by the context formed by a sequence of events and the surprise that quantifies the information conveyed by a specific type of event in the context. We manipulated entropy and surprise in this functional magnetic resonance imaging study by varying the probability of occurrence of two types of events in both the visual and auditory modalities and measured brain response as a function of entropy and surprise. We found that activation in regions of the CCN increased as a function of entropy and surprise in both the visual and auditory tasks. The frontoparietal network and additional structures in the CCN mediated the relationship between these information measures and behavioral response. These results suggest that the CCN is a high-level modality-general neural entity for the control of the processing of information conveyed by both context and event.

Supramodal Mechanisms of the Cognitive Control Network in Uncertainty Processing.

Information processing under conditions of uncertainty requires the involvement of cognitive control. Despite behavioral evidence of the supramodal function (i.e., independent of sensory modality) of cognitive control, the underlying neural mechanism needs to be directly tested. This study used functional magnetic imaging together with visual and auditory perceptual decision-making tasks to examine brain activation as a function of uncertainty in the two stimulus modalities. The results revealed a monotonic increase in activation in the cortical regions of the cognitive control network (CCN) as a function of uncertainty in the visual and auditory modalities. The intrinsic connectivity between the CCN and sensory regions was similar for the visual and auditory modalities. Furthermore, multivariate patterns of activation in the CCN predicted the level of uncertainty within and across stimulus modalities. These findings suggest that the CCN implements cognitive control by processing uncertainty as abstract information independent of stimulus modality.

Distinct Topological Properties of the Reward Anticipation Network in Preadolescent Children With Binge Eating Disorder Symptoms.

OBJECTIVE: Few studies have considered the neural underpinnings of binge eating disorder (BED) in children, despite clinical and subclinical symptom presentation occurring in this age group. Symptom presentation at this age is of clinical relevance, as early onset of binge eating is linked to negative health outcomes. Studies in adults have highlighted dysfunction in the frontostriatal reward system as a potential candidate for binge eating pathophysiology, although the exact nature of such dysfunction is currently unclear. METHOD: Data from 83 children (mean age 9.9 years, SD = 0.60) with symptoms of BED (57% girls) and 123 control participants (mean age 10.0 years, SD = 0.60) (52% girls) were acquired from the 4.0 baseline release of the Adolescent Brain Cognitive Development Study. Task-based graph theoretic techniques were used to analyze data from anticipation trials of the monetary incentive delay task. Network and nodal properties were compared between groups. RESULTS: The BED-S group showed alterations in topological properties associated with the frontostriatal subnetwork, such as reduced nodal efficiency in the superior frontal gyrus, nucleus accumbens, putamen, and in normal sex-difference patterns of these properties, such as diminished girls-greater-than-boys pattern of betweenness-centrality in nucleus accumbens observed in controls. CONCLUSION: Distinct network properties and sex-difference patterns in preadolescent children with BED-S suggest dysregulation in the reward system compared to those of matched controls. For the first time, these results quantify this dysregulation in terms of systems-level properties during anticipation of monetary reward and significantly inform the early and sex-related brain markers of BED symptoms.

Neurobiological basis of reinforcement-based decision making in adults with ADHD treated with lisdexamfetamine dimesylate: Preliminary findings and implications for mechanisms influencing clinical improvement.

BACKGROUND: ADHD is often described as a disorder of altered reward sensitivity, yet few studies have examined the extent to which: (i) treatments for ADHD impact reward-related mechanisms; and (ii) changes in the reward system are associated with clinical improvement. This study addresses these issues - examining the extent to which clinical improvement following lisdexamfetamine (LDX) treatment is associated with changes in brain reward system activation. METHODS: Twenty adults (M = 11, 55%, F = 9, 45%), ages 19-52 (M = 33.9, SD = 10.0) with ADHD participated in a randomized cross-over study with lisdexamfetamine (LDX) and placebo (PB). Changes in brain activation were assessed during functional magnetic resonance (fMRI) scans: after receiving 3-5 weeks of treatment with LDX and 3-5 weeks of no drug/PB. fMRI contrasts were derived from the passive-avoidance (PA) learning task, which assessed reward-related learning using computational variables. We analyzed the following conditions: the Choice-Phase, modulated by the expected value (EV; i.e., object-choose and object-reject), and the Feedback-Phase, modulated by the prediction error (PE; i.e., reward and punish). Clinical symptom severity was assessed via interview with the ADHD-Rating Scale (ADHD-RS-IV). To address the primary objective, we performed group-level mass-univariate regression analyses between LDX and PB of percent change of the ADHD-RS total scores and the four contrast images under the Choice- and Feedback-conditions. Significance was set at a whole-brain voxel-wise threshold of p < 0.05 with family-wise error (FWE) correction and an extent (cluster) threshold of 50 contiguous voxels. RESULTS: Improvement in ADHD symptoms with LDX was accompanied by significantly increased activation in a series of brain regions previously implicated in reinforcement processing in the choice and feedback conditions (e.g., left caudate and putamen, right orbitofrontal cortex, left middle frontal, superior frontal, and precentral gyri). CONCLUSIONS: These findings, while preliminary, are the first to show that ADHD symptom improvement with stimulant treatment is associated with increased responsiveness of brain systems engaged in reward processing. Results support the hypothesis that LDX treatment may restore balance to dysfunction (e.g., hypoactivation) within the brain reward circuitry in adults with ADHD. Trial RegistrationClinicaltrials.gov Identifier: NCT01924429.

Training in cognitive reappraisal normalizes whole-brain indices of emotion regulation in borderline personality disorder.

BACKGROUND: Borderline personality disorder is the prototypical disorder of emotion dysregulation. We have previously shown that borderline personality disorder patients are impaired in their capacity to engage cognitive reappraisal, a frequently-employed adaptive emotion regulation strategy. METHODS: Here we report on the efficacy of longitudinal training in cognitive reappraisal to enhance emotion regulation in borderline patients. Specifically, the training targeted psychological distancing, a reappraisal tactic whereby negative stimuli are viewed dispassionately as though experienced by an objective, impartial observer. At each of 5 sessions over 2 weeks, 22 borderline (14 Female) and 22 healthy control (13 Female) participants received training in psychological distancing and then completed a widely-used picture-based reappraisal task. Self-reported negative affect ratings and functional magnetic resonance imaging (fMRI) data were acquired at the first and fifth sessions. In addition to behavioral analyses, we performed whole-brain pattern expression analyses using independently-defined patterns for negative affect and cognitive reappraisal implementation for each session. RESULTS: Borderline patients showed a decrease in negative affect pattern expression following reappraisal training, reflecting a normalization in neural activity. They did not, however, show significant change in behavioral self-reports. CONCLUSIONS: To our knowledge, this study represents the first longitudinal fMRI examination of task-based cognitive reappraisal training. Using a brief, proof-of-concept design, the results suggest a potential role for reappraisal training in the treatment of borderline patients.

Preparatory activity and connectivity in dorsal anterior cingulate cortex for cognitive control.

Dorsal anterior cingulate cortex (dACC) is composed of functionally distinct subregions that may contribute to the top-down control of response selection and preparation. Multiple motor areas have been identified in dACC, including an anterior zone implicated in conflict monitoring and a caudal zone involved in movement execution. This study tested the involvement of a third cingulate area, the posterior zone of dACC, in the top-down control of response selection and preparation. Sixteen healthy young adults were scanned with event-related functional magnetic resonance imaging while performing a cued go/no-go task that was designed to minimize response conflicts. The activation and functional connectivity of dACC were tested with standard convolution models and psychophysiological interaction analyses, respectively. Ready cues that informed the direction of the impending response triggered preparatory neural activity in the posterior zone of dACC and strengthened functional connectivity with the anterior and caudal zones of dACC, as well as perigenual anterior cingulate cortex, frontal operculum, dorsolateral prefrontal cortex, sensory association cortices, and extra-pyramidal motor areas. The preparatory cues activated dACC above and beyond the general arousing effects common to cues despite negligible conflict in the go/no-go task. The integration of cognitive, sensorimotor, and incentive signals in dACC places the region in an ideal position to select and prepare appropriate behavioral responses to achieve higher-level goals.

Dopamine transporter gene variation modulates activation of striatum in youth with ADHD.

Polymorphisms in the 3'UTR variable number tandem repeat (VNTR) of exon 15 of the dopamine transporter gene (DAT1) have been linked to attention-deficit hyperactivity disorder (ADHD); moreover, variability in DAT1 3'UTR genotype may contribute to both heterogeneity of the ADHD phenotype and differences in response to stimulant medications. The impact of this VNTR on neuronal function in individuals with ADHD remains unclear despite evidence that the polymorphisms influence dopamine transporter expression. Thus, we used event-related functional magnetic resonance imaging to examine the impact of DAT1 3'UTR genotype on brain activation during response inhibition in unmedicated children and adolescents with ADHD. Twenty-one youth with ADHD who were homozygous for the 10-repeat (10R) allele of the DAT1 3'UTR and 12 youth who were carriers of the 9-repeat (9R) allele were scanned while they performed a Go/No-Go task. Response inhibition was modeled by contrasting activation during correct No-Go trials versus correct Go trials. Participants who were homozygous for the DAT1 3'UTR 10R allele and those who had a single 9R allele did not differ on percent of trials with successful inhibition, which was the primary measure of inhibitory control. Yet, youth with the DAT1 3'UTR 10R/10R genotype had significantly greater inhibitory control-related activation than those with one 9R allele in the left striatum, right dorsal premotor cortex, and bilaterally in the temporoparietal cortical junction. These findings provide preliminary evidence that neural activity related to inhibitory control may differ as a function of DAT1 3'UTR genotype in youth with ADHD.

Dissociable neural effects of stimulus valence and preceding context during the inhibition of responses to emotional faces.

Socially appropriate behavior requires the concurrent inhibition of actions that are inappropriate in the context. This self-regulatory function requires an interaction of inhibitory and emotional processes that recruits brain regions beyond those engaged by either processes alone. In this study, we isolated brain activity associated with response inhibition and emotional processing in 24 healthy adults using event-related functional magnetic resonance imaging (fMRI) and a go/no-go task that independently manipulated the context preceding no-go trials (ie, number of go trials) and the valence (ie, happy, sad, and neutral) of the face stimuli used as trial cues. Parallel quadratic trends were seen in correct inhibitions on no-go trials preceded by increasing numbers of go trials and associated activation for correct no-go trials in inferior frontal gyrus pars opercularis, pars triangularis, and pars orbitalis, temporoparietal junction, superior parietal lobule, and temporal sensory association cortices. Conversely, the comparison of happy versus neutral faces and sad versus neutral faces revealed valence-dependent activation in the amygdala, anterior insula cortex, and posterior midcingulate cortex. Further, an interaction between inhibition and emotion was seen in valence-dependent variations in the quadratic trend in no-go activation in the right inferior frontal gyrus and left posterior insula cortex. These results suggest that the inhibition of response to emotional cues involves the interaction of partly dissociable limbic and frontoparietal networks that encode emotional cues and use these cues to exert inhibitory control over the motor, attention, and sensory functions needed to perform the task, respectively.

Inhibitory control deficits in childhood and risk for substance use disorders: a review.

Identification of neurobiological factors that confer risk for the development of addiction may substantially advance development of new prevention and treatment strategies to combat substance use disorders. This review focuses on the relationship between impulsivity - a behavior that is common to the clinical picture of both substance use disorders (SUD) and childhood disruptive behavior disorders - and neurobiological risk for SUD. It further examines various behaviors within the over-arching domain of impulsivity, ultimately focusing on the more narrowly defined and measurable construct of inhibitory control, and concluding that underlying deficits in inhibitory control may be central to many of the behaviors associated with high risk for SUD. Targeted cross-sectional study of the neural basis of inhibitory dyscontrol in subjects at high risk for SUD, who have not yet begun to abuse drugs, has the potential to generate important hypotheses regarding the neurobiological underpinnings of SUD risk. Hypotheses developed using this approach can be more definitively evaluated in longitudinal studies with these same populations, extending through the period of maximal risk for SUD in adolescence and early adulthood.

Distinct topological properties of cue-evoked attention processing network in persisters and remitters of childhood ADHD.

Attention deficit/hyperactivity disorder (ADHD) is a highly prevalent and impairing neurodevelopmental disorder that persists into adulthood in a sizeable portion of afflicted children. The persistence of ADHD elevates the risk for adverse outcomes that result in substantial individual and societal burden. The objective of this study is to assess neurobiological substrates associated with variability of clinical outcomes in childhood ADHD, which has considerable value for the development of novel interventions that target mechanisms associated with recovery. A total of 36 young adults who were diagnosed with ADHD combined-type during childhood and 33 group-matched controls were involved in the study. Adults with childhood ADHD were further divided into 17 persisters and 19 remitters based on DSM-5 criteria. Functional magnetic resonance imaging data during a cue-evoked attention task were collected from each subject. The cue-evoked attention processing network was constructed using graph theoretic techniques. Network properties, including global-, local-, and nodal-efficiency, and network hubs were computed. Group comparisons of the network properties were conducted. Significantly lower nodal efficiency in right inferior frontal gyrus and reduced left side frontal-parietal functional interactions were observed in both remitters and persisters relative to the controls. The ADHD persisters showed a unique pattern of significantly lower nodal efficiency in right middle frontal gyrus (MFG) and hyper-interactions between bilateral MFG. This study suggests that right MFG functional impairments may relate to inactive fronto-parietal functional interactions for sensory and cognitive information processing and symptom persistence in young adults with childhood ADHD.

Lisdexamfetamine Targets Amygdala Mechanisms That Bias Cognitive Control in Attention-Deficit/Hyperactivity Disorder.

BACKGROUND: Prefrontal-limbic circuits that form the neural architecture for emotion to influence behavior have been implicated in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD) and represent a potentially important target of medication treatment that has not been substantively evaluated. This study tested the effect of the psychostimulant prodrug lisdexamfetamine dimesylate on amygdala activation and connectivity during the emotional bias of response execution and inhibition. METHODS: Twenty-five adults with ADHD were scanned twice with event-related functional magnetic resonance imaging while performing an emotional go/no-go task after 3 to 4 weeks of lisdexamfetamine treatment and 3 weeks off medication in a randomized, counterbalanced, hybrid crossover design. Drug, trial type, and face emotion (happy, sad, or neutral) were included as within-subjects factors in repeated measures analyses of activation and connectivity. RESULTS: Lisdexamfetamine was associated with increased right amygdala activation and reduced psychophysiological interactions with the orbital aspect of the left inferior frontal gyrus specifically for responses to sad faces compared with placebo, but there was no effect on the accuracy of response execution or inhibition. The relative gain in right amygdala activation in response to sad faces for lisdexamfetamine was correlated with a reduction in symptoms of ADHD. CONCLUSIONS: Treatment with lisdexamfetamine potentiates affective encoding in amygdala, purportedly via catecholaminergic mechanisms, but functionally disconnects the amygdala from inferior frontal regions that encode behavioral significance-resulting in reduced emotional bias of cognitive control. Pinpointing the neurophysiologic underpinnings of therapeutic improvement with lisdexamfetamine represents a first step in developing targeted approaches to treatment of ADHD.

The interaction of psychosocial adversity and biological risk in childhood aggression.

Childhood aggression has both biological and environmental underpinnings. However, the manner in which these factors interact to influence various types of aggression remains an important area of study. The current study examined the degree to which biological risk and psychosocial adversity, both alone and in combination, are associated with childhood aggression. Linear regression procedures were used to assess the extent to which biological risk status (low vs. high serotonergic responsivity, as measured by prolactin response to fenfluramine), magnitude of psychosocial risk, and the interaction of these factors predicted parent and teacher ratings of aggression and delinquency. After accounting for the independent contribution of biological and psychosocial risk, the interaction of biological and psychosocial risk was significantly associated with parent-rated aggression and marginally related to parent-rated delinquency. In contrast, no such interaction was observed for teacher-rated aggression. Findings suggest that individuals at biological risk for aggression may be particularly vulnerable to the impact of psychosocial adversity.

Does the emotional go/no-go task really measure behavioral inhibition? Convergence with measures on a non-emotional analog.

This study tested the convergence of behavioral inhibition measures across emotional and non-emotional versions of the same go/no-go task in 85 college students. The two tasks differed only in the stimuli used for trial cues (i.e., circles versus facial expressions). Moderate correlations (r=.51-.56) between commission errors across the emotional and non-emotional tasks support the construct validity of behavioral inhibition. Further, parametric manipulation of preceding context had comparable effects on performance on the two tasks. Responses were slower and more variable, commission errors were more numerous, and perceptual sensitivity was lower on the emotional than the non-emotional task. A bias for happy faces on the emotional task resulted in faster responses and more commission errors for happy than sad faces despite marginally greater sensitivity for the latter. These results suggest that the basic neuropsychological constructs of the original go/no-go task were preserved in the emotional adaptation.

Striatal Activation Predicts Differential Therapeutic Responses to Methylphenidate and Atomoxetine.

OBJECTIVE: Methylphenidate has prominent effects in the dopamine-rich striatum that are absent for the selective norepinephrine transporter inhibitor atomoxetine. This study tested whether baseline striatal activation would predict differential response to the two medications in youth with attention-deficit/hyperactivity disorder (ADHD). METHOD: A total of 36 youth with ADHD performed a Go/No-Go test during functional magnetic resonance imaging at baseline and were treated with methylphenidate and atomoxetine using a randomized cross-over design. Whole-brain task-related activation was regressed on clinical response. RESULTS: Task-related activation in right caudate nucleus was predicted by an interaction of clinical responses to methylphenidate and atomoxetine (F1,30 = 17.00; p < .001). Elevated caudate activation was associated with robust improvement for methylphenidate and little improvement for atomoxetine. The rate of robust response was higher for methylphenidate than for atomoxetine in youth with high (94.4% vs. 38.8%; p = .003; number needed to treat = 2, 95% CI = 1.31-3.73) but not low (33.3% vs. 50.0%; p = .375) caudate activation. Furthermore, response to atomoxetine predicted motor cortex activation (F1,30 = 14.99; p < .001). CONCLUSION: Enhanced caudate activation for response inhibition may be a candidate biomarker of superior response to methylphenidate over atomoxetine in youth with ADHD, purportedly reflecting the dopaminergic effects of methylphenidate but not atomoxetine in the striatum, whereas motor cortex activation may predict response to atomoxetine. These data do not yet translate directly to the clinical setting, but the approach is potentially important for informing future research and illustrates that it may be possible to predict differential treatment response using a biomarker-driven approach. CLINICAL TRIAL REGISTRATION INFORMATION: Stimulant Versus Nonstimulant Medication for Attention Deficit Hyperactivity Disorder in Children; https://clinicaltrials.gov/; NCT00183391.

Prefrontal and parietal correlates of cognitive control related to the adult outcome of attention-deficit/hyperactivity disorder diagnosed in childhood.

The protracted and highly variable development of prefrontal cortex regions that support cognitive control has been purported to shape the adult outcome of attention-deficit/hyperactivity disorder (ADHD). This neurodevelopmental model was tested in a prospectively followed sample of 27 adult probands who were diagnosed with ADHD in childhood and 28 carefully matched comparison subjects aged 21-28 years. Probands were classified with persistent ADHD or remitted ADHD. Behavioral and neural responses to the Stimulus and Response Conflict Task (SRCT) performed during functional magnetic resonance imaging (fMRI) were compared in probands and comparison subjects and in probands with persistent and remitted ADHD. Response speed and accuracy for stimulus, response, and combined conflicts did not differ across groups. Orbitofrontal, inferior frontal and parietal activation was lower in probands than comparison subjects, but only for combined conflicts, when demand for cognitive control was highest. Reduced activation for combined conflicts in probands was almost wholly attributable to the persistence of ADHD; orbitofrontal, inferior frontal, anterior cingulate and parietal activation was lower in probands with persistent ADHD than both probands with remitted ADHD and comparison subjects, but did not differ between probands with remitted ADHD and comparison subjects. These data provide the first evidence that prefrontal and parietal activation during cognitive control parallels the adult outcome of ADHD diagnosed in childhood, with persistence of symptoms linked to reduced activation and symptom recovery associated with activation indistinguishable from adults with no history of ADHD.

Revisiting the role of the prefrontal cortex in the pathophysiology of attention-deficit/hyperactivity disorder.

Most neural models for the pathophysiology of attention-deficit/hyperactivity disorder (ADHD) have centered on the prefrontal cortex and its interconnections with the striatum and other subcortical structures. However, research only partially supports these models, and they do not correspond with the development of the prefrontal cortex and its interrelated neurocircuitry. The neural and functional development of the prefrontal cortex more closely parallels recovery from ADHD as indicated by the developmental remission of symptomatology. The authors hypothesize that ADHD is due to noncortical dysfunction that manifests early in ontogeny, remains static throughout the lifetime, and is not associated with the remission of symptomatology. Data supporting this neurodevelopmental model of prefrontal cortex function in ADHD are reviewed. Research and treatment implications are discussed.

Elevated childhood serotonergic function protects against adolescent aggression in disruptive boys.

OBJECTIVE: This longitudinal study examined whether responsiveness of the neurotransmitter serotonin (5-HT) in childhood predicts adolescent aggression. METHOD: Boys (N = 33) with disruptive behavior disorders who received assessments of central 5-HT function via the prolactin response to fenfluramine between 1990 and 1994 when they were 7 to 11 years old were re-evaluated clinically on average 6.7 years later. RESULTS: After accounting for baseline aggression, early 5-HT function accounted for a significant proportion of variance in adolescent aggression. This prospective relationship of childhood 5-HT function with adolescent aggression (r = -0.71) and antisocial behavior (r = -0.59) was found primarily in adolescents who were aggressive during childhood. Irrespective of childhood aggression, no child with high 5-HT function was particularly aggressive at follow-up. CONCLUSIONS: Low childhood 5-HT function appears important, but not sufficient, for the emergence of adolescent aggression. However, early high 5-HT function may protect against adolescent violence and aggression.

Neurorobiology and evidence-based biological treatments for substance abuse disorders.

Behavioral patterns of addiction include compulsive drug-seeking, persistent abuse of substances despite the often dire consequences on social functioning and physical health, and the high probability of relapse even after prolonged drug-free periods. The recent focus on the biological basis of addiction has provided evidence to support the hypothesis that behavioral manifestations for addiction are influenced by biological factors, and biological factors often produce behavioral changes that can further increase risk. The current understanding of the role of the dopaminergic, glutamatergic, Upsilon-aminobutyric acidergic, and opioid receptor systems in the pathophysiology of addiction as well as the clinical implications of these systems for new and emerging treatments will be discussed. This article will also review the pharmacologic agents used in the treatment of substance abuse disorders and presents evidence-based data for their safety, efficacy, and feasibility of use in different patient populations.

Brain activation gradients in ventrolateral prefrontal cortex related to persistence of ADHD in adolescent boys.

OBJECTIVE: To explore the possible role that functional abnormalities of the prefrontal cortex and basal ganglia play in the persistence of attention-deficit/hyperactivity disorder (ADHD) in adolescents aged 15 to 19 years. METHOD: Ten male adolescents who were diagnosed with ADHD during childhood were grouped into those who continued to meet full diagnostic criteria for DSM-IV ADHD (persisters; n = 5) and those in whom symptoms had remitted sufficiently to warrant a diagnosis of ADHD in partial remission (remitters; n = 5). Persisters, remitters, and five carefully matched controls with no history of ADHD were scanned using functional magnetic resonance imaging while performing a go/no-go task. RESULTS: Parallel linear trends were found in performance on the go/no-go task and activation of ventrolateral prefrontal cortex, such that persisters made the most commission errors (33%) and showed the greatest activation, remitters made fewer commission errors (24%) and had lower activity, and activation was lowest in controls who made the fewest errors (13%). CONCLUSIONS: These preliminary results suggest that developmental changes in ADHD symptomatology are associated with functional changes in ventrolateral prefrontal cortex activity.