Functional Connectivity Mechanisms Underlying Symptom Reduction Following Lisdexamfetamine Treatment in Binge-Eating Disorder: A Clinical Trial.

Background: Speculation exists as to whether lisdexamfetamine dimesylate (LDX) acts on the functional connectivity (FC) of brain networks that modulate appetite, reward, or inhibitory control in binge-eating disorder (BED). Better insights into its action may help guide the development of more targeted therapeutics and identify who will benefit most from this medication. Here, we use a comprehensive data-driven approach to investigate the brain FC changes that underlie the therapeutic action of LDX in patients with BED. Methods: Forty-six participants with moderate to severe BED received LDX titrated to 50 or 70 mg for an 8-week period. Twenty age-matched healthy control participants were also recruited. Resting-state functional magnetic resonance imaging was used to probe changes in brain FC pre- and post treatment and correlated with change in clinical measures. Results: Ninety-seven percent of trial completers (n = 31) experienced remission or a reduction to mild BED during the 8-week LDX trial. Widespread neural FC changes occurred, with changes in default mode to limbic, executive control to subcortical, and default mode to executive control networks associated with improvements in clinical outcomes. These connections were not distinct from control participants at pretreatment but were different from control participants following LDX treatment. Pretreatment connectivity did not predict treatment response. Conclusions: FC between networks associated with self-referential processing, executive function, and reward seem to underlie the therapeutic effect of LDX in BED. This suggests that LDX activates change via multiple systems, with most changes in compensatory networks rather than in those characterizing the BED diagnosis.

Functional Magnetic Resonance Imaging of the Amygdala and Subregions at 3 Tesla: A Scoping Review.

The amygdalae are a pair of small brain structures, each of which is composed of three main subregions and whose function is implicated in neuropsychiatric conditions. Functional Magnetic Resonance Imaging (fMRI) has been utilized extensively in investigation of amygdala activation and functional connectivity (FC) with most clinical research sites now utilizing 3 Tesla (3T) MR systems. However, accurate imaging and analysis remains challenging not just due to the small size of the amygdala, but also its location deep in the temporal lobe. Selection of imaging parameters can significantly impact data quality with implications for the accuracy of study results and validity of conclusions. Wide variation exists in acquisition protocols with spatial resolution of some protocols suboptimal for accurate assessment of the amygdala as a whole, and for measuring activation and FC of the three main subregions, each of which contains multiple nuclei with specialized roles. The primary objective of this scoping review is to provide a broad overview of 3T fMRI protocols in use to image the activation and FC of the amygdala with particular reference to spatial resolution. The secondary objective is to provide context for a discussion culminating in recommendations for a standardized protocol for imaging activation of the amygdala and its subregions. As the advantages of big data and protocol harmonization in imaging become more apparent so, too, do the disadvantages of data heterogeneity. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Association of Neural Connectome With Early Experiences of Abuse in Adults.

Importance: More than 10% of children experience sexual, physical, or emotional abuse, and abuse experienced during sensitive neurodevelopmental periods is associated with a greater risk of psychiatric disorders. Objective: To investigate the extent to which a history of abuse is associated with alterations in the intrinsic functional connectome of the adult brain independent from the restriction of associated psychiatric conditions. Design, Setting, and Participants: This cohort study assessed data from 768 adult participants from the greater Sydney, Australia, area who were included in the study without diagnostic restrictions and categorized based on a history of childhood sexual, physical, and/or emotional abuse. Data were collected from January 1, 2009, to December 31, 2015; data analysis was performed from October 1, 2020, to March 31, 2022. Main Outcomes and Measures: Outcomes were structured psychiatric interview responses, self-report of the frequency and extent of various types of negative experiences in childhood and adolescence, and intrinsic functional connectivity derived from 5 functional magnetic resonance imaging tasks and estimated among 436 brain regions, comprising intranetwork and internetwork connectivity of 8 large-scale brain networks. Results: Among the 647 individuals with usable data (330 female [51.0%]; mean [SD] age, 33.3 [12.0] years; age range, 18.2-69.2 years), history of abuse was associated with greater likelihood of a current psychiatric illness (odds ratio, 4.55; 95% CI, 3.07-6.72; P < .001) and with greater depressive, anxiety, and stress symptoms (mean difference, 20.4; 95% CI, 16.1-24.7; P < .001). An altered connectome signature of higher connectivity within somatomotor, dorsal, and ventral attention networks and between these networks and executive control and default mode networks was observed in individuals with a history of abuse experienced during childhood (n = 127) vs those without a history of abuse (n = 442; mean difference, 0.07; 95% CI, 0.05-0.08; familywise, Bonferroni-corrected P = .01; Cohen d = 0.82) and compared with those who experienced abuse in adolescence (n = 78; mean difference, 0.06; 95% CI, 0.04-0.08]; familywise, Bonferroni-corrected P < .001; Cohen d = 0.68). Connectome alterations were not observed for those who experienced abuse in adolescence. Connectivity of this signature was transdiagnostic and independent of the nature and frequency of abuse, sex, or current symptomatic state. Conclusions and Relevance: Findings highlight the associations of exposure to abuse before and during adolescence with the whole-brain functional connectome. The experience of child abuse was found to be associated with physiologic changes in intrinsic connectivity, independent of psychopathology, in a way that may affect functioning of systems responsible for perceptual processing and attention.

A comparison of the functional connectome in mild traumatic brain injury and post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) often co-occur in the context of threat to one's life. These conditions also have an overlapping symptomatology and include symptoms of anxiety, poor concentration and memory problems. A major challenge has been articulating the underlying neurobiology of these overlapping conditions. The primary aim of this study was to compare intrinsic functional connectivity between mTBI (without PTSD) and PTSD (without mTBI). The study included functional MRI data from 176 participants: 42 participants with mTBI, 67 with PTSD and a comparison group of 66 age and sex-matched healthy controls. We used network-based statistical analyses for connectome-wide comparisons of intrinsic functional connectivity between mTBI relative to PTSD and controls. Our results showed no connectivity differences between mTBI and PTSD groups. However, we did find that mTBI had significantly reduced connectivity relative to healthy controls within an extensive network of regions including default mode, executive control, visual and auditory networks. The mTBI group also displayed hyperconnectivity between dorsal and ventral attention networks and perceptual regions. The PTSD group also demonstrated abnormal connectivity within these networks relative to controls. Connectivity alterations were not associated with severity of PTSD or post-concussive symptoms in either clinical group. Taken together, the similar profiles of intrinsic connectivity alterations in these two conditions provide neural evidence that can explain, in part, the overlapping symptomatology between mTBI and PTSD.

Altered resting-state neural networks in children and adolescents with functional neurological disorder.

OBJECTIVES: Previous studies with adults suggest that aberrant communication between neural networks underpins functional neurological disorder (FND). The current study adopts a data-driven approach to investigate the extent that functional resting-state networks are disrupted in a pediatric mixed-FND cohort. METHODS: 31 children with mixed FND and 33 age- and sex-matched healthy controls completed resting-state fMRI scans. Whole-brain independent component analysis (pFWE < 0.05) was then used to identify group differences in resting-state connectivity. Self-report measures included the Depression, Anxiety and Stress Scale (DASS-21) and Early Life Stress Questionnaire (ELSQ). Resting-state heart rate (HR) and cortisol-awakening response (CAR) were available in a subset. RESULTS: Children with FND showed wide-ranging connectivity changes in eight independent components corresponding to eight resting-state neural networks: language networks (IC6 and IC1), visual network, frontoparietal network, salience network, dorsal attention network, cerebellar network, and sensorimotor network. Children whose clinical presentation included functional seizures (vs children with other FND symptoms) showed greater connectivity decreases in the frontoparietal and dorsal attentional networks. Subjective distress (total DASS score), autonomic arousal (indexed by HR), and HPA dysregulation (attenuated/reversed CAR) contributed to changes in neural network connectivity. Children with FND (vs controls) reported more subjective distress (total DASS score) and more adverse childhood experiences (ACEs) across their lifespan. CONCLUSIONS: Children with FND demonstrate changes in resting-state connectivity. Identified network alterations underpin a broad range of functions typically disrupted in children with FND. This study complements the adult literature by suggesting that FND in children and adolescents emerges in the context of their lived experience and that it reflects aberrant communication across neural networks.

Common and differential neural mechanisms underlying mood disorders.

BACKGROUND: Despite homogenous clinical presentations between bipolar and unipolar disorders, there are distinct neurobiological differences. Chronicity of illness may be a factor impacting and sustaining certain neural features. The goal of this study was to investigate common and shared neural mechanisms underlying mood disorders, and possible sustained neural changes relating to illness chronicity by investigating a cohort of euthymic patients with bipolar disorder (BD), unipolar depression who had responded to treatment (treatment-sensitive depression, TSD), and a chronically treatment-resistant depressed (TRD) group. METHODS: One hundred and seventy-two participants (40 BD, 39 TSD, 40 TRD, and 53 age-gender-matched healthy controls) underwent resting-state fMRI scans. Seed-based and independent component analyses were performed to investigate group differences in resting-state connectivity between the four groups. RESULTS: All three clinical groups had significantly lower connectivity within the frontoparietal network (FPN) relative to controls. TRD and BD were significantly different from TSD (TRD, BD > TSD) but were not significantly different from each other. TRDs were also significantly different from both BD and TSD for salience network connectivity with the posterior cingulate (DMN) and the FPN with frontal pole (DMN). Additionally, the BD group exhibited greater DMN-FPN (sgACC-RDLPFC) connectivity relative to TRD, TSD, and controls, which was correlated with a previous number of depressive episodes, in the BD group only. CONCLUSIONS: BD demonstrated shared and differential connectivity features relative to symptomatic TRD and euthymic TSD groups. The increased sgACC-RDLPFC connectivity in BD and its correlation with a number of depressive episodes could be a neural feature associated with illness chronicity.

Genetic variants associated with longitudinal changes in brain structure across the lifespan.

Human brain structure changes throughout the lifespan. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental and neurodegenerative diseases. In this study, we identified common genetic variants that affect rates of brain growth or atrophy in what is, to our knowledge, the first genome-wide association meta-analysis of changes in brain morphology across the lifespan. Longitudinal magnetic resonance imaging data from 15,640 individuals were used to compute rates of change for 15 brain structures. The most robustly identified genes GPR139, DACH1 and APOE are associated with metabolic processes. We demonstrate global genetic overlap with depression, schizophrenia, cognitive functioning, insomnia, height, body mass index and smoking. Gene set findings implicate both early brain development and neurodegenerative processes in the rates of brain changes. Identifying variants involved in structural brain changes may help to determine biological pathways underlying optimal and dysfunctional brain development and aging.

Intrinsic Functional Connectomes Characterize Neuroticism in Major Depressive Disorder and Predict Antidepressant Treatment Outcomes.

BACKGROUND: Antidepressant efficacy in people with major depressive disorder remains modest, yet identifying treatment-predictive neurobiological markers may improve outcomes. While disruptions in functional connectivity within and between large-scale brain networks predict poorer treatment outcome, it is unclear whether higher trait neuroticism, which has been associated with generally poorer outcomes, contributes to these disruptions and to antidepressant-specific treatment outcomes. Here, we used whole-brain functional connectivity analysis to identify a neural connectomic signature of neuroticism and tested whether this signature predicted antidepressant treatment outcome. METHODS: Participants were 226 adults with major depressive disorder and 68 healthy control subjects who underwent functional magnetic resonance imaging and were assessed on clinical features at baseline. Participants with major depressive disorder were then randomized to 1 of 3 commonly prescribed antidepressants and after 8 weeks completed a second functional magnetic resonance imaging and were reassessed for depressive symptom remission/response. Baseline intrinsic functional connectivity between each pair of 436 brain regions was analyzed using network-based statistics to identify connectomic features associated with neuroticism. Features were then assessed on their ability to predict treatment outcome and whether they changed after 8 weeks of treatment. RESULTS: Higher baseline neuroticism was associated with greater connectivity within and between the salience, executive control, and somatomotor brain networks. Greater connectivity across these networks predicted poorer treatment outcome that was not mediated by baseline neuroticism, and connectivity strength decreased after antidepressant treatment. CONCLUSIONS: Our findings demonstrate that neuroticism is associated with organization of intrinsic neural networks that predict treatment outcome, elucidating its biological underpinnings and opportunity for better treatment personalization.

Default-mode and fronto-parietal network connectivity during rest distinguishes asymptomatic patients with bipolar disorder and major depressive disorder.

Bipolar disorder (BD) is commonly misdiagnosed as major depressive disorder (MDD). This is understandable, as depression often precedes mania and is otherwise indistinguishable in both. It is therefore imperative to identify neural mechanisms that can differentiate the two disorders. Interrogating resting brain neural activity may reveal core distinguishing abnormalities. We adopted an a priori approach, examining three key networks documented in previous mood disorder literature subserving executive function, salience and rumination that may differentiate euthymic BD and MDD patients. Thirty-eight patients with BD, 39 patients with MDD matched for depression severity, and 39 age-gender matched healthy controls, completed resting-state fMRI scans. Seed-based and data-driven Independent Component analyses (ICA) were implemented to examine group differences in resting-state connectivity (pFDR < 0.05). Seed analysis masks were target regions identified from the fronto-parietal (FPN), salience (SN) and default-mode (DMN) networks. Seed-based analyses identified significantly greater connectivity between the subgenual cingulate cortex (DMN) and right dorsolateral prefrontal cortex (FPN) in BD relative to MDD and controls. The ICA analyses also found greater connectivity between the DMN and inferior frontal gyrus, an FPN region in BD relative to MDD. There were also significant group differences across the three networks in both clinical groups relative to controls. Altered DMN-FPN functional connectivity is thought to underlie deficits in the processing, management and regulation of affective stimuli. Our results suggest that connectivity between these networks could potentially distinguish the two disorders and could be a possible trait mechanism in BD persisting even in the absence of symptoms.

The functional connectome in posttraumatic stress disorder.

BACKGROUND: Previous fMRI studies of posttraumatic stress disorder (PTSD) have investigated region-specific alterations in intrinsic connectivity but connectome-wide changes in connectivity are yet to be characterized. Understanding the neurobiology of this is important to develop novel treatment interventions for PTSD. This study aims to identify connectome-wide disruptions in PTSD to provide a more comprehensive analysis of nseural networks in this disorder. METHODS: A functional MRI scan was completed by 138 individuals (67 PTSD and 71 non-trauma-exposed healthy controls [HC]). For every individual, inter-regional intrinsic functional connectivity was estimated between 436 brain regions, comprising intra and inter-network connectivity of eight large-scale brain networks. Group-wise differences between PTSD and HC were investigated using network-based statistics at a family-wise error rate of p < 0.05. Significant network differences were then further investigated in 27 individuals with trauma exposure but no PTSD [TC]). RESULTS: Compared to HC, PTSD displayed lower intrinsic functional connectivity in a network of 203 connections between 420 regions within and between mid-posterior default mode, central executive, limbic, visual and somatomotor regions. Additionally, PTSD displayed higher connectivity across a network of 50 connections from thalamic and limbic to sensory and default-mode regions. Connectivity in TC in both these networks was intermediate and significantly different to PTSD and HC. CONCLUSION: A large-scale imbalance between hypoconnectivity of higher-order cortical networks and hyperconnectivity of emotional and arousal response systems seems to occur on a sliding scale from trauma exposure to clinical manifestation as PTSD. Novel interventions that target this systemic functional imbalance could provide potential mitigation of PTSD.

Investigating neural circuits of emotion regulation to distinguish euthymic patients with bipolar disorder and major depressive disorder.

BACKGROUND: Up to 40% of patients with bipolar disorder (BD) are initially diagnosed as having major depressive disorder (MDD), and emotional lability is a key aspect of both sets of mood disorders. However, it remains unknown whether differences in the regulation of emotions through cognitive reappraisal may serve to distinguish BD and MDD. Therefore, we examined this question in euthymic BD and MDD patients. METHODS: Thirty-eight euthymic BD, 33 euthymic MDD and 37 healthy control (HC) participants, matched for age, gender and depression severity, engaged in an emotion regulation (ER) cognitive reappraisal task during an fMRI scan were examined. Participants either reappraised (Think condition) or passively watched negative (Watch condition) or neutral (Neutral condition) pictures and rated their affect. Activation and connectivity analyses were used to examine group differences in reappraisal (Think vs Watch) and reactivity (Watch vs Neutral) conditions in ER-specific neural circuits. RESULTS: Irrespective of group, participants rated most negatively the images during the Watch condition relative to Think and Neutral conditions, and more negatively to Think relative to Neutral. Notably, BD participants exhibited reduced subgenual anterior cingulate activation (sgACC) relative to MDD during reappraisal, but exhibited greater sgACC activation relative to MDD during reactivity, whereas MDD participants elicited greater activation in right amygdala relative to BD during reactivity. We found no group differences in task-related connectivity. CONCLUSIONS: Euthymic BD and MDD patients engage differential brain regions to process and regulate emotional information. These differences could serve to distinguish the clinical groups and provide novel insights into the underlying pathophysiology of BD.

Intrinsic functional connectivity of the default mode and cognitive control networks relate to change in behavioral performance over two years.

Understanding how brain circuitry mediates cognitive control of behavior is crucial for understanding both mental health and disease. Cognitive control describes the group of behaviors that guide goal-directed action such as sustaining attention, processing information and inhibiting impulsive responses. We rely on these behaviors for daily social, occupational and emotional functioning. Two brain networks, the cognitive control network (CCN) and default mode network (DMN), are thought to cooperate in an inverse relationship to support these functions. However, we do not yet know how connectivity within and between these networks directly relates to healthy cognitive control behaviors, and whether these interactions change over time. Here, we employed a longitudinal design to investigate if change in intrinsic connectivity in these networks will correlate with change in a range of cognitive control functions. Over two years, 109 healthy individuals, aged eight to thirty-eight, were tested twice using fMRI to assess intrinsic functional connectivity of the CCN and DMN and a validated cognitive battery. We found that increased within-network connectivity through central and left DMN was associated with increased memory performance. Additionally, decreased connectivity between posterior parietal CCN and DMN nodes and decreased connectivity between left and right dorsolateral prefrontal nodes was associated with increased cognitive performance. These findings were age and gender controlled, suggesting that age-independent plastic change in intrinsic connectivity through these networks directly relate to changing behavior. This has implications for targeting intrinsic connectivity as a possible mechanism to improve cognitive function.

Intrinsic connectomes underlying response to trauma-focused psychotherapy in post-traumatic stress disorder.

Although trauma-focused cognitive behavior therapy (TF-CBT) is the frontline treatment for post-traumatic stress disorder (PTSD), up to one-half of patients are treatment nonresponders. To understand treatment nonresponse, it is important to understand the neural mechanisms of TF-CBT. Here, we used whole-brain intrinsic functional connectivity analysis to identify neural connectomic signatures of treatment outcome. In total, 36 PTSD patients and 36 healthy individuals underwent functional MRI at pre-treatment baseline. Patients then underwent nine sessions of TF-CBT and completed clinical and follow-up MRIs. We used an established large-scale brain network atlas to parcellate the brain into 343 brain regions. Pairwise intrinsic task-free functional connectivity was calculated and used to identify pre-treatment connectomic features that were correlated with reduction of PTSD severity from pretreatment to post treatment. We formed a composite metric of intrinsic connections associated with therapeutic outcome, and then interrogated this composite metric to determine if it distinguished PTSD treatment responders and nonresponders from healthy control status and changed post treatment. Lower pre-treatment connectivity for the cingulo-opercular, salience, default mode, dorsal attention, and frontoparietal executive control brain networks was associated with treatment improvement. Treatment responders had lower while nonresponders had significantly greater connectivity than controls at pretreatment. With therapy, connectivity significantly increased for responders and decreased for nonresponders, while controls remain unchanged over this time period. We provide evidence that the intrinsic functional architecture of the brain, specifically connectivity within and between brain networks associated with external vigilance, self-awareness, and cognitive control, may characterize a positive response to TF-CBT for PTSD.

Neurophysiological markers of attention distinguish bipolar disorder and unipolar depression.

BACKGROUND: Attentional deficits are common in both symptomatic and symptom-remitted patients with bipolar disorder (BP) and major depressive disorder (MDD). However, whether the level of neurocognitive impairment in attentional processing is different between these two disorders, or not, is still unclear. Thus, we investigated the P300 event-related potential component as a biomarker of cognitive dysfunction to differentiate BP and MDD. METHODS: Twenty-three age and gender matched BP, 20 MDD and 23 healthy controls (HC) were part of a discovery cohort to identify neurophysiological differences between groups and build a classification model of these disorders. The replication of this model was then tested in an independent second cohort of 17 BP, 19 MDD and 19 HC. All participants were symptom-remitted for at least two weeks. We compared neural responses to target stimuli during an auditory oddball task, computing peak amplitude and latency of the P300 component extracted from the midline centro-parietal electrode. RESULTS: BP had significantly smaller P300 amplitudes compared to both MDD and HC, whereas there were no differences between MDD and HC. The differences between groups were replicated in the second cohort, however the accuracy level of the classification model was only 53.5%. LIMITATIONS: Small sample sizes may have led to low accuracy levels of the classification model. CONCLUSION: Specific neural mechanisms of attention and context updating seem not to recover with symptom remission in BP. These findings contribute to the detection of a potential electrophysiological marker for BP, which may allow its differentiation from unipolar major depressive disorder.

Investigating the neural basis of cognitive control dysfunction in mood disorders.

OBJECTIVES: Dysfunction of cognitive control is a feature of both bipolar disorder (BP) and major depression (MDD) and persists through to remission. However, it is unknown whether these disorders are characterized by common or distinct disruptions of cognitive control function and its neural basis. We investigated this gap in knowledge in asymptomatic BP and MDD participants, interpreted within a framework of normative function. METHODS: Participants underwent fMRI scans engaging cognitive control through a working memory task and completed a cognitive battery evaluating performance across multiple subdomains of cognitive control, including attention, impulsivity, processing speed, executive function, and memory. Analysis was performed in two stages: (i) cognitive control-related brain activation and deactivation were correlated with cognitive control performance in 115 healthy controls (HCs), then, (ii) significantly correlated regions from (i) were compared between 25 asymptomatic BP, 25 remitted MDD, and with 25 different HCs, matched for age and gender. RESULTS: Impulsivity and executive function performance were significantly worse in BP compared to both MDD and HCs. Both BP and MDD had significantly poorer memory performance compared to HCs. Greater deactivation of the medial prefrontal cortex (MPFC) during the fMRI task was associated with better executive function in healthy controls. Significantly less deactivation in this region was present in both BP and MDD compared to HCs. CONCLUSIONS: Failure to deactivate the MPFC, a key region of the default mode network, during working memory processing is a shared neural feature present in both bipolar and major depression and could be a source of common cognitive dysfunction.

Amygdala Activation and Connectivity to Emotional Processing Distinguishes Asymptomatic Patients With Bipolar Disorders and Unipolar Depression.

BACKGROUND: Mechanistically based neural markers, such as amygdala reactivity, offer one approach to addressing the challenges of differentiating bipolar and unipolar depressive disorders independently from mood state and acute symptoms. Although emotion-elicited amygdala reactivity has been found to distinguish patients with bipolar depression from patients with unipolar depression, it remains unknown whether this distinction is traitlike and present in the absence of an acutely depressed mood. We addressed this gap by investigating patients with bipolar disorder (BP) and unipolar major depressive disorder (MDD) in remission. METHODS: Supraliminal and subliminal processing of faces exhibiting threat, sad, happy, and neutral emotions during functional magnetic resonance imaging was completed by 73 participants (23 BP patients and 25 MDD patients matched for age and gender, number of depressive episodes and severity; 25 age- and gender-matched healthy control subjects). We compared groups for activation and connectivity for the amygdala. RESULTS: BP patients had lower left amygdala activation than MDD patients during supraliminal and subliminal threat, sad, and neutral emotion processing and for subliminal happy faces. BP patients also exhibited lower amygdala connectivity to the insula and hippocampus for threat and to medial orbitofrontal cortex for happy supraliminal and subliminal processing. BP patients also demonstrated greater amygdala-insula connectivity for sad supraliminal and subliminal face processing. Both patient groups were distinct from control subjects across several measures for activation and connectivity. CONCLUSIONS: Independent of valence or level of emotional awareness, amygdala activation and connectivity during facial emotion processing can distinguish BP patients and MDD patients. These findings provide evidence that this neural substrate could be a potential trait marker to differentiate these two disorders largely independent of illness state.

Cognitive control network anatomy correlates with neurocognitive behavior: A longitudinal study.

Cognitive control is the process of employing executive functions, such as attention, planning or working memory, to guide appropriate behaviors in order to achieve a specific goal. Functional magnetic resonance imaging studies suggest a superordinate cognitive control network, comprising the dorsal regions of the lateral prefrontal cortex (DLPFC), anterior cingulate cortex (dACC) and parietal cortex (DPC). How gray matter structure changes across this network throughout neurodevelopment and how these changes impact cognitive control are not yet fully understood. Here we investigate changes in gray matter volume of the key nodes of the cognitive control network using structural MRI scans from 176 participants aged 8-38 years. One hundred and eleven of these also completed a longitudinal follow-up at two years. We compare these with performance on a cognitive battery also measured at these two time points. We found that volume decreases in the cognitive control network were associated with improved performance in executive function (in left DLPFC and bilateral DPC), information processing (in bilateral dACC and right DPC) and emotion identification tasks (left DLPFC). These results were significant after controlling for age. Furthermore, gray matter changes were coordinated across the network. These findings imply age-independent synaptic pruning in the cognitive control network may have a role in improving performance in cognitive domains. This study provides insight into the direct impact of structural changes on behavior within this network during neurodevelopment and provides a normative evidence base to better understand development of cognitive dysfunction in brain disorders. Hum Brain Mapp 38:631-643, 2017. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.