In a groundbreaking advancement in neurodevelopmental research, a comprehensive meta-analysis published in BMC Psychiatry in 2025 illuminates the intricate brain-behavior dynamics underlying executive function (EF) deficits in children and adolescents diagnosed with Attention-Deficit/Hyperactivity Disorder (ADHD). Employing state-of-the-art task-based functional magnetic resonance imaging (tb-fMRI) and activation likelihood estimation (ALE) analysis, researchers have meticulously aggregated data from 32 published studies to reveal distinct neural activation patterns that differentiate youth with ADHD from their neurotypical peers. This landmark investigation not only deepens our comprehension of ADHD’s neurological underpinnings but also charts a course toward targeted therapeutic innovation.
Attention-Deficit/Hyperactivity Disorder, affecting approximately 5% of the global pediatric population, manifests through pervasive symptoms that often stem from compromised executive functions—cognitive processes critical for goal-directed behavior, such as inhibitory control, working memory, and cognitive flexibility. Despite decades of clinical and cognitive research, the neural substrates mapping these deficits remained elusive, fueling controversies and limiting intervention precision. The present study’s expansive synthesis stands as a pivotal effort to consolidate scattered findings and reveal consistent neural correlates of executive dysfunction through the lens of task-based fMRI, a technique capturing real-time brain activation in response to cognitive challenges.
Task-based fMRI, favored for its temporal and spatial specificity, allows for the identification of regional brain activation during cognitive tasks. By leveraging ALE meta-analysis—a robust, coordinate-based statistical approach—the researchers quantified convergence across studies, effectively highlighting brain regions repeatedly implicated in EF anomalies among youth with ADHD. This meta-analytical rigor surmounts variability inherent in individual studies, such as task paradigms, sample demographics, and data acquisition parameters, yielding aggregated insights with enhanced reliability and generalizability.
Central to the findings was the demonstration of significantly reduced activation in multiple brain regions integral to executive processing in children and adolescents with ADHD during EF tasks. Notably, diminished activity emerged bilaterally in the inferior frontal gyrus, a region implicated in inhibitory control and cognitive regulation. Alongside this, hypoactivation was observed in the supramarginal gyrus and inferior parietal gyrus, areas traditionally associated with attentional processes and working memory manipulation. Such widespread neural deficits elucidate the multifaceted nature of EF impairments, bridging cognitive deficits with concrete neuroanatomical substrates.
Further neural deficits extended to the angular gyrus, caudate nucleus, occipital gyrus, and cerebellum. The angular gyrus plays a role in attention reorientation and semantic processing, while the caudate is central to goal-directed action and cognitive control circuits. Hypoactivation in the occipital gyrus may reflect aberrant processing of visual stimuli during EF tasks, whereas alterations in cerebellar function underscore the growing recognition of its contributions beyond motor coordination, including executive and affective modulation. Collectively, these regional hypofunctions depict a complex, system-wide disruption in neural networks supporting executive control in ADHD.
Beyond delineating regional deficits, the meta-analysis spotlighted compelling associations between brain activation and behavioral EF measures within the ADHD cohort. Particularly, increased activation in the inferior frontal gyrus and anterior cingulate cortex—both key nodes in cognitive control and conflict monitoring networks—correlated positively with performance in inhibitory control tasks. This brain-behavior coupling provides neurobiological validation for observed clinical heterogeneity, emphasizing that preserved or enhanced activation within these circuits may confer relative cognitive advantages even amid disorder-related challenges.
These findings bear tremendous implications for conceptualizing ADHD pathophysiology. While traditional models often focused on discrete brain regions or neurotransmitter imbalances, this research advocates for a holistic circuit-based understanding. The identified neural signatures suggest that EF impairments arise from coordinated dysfunction across frontal, parietal, basal ganglia, visual, and cerebellar regions, each contributing uniquely to the cognitive mosaic disrupted in ADHD. Such insights pave the way for precision diagnostics and personalized interventions, potentially guided by neuroimaging biomarkers.
Indeed, the study’s revelations suggest novel avenues for treatment innovations. Neuromodulatory approaches, such as transcranial magnetic stimulation targeting the inferior frontal gyrus or anterior cingulate cortex, might enhance EF-related neural activation and ameliorate cognitive symptoms. Likewise, neurofeedback and cognitive training regimens could be tailored to recruit and strengthen these deficient networks. The integration of tb-fMRI findings with behavioral phenotyping promises a future where therapeutic strategies are not one-size-fits-all but neurobiologically informed and individualized.
Moreover, this meta-analysis underscores the utility of task-based fMRI as a powerful investigative tool in developmental psychopathology research. By capturing brain activity during active EF engagement, tb-fMRI transcends resting-state paradigms and static anatomical imaging, offering dynamic insights into neural processing disruptions. This methodological approach, coupled with ALE meta-analysis, establishes a gold standard for synthesizing functional neuroimaging data in clinical populations, fostering consistency and replicability—a critical advance given the field’s reported heterogeneity.
Importantly, the systematic review also highlights gaps and prospects for future research. While the current studies provide a robust foundation, variability in task design, imaging protocols, and sample characteristics calls for standardized frameworks to optimize comparability. Longitudinal investigations integrating tb-fMRI with genetic, environmental, and behavioral data are necessary to unravel developmental trajectories and causal mechanisms. Additionally, expanding research to encompass diverse populations will enhance the external validity of neural biomarkers and interventions.
In conclusion, this comprehensive meta-analysis provides compelling evidence of altered neural activation patterns during executive function tasks in children and adolescents with ADHD, elucidating brain-behavior relationships with profound clinical relevance. Regions such as the inferior frontal gyrus and anterior cingulate cortex emerge as critical hubs where enhanced activation correlates with better inhibitory control, spotlighting potential targets for therapeutic innovation. These insights elevate the understanding of ADHD beyond symptom checklists toward a nuanced neurobiological framework, offering hope for more effective and personalized approaches to treatment in the near future.
As neuroscience endeavors to decode the complex interplay between brain function and behavior in neurodevelopmental disorders, studies like this pave the way for a paradigm shift—where cognitive deficits are mapped onto specific neural circuits, enabling targeted, empirically grounded interventions. The interdisciplinary synergy between neuroimaging, cognitive neuroscience, and clinical psychiatry epitomized by this research heralds a new era of precision medicine for ADHD and related disorders, with the potential to transform countless young lives worldwide.
Subject of Research: Brain activation and executive function deficits in children and adolescents with ADHD assessed through task-based fMRI.
Article Title: Brain–behavior relationships in task-based fMRI assessments of executive functions in children and adolescents with and without ADHD: a systematic review and ALE meta-analysis.
Article References: Zhang, H., Liang, X., Hsu, C.L. et al. Brain–behavior relationships in task-based fMRI assessments of executive functions in children and adolescents with and without ADHD: a systematic review and ALE meta-analysis. BMC Psychiatry (2025). https://doi.org/10.1186/s12888-025-07593-7
Image Credits: AI Generated
DOI: https://doi.org/10.1186/s12888-025-07593-7
Keywords: ADHD, executive functions, task-based fMRI, ALE meta-analysis, inhibitory control, working memory, brain activation, inferior frontal gyrus, anterior cingulate cortex, pediatric neuroimaging, neurodevelopment
