110 - Network Inefficiency and Cortical Development in ADHD: An Integrative Systematic Review

Publication Number: 1101.110

Unaisa Bhayat, Texas Tech University Health Sciences Center Paul L. Foster School of Medicine, El Paso, TX, United States; Sanjeet Panda, Texas Tech University Health Sciences Center Paul L. Foster School of Medicine, El Paso, TX, United States

Background: Attention-Deficit/Hyperactivity Disorder (ADHD) remains a controversial diagnosis with an incomplete understanding of its pathophysiology. Current evidence suggests a maturational lag in neural development, particularly involving dysregulated interaction between the default mode network (DMN) and the task-positive/cognitive control network (TPN).

Objective: Although this impaired network reciprocity is well-documented, the underlying causal mechanisms remain unclear. Regular synthesis of emerging research is essential to clarify the developmental trajectory of ADHD, refine theoretical models, and support the design of more targeted and rigorous interventions.

Design/Methods: A PubMed search was conducted using the terms: (ADHD OR "default mode" OR "task positive") AND dopamine AND age. Of the 579 articles identified, 51 met inclusion criteria after excluding secondary literature and studies primarily focused on treatment, genetics, sex differences, environmental factors, comorbidities, or personality development. The selected articles were categorized by thematic focus, and their findings were systematically reviewed and interpreted.

Results: Current evidence indicates that children with ADHD exhibit fronto-parietal cortical thinning, likely driven by an imbalance between synaptogenesis and synaptic pruning within developing dopaminergic networks. This is a process that normally occurs through adolescence. This imbalance reduces global network efficiency by weakening interhemispheric communication, resulting in compensatory over-reliance on the right hemisphere and increased local efficiency within the DMN. In parallel, heightened functional connectivity between the ventral tegmental area (VTA) and amygdala, along with elevated local DMN connectivity, suggests impaired modulation of emotion-related outcome evaluation. Persistent hyperconnectivity into adolescence may be partially explained by inadequate mediation of DMN-TPN dynamics by the putamen.

Conclusion(s): This review proposes that research should shift from framing ADHD primarily as a maturational delay toward investigating the pathogenic mechanisms driving premature cortical thinning and disrupted synaptogenesis-pruning balance. We further propose that future interventions prioritize enhancing interhemispheric connectivity to improve global network efficiency and TPN engagement, complementing current pharmacologic strategies that focus predominantly on dopaminergic replacement in adolescents.

Figure 1: Prisma diagram of the integrative systematic review process
Of the 579 articles identified, 88 secondary literature articles were excluded. Of the remaining 491, 356 were excluded for focusing primarily on ADHD treatment and/or genetics. Ultimately, 51 primary research articles met inclusion criteria. These were categorized by thematic focus and synthesized accordingly.

Figure 2: Suggested neurobiological process of network development
In neurotypical children, there is a dynamic balance between the default mode network (DMN) and the task-positive network (TPN). In childhood, the substantia nigra dominates dopaminergic connectivity, which gradually shifts to increased ventral tegmental area (VTA) connectivity with maturation. The VTA-amygdala connection supports appropriate emotional learning, allowing the amygdala to distinguish safe from threatening stimuli, thereby modulating stress responses effectively. As development progresses, the putamen transitions from coupling with the DMN to integrating with the TPN, facilitating a shift from self-referential thought to goal-directed behavior. This is accompanied by strengthened interhemispheric communication and increased global network efficiency, supporting lateralization that optimizes cognitive capacity and fine motor skills, as well as delayed gratification, accurate error prediction and complex task switching.

Figure 3: Suggested pathologic neurobiological process of network development in children with ADHD
This diagram suggests that children with ADHD show increased connectivity within dopaminergic pathways-the substantia nigra (SN) and ventral tegmental area (VTA)-with heightened VTA-amygdala coupling. This is coupled with fronto-parietal cortical thinning, decreased global network efficiency, and compensatory local hyperconnectivity, especially in ventral brain regions, which favors accuracy in goal-directed tasks despite impaired hemispheric cross-talk. Developmentally, the putamen's failure to shift from DMN to TPN coupling may underlie persistent internal focus and reduced task engagement.