Utilizing Precision Functional Mapping to identify functional brain biomarkers of stimulant use
Background: ADHD is a complex neurodevelopmental disorder characterized by functional differences in the brain. Despite extensive research on ADHD, etiological biomarkers and clinical prediction are weak due to phenotypic and mechanistic heterogeneity. Consequently, treatment efficacy is behaviorally monitored and requires strenuous trial and error. To address this, personalized medicine approaches are needed. In the present study, we attempt to address whether a precision functional mapping (PFM) approach is an efficacious tool for identifying neurological biomarkers of treatment efficacy.
Methods: 37 medication-naïve children with ADHD and 32 TD children (M age = 9.99, 33 female) were assessed. All participants completed two sessions of resting-state fMRI and go-no-go (GNG) task-based fMRI. Children with ADHD completed one scan session on methylphenidate (MPH) and one after being given a placebo. Using PFM procedures outlined by Hermosillo et al. (2022), personalized networks were generated for each participant. Personalized networks were used to identify changes in functional connectivity in response to stimulants (i.e. methylphenidate, MPH) that are specific to each individual child. These changes, or lack thereof, were compared to behavioral data for each participant to inspect if functional connectivity variability corresponded with behavioral variability. The relationship between these variables was assessed using a repeated measures correlation.
Results: Results demonstrate that PFM allows for the identification of individualistic network organization across participants. In addition, this individuality provided the means to detect a response to MPH intervention for each individual child. Across the group, consistent changes in mean whole-brain functional connectivity were observed for ADHD participants relative to controls (who did not receive the intervention between sessions). These changes were correlated with performance on the GNG task (r = -0.678, p < 0.001).
Conclusions: PFM is a viable methodology for identifying functional brain changes as a result of stimulant use. Additionally, the ADHD participants with the largest improvements in performance on the GNG task also displayed some of the largest changes in functional connectivity as a result of MPH intervention; this result demonstrates the utility of PFM to assess the impact of pharmaceutical interventions on brain connectivity. PFM could be used in future research to identify specific brain biomarkers of treatment efficacy in individuals, eliminating the need for trial and error assessment.