Associations between greenspace and memory: Evidence from the COMPASS cohort in Chicago.

Autism spectrum disorder (ASD), a neurodevelopmental condition hallmarked by early-onset social communication deficits and restricted repetitive behaviors [], affects approximately 1% of the global population with marked regional heterogeneity (prevalence range: 0.01% to 4.36%) []. Convergent evidence indicated polygenic susceptibility interacting with environmental factors [–], culminating in circuit-level neurodevelopmental dysfunction such as excitation-inhibition (E–I) imbalance [–]. While early intensive behavioral interventions in preschool children [] and social cognitive training in mildly impaired adolescents [] show promise in improving social communication ability, and pharmacological agents demonstrate limited benefits for comorbid symptoms (e.g., irritability) [, ], no psychopharmacological treatment has shown robust efficacy for core symptoms in ASD [, ]. This treatment gap is particularly pronounced in school-aged and older individuals, especially those with profound autism and significant functional impairments, underscoring an urgent clinical need for targeted, mechanism-based interventions []. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive technique for modulating neural activity [], has demonstrated clinical efficacy in treating various mental disorders, including FDA-approved applications for depression [, ]. The efficacy of neuromodulation depends critically on targeting functionally relevant neural circuits [, ]. However, substantial interindividual variability in functional organization makes standardized anatomical targeting suboptimal, as identical stereotaxic coordinates may engage distinct functional networks across different subjects []. In ASD pathophysiology, dysfunction in the fronto-parietal network (FPN), a system governing goal-directed behavior and cognitive flexibility [, ], has been mechanistically linked to core symptom domains [, ]. Specifically, multi-level FPN dysfunction, including atypical task activation, static and dynamic functional connectivity and disruption to its hierarchical organization, has been associated with ASD [–]. Critically, FPN demonstrates the highest degree of interindividual variability among all large-scale functional networks, including differences in network location, size, and topology [, ]. Emerging evidence indicates that individualized targeting guided by functional neuroimaging enhances both spatial precision and therapeutic efficacy [, ]. Building on our prior individualized functional mapping technique [, , ], we developed a precision targeting protocol that identifies the target in each individual’s FPN within the middle dorsolateral prefrontal cortex (DLPFC), a node critical for contextual adaptation []. Given the high contextual adaptation is critical for dynamically shifting social interactions, the individualized approach directly targets the circuit-level dysfunction and enables testing its potential in treating ASD. Although rTMS shows potential for improving core symptoms of ASD, current evidence remains inconclusive due to methodological limitations, including heterogeneous protocols, small sample sizes, and reliance on subjective outcome measures [, ]. These constraints underscore the need for innovative protocols to address ASD’s unique neurobiology. Specifically, the chronic neurodevelopmental trajectory of ASD necessitates sustained therapeutic interventions [], as transient effects from short-term rTMS protocols have demonstrated limited clinical durability. Intensive, optimized rTMS regimens may therefore offer superior and more enduring treatment efficacy. Moreover, optimized rTMS protocols, including theta-burst stimulation [], higher pulse doses [] and condensed schedules [] have demonstrated improved therapeutic efficacy across multiple neuropsychiatric conditions []. For ASD, translating these approaches would require tailoring both spatial (precise targeting) and temporal (extended duration) parameters to drive lasting network changes [, ].