EEG functional connectivity as a prognostic biomarker of adaptive function in autistic people

Many autistic people have challenges with adaptive function, impacting education, employment and independent-living goals. Adaptive function outcomes of autistic people vary considerably, which makes planning for future needs challenging. Here, using a developmentally sensitive approach, we investigated if cortico-cortical functional connectivity - a core neurobiological feature that differs in autism - could predict longitudinal changes in adaptive function in autistic people. Using electroencephalography in 150 autistic and 159 non- autistic participants aged 6-31 years, we investigated if mean degree and network organisation (small-world index) predict longitudinal changes in adaptive function over 19-months. We assessed both metrics for properties desired in prognostic biomarkers: reliability and convergence with biology (polygenic variation). We found that small-world index significantly predicted changes in adaptive function in autistic people across the entire age-range. Predictive performance was best in 15-21-year-olds, where small-world index and mean degree explained 30-33% of additional variance in outcomes, outperforming measures of intelligence and autistic features. In categorising binary (improved versus not-improved) outcomes, the model containing mean degree had an AUC of 0.80 [95% CI: 0.63-0.97] in 15-21-year-olds, while that containing small-world index had an AUC of 0.76 [95% CI: 0.63-0.89] across the 6-31- year age-range. Both metrics demonstrated high test-retest reliability and significant associations with polygenic variation in brain volume. We demonstrate the first evidence that electroencephalography-derived functional connectivity metrics show promise as prognostic biomarkers of adaptive function in autistic people. Potential precision-medicine applications include stratifying participants in clinical trials and identifying those at risk of declining function in clinical settings.