Polyconnectomic Scoring of Functional Connectivity Patterns Across Eight Neuropsychiatric and Three Neurodegenerative Disorders
Bibliographic record
Abstract
Background Neuropsychiatric and neurodegenerative disorders involve diverse changes in brain functional connectivity. As an alternative to approaches that search for specific mosaic patterns of affected connections and networks, we used polyconnectomic scoring to quantify disorder-related whole-brain connectivity signatures into interpretable, personalized scores. Methods The polyconnectomic score (PCS) measures the extent to which an individual's functional connectivity mirrors the whole-brain circuitry characteristics of a trait. We computed PCSs for 8 neuropsychiatric conditions (attention-deficit/hyperactivity disorder, anxiety-related disorders, autism spectrum disorder, obsessive-compulsive disorder, bipolar disorder, major depressive disorder, schizoaffective disorder, and schizophrenia) and 3 neurodegenerative conditions (Alzheimer's disease, frontotemporal dementia, and Parkinson's disease) across 22 datasets with resting-state functional magnetic resonance imaging data from 10,667 individuals (5325 patients, 5342 control participants). We also examined PCSs in 26,673 individuals from the population-based UK Biobank cohort. Results PCSs were consistently higher in out-of-sample patients across 6 of the 8 neuropsychiatric and across all 3 investigated neurodegenerative disorders ([minimum, maximum]: area under the receiver operating characteristic curve=[0.55, 0.73], false discovery rate–corrected p [ p FDR ] = [1.8 × 10 −16 , 4.5 × 10 −2 ]). Individuals with elevated PCS levels for neuropsychiatric conditions exhibited higher neuroticism ( p FDR < 9.7 × 10 −5 ), lower cognitive performance ( p FDR < 5.3 × 10 −5 ), and lower general well-being ( p FDR < 9.7 × 10 −4 ). Conclusions Our findings reveal generalizable whole-brain connectivity alterations in brain disorders. Polyconnectomic scoring effectively aggregates disorder-related signatures across the entire brain into an interpretable, participant-specific metric. A toolbox is provided for PCS computation.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.006 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.003 | 0.002 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".