Functional brain network controllability dysfunction in Alzheimer’s disease and its relationship with cognition and gene expression profiling
Bibliographic record
Abstract
Abstract Objective . In recent studies, network control theory has been applied to clarify transitions between brain states, emphasizing the significance of assessing the controllability of brain networks in facilitating transitions from one state to another. Despite these advancements, the potential alterations in functional network controllability associated with Alzheimer’s disease (AD), along with the underlying genetic mechanisms responsible for these alterations, remain unclear. Approach . We conducted a comparative analysis of functional network controllability measures between patients with AD ( n = 64) and matched normal controls (NCs, n = 64). We investigated the association between altered controllability measures and cognitive function in AD. Additionally, we conducted correlation analyses in conjunction with the Allen Human Brain Atlas to identify genes whose expression was correlated with changes in functional network controllability in AD, followed by a set of analyses on the functional features of the identified genes. Main results . In comparison to NCs, patients with AD exhibited a reduction in average controllability, predominantly within the default mode network (DMN) (63% of parcellations), and an increase in average controllability within the limbic (LIM) network (33% of parcellations). Conversely, AD patients displayed a decrease in modal controllability within the LIM network (27% of parcellations) and an increase in modal controllability within the DMN (80% of parcellations). In AD patients, a significant positive correlation was found between the average controllability of the salience network and the mini-mental state examination scores. The changes in controllability measures exhibited spatial correlation with transcriptome profiles. The significant genes identified exhibited enrichment in neurobiologically relevant pathways and demonstrated preferential expression in various tissues, cell types, and developmental periods. Significance . Our findings have the potential to offer new insights into the genetic mechanisms underlying alterations in the controllability of functional networks in AD. Additionally, these results offered perspectives for a deeper understanding of the pathogenesis and the development of therapeutic strategies for AD.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".