ELEVATED INTRINSIC CORTICAL CURVATURE IN TREATMENT-RESISTANT SCHIZOPHRENIA: STRUCTURAL DEFORMATION OF FUNCTIONAL ACTIVITY AREAS
Bibliographic record
Abstract
Abstract Background Growing research shows abnormal brain structure and connectivity in patients with treatment-resistant schizophrenia (TRS) compared to first-line-responders (TxR) and healthy-controls (HC). While differences are documented as early as first-episode-psychosis (FEP), standard measures of structure and connectivity including thickness, volume, functional connectivity, and diffusion, show susceptibility to antipsychotic treatment and interpatient heterogeneity that limit their clinical and research use for TRS. In this regard, Intrinsic-Cortical-Curvature (ICC), a highly sensitive neurodevelopmental measure of both structure and connectivity, associated with the position and spread of functional activity areas, may provide a novel approach for the assessment and differentiation of TRS. Indeed, preliminary studies have not only linked elevations of ICC with TRS-like traits in FEP, including worsening cognition at follow-ups and reduced response to treatment, but methodology comparison studies have also proven ICC to be especially sensitive to schizophrenia differences compared to more common extrinsic gyrification measures. Despite this evidence, due to the previous complexity and computational demands required for ICC quantification, ICC research in schizophrenia and TRS remains scarce. Aim Our goal was to investigate whether differences in ICC between TRS, TxR and HC exist, their association to symptomology, and susceptibility to antipsychotic treatment, as a possible marker for treatment-resistance. Methods ICC was assessed from brain imaging data acquired using 3T high resolution magnetic resonance imaging (MRI). Regions of interest associated with TRS literature were processed, including the bilateral anterior-cingulate-cortices (ACC), dorsolateral-prefrontal- cortices (DLPFC), temporal-cortices, and parietal-cortices of TxR=38, TRS (clozapine-resistant ClzR- =30, clozapine-responders ClzR+=37), and HC=52. Positive, negative, and cognitive symptom severity was assessed (PANSS, MMSE, EXIT), along with chlorpromazine-equivalence (APT) and nicotine-use (NIC) to assess possible interactions. Results ICC elevations were observed in temporal-cortices of ClzR- and ClzR+ compared to HC (p=0.001), and DLPFC of ClzR- compared to TxR and HC (p<0.001). ICC elevations correlated with reduced cognition (p<0.007) and negative symptomology (p=0.036) in ClzR-. LH- temporal and parietal-cortices correlated with reduced cognition in ClzR+ (p=0.018) and TxR (p=0.008), respectively. No ICC/APT/NIC interactions were found (p>0.092). Conclusion Results show elevations of ICC in patients with TRS, particularly in regions associated with glutamatergic dysregulation. Elevations of ICC were also associated with reduced cognition, primarily in ClzR-. Considering ICC was not associated with APT or NIC, future research may prove ICC a resilient marker associated with TRS abnormalities.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".