O7.2. ALTERED HIPPOCAMPAL CENTRALITY IN RELATION TO COORDINATED CHANGES OF INTRACORTICAL MICROSTRUCTURE IN FIRST EPISODE PSYCHOSIS
Bibliographic record
Abstract
The hippocampus and associated circuitry are integral to the manifestation of psychosis and associated symptoms. There is evidence for the hippocampus as a key hub in healthy brain networks, which situates the hippocampus as an important target in the emerging view of psychosis as a disorder of altered connectome development. Here, we test the hypothesis that longitudinal changes in the hippocampus and surrounding white matter in relation to coordinated changes within intracortical (IC) and superficial white matter (SWM) microstructure in first episode psychosis (FEP) patients is altered compared to controls. We also examine whether such alterations are associated with changes in negative symptoms and verbal memory, two significant predictors of functional outcome. Longitudinal MRI scans (3T; 2–4 visits over 3–21 months) were acquired for 23 FEP and 26 HC. MP2RAGE quantitative T1 (qT1) maps, sensitive to myelin content, were used to sample microstructure of the hippocampus, IC and SWM regions. Mean qT1 for hippocampal subfields and output circuitry (fimbria, alveus, fornix, mammillary bodies) were calculated based on labels extracted from high-resolution T2-weighted scans (0.64 mm3) with MAGeT-Brain. IC qT1 was defined as the average qT1 at 35/45/55/65% cortical depths, and SWM qT1 was sampled 1mm below the grey-white matter boundary, across 81924 points of the brain surface, in relation to grey and white matter surfaces generated by CIVET. Cortical regions were then parcellated based on the Desikan-Killiany-Tourville atlas. Relationships between pair-wise regional trajectories were calculated for each subject, defined as the theta angle of separation between the qT1 rates of change of any two brain regions between timepoints. Parcellations of brain regions were defined a priori, where hippocampal subfields and surrounding white matter formed one parcel, and cortical regions were assigned to 7 parcels based on known functional networks. Graph theory was used to calculate participation coefficient (PC), to measure the distribution of connections between the hippocampal parcel to IC and SWM of the 7 cortical parcels. Mean PC of the hippocampal module was compared between FEP and controls, then correlated to changes in negative symptoms and Logical Memory from the Weschler Memory Scale in FEP. The PC of the hippocampal parcel in relation to IC networks was significantly reduced in FEP compared to HC (F1,45=9.85, p=0.003), and nominally reduced in relation to SWM (F1,45=4.67, p=0.036). Post-hoc analyses of individual subregions were restricted to hippocampal-IC networks, where CA1 and alveus bilaterally, left molecular layer, fornix, mammillary body and right fimbria significantly contributed to reduced hippocampal PC (p<0.05). Lower PC of the hippocampal parcel was significantly associated with worsening negative symptoms (r=-0.58, p=0.0043) and nominally associated with worsening verbal memory (r=0.46, p=0.031). These associations were driven by left CA1, alveus, mammillary body, and right fimbria (p<0.05). This study provides evidence for reduced hippocampal centrality in FEP in relation to coordinated anatomical changes within intracortical microstructure, suggesting the hippocampus may be related to changes in cortico-cortical connectivity. Particularly, centrality of output structures of the hippocampus, situated as putative connector hubs, are significantly related to changes in factors that contribute to patient functional outcomes. The myelin-rich output regions of the hippocampus may serve as an important therapeutic target in early psychosis, with cascading effects on broader cortical networks and resultant clinical profiles.
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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 | 0.000 | 0.001 |
| 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 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.005 | 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".