S71. NEUROVASCULAR UNCOUPLING IN SCHIZOPHRENIA: A BIMODAL META-ANALYSIS OF BRAIN PERFUSION AND GLUCOSE METABOLISM
Bibliographic record
Abstract
Since the time of Ernst von Feuchtersleben who coined the term psychosis (1845), psychotic disorders have been suspected to be associated with disturbances in cerebral blood supply. The use of modern neuroimaging approaches has uncovered abnormalities in the resting-state regional cerebral blood flow (rCBF) across various brain regions in schizophrenia. In a healthy brain, rCBF is tightly coupled to resting cerebral glucose metabolism (rCMRglu), which increases with synaptic activity. The coupling of rCBF (measured using arterial spin labelling, ASL) and rCMRglu (measured using 18flurodeoxyglucose positron emission tomography, FDG-PET) depends on the integrity of the neurovascular unit. In schizophrenia, several lines of evidence point towards aberrant neurovascular coupling especially in the prefrontal regions, though no simultaneous ASL-PET studies identifying regions with concordance or discordance between metabolism and perfusion have been reported to our knowledge. To address this gap, we undertook a voxel-based bimodal meta-analysis to examine the relationship between rCBF and rCMRglu in schizophrenia. We hypothesized that several brain regions would show combined abnormalities of perfusion and metabolism, while uncoupling of these 2 parameters will be observed in prefrontal regions. We undertook a systematic literature search to include all available studies reporting voxelwise ASL or FDG-PET changes in schizophrenia using coordinates based multimodal meta-analysis implemented using Signed Differential Mapping (SDM) software. 31 studies met the inclusion criteria, comprised of data from 599 patients and 590 controls, available for meta-analysis. We used conjunction and moderator analyses to evaluate areas with concordant and discordant abnormalities in rCBF and rCMRglu respectively. We also undertook meta-regression analyses to study the effect of age, gender, duration of illness, anti-psychotic dosage, and illness severity on the illness-related changes in rCBF and rCMRglu. Among patients with schizophrenia, we observed a conjoint reduction in rCBF and rCMRglu in the left frontoinsular cortex and bilateral dorsal anterior cingulate cortex (z>2, cluster inclusion p<0.0001). A conjoint increase in rCBF and rCMRglu was noted in bilateral striatum and temporal pole. Regional neurovascular uncoupling was notable in the superior frontal gyrus (reduced rCMRglu, normal rCBF) and cerebellum (increased rCMRglu, normal rCBF). Meta-regression analyses were unstable due to the low number of eligible studies. Our results suggest that several key regions implicated in the pathophysiology of schizophrenia such as the frontoinsular cortex, dorsal ACC, putamen and temporal pole (constituting the regions of the Salience Network) show conjoint metabolic and perfusion abnormalities in patients. In contrast, discordance between metabolism and perfusion was seen in the superior frontal gyrus and the cerebellum, indicating that factors contributing to neurovascular uncoupling (e.g. inflammation, mitochondrial dysfunction or oxidative stress) are likely to operate at these loci. Hybrid ASL-PET studies focusing on these regions could confirm our proposition.
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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 | 0.011 | 0.025 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.008 | 0.044 |
| Bibliometrics | 0.004 | 0.005 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.001 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.007 | 0.001 |
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".