The Functional Neuroanatomy of the Placebo Effect
Bibliographic record
Abstract
OBJECTIVE: Administration of placebo can result in a clinical response indistinguishable from that seen with active antidepressant treatment. Functional brain correlates of this phenomenon have not been fully characterized. METHOD: Changes in brain glucose metabolism were measured by using positron emission tomography in hospitalized men with unipolar depression who were administered placebo as part of an inpatient imaging study of fluoxetine. Common and unique response effects to administration of placebo or fluoxetine were assessed after a 6-week, double-blind trial. RESULTS: Placebo response was associated with regional metabolic increases involving the prefrontal, anterior cingulate, premotor, parietal, posterior insula, and posterior cingulate and metabolic decreases involving the subgenual cingulate, parahippocampus, and thalamus. Regions of change overlapped those seen in responders administered active fluoxetine. Fluoxetine response, however, was associated with additional subcortical and limbic changes in the brainstem, striatum, anterior insula, and hippocampus, sources of efferent input to the response-specific regions identified with both agents. CONCLUSIONS: The common pattern of cortical glucose metabolism increases and limbic-paralimbic metabolism decreases in placebo and fluoxetine responders suggests that facilitation of these changes may be necessary for depression remission, regardless of treatment modality. Clinical improvement in the group receiving placebo as part of an inpatient study is consistent with the well-recognized effect that altering the therapeutic environment may significantly contribute to reducing clinical symptoms. The additional subcortical and limbic metabolism decreases seen uniquely in fluoxetine responders may convey additional advantage in maintaining long-term clinical response and in relapse prevention.
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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 | 0.002 |
| 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 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 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".