Human cerebral evolution and the clinical syndrome of amyotrophic lateral sclerosis
Bibliographic record
Abstract
The adult neurodegenerative disorder amyotrophic lateral sclerosis (ALS) is unmistakeable from clinical descriptions now more than a century old.1 Neither the site of symptom onset in ALS2 nor pattern of symptom spread3–5 is truly random. While the most consistent signs relate to motor system dysfunction, it is recognised that ALS represents an anatomically widespread neocortical disease,6 involving significant pathological and genetic overlap with Frontotemporal Dementia (FTD).7 8 Nearly all cases of ALS, and half of FTD, are associated with cytoplasmic, ubiquitinated inclusions of aggregated TDP-43.9 The linkage of apparently disparate cortical networks in the ALS-FTD pathological spectrum has been conceptualised as ‘what wires together, fires together and dies together’,10 based on a wider concept that neurodegenerative syndromes are defined by the architecture of large-scale brain networks.11 The motor system is perhaps one of the most fundamental to evolution, and the relative rarity of its targeted disintegration within the spectrum of neocortical disorders12 encapsulates a fundamental conundrum of understanding selective vulnerability in cerebral neurodegeneration.13 Approximately 600 000 years ago, Homo sapiens evolved from a common ancestor along with Neanderthal and other Hominid species, with evidence that Homo Sapiens of African origin exhibited the greatest genomic diversity.14–16 During this time, efficient cerebral processing for complex functioning evolved. This included versatile vocalisation accompanied by complexity of respiration, language and associated socialisation, increased fractionation of digits and thumb opposability, and upright walking with ability to navigate uneven and tricky surfaces while erect (figure 1). Failure of all of these functions characterises clinical manifestations of ALS.17 Paralleling functional advances, the shape and development of the brain have also evolved,18 including a diversification of different cell types. To achieve the fast, efficient motor processing required, particular motor output systems developed, best exemplified by the monosynaptic corticomotoneuronal …
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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 | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.005 | 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".