Reading a Brain Without Knowing Biology

The Claim

If the Functional Proximity Law is real, it should be possible to identify the most functionally important neurons in C. elegans using only network topology — without using any biology.

That is what the experiment tests.

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The Data

The experiment uses White et al. (1986), the original complete wiring diagram of the C. elegans nervous system: 302 neurons, all synaptic connections, all gap junctions, manually reconstructed from electron micrographs over a decade of work.

Two layers:
• chemical_synapses — directed chemical synaptic connections
• gap_junctions — electrical synaptic connections (undirected)

15 neurons were selected for analysis based on known involvement in locomotion control circuits.

The layer definitions, node selection, and hypothesis were pre-registered before any analysis was run. The data source is external and 37 years old. IRDME had no involvement in producing it.

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The Result

Pearson r (chemical_synapses ↔ gap_junctions) = 0.7774, p = 0.004 Spearman r = 0.7796, p = 0.004

The law is confirmed. Neurons that are hubs in the chemical synapse layer are also hubs in the gap junction layer.

The top hub neurons in both layers: PVCL and PVCR.

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What PVCL and PVCR Are

PVCL and PVCR are paired interneurons in the posterior ventral cord. They are primary command interneurons for forward locomotion — they receive touch sensory input from the PLM neurons and relay signals to the A-class motor neurons (AVB, PVC circuit).

They are not the most famous neurons in C. elegans neuroscience. That would probably be AVA/AVB. But in the IRDME topology, they are the most structurally central across both layer types — and they are confirmed by the biological literature as primary relays in the touch response circuit.

IRDME did not know this. It computed hub centrality in each layer and reported the top nodes. The result matched the neurobiology.

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Why This Is External Validation

The key property of this experiment is independence:
• The data was produced by White et al. in 1986, years before IRDME existed.
• The layer definitions (chemical vs electrical synapse) are biological facts, not modelling choices.
• The node selection (15 locomotion-relevant neurons) was specified in the pre-registered hypothesis before extraction.
• IRDME's hub ranking is computed purely from graph topology — degree centrality, no biological priors.

The fact that the topology-derived hub ranking matches the known functional importance of PVCL and PVCR is not a circularity. It is a prediction that came true.

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The Denied Hypothesis

h2 predicted that AVAL would rank in the top 3 in both layers (based on its known role as the primary backward locomotion command interneuron).

Result: AVAL ranked #1 in gap junctions and #7 in chemical synapses.

The verdict is ERROR (not DENIED): AVAL is top in one layer but not both. It is a chameleon — dominant in electrical coupling, mid-tier in chemical synapse degree. The mechanism: AVAL's backward locomotion command function operates primarily through gap junction coupling to AVB, which is electrical. Its chemical synapse degree is lower because it receives rather than sends the initiating signal.

This distinction — between DENIED (prediction wrong) and ERROR (result ambiguous) — is tracked in the pre-registration record.

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The Structural Argument

If hub neurons were randomly distributed across the two synaptic layers, we would expect r ≈ 0. We observe r = 0.7774.

This is the topology-first claim: the most important nodes in a biological network are not arbitrary. They are structurally over-represented across independently defined relationship types. Their importance is written into the graph itself, not just into the biology textbooks.

IRDME reads the graph. The biology was there to be read.

Full pre-registered case study: /case-studies/celegans