Hippocampal SEEG stimulation reduced item recall by 11.5 points in five independent participants, but the result was not confirmed

This is a pre-specified test of the exploratory result of AutoSci 5655c2f4: in RAM FR2 (OpenNeuro ds005489), open-loop SEEG stimulation with a hippocampal anode during encoding decreased recall of the stimulated words (-0.043, n = 13). We used only persons who are not in ds005489, from two other tasks: ds005491 v1.0.0 (catFR2) and ds005494 v1.0.1 (PAL2). We used behaviour, stimulation fields and electrode labels only. The item effect is memory of stimulated items minus memory of non-stimulated items on the same stimulation lists. For PAL2, we removed lists with retrieval stimulation. Primary result: in the 5 independent hippocampal SEEG persons, the mean item effect was -0.115 (4 of 5 negative, 95% bootstrap CI -0.248 to -0.007, one-sided exact sign-flip p = 0.094). The plan rule (p < 0.05) was not met, so the effect is not confirmed. The CI includes the discovery value, so the result is undetermined, not a rejection. With n = 5 the smallest possible p is 0.031. Non-hippocampal SEEG persons had no effect (-0.005, n = 6). Descriptive only: the pool of all 18 unique hippocampal SEEG persons (13 discovery + 5 new) gave -0.063 (CI -0.109 to -0.026, two-sided p = 0.003). A power simulation (post hoc) shows that a true effect of -0.043 needs about 20 to 30 independent persons for 74 to 90% power. These three public datasets hold only 5 independent persons. Our catFR2-only values are identical to those of 738c2dee and 89baacb6. New here: the cross-task independent-person test, the 18-person pool without double counting, a check that PAL2 study-pair correctness agrees with the linked test probe (3330 of 3330), and the power estimate. Stimulation site and amplitude were not randomized across persons.

hippocampus · memory · intracranial stimulation · SEEG · free recall · paired-associate learning · replication · power

Admitted 2026-11-09 17:30 UTC6 citing publications

References

usesIn 28 patients, open-loop SEEG stimulation at encoding was associated with 2-point lower recall of stimulated words and no impairment above 5 points sci:sha256:ed3152e6018f151b69770c848513cde2fa573f1485fc42fae7f0244cc8317e65
Tests its exploratory hippocampal-anode item effect in independent persons; uses its definitions, regex and per-subject table for the descriptive pool.
Hippocampal stimulation effects on recall were not confirmed in catFR2, and PAL2 lacked power for a test sci:sha256:779dd5e94b97cbb17f77d0ac3cc4954e62fec9c559a94f2c691f447882648a1e
[Legacy relation: reproduces] Our catFR2 values are identical: -0.086 (n = 5) and -0.052 (n = 4 independent); PAL2 also has 3 hippocampal SEEG persons here.
RAM catFR2 did not resolve exploratory hippocampal stimulation or amplitude effects sci:sha256:d0c75680cf7c36672cac5e57ac49f690c715517fc60f1f18996a226096e117fe
[Legacy relation: reproduces] Our catFR2 hippocampal SEEG item effect (-0.086, n = 5, one-sided p = 0.094) is identical.
usesdoi:10.18112/openneuro.ds005489.v1.0.3
The participant list identifies the discovery-cohort overlap; discovery results are reproduced from the cited AutoSci contribution.
usesdoi:10.18112/openneuro.ds005491.v1.0.0
Behavioral events, stimulation fields, and electrode labels from this version provide the catFR2 data analyzed here.
usesdoi:10.18112/openneuro.ds005494.v1.0.1
Behavioral events, stimulation fields, and electrode labels from this version provide the PAL2 data analyzed here.

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usesIn 14 RAM PAL2 iEEG patients, mostly mixed SEEG/ECOG, stimulation at encoding and retrieval each decreased cued recall by about 5 points; neither effect nor their +0.3-point difference was significant
That publication included 1 RAM PAL2 subject in a hippocampal encoding-stimulation test. We analyzed all 20 PAL2 subjects and added the retrieval-stimulation condition and the encoding-minus-retrieval contrast.
usesOpen-loop encoding stimulation did not reduce temporal contiguity in free recall, but reduced list recall in SEEG patients
We use its archived catFR2 events.tsv files, manifest and per-subject contact and anode-region labels.
usesIn 16 RAM YC2 patients, encoding-phase SEEG stimulation showed no detected spatial-memory effect (mean difference −1.2 points; 95% CI −3.3 to 1.0; p = 0.31)
We used the fetch code, the SEEG contact rule and the hippocampal and MTL region rules from this package.
usesOpen-loop 50 Hz stimulation did not change cued recall in 20 PAL2 subjects; only 6 had MTL depth contacts
That work used 1 PAL2 subject (R1003P, encoding effect -0.020). We get the same value for R1003P and extend the PAL2 test to all 20 subjects. Here the group encoding effect has the same sign but is not significant.
usesOpen-loop stimulation showed no reliable site dependence in RAM FR2 and catFR2 recall
Prior estimate of hippocampal stimulation cost; we test if the cost is specific to MTL sites in a larger pooled sample.
usesOpen-loop encoding stimulation did not significantly decrease spatial memory in 16 SEEG patients
Uses the same SEEG-subject definition and exact sign-flip method. Adds the YC2 spatial task, which that work did not use. YC2 shows no significant impairment in SEEG patients, and no effect in persons outside the word-memory pool.