Claims 52
From the paper Conserved brain-wide emergence of emotional response from sensory experience in humans and mice · claims file · checked 2026-10-21: ready
- fig1e-human-ketamine-late-closure
In four non-implanted participants, late eye closure after the eyepuff (0.3 to 0.8 s), normalized by early closure (0.1 to 0.2 s), was lower during ketamine (0.43) than during saline (0.71).
Late eye closure, normalized by early eye closure (0.1 to 0.2 s after airpuff onset), decreases during ketamine ( n = 4 human participants
Figure 1E; table S3, Fig. 1EHow it will be judged
Per participant, the mean over trials (the first two excluded, table S3 and fig. S1A) of late closure (0.3 to 0.8 s) divided by early closure (0.1 to 0.2 s), as in the Fig. 1 legend. Reproduced when both group means are within tolerance and a paired t-test of saline against ketamine gives p < 0.05 with ketamine lower.
- figs1b-human-early-closure-unchanged
Ketamine did not change the early reflexive eye closure of the same participants (0.84 against 0.78).
Early eye closure (during 0.1 to 0.2 s after puff onset) does not
Figure S1B; table S3, fig. S1 BHow it will be judged
A claim of absence, judged on the paper's test, a paired t-test of per-participant mean early closure (sum over 0.1 to 0.2 s, table S3) under saline against ketamine. Reproduced when p >= 0.05; the difference is reported either way.
- fig1f-human-reports
Under saline the participants described the eyepuffs as unpleasant and arousing; under ketamine they remained aware of the puffs but the aversive quality was largely gone.
subjective reports of the aversive quality of the stimulus were largely abolished by ketamine without blocking awareness of the eyepuffs
Figure 1F; fig. S1F; Results, Precisely timed affective behavior in mice and humansHow it will be judged
Judged on the participants' reports if the deposit holds them. Reproduced when every saline report describes the puffs as aversive and the ketamine reports of most participants (three or four of four) describe awareness of the puffs without aversion, as fig. S1F tabulates. The paper gives no measure beyond the table.
- fig2d-cadss-ketamine
In the seven iEEG participants who met the inclusion criteria, dissociation (CADSS) rose from 0.86 before infusion to 22.43 during ketamine and returned to 0.86 after.
the iEEG-recorded participants also reported fully reversible induction of dissociation (measured with the CADSS instrument) during recordings
Figure 2D; table S3, Fig. 2D - fig2g-six-factors
Nonnegative matrix factorization of the preinfusion puff-triggered spectrograms of 458 channels from seven participants is best described by six factors, which explain 0.47 of the variance on held-out trials.
Factoring the responses into six components ( Fig. 2G ) was found to be optimal, with an explained variance of 0.47 on held-out trials and diminishing returns with more components
Figure 2G; fig. S17; table S3, Fig. 2GHow it will be judged
As in the Methods (Factorization) and table S3, Fig. 2G. Puff-triggered z-scored spectrograms, 0 to 1.4 s after onset, averaged over every other preinfusion and postinfusion trial (training half), split into positive and negative parts, each factored with k = 3; the other half of the trials is the test set. Reproduced when the held-out explained variance at six factors is within tolerance and the test-set curve shows its elbow at six.
- fig2i-factors-1-2-ketamine
Factors 1 and 2 (a fast high-frequency rise and a delayed low-frequency fall) were less represented during ketamine than the average of pre- and postinfusion.
Two of these factors (1 and 2) showed decreased representation during ketamine followed by post infusion recovery
Figure 2I; table S3, Fig. 2IHow it will be judged
Channels with a mean loading of at least 0.1 on the factor over the pre- and postinfusion test trials; infusion loading against the mean of pre- and postinfusion loadings by a mixed-effects linear model grouped by participant, FDR across the six factors, as table S3 gives. Reproduced when factors 1 and 2 both have a negative coefficient with corrected p < 0.05.
- fig3b-cluster-test-networks
Permutation cluster tests found ketamine-altered spectrotemporal clusters in the limbic, ventral attention and somatomotor networks, and in regions including insula, cingulate, orbitofrontal and posteromedial cortex, supramarginal gyrus, motor cortex, hippocampus, basal ganglia and thalamus, while many other regions were not changed.
Permutation cluster testing resolved ketamine-altered spectrotemporal clusters which reached statistical significance in the limbic, ventral attention, and somatomotor Yeo7 resting-state networks
Figure 3B and 3C; Results, Brain-wide activity screen during emergence of affect in human beingsHow it will be judged
As in the Methods (Permutation cluster test) and table S3, Fig. 3B and 3C. Regional (or network) spectrograms per trial, trials paired by position in the puff sequence, a one-sample t-test of infusion minus preinfusion with mne permutation_cluster_1samp_test, cluster-forming threshold 0.01, the lowest cluster p of each region or network FDR-corrected across regions, significance at corrected p < 0.01; regions sampled in at least two participants. Reproduced when limbic, ventral attention and somatomotor networks are significant, and partially reproduced when one or two of them are.
- figs12-erp-not-blink
The eyepuff-evoked potentials are not a signature of eyelid closure; spontaneous blinks of the same magnitude evoke much smaller potentials, and the sound of the puff directed away from the participant does not evoke the brain-wide pattern.
Despite similar magnitude of measured eyelid closure in spontaneous versus puff-triggered eyeblinks, the ERP pattern was not seen in spontaneous eyeblinks
Figure S12A to S12D; fig. S13D; Results, Brain-wide activity screen during emergence of affect in human beingsHow it will be judged
As in table S3, fig. S12 C and D. Mean absolute baseline-subtracted LFP across 773 channels from 7 participants, triggered on 52 puff-triggered and 52 spontaneous blinks. Reproduced when the puff-triggered magnitude exceeds the spontaneous one with non-overlapping mean +- 1.96 s.e.m. bands in the first 0.5 s after blink onset while the eye-closure traces of the two kinds of blink overlap. The paper reports no test; the window is a reading of the figure range.
- figs14g-cadss-correlation
Across participants, the dissociation score was correlated with the ketamine-induced loss of affective eye closure (Spearman 0.744).
We observed that the overall CADSS dissociation score was correlated at the individual participant level with inhibition of the affective eyepuff response
Figure S14G; table S3, fig. S14 GHow it will be judged
Participants with preinfusion normalized affective closure above 0.5 (fig. S14G legend); change defined as infusion minus the mean of pre- and postinfusion (legend) or as ketamine minus preinfusion (table S3), both shown. Reproduced when, under either, rho is within tolerance with p < 0.05, taking the sign of the change so that a larger loss scores higher.
- fig6c-human-persistent
In the human participants, activity along the persistent (0.5 to 1.5 s) beta-power coding dimension fell during ketamine (1.36 to 0.41) and recovered after infusion (0.72).
Across species we observed a decrease, caused by ketamine, in eyepuff-triggered persistence that recovered post infusion
Figure 6C; table S3, Fig. 6C - fig6e-human-fast-unchanged
In the human participants, activity along the fast (50 to 100 ms) coding dimension was not changed by ketamine.
Fast population activity is not significantly altered by ketamine in humans
Figure 6E; table S3, Fig. 6EHow it will be judged
A claim of absence, judged on the paper's test (paired t-tests with FDR correction). Reproduced when neither corrected p is below 0.05.
- fig6g-human-timescale
In the human participants, the intrinsic timescale of the persistent dimension at baseline was shorter during ketamine (0.09 s) than before (0.11 s).
In both humans and mice, we observed that ketamine robustly accelerated the baseline intrinsic timescale of the population
Figure 6G; table S3, Fig. 6GHow it will be judged
The Methods (Intrinsic timescale) take an eight-minute period before the eyepuff assay; table S3 says the ten minutes before. Both are shown. Exponential a*exp(-x/b) + c fitted from the autocorrelation peak to 2.5 s, initial a=1, b=0.2, c=0. Reproduced when, under either period, both means are within tolerance and the paired t-test gives p < 0.05 with ketamine shorter.
- fig6i-human-phase-locking
In the human participants, beta phase locking among the most persistent channels at baseline fell during ketamine (0.979 of preinfusion).
in both mice and humans, we discovered that ketamine decreased coupling among these sites
Figure 6I; table S3, Fig. 6IHow it will be judged
The top 10% of sites per participant by persistent-dimension weight, white matter excluded (Methods, Phase-locking Value); table S3 says channels above the 90th percentile. Sliding 5 s windows, preinfusion 25 min before infusion and the final 25 min of infusion outside the assay; the Methods also name the ten minutes before the eyepuff assay (table S3), shown as a variant. Reproduced when the normalized value is within tolerance and the paired t-test gives p < 0.05 with ketamine lower.
- fig1k-mouse-ketamine-late-closure
In mice, ketamine (50 mg/kg) reduced late eye closure normalized by early closure on the first puff of each series (0.26 under saline, -0.07 under ketamine).
Late eye closure, normalized by early eye closure (0.1 to 0.2 s afterpuff onset), decreases during ketamine ( n = 5 mice
Figure 1K; table S3, Fig. 1K - fig1l-dissociatives-preinfusion
Compared with preinfusion, normalized late closure was unchanged by saline but reduced by ketamine (50 mg/kg) and PCP (20 mg/kg).
dissociative drugs such as ketamine and phencyclidine [(PCP), uniquely enabled for mice] similarly reduced late but not early eye closure
Figure 1L; table S3, Fig. 1L - figs2bc-mouse-early-late
Under ketamine the early (reflexive) closure of mice was reduced but present (0.78 to 0.45), while late (affective) closure was abolished (0.34 to -0.02).
Late eye ... closure (during 0.3 to 0.8 s after puff onset) is abolished by ketamine
Figure S2B and S2C; table S3, fig. S2 B and C - fig1m-accumulation-persistence
Late eye closure accumulated across the eight puffs of a series and decayed slowly after the last puff, with a Kaplan-Meier median persistence of 15.16 s.
We found that late-phase eye closure in mice accumulated across a sequence of eyepuffs and decayed slowly after the final eyepuff in the sequence
Figure 1M; fig. S2E; table S3, fig. S2 EHow it will be judged
Preinfusion trials, 20 per mouse in 5 mice (table S3, fig. S2 E). Reproduced when the Kaplan-Meier median is within tolerance and the mean late closure (0.3 to 0.8 s) after the eighth puff exceeds that after the first, with non-overlapping mean +- 1.96 s.e.m. across mice. The paper does not state the event that ends survival; that detail is open.
- figs2g-scaling-puff-number
In mice, normalized late eye closure was larger after the eighth puff of a series than after the first at each of three puff pressures (8, 18 and 28 PSI), while it did not differ between pressures at the eighth puff.
Late (normed by early) eye closure scales with puff number but not puff intensity, comparing air puffs of different pressure
Figure S2F and S2G; table S3, fig. S2 GHow it will be judged
The paper's tests (table S3, fig. S2 G), paired t-tests across 8 mice with FDR correction over the six comparisons, on per-mouse means of late (0.3 to 0.8 s) divided by early (0.1 to 0.2 s) closure, preinfusion. Reproduced when the three puff 1 against puff 8 tests give corrected p < 0.05 with puff 8 higher and the three pressure comparisons give corrected p >= 0.05 (the absence is judged on the paper's test); the differences are reported either way.
- figs2h-dose-response
The dissociative reduction of normalized late eye closure began around 35 mg/kg ketamine and 10 mg/kg PCP; lower doses did not significantly reduce it.
Dose-response investigation showed that these robust dissociative effects begin around 35 mg/kg ketamine and 10 mg/kg PCP
Figure S2H to S2J; table S3, fig. S2 H; Results, Precisely timed affective behavior in mice and humansHow it will be judged
The paper's tests (table S3, fig. S2 H), paired t-tests of preinfusion against infusion of normalized late closure after the eighth puff at each dose, FDR-corrected. The family of the correction is not given; the readings are (a) all ten comparisons of the table together (saline included), (b) each drug apart. Reproduced when, under both readings, ketamine 35 and 50 mg/kg and PCP 10 and 20 mg/kg give corrected p < 0.05 with a decrease and the lower doses give corrected p >= 0.05.
- fig1p-anesthesia-abolishes-both
A general anesthetic dose of ketamine with xylazine abolished both reflexive and affective eye closure, while ketamine or PCP alone kept the reflexive blink.
By contrast, general anesthesia, achieved through addition of xylazine to ketamine ... abolished both reflexive and affective responses
Figure 1N to 1P; fig. S5D and S5E; Results, Precisely timed affective behavior in mice and humansHow it will be judged
The paper's tests (table S3, fig. S5 D and E), paired t-tests with FDR correction of reflexive (0.1 to 0.2 s) and affective (0.3 to 0.8 s) closure after the eighth puff, 5 mice, 15 trials each. Reproduced when both K/X tests give corrected p < 0.05 with K/X lower, the K/X values are within tolerance, and the reflexive closure under ketamine and under PCP is within tolerance (present, unlike K/X). Fig. 1N to 1P themselves carry no test.
- figs5-other-drugs
Buprenorphine and diazepam did not reduce normalized late closure, unlike ketamine and PCP.
Only ketamine (50 mg/kg) and PCP (20 mg/kg) decrease late normalized by early eye closure
Figure S5C; table S3, fig. S5 CHow it will be judged
The paper's test, paired t-tests with FDR correction on normalized late closure of the eighth puff. Reproduced when ketamine and PCP give corrected p < 0.05 with a decrease and buprenorphine and diazepam give corrected p >= 0.05.
- figs6-vpm-muscimol
Inhibiting VPM thalamus with muscimol reduced normalized affective closure (0.60 after saline injection, 0.11 after muscimol) while the fast early closure remained.
With muscimol, there is early eye closure after each puff, but no accumulating late eye closure
Figure S6B, S6C and S6H; table S3, fig. S6 C - figs4-reward-licking
Eyepuff series persistently reduced licking for a liquid reward, which recovered slowly after the last puff.
Lick probability decreased persistently during the air puff sequences and slowly recovered after the final air puff of the sequence
Figure S4BHow it will be judged
Lick probability in 3 s bins, both series per mouse combined, averaged over 6 mice (Methods and fig. S4B). Reproduced when the mean lick probability over the series (0 to 24 s from the first puff) is below that of the 24 s before it, with non-overlapping mean +- 1.96 s.e.m. across mice. The paper reports no test.
- fig5hi-behavior-model-doses
Varying only the persistence timescale of the two-phase model explained much of the variation in affective eye closure across doses of ketamine and of PCP.
We found that varying τ PERSIST alone across different doses of ketamine explained substantial variance across doses
Figure 5H and 5I; table S3, Fig. 5H, IHow it will be judged
Fit as for fig5g-tau-persist-model on the dose series (ketamine 6, 13, 25, 35 mg/kg; PCP 1, 5, 10 mg/kg; 5 mice), 750 ms after each puff masked (Methods, Model fitting, behavioral data; analysis.py filter_reflex). Variance explained is 1 - MSE_model/MSE_null against the fit with no parameter varying. The paper gives no value and no threshold; reproduced when the variance explained is positive for each drug and the fitted persistence timescale falls with dose.
- fig4-recordings-scale
Many thousands of single units were recorded across 13 sessions from 10 mice, with dozens of regions recorded simultaneously.
We obtained recordings from many thousands of single units throughout the brain, with simultaneous recording of dozens of regions
Figure 4C; fig. S29A and S29B; table S2; table S3, Fig. 4EHow it will be judged
Counts of sessions and mice must match exactly. Units counted after the paper's quality criteria (Methods); "dozens of regions" holds when the median session has units in at least 24 Allen CCFv3 regions at the finest level, a reading of "dozens" as two dozen since the paper gives no count. The puff-modulated count uses the selection in the opening comment and depends on it.
- fig4b-recorded-eye-closure-ketamine
The recorded mice showed affective eye closure after the first puff of each series, and ketamine reduced it.
In response to eyepuffs, mice showed affective eye closure that was reduced by ketamine
Figure 4B; fig. S28A; table S3, Fig. 4BHow it will be judged
Eye closure of the 13 recorded sessions, baseline-subtracted with the 1 s before the puff (table S3), first puff of each series, Pre series 1 to 20 against Ketamine series 23 to 32 (code; Methods-literal 22 to 32 as a variant); the code normalizes each session's trace by its maximum before averaging, shown with and without. Late closure is the mean over 0.3 to 0.8 s (the paper's late window). Reproduced when the across-session mean of Pre minus Ketamine late closure has a 95% interval (1.96 s.e.m., table S3) above zero. The paper reports no test.
- fig5b-recorded-accumulation
In the recorded mice, eye closure accumulated across each puff series, and ketamine abolished the accumulation.
recorded animals exhibited progressively accumulating eye closure behavior during each eyepuff series, which was abolished by ketamine
Figure 5B; table S3, Fig. 5BHow it will be judged
11 sessions from 9 mice (the excluded animal is open, see fig5d-emotion-dimension-accumulates), eye closure baseline-subtracted with the 1 s before each series (table S3). Accumulation is the late closure (0.3 to 0.8 s) after puff 8 minus that after puff 1. Reproduced when the 95% interval (1.96 s.e.m. across sessions) of accumulation is above zero for Pre and includes zero or lies below the Pre mean for Ketamine (series 23 to 32). The paper reports no test.
- fig4de-response-clusters
Unsupervised clustering of peri-puff responses of puff-modulated units from all sessions gave twelve clusters spread over many regions, some responding rapidly and briefly and others persistently after rapid (clusters 0 and 1) or delayed (cluster 2) onset.
Some clusters responded rapidly and briefly to the eyepuff whereas others responded persistently after either rapid (clusters 0 and 1) or delayed onset (cluster 2)
Figure 4D and 4E; fig. S31A; table S3, Fig. 4EHow it will be judged
Method from the Methods (Unsupervised clustering) and analysis.py get_cell_clusters. Puff-modulated units of all 13 sessions; per unit, the z-scored rate from -1 to 2 s around each puff averaged over the 160 Pre puffs, minus its mean over -1 to 0 s; scanpy PCA (arpack), neighbors (n_neighbors 30, n_pcs 20), UMAP, Leiden with default resolution, seeds 42. The Methods say Leiden runs on the UMAP embedding; scanpy's leiden, as the code calls it, runs on the neighbor graph, which is followed. Cluster sizes are compared in descending order, since the numbering of table S3 is by size while the figure numbers clusters top to bottom after a hierarchical reordering; which numbering the text's "clusters 0, 1 and 2" uses is open, and the response shapes are judged under both. Rapid and brief means the cluster mean decays to 25% of its post-puff peak (Methods, Cumulative fraction of cells, and code find_decay) within 0.25 s of onset; persistent means it is still above 25% of its peak over 1 to 2 s, the window the Methods use to quantify persistent activity. The 25% level is the paper's; the 0.25 s bound and the use of the 1 to 2 s window for "persistent" are readings, since the paper gives no cut-off for "rapidly and briefly" or "persistently". Reproduced when the cluster count and sizes are within tolerance and at least one cluster is rapid and brief while three are persistent, two with peaks in the first 250 ms and one later.
- figs31b-cluster-overrepresentation
Clusters overrepresented in the periaqueductal gray and VPM thalamus had fast, sharp responses, while clusters overrepresented in frontal cortex and limbic regions responded more slowly and persistently.
Indeed, clusters overrepresented in midbrain (PAG) and thalamus (VPM) exhibited fast and sharp response dynamics, whereas clusters overrepresented in frontal cortex and limbic regions responded more slowly and persistently following the eyepuff
Figure 4G; fig. S31A and S31B; table S3, fig. S31 BHow it will be judged
As in table S3, fig. S31 B and analysis.py get_cluster_null_distribution. Regions with more than 30 clustered cells; for each region and cluster, the fraction of the region's cells in the cluster against 20,000 draws of uniformly random labels, two-sided, FDR across regions. The threshold is 0.05 in the Methods and the code and 0.01 in table S3; both are shown. Clusters are ranked by the time their mean falls to 25% of its post-puff peak. Reproduced when PAG and VPM are each significantly overrepresented in a cluster from the faster half, and at least one frontal cortical or limbic region (ORB, ACA, PL, ILA, MOs, AI, as Supplemental Note 1 maps them) in a cluster from the slower half.
- fig4g-ketamine-alters-slow-clusters
Ketamine substantially changed the responses of clusters with slow, persistent preinfusion dynamics but left fast clusters little changed.
Clusters with more rapid preinfusion dynamics were minimally altered or unaltered by ketamine, whereas clusters with slower and more persistent preinfusion dynamics were substantially altered
Figure 4G; fig. S31C; table S3, Fig 4GHow it will be judged
Cluster means as in table S3 (all cells of the cluster pooled, baseline-subtracted with the 1 s before the puff, z-scored over the peri-puff window within cluster and condition), Pre series 1 to 20 against Ketamine series 23 to 32 (code plot_avg_psth_prepost_ket, 10 series). Table S3 gives 64 Ketamine puffs per cluster (8 series), which the code does not reproduce and the paper does not place; the code is followed and the conflict is a deviation. The paper gives no measure of change. The readings are (a) the cosine distance between the Pre and Ketamine mean traces from -1 to 2 s, the similarity measure of the Methods (Analysis of similarity); (b) the absolute difference of the means over 1 to 2 s. Reproduced when, under both, the change correlates positively with the Pre decay time (to 25% of peak) across clusters by Spearman correlation at p < 0.05.
- fig4i-rise-times-unchanged
Most regions responded to the puff with fast rise times, and ketamine did not change regional rise times.
On a regional basis as well, the rise times of average neural activity were not altered by ketamine
Figure 4I; fig. S31D to S31F; table S3, Fig. 4H, IHow it will be judged
Method from the Methods (Regional rise and decay time), table S3 and analysis.py region_time_course. Regions merged across cortical layers (code reduce_region) with more than 30 puff-modulated units (code; the Methods say at least 30, shown as a variant); per region and cluster (cluster 11 skipped, as the code does) the first two puffs of each series, baseline-subtracted, turned into d' against the 1 s before the puff; rise is the time to 25% of the peak, combined across clusters weighted by the region's cell fractions; regions whose peak comes after 750 ms dropped; 1000 bootstraps over puffs; Ketamine series 23 to 32. Regions are excluded when their peak d' is below 1.3 (Methods and code) or below 2 (table S3); both are shown. The paper reports no test of absence. Reproduced when, under both thresholds, the median over regions of the bootstrap median change in rise time (Ketamine minus Pre, as fig. S31F) lies within one 10 ms bin of zero and the Pre median rise time is below 0.1 s in most regions.
- fig4h-decay-shortened
Ketamine shortened the time for regional puff responses to decay from their peak.
whereas regional times to decay from peak response were shortened
Figure 4H; fig. S31GHow it will be judged
Decay time is the time from the d' peak to fall to 25% of the peak, computed as for fig4i-rise-times-unchanged, under both d' thresholds. Reproduced when the median of the distribution of bootstrapped changes (Ketamine minus Pre) across regions, as fig. S31G draws it, is below zero and more than half the regions have a Ketamine median decay below their Pre median. The paper reports no test.
- fig4h-decay-anatomical-progression
Before ketamine, regional decay times followed a progression from subcortical to frontal cortical regions, with long decays in frontal and limbic cortex and in VPM and MD thalamus.
decay times of regional neural activity were more variable and followed a general anatomical progression from subcortical to frontal cortical regions
Figure 4H; Results, Brain-wide activity screen during emergence of affect in miceHow it will be judged
Pre decay medians per region, computed as for fig4i-rise-times-unchanged under both d' thresholds. Frontal and limbic cortex is ORB, ACA, PL, ILA, MOs, MOp and AI (the mouse regions Supplemental Note 1 maps to the human frontal and limbic regions); midbrain is the regions under MB in the Allen hierarchy. Reproduced when the median decay of the frontal and limbic regions exceeds that of the midbrain regions, and VPM and MD each lie above the median decay of all regions. The paper reports no test.
- fig5d-emotion-dimension-accumulates
Population activity along an emotion-like dimension (after the series against before it) rose and saturated across the puff series and decayed over tens of seconds afterwards; under ketamine it did not accumulate.
Measuring neural activity along this dimension revealed emotion-like properties of scalability through a saturating rise across the series of eyepuffs and of persistence through a decay lasting tens of seconds following each eyepuff series before returning to baseline
Figure 5C and 5D; table S3, Fig. 5DHow it will be judged
Sessions. 11 sessions from 9 mice; the paper does not name the excluded animal, so each mouse with more than one session whose removal leaves 11 sessions from 9 mice is a reading, and the outcome must hold under all of them. Dimension (Methods, Emotion-like neural dimension, and analysis.py get_affective_projections), per session from puff-modulated units (sessions with at least 20). Target window is the 1 s starting 5 s after the last puff onset (Methods); the code's window falls 3 to 4 s after it (bins 400 to 500 of a post-series window that its plotting places 1 s before the last puff), shown as a variant. Reference is the 750 ms ending 250 ms before the first puff. Weights are mean differences normalized by per-unit variance (Methods; the code divides by the variance pooled over all units, a variant), made orthogonal by QR to an eye-reflex dimension from the last four puffs (200 ms after against 200 ms before onset), signed so that puff 8 exceeds puff 1 (code). Projections are baseline- subtracted per series with the 250 ms before the first puff. Reproduced when, for Pre, the 95% interval across sessions (1.96 s.e.m., table S3) of the mean projection in the 250 ms before puff 8 is above zero and higher than before puff 2, the projection 10 to 11 s after the last puff onset is still above zero and the last 5 s of the 45 s shown after the series include zero; and, for Ketamine (series 23 to 32), the interval before puff 8 includes zero or lies below the Pre mean.
- fig5e-late-reduced
On the first puff of a series, late emotion-like activity (2 to 3 s after onset) was reduced by ketamine (0.546 to 0.005).
late changes along the emotion-like dimension (seconds after each eyepuff) were reduced
Figure 5E; table S3, Fig. 5EHow it will be judged
Dimension and readings as in fig5d-emotion-dimension-accumulates; per session the mean over series of the first-puff projection in 2 to 3 s, baseline the 250 ms before the puff (analysis.py plot_affective_firstpuff_persist); two-sided paired t-test across sessions, FDR over the two windows. Reproduced when corrected p < 0.05 with Ketamine lower. The expected values are met when, under one weight scaling (unit vector or sum of absolute values), both are within tolerance; otherwise the claim is partially reproduced if the test holds.
- fig5e-rapid-unchanged
The rapid emotion-like response to the first puff (0 to 0.25 s) did not differ between preinfusion and ketamine.
These transient increases on ketamine were not different from those prior to ketamine
Figure 5E; table S3, Fig. 5EHow it will be judged
A claim of absence, judged on the paper's test, the two-sided paired t-test with FDR over the two windows, as for fig5e-late-reduced. Reproduced when corrected p >= 0.05; the difference is reported either way.
- fig5g-tau-persist-model
A two-phase first-order model in which only the persistence timescale differs between preinfusion and ketamine closely matched the emotion-like population activity.
Despite only varying the single parameter τ PERSIST across preinfusion and ketamine conditions, we observed a close match between the model and the experimental data
Figure 5F and 5G; table S3, Fig. 5GHow it will be judged
Model and fit from the Methods (Theoretical model) and analysis.py (model_system, theoretical_persist, compare_model). Inputs are eight 250 ms steps 3 s apart; broadcast phase x = (S - x0)(1 - exp(-t/tauB)) + x0, persistence phase x = x0 exp(-t/tauP). Fitted with scipy curve_fit to the across-session mean of Pre and Ketamine traces concatenated, from -0.25 to 23 s and 25 to 70 s after the first puff (the dimension's training window left out), S and tauB shared, tauP times a factor in [0, 1] per condition (null factor in [0.99999, 1]), bounds [0, 100]. Variance explained is 1 - MSE_model/MSE_null. The paper gives no value for "close match". Reproduced when the variance explained is positive and the fitted Ketamine persistence timescale is shorter than the Pre one, under each reading of the dimension.
- figs33-alternative-models
Alternative models in which ketamine changes the input scale S or the broadcast rate, or a symmetric single-timescale model, fit the ketamine puff-series activity worse than the model in which ketamine changes the persistence timescale.
other alternative models in which ketamine modulated the input scale S or the broadcast rate τ BROADCAST instead of τ PERSIST also did not fit the data well
Figure S33A to S33D; Results, Brain-wide activity screen during emergence of affect in miceHow it will be judged
The same fit with the factor on S (theoretical_saturation), on tauB (theoretical_broadcast), or a single timescale (theoretical_symmetric). Variance explained on the Ketamine puff-series segment (fig. S33D). Reproduced when the tauP model has the highest variance explained there of the four.
- figs32c-regional-emotion-dimension
Emotion-like dimensions computed within each high-level brain area all showed accumulating persistent dynamics before ketamine that ketamine abolished.
All high-level brain areas ... exhibit some ... degree of accumulating persistent dynamics during preinfusion that is abolished by ketamine
Figure S32CHow it will be judged
As fig5d-emotion-dimension-accumulates, with units restricted per session to one high-level area (Methods, emotion-like dimension, last sentences); areas and sessions with at least 20 simultaneously recorded puff-modulated units (code min_cells). High-level areas are the Allen top-level divisions; the paper does not list them. Reproduced when every area that has at least two qualifying sessions meets the Pre and Ketamine conditions of that criterion for the value before puff 8; partially reproduced when most do.
- fig6b-persistent-dimension-distributed
The neurons carrying the persistent peri-puff dimension were not focally localized but distributed over much of the brain.
We found that the persistent dimension was not focally localized in either mice or humans; instead, a distribution spanning much of the brain was observed across both species
Figure 6B; fig. S36AHow it will be judged
Persistent-dimension weights as in fig6d-mouse-persistent. The paper gives no measure. Reproduced when the units with the top 10% of absolute weight in each session (the paper's "persistent neurons", table S3, Fig. 6J) are found in every Allen top-level division that holds at least 30 included units (the Methods' regional minimum) and no single division holds more than half of them.
- fig6d-mouse-persistent
In mice, activity along the persistent (0.5 to 1 s) coding dimension 1 to 2 s after the puff fell during ketamine (0.86 to 0.02) and partly recovered afterwards (0.52).
Across species we observed a decrease, caused by ketamine, in eyepuff-triggered persistence that recovered post infusion
Figure 6D; table S3, Fig. 6DHow it will be judged
Method from the Methods (Coding dimension, mouse peri-puff), table S3 and analysis.py plot_coding_dimension_early_late. Per session (sessions as in fig5d-emotion-dimension-accumulates), weights from Pre puffs of puff-modulated units, mean over 0.5 to 1 s against the 1 s before the puff, normalized by variance (per unit, Methods; pooled, code variant). The projection is averaged over series, z-scored over -1 to 2 s within session and condition and baseline- subtracted over -1 to 0 s (code); quantified as its mean over 1 to 2 s. The code projects the first puff of each series only; all eight puffs is a variant. Pre series 1 to 20, Ketamine 23 to 32, Post 35 to 40. Two paired t-tests, FDR over the two. Reproduced when both corrected p < 0.05 with Ketamine lowest and the means are within tolerance; partially reproduced when only Pre against Ketamine holds.
- fig6f-mouse-fast-unchanged
In mice, activity along the fast (0 to 70 ms) coding dimension was not changed by ketamine.
whereas similar analysis of a dimension encoding fast eyepuff-triggered activity exhibited no decrease during infusion
Figure 6F; table S3, Fig. 6FHow it will be judged
A claim of absence, judged on the paper's test, two-sided paired t-tests with FDR over the two comparisons. Target window 0 to 70 ms after onset; the Methods compare it with the 1 s before the puff, the code (cd_end 107) with the 70 ms before, and the Methods are followed with the code as a variant. Projection over all series and all eight puffs, z-scored over -1 to 2 s within session and condition, quantified over 0 to 70 ms (code). Reproduced when the Pre against Ketamine corrected p >= 0.05; the differences are reported either way.
- fig6h-mouse-timescale
In mice, the intrinsic timescale of the persistent dimension in the 30 s before each series was shorter during ketamine (0.14 s) than before (0.45 s).
In both humans and mice, we observed that ketamine robustly accelerated the baseline intrinsic timescale of the population
Figure 6H; fig. S34B; table S3, Fig. 6HHow it will be judged
Method from the Methods (Intrinsic timescale analysis, mouse) and analysis.py stimulus_timescales and extract_timescale. Rates in the 30 s before the first puff of each series projected on the persistent weights of fig6d-mouse-persistent; autocorrelation (scipy.signal.correlate) normalized to its maximum, a*exp(-x/b) + c fitted over the 2.5 s after the peak, initial a=1, b=0.2, c=0; b is the timescale. Series used are Pre 11 to 20 and Ketamine 23 to 32 (code, ten each as table S3). Two readings of how series are combined (a) per series fits averaged within session (Methods and table S3); (b) one fit to the series concatenated (code). Reproduced when, under both, the paired t-test gives p < 0.05 with Ketamine shorter and both means are within tolerance; partially reproduced when the test holds but the means do not.
- fig6j-mouse-coupling
In mice, correlations among the most persistent neurons in the 30 s before each series fell during ketamine to 0.49 of their preinfusion value.
in both mice and humans, we discovered that ketamine decreased coupling among these sites
Figure 6J; table S3, Fig. 6JHow it will be judged
Persistent neurons and coupling. The Methods take edges between neurons in the top 10% of absolute persistent weight, Pearson correlation averaged within session; the code (plot_coding_dimension_early_late) takes neurons whose signed weight exceeds the 90th percentile of absolute weights and the median absolute correlation of z-scored rates over the concatenated 30 s windows of Pre series 1 to 10 and Ketamine series 23 to 32. Readings are (a) the Methods, per-series 30 s windows, mean r over edges, averaged over series (table S3), on the code's series (Pre 1 to 10, Ketamine 23 to 32), since table S3 gives ten series per condition without naming them; (b) the code. Ketamine values divided by Pre within session; paired t-test across sessions. Reproduced when, under both, p < 0.05 with Ketamine lower; the expected value is met under either.
- figs34c-tone-no-eye-closure
Mice did not close their eyes appreciably to a series of auditory tones, before or during ketamine.
mice do not increase eye closure during tone presentation
Figure S34C; table S3, fig. S34 CHow it will be judged
Eye closure across the tone series, 7 sessions from 7 mice, Pre 10 series, Ketamine 5 (table S3). Reproduced when the 95% interval across sessions (1.96 s.e.m.) of the mean closure from 0.3 to 0.8 s after each tone, averaged over the eight tones, lies below the corresponding eyepuff value of the same sessions and below 0.1 of full closure. The 0.1 bound is a reading of "not substantial"; the paper reports no test.
- figs34d-tone-fast-unchanged
Fast tone-related population activity (0 to 70 ms) was not changed by ketamine.
Whereas fast tone-related neural activity was unchanged on ketamine
Figure S34D; table S3, fig. S34 DHow it will be judged
A claim of absence, judged on the paper's test, as fig6f-mouse-fast-unchanged with tone onsets, puff-modulated units (code selects units by their puff responses), tone series Pre (first 10 before infusion), Ketamine and Post. Table S3 gives 5 Ketamine and 3 Post series and the code takes post-infusion tone series 2 to 6 and 8 to 10 (1-based); the code is followed. Reproduced when the Pre against Ketamine corrected p >= 0.05.
- figs34e-tone-persistent
Persistent tone-related activity (350 to 500 ms) fell during ketamine (1.531 to 0.392) and recovered (1.385).
persistent tone-related activity decreased on ketamine and then recovered
Figure S34E; table S3, fig. S34 EHow it will be judged
As fig6d-mouse-persistent with tone onsets. Weights from 150 to 350 ms (Methods and table S3) against the 1 s before the tone; the code uses bins 115 to 135 (150 to 350 ms after onset), the same. Quantified over 350 to 500 ms (Methods and table S3); the code's window is bins 135 to 150, the same. The code averages the projection over all eight tones (limit 8). Reproduced when both corrected p < 0.05, with Ketamine lowest.
- figs34f-tone-shorter-than-puff
Persistent responses to the neutral tone were shorter than those to the eyepuff.
The affectively salient eyepuff elicits substantially longer persistent dynamics than the neutral tone
Figure S34F; table S3, fig. S34 FHow it will be judged
As analysis.py compare_tone_puff_late_proj. Per session, the Pre projection on each stimulus's persistent dimension averaged over the eight stimuli of a series, turned into d' against the 1 s before onset. Reproduced when the time at which the across-session mean d' falls back below half its peak is later for the puff than for the tone, and the puff mean d' over 1 to 2 s lies above the tone's with non-overlapping 95% intervals. The half-peak measure is a reading of "longer"; the paper reports no test.
- figs34g-tone-timescale
The baseline intrinsic timescale of the persistent tone population was shorter during ketamine (0.089 s) than before (0.268 s).
we still could detect a ketamine-mediated acceleration in the intrinsic timescale of populations that (prior to ketamine) exhibited modestly persistent responses to the tone
Figure S34G; table S3, fig. S34 GHow it will be judged
As fig6h-mouse-timescale with the tone dimension and the 30 s before each tone series. The code takes Pre tone series 5 to 10 and Ketamine 2 to 6 (1-based); table S3 gives 10 and 5; both are shown, as are the two readings of how series are combined.
- figs34h-tone-coupling
Correlations among the persistent tone neurons before the tone series fell during ketamine to 0.460 of their preinfusion value.
under ketamine these populations exhibited reduced functional coupling even before tone presentation
Figure S34H; table S3, fig. S34 HHow it will be judged
As fig6j-mouse-coupling, with the tone dimension and the 30 s before each tone series, under both readings.
- figs30-correlation-structure
Ketamine changed the correlation structure of single units at rest, increasing correlations within regions such as retrosplenial/posteromedial and orbitofrontal cortex while reducing correlations between regions.
ketamine altered single-unit correlation structure at rest by increasing within-region correlations such as within PMC and ORB (while also reducing correlations between regions
Figure S30A; Results, Brain-wide activity screen during emergence of affect in miceHow it will be judged
Method from the Methods (Regional correlation analysis). Pearson correlations between all units of a session over the whole preinfusion period and over the 10 minutes from ketamine onset (taken as 30 s after the last puff of series 20, as the code's ket_start). The paper shows one example session and no test. Per session, the mean within-region and the mean between-region change (Ketamine minus Pre), regions at the finest Allen level. Reproduced when, across the 13 sessions, the within-region change is above zero and the between-region change below zero by paired t-tests at p < 0.05 (the paper's test for session-level comparisons in table S3, Fig. 6J), and RSP and ORB within-region changes are positive in most sessions that record them.
- figs29-rsp-oscillations
Ketamine brought low-frequency oscillations into the population activity, especially strong in retrosplenial cortex.
noted the prominent appearance of low frequency oscillations as we previously reported ( 28 ), with especially strong low frequency oscillations in PMC/retrosplenial cortex (RSP)
Figure S29C and S29D; Results, Brain-wide activity screen during emergence of affect in miceHow it will be judged
Method from the Methods (Example-session unsupervised clustering and spectral analysis) and analysis.py plot_session_rastermap. Welch power spectra (nperseg 2048, 100 Hz) of each unit's z-scored rate, z-scored across frequency, over 0 to 7.5 Hz (the plotted range). The paper gives the windows only as "the given 1 minute windows" of an example; the readings are the minute before infusion against (a) the minute starting 5 min after it and (b) the minute starting 10 min after it. The peak of the z-scored spectrum below 7.5 Hz, averaged per region. Reproduced when, under both, it rises after ketamine in RSP units in most sessions that record RSP and RSP has the largest rise of all regions with at least 30 units in the pooled data. The paper reports no test.
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