Table 2

Statistical table indicating the results of all analyses

NoFig.Description*StatisticsPower
EPM test
 aa 3A Open arm #CRS group (n = 24/timepoint)Paired median difference= –1.0
p = 0.0
–1.0, –1.0
baseline = 0.88 ± 0.18
restraint = 0.32 ± 0.13
 abHealthy group (n = 8/timepoint)Paired median difference= –1.0
p = 0.246
–1.0, –1.0
baseline = 1.75 ± 0.62
restraint = 0.38 ± 0.26
 acOpen arm timeCRS group (n = 24/timepoint)Paired median difference= –1.5
p = 0.15
–8.0, 0.0
baseline = 5.79 ± 1.43 s
restraint = 2.52 ± 1.15 s
 adHealthy group (n = 6/timepoint)Paired median difference= –3.0
p = 0.38
–24.0, 0.0
baseline = 6.83 ± 3.89 s
restraint = 2.63 ± 2.01 s
 ae 3B Closed arm #CRS group (n = 24/timepoint)Paired Cohen’s d = 0.462
p = 0.0282
–0.0122, 0.856
baseline = 5.63 ± 0.66
restraint = 7.20 ± 0.74
 afHealthy group (n = 8/timepoint)Paired Cohen’s d = 0.114
p = 0.639
–0.647, 0.51
baseline = 8.00 ± 1.72
restraint = 8.63 ± 2.13
 agClosed arm timeCRS group (n = 24/timepoint)Paired Cohen’s d = 0.212
p = 0.47
–0.415, 0.777
baseline = 220.83 ± 9.06 s
restraint = 230.60 ± 7.81 s
 ahHealthy group (n = 8/timepoint)Paired Cohen’s d = 0.056
p = 0.888
–0.848, 0.851
baseline = 221.75 ± 12.82 s
restraint = 224.13 ± 16.89 s
 ai 3C Grooming #CRS group (n = 24/timepoint)Paired Cohen’s d = –0.921
p = 0.001
–1.41, –0.357
baseline = 4.63 ± 0.64
restraint = 2.28 ± 0.31
 ajHealthy group (n = 8/timepoint)Paired Cohen’s d = 0.232
p = 0.464
–0.511, 1.17
baseline = 3.00 ± 1.10
restraint = 3.63 ± 0.78
 akGrooming timeCRS group (n = 23/timepoint)Paired Cohen’s d = –0.642
p = 0.0016
–1.09, –0.185
baseline = 24.70 ± 3.93 s
restraint = 14.48 ± 3.30 s
 alHealthy group (n = 8/timepoint)Paired Cohen’s d = –0.326
p = 0.411
–1.11, 0.352
baseline = 24.63 ± 9.89 s
restraint = 17.75 ± 3.70 s
 am 3D Rearing #CRS group (n = 23/timepoint)Paired Cohen’s d = –0.2
p = 0.422
–0.732, 0.327
baseline = 17.79 ± 0.86
restraint = 16.92 ± 1.14
 anHealthy group (n = 7/timepoint)Paired Cohen’s d = 0.533
p = 0.19
–0.852, 1.13
baseline = 16.14 ± 1.52
restraint = 17.38 ± 1.82
 aoRearing timeCRS group (n = 24/timepoint)Paired Cohen’s d = 0.187
p = 0.501
–0.364, 0.73
baseline = 41.38 ± 1.72 s
restraint = 44.36 ± 3.36 s
 apHealthy group (n = 8/timepoint)Paired Cohen’s d = 0.117
p = 0.618
–0.639, 0.552
baseline = 41.88 ± 5.43 s
restraint = 43.38 ± 3.42 s
SPT
 aqCRS group (n = 25/timepoint)Paired Cohen’s d = 0.289
p = 0.312
–0.294, 0.889
baseline = 0.63 ± 0.03
restraint = 0.69 ± 0.04
 arHealthy group (n = 5/timepoint)Paired Cohen’s d = –0.191
p = 0.807
–1.52, 0.831
baseline = 0.81 ± 0.03
restraint = 0.78 ± 0.07
FST
 as 4A Total
activity
CRS group (n = 19/timepoint)Paired Cohen’s d = –0.62
p = 0.0414
–1.19, –0.0902
baseline = 42 ± 2
restraint = 37 ± 1
 atHealthy group (n = 8/timepoint)Paired Cohen’s d = –0.726
p = 0.22
–1.91, 0.489
baseline = 45 ± 3
restraint = 40 ± 2
 au 4B SwimmingCRS group (n = 19/timepoint)Paired Cohen’s d = 0.0269
p = 0.896
–0.526, 0.489
baseline = 26 ± 2
restraint = 26 ± 2
 avHealthy group (n = 8/timepoint)Paired Cohen’s d = 0.0
p = 0.969
–1.54, 1.17
baseline = 30 ± 3
restraint = 30 ± 4
 awClimbingCRS group (n = 19/timepoint)Paired Cohen’s d = –0.696
p = 0.021
–1.22, –0.202
baseline = 16 ± 2
restraint = 11 ± 1
 axHealthy group (n = 8/timepoint)Paired Cohen’s d = –0.8
p = 0.12
–1.92, 0.327
baseline = 15 ± 2
restraint = 10 ± 2
 ay 4C ImmobilityCRS group (n = 19/timepoint)Paired Cohen’s d = 0.611
p = 0.0438
0.0902, 1.19
baseline = 18 ± 2
restraint = 23 ± 1
 azHealthy group (n = 8/timepoint)Paired Cohen’s d = 0.726
p = 0.22
0.0902, 1.19
baseline = 15 ± 3
restraint = 20 ± 2
 baLatencyCRS group (n = 19/timepoint)Paired Cohen’s d = –1.34
p = 0.0006
–2.03, –0.578
baseline = 119 ± 9 s
restraint = 71 ± 7 s
 bbHealthy group (n = 8/timepoint)Paired Cohen’s d = –0.0967
p = 0.92
–1.59, 1.21
baseline = 101 ± 32
restraint = 95 ± 16
rs-fMRI
 bc 5A,B ICA/dual regressionCRS group with all restraint data [baseline: n = 11 from current cohort and n = 22from Seewoo et al. (2019); restraint: n = 15]Dual regression
p < 0.05
 bdCRS group with restraint data based on FST findings [baseline: n = 11 from currentcohort and n = 22 from Seewoo et al. (2019); restraint: n = 9]Dual regression
p < 0.05
 be 5C Salience network
CRS group (baseline: n = 9 from current cohort; restraint: n = 15)
Unpaired Cohen’s d = –2.33
p = 0.0
–3.2, –1.29
baseline = 36 ± 3
restraint = 19 ± 1
 bfSalience network
Healthy group (baseline: n = 5 from current cohort; restraint: n = 8)
Unpaired Cohen’s d = –0.208
p = 0.718
–1.68, 0.93
baseline = 29 ± 5
restraint = 27 ± 4
 bg 5D Interoceptive network
CRS group (baseline: n = 9 from current cohort; restraint: n = 15)
Unpaired Cohen’s d = –1.38
p = 0.0032
–2.13, –0.574
baseline = 39 ± 5
restraint = 23 ± 2
 bhInteroceptive network
Healthy group (baseline: n = 5 from current cohort; restraint: n = 8)
Unpaired Cohen’s d = –0.539
p = 0.374
–1.47, 0.685
baseline = 27 ± 2
restraint = 22 ± 4
 bi 6A Seed-based analysisCRS group with all restraint data [baseline: n = 11 from current cohort and n = 22from Seewoo et al. (2019); restraint: n = 15]Higher-level FEAT
p < 0.05, z > 2
 bj 6B CRS group (baseline: n = 9 from current cohort; restraint: n = 15)Unpaired Cohen’s d = 1.51
p = 0.0018
0.712, 2.18
baseline = 0.13 ± 0.02
restraint = 0.29 ± 0.03
 bkHealthy group (baseline: n = 5 from current cohort; restraint: n = 8)Unpaired Cohen’s d = 0.752
p = 0.214
–0.318, 1.74
baseline = 0.15 ± 0.03
restraint = 0.24 ± 0.05
Proton magnetic resonance spectroscopy
 bl 7C GlnCRS group (n = 17/timepoint)Paired Cohen’s d = –0.538
p = 0.027
–1.19, –0.0217
baseline: 0.53 ± 0.01
restraint: 0.50 ± 0.01
 bmHealthy group (n = 8/timepoint)Paired Cohen’s d = 0.743
p = 0.174
–0.127, 1.95
baseline = 0.50 ± 0.02
restraint = 0.54 ± 0.02
 bn 7D GluCRS group (n = 17/timepoint)Paired Cohen’s d = –0.711
p = 0.0706
–1.46, 0.134
baseline: 1.41 ± 0.02
restraint: 1.35 ± 0.02
 boHealthy group (n = 6/timepoint)Paired Cohen’s d = –1.1
p = 0.121
–2.15, –0.122
baseline = 1.48 ± 0.04
restraint = 1.37 ± 0.04
 bp 7E Gln + Glu
(Glx)
CRS group (n = 17/timepoint)Paired Cohen’s d = –0.84
p = 0.0186
–1.49, –0.115
baseline: 1.94 ± 0.02
restraint: 1.85 ± 0.03
 bqHealthy group (n = 7/timepoint)Paired Cohen’s d = –0.41
p = 0.529
–1.83, 1.12
baseline = 1.97 ± 0.04
restraint = 1.92 ± 0.05
 brGABACRS group (n = 16/timepoint)Paired Cohen’s d = –0.137
p = 0.74
–0.959, 0.632
baseline: 0.35 ± 0.01
restraint: 0.34 ± 0.01
 bsHealthy group (n = 8/timepoint)Paired Cohen’s d = –0.558
p = 0.378
–1.82, 0.926
baseline = 0.37 ± 0.02
restraint = 0.34 ± 0.02
 btGln/GluCRS group (n = 17/timepoint)Paired Cohen’s d = –0.171
p = 0.552
–0.767, 0.275
baseline = 0.38 ± 0.01
restraint = 0.37 ± 0.01
 buHealthy group (n = 6/timepoint)Paired Cohen’s d = 1.15
p = 0.0632
0.45, 2.51
baseline = 0.35 ± 0.02
restraint = 0.41 ± 0.02
Animal weight and whole-brain volume
 bv 8A Spearman’s rank correlation rho because baseline weights were not normally distributed [n = 33 fromcurrent cohort, n = 41 from Seewoo et al. (2019) and our unpublished data]S = 28632
p = 7.909e-08
r = 0.58
Mean whole-brain volume to weight ratio = 6.64 ± 0.16 mm3/g
Hippocampal volume
 bw 8B CRS group (n = 18/timepoint)Paired Cohen’s d = –0.811
p = 0.0032
–1.33, –0.318
baseline: 5.88 ± 0.01
restraint: 5.85 ± 0.01
 bxHealthy group (n = 8/timepoint)Paired Cohen’s d = –0.409
p = 0.327
–1.64, 0.467
baseline = 5.87 ± 0.01
restraint = 5.85 ± 0.02
Correlations
 by 9A Latency and salience network functional connectivity (not normal; Spearman’s rank correlationrho; n = 35)R = 0.180
S = 5853.7
p = 0.3004
padj = 0.4440
 bz 9B Latency and interoceptive network functional connectivity (not normal; Spearman’s rank correlationrho; n = 35)R = 0.312
S = 4909.9
p = 0.0678
padj = 0.3627
 ca 9C Salience and interoceptive network functional connectivity (not normal; Spearman’s rank correlationrho; n = 37)R = 0.595
S = 3414
p = 0.0001
padj = 0.0017
 cb 9D Latency and cingulate cortex functional connectivity (not normal; Spearman’s rank correlationrho; n = 35)R = –0.484
S = 10597
p = 0.0032
padj = 0.0320
 cc 9E Cingulate cortex and salience network functional connectivity (not normal; Spearman’s rankcorrelation rho; n = 37)R = –0.560
S = 13158
p = 0.0004
padj = 0.0044
 cd  9F Cingulate cortex and interoceptive network functional connectivity (not normal; Spearman’srank correlation rho; n = 37)R = –0.402
S = 11828
p = 0.0142
padj = 0.1137
 ce 9G Latency and Glx/tCr (latency not normal; Spearman’s rank correlation rho; n = 51)R = 0.180
S = 18116
p = 0.2055
padj = 0.4440
 cf 9H Latency and hippocampal volume (latency not normal; Spearman’s rank correlation rho; n = 52)R = 0.262
S = 17285
p = 0.0605
padj = 0.3627
 cg 9I Postrestraint latency and baseline hippocampal volume of CRS group (normal; Pearson’s product-moment correlation; n = 23)R = 0.311
t(21) = 1.50
p = 0.1480
padj = 0.4440
–0.116, 0.641
 ch 9J Hippocampal volume and salience network functional connectivity (salience network functionalconnectivity not normal; Spearman’s rank correlation rho; n = 36)R = 0.341
S = 5124
p = 0.0427
padj = 0.2990
 ci 9K Hippocampal volume and interoceptive network functional connectivity (interoceptive networkfunctional connectivity not normal; Spearman’s rank correlation rho; n = 36)R = 0.299
S = 5444
p = 0.0764
padj = 0.3627
 cj 9L Hippocampal volume and cingulate cortex functional connectivity (cingulate cortex functionalconnectivity not normal; Spearman’s rank correlation rho; n = 36)R = –0.431
S = 11122
p = 0.0091
padj = 0.0822
  • Each analysis includes a letter indicator linking the test in the table to the analysis in the text. The link to the corresponding figure, if any, is indicated under Fig. The estimation statistics, critical value, degrees of freedom, and exact p values are listed for each test under statistics, and the CIs of the tests and mean ± SE are under power.

  • * Number of animals are different between groups and among tests because (1) one animal fell off the open arm during baseline EPM testing and baseline and postrestraint EPM data from this animal was excluded from the analyses; (2) FST trials during which the animals managed to escape more than once or were floating horizontally for the duration of the test (with most of their body being completely dry at the end) were excluded from the analyses; (3) sessions during which the CRLB of a metabolite of interest was greater than 20% in the 1H-MRS data were excluded from the analyses; (4) not all animals were imaged at baseline and following restraint because of limited access to the MRI instrument and time taken to scan each animal (∼1.5 h per animal); and (5) animals with variable physiology (e.g., rapidly increasing/decreasing breathing rates) during rs-fMRI scans were excluded from the analyses.