Table 1 Details of all 70 (68 + 2 corresponding to 2 search periods) studies included in the systematic review.

From: Neural correlates of co-occurring pain and depression: an activation-likelihood estimation (ALE) meta-analysis and systematic review

Refs.	N	Age (year)	Pain type	Pain severity	Dep type	Dep severity	Disease duration (month)	Medication	Comparison type	Direction of effects	Brain region	Neuroimaging	ALE
Details of 68 studies (inception to August 2020 search) included in the systematic review
Adler-Neal 2019 [74]	HC = 76	HC = 27	Exp.	HC = Moderate	Trait	HC = Minimal	NA	Exc	Pain/Dep	Pos Moderation between dep & pain	S2 Operculum Insula OFC VLPFC	task-fMRI	N
Albrecht 2019 [75]	P = 25 HC = 27	P = 42 HC = 49	CBP	P = Mild HC = None	Trait	P = Minimal HC = Minimal	P = 6 D = NA	NR	Pain corr dep	Pos	ACC DLPFC	rs-fMRI	Y
Apkarian 2004 [76]	P = 26 HC = 26	P = 43 HC = 43	CBP	P = Moderate HC = NR	Trait	P = Mild HC = NR	P = 136 D = NA	NR	Pain corr dep	ns	ns	MRI	N
As-Sanie 2016 [41]	P = 36 HC = 37	P = 31 HC = 29	CPP	P = Moderate HC = Minimal	Trait	P = Mild HC = NR	P = 6 D = NA	Inc	Pain corr dep	Pos	Insula MPFC	rs-fMRI	Y
Bär 2007 [47]	D = 13 HC = 13	D = 36 HC = 34	Exp.	P = threshold at 44 °C HC = threshold at 41 °C	Trait	D = Moderate HC = Minimal	P = NA D = 97	Exc	Dep v HC	Dep > HC	L thalamus	task-fMRI	Y^a
Berna 2010⁵³	HC = 20	HC = 28	Exp.	P = Moderate HC = Moderate	Exp.	HC = Minimal	NA	NR	Dep v HC	Dep > HC Dep < HC	Superior parietal lobe Precuneus Supramarginal gyrus IFG S2 DLPFC ACC OFC Temporal gyrus Insula Hippocampus Thalamus Caudate Occipital Intraparietal sulcus Temporal gyrus B S1 Precuneus	task-fMRI	Y^a,b
Bilek 2019 [77]	D = 37 HC = 33	D = 34 HC = 26	Exp.	D = Moderate HC = Moderate	Dx	D = NR HC = NR	P = NA D = NR	NR	Dep corr pain	Dep < HC	Frontal, temporal and occipital network	task-fMRI	N
Cifre 2012 [78]	P = 9 HC = 11	P = 52 HC = 49	FM	P = Severe HC = NR	Trait	P = Severe HC = Minimal	P = 322 D = NA	Inc	Pain v HC	Pain < HC	R Thalamus^a R PAG L ACC^a L PAG	rs-fMRI	Y
Coulombe 2017 [79]	P = 23 HC = 16	P = 51 HC = 50	FM	P = Moderate HC = NR	Trait	P = Minimal HC = NR	P = NR D = NA	Exc	Pain v HC	ns	ns	rs-fMRI	N
Diaz-Piedra 2016 [33]	P = 23 HC = 23	P = 42 HC = 40	FM	P = Moderate HC = Minimal	Trait	P = Moderate HC = Minimal	P = 103 D = NA	Inc	Pain v HC	ns	ns	MRI	N
Fan 2020 [27]	P = 42 HC = 35	P = 30 HC = 31	CD	P = Minimal HC = NR	Trait	P = Minimal HC = NR	P = 59 D = NA	NR	Pain corr dep	ns	ns	rs-fMRI	N
Feliu-Soler 2020 [48]	P = 47	P = 52	FM	P = Moderate	Trait	P = Mild	P = 145 D = 20 episodes	Inc	Pain corr dep	Pos	Bed nucleus of the stria terminalis	MRI	Y
Giesecke 2005 [35]	P = 53 HC = 42	P = 42 HC = 38	FM	P = Moderate HC = None	Trait	P = Mild HC = Minimal	P = NR D = NA	Exc	Pain corr dep	Neg	Insula B amygdala	task-fMRI	Y^a
Grachev 2003 [43]	P + D = 10 HC = 10	P + D = 29 HC = 48	CBP	P + D = Moderate HC = NR	Trait	P + D = Mild HC = Minimal	P = 151 D = 114	Exc	Pain v HC	Pain < HC	R DLPFC	MRS	N
Guedj 2008 [80]	P = 20 HC = 10	P = 48 HC = 52	FM	P = Severe HC = None	Trait	P = Moderate HC = Minimal	P = NR D = NA	NR	Pain corr dep	ns	ns	SPECT	N
Gustin 2013 [39]	P = 42 HC = 35	P = 49 HC = 50	NeuP	P = Mild HC = NR	Trait	P = Mild HC = Minimal	P = 144 D = NA	NR	Pain corr dep	Neg (state dep) Pos (state dep) Neg (trait dep) Pos (trait dep)	B thalamus ACC DLPFC PCC B hippocampus B thalamus DLPFC PCC Insula B hippocampus	MRI	N
Harfeldt 2018 [28]	P = 36 HC = 10	P = 42 HC = 36	NeuP	P = Moderate HC = None	Trait	P = Moderate HC = Minimal	P = NR D = NA	Exc	Pain corr dep	ns	ns	MRS	N
Icenhour 2019 [81]	P = 64 HC = 32	P = 30 HC = 33	IBS	P = Moderate HC = Minimal	Trait	P = Minimal HC = Minimal	P = NR D = NA	NR	Pain corr dep	ns	ns	MRS	N
Ikeda 2018 [82]	P = 23 HC = 17	P = 48 HC = 42	Unspecified CP	P = Moderate HC = None	Trait	P = Mild HC = Minimal	P = 103 D = NA	NR	Pain corr dep	Neg	R insula^a L nucleus accumbens	rs-fMRI	Y
Ivo 2013 [83]	P = 14 HC = 14	P = 54 HC = NR	CBP	P = Severe HC = NR	Trait	P = Moderate HC = Minimal	P = 120 D = NA	NR	Pain v HC	ns	ns	MRI	N
Jensen 2013 [84]	P = 26 HC = 13	P = 38 HC = 34	FM	P = Moderate HC = NR	Trait	P = Moderate HC = NR	P = 132 D = NA	Exc	Pain corr dep	Neg	R percalcarine R fusiform R occipital L inferior parietal L caudal middle frontal L precuneus L fusiform L supra marginal	task-fMRI	Y^a
Jin 2017 [85]	P = 33 HC = 32	P = 22 HC = 22	PD	P = Moderate HC = Minimal	Trait	P = Minimal HC = Minimal	P = 78 D = NA	NR	Pain corr dep	ns	ns	rs-fMRI	N
Kameda 2018 [86]	P = 34 HC = 56	P = 59 HC = 40	CBP	P = Moderate HC = NR	Trait	P = Minimal HC = NR	P = NR D = NA	Inc	Pain corr dep	Neg	ACC	MRS	N
Ke 2015 [87]	P = 31 HC = 32	P = 29 HC = 28	IBS	P = Moderate HC = NR	Trait	P = Minimal HC = Minimal	P = 33 D = NA	NR	Pain corr dep	ns	ns	rs-fMRI	N
Khan 2014 [36]	P = 9 HC = 9	P = 54 HC = 56	BMS	P = Minimal HC = NR	Trait	P = Minimal HC = Minimal	P = 48 D = NA	Exc	Pain corr dep Pain v HC	Pos Pain > HC	L MPFC^a R hippocampus L MPFC^a R Hippocampus	rs-fMRI	Y
Kim 2015 [40]	P = 42 HC = 63	P = 45 HC = 43	FM	P = Moderate HC = NR	Trait	P = Mild HC = Minimal	P = 167 D = NA	NR	Pain corr dep	Pos	Orbital frontal gyrus Gyrus rectus Superior medial frontal gyrus L lingual gyrus B supramarginal gyrus Fusiform gyrus B medial temporal lobe R inferior parietal	MRI	N
Klega & Eberle 2010 [88]	P = 10 HC = 10	P = 46 HC = NR	CRPS	P = Mild HC = None	Trait	P = Minimal HC = NR	P = 4 D = NA	NR	Pain corr dep	Pos	Temporal cortex	PET	Y
Ledermann 2016 [89]	P + D = 11 P = 13 HC = 17	P + D = 55 P = 45 HC = 43	FM	P + D = Mild P = Mild HC = Minimal	Trait	P + D = Mild P = Minimal HC = Minimal	P = 162 D = NA	Inc	Pain/Dep	P-D > P	L ventral striatum	PET	N
Lee 2015 [90]	P = 24 HC = 25	P = 36 HC = 32	CRPS	P = NR HC = NR	Trait	P = Moderate HC = Minimal	P = 34 D = NA	Inc	Pain v HC	ns	ns	MRI	N
J. Li 2020 [44]	P + D = 28 P = 21 HC = 36	P + D = 36 P = 32 HC = 32	IBS	P + D = Mild P = Minimal HC = NR	Trait	P + D = Mild P = Minimal HC = Minimal	P + D = 21 P = 19	Exc	Pain/Dep Pain v HC	P-D < P Pain < HC	B MFG L IFG L SFG L Insula L IFG	MRI	Y
H. Li 2020 [91]	P = 24 HC = 23	P = 64 HC = 61	NeuP	P = Moderate HC = None	Trait	P = Minimal HC = Minimal	P = 22 D = NA	NR	Pain corr dep	Neg	PAG^a S1	rs-fMRI	N
Lirng 2015 [92]	P + D = 16 P = 14	P + D = 41 P = 40	H/M	P + D = Severe P = Moderate	Trait	P + D = Moderate P = Minimal	P = 200 (P + D) P = 154 (P) D = NA (P + D) D = NA (P)	Inc	Pain/Dep	P-D > P	R DLPFC	MRS	N
P. Liu 2013 [93]	P = 49 HC = 39	P = 22 HC = 22	FD	P = Minimal HC = Minimal	Trait	P = Minimal HC = Minimal	P = 36 D = NA	Exc	Pain corr dep	ns	ns	rs-fMRI	N
B-L. Liu 2015 [94]	P = 29 HC = 10	P = 54 HC = 52	BMS	P = Mild HC = NR	Trait	P = Minimal HC = Minimal	P = 10 D = NA	NR	Pain/Dep Pain v HC	P-D < P Pain < HC	L Parietal L Temporal L Parieto-occipital lobe	SPECT	N
P. Liu 2017 [25]	P = 66 HC = 42	P = 23 HC = 23	FD	P = NR HC = NR	Trait	P = Minimal HC = Minimal	P = 35 D = NA	NR	Pain/Dep	ns	ns	rs-fMRI	N
P. Liu, Li, 2018 [26]	P = 43 HC = 37	P = 32 HC = 31	CD	P = NR HC = NR	Trait	P = Minimal HC = Minimal	P = 80 D = NA	NR	Pain/dep	ns	ns	rs-fMRI	N
P. Liu, Wang 2018 [95]	P = 69 HC = 49	P = 23 HC = 23	FD	P = Minimal HC = NR	Trait	P = Minimal HC = Minimal	P = NR D = NA	Exc	Pain corr dep	ns	ns	MRI	N
Q. Liu 2019 [34]	P = 21 HC = 17	P = 43 HC = 43	PSPD	P = Moderate HC = NR	Trait	P = Moderate HC = Minimal	P = 42 D = NA	Exc	Pain v HC	ns	ns	SPECT	N
López-Solà 2017 [96]	P = 37 HC = 35	P = 46 HC = 44	FM	P = Moderate HC = NR	Trait	P = Mild HC = NR	P = 80 D = NA	Inc	Pain corr dep	Pos	ACC Precuneus	task-fMRI	N
Luo 2016 [97]	P = 12 HC = 10	P = 46 HC = 35	PSPD	P = Moderate HC = None	Trait	P = Minimal HC = Minimal	P = 6 D = NA	Exc	Pain/Dep	P-D > D	L Fusiform gyrus B DLPFC L VLPFC MPFC	task-fMRI	N
Ma 2018 [98]	P + D = 10 P = 22 HC = 27	P + D = 28 P = 34 HC = 30	H/M	P = Severe HC = NR	Trait	P + D = Moderate P = Minimal HC = Minimal	P = 86 (P + D) P = 118 (P) D = NA (P + D) D = NA (P)	NR	Pain/Dep	P-D < P P-D > P	Thalamus Fusiform	rs-fMRI	Y
Malejko 2021 [45]	D = 22 HC = 25	D = 23 HC = 20	Exp.	Not compared	Dx	D = Severe HC = Minimal	P = NA D = NA	Inc	Dep corr pain	Neg	R S1	task-fMRI	Y^a
Mao & Yang 2015 [99]	P = 33 HC = 33	P = 51 HC = 51	CBP	P = Moderate HC = NR	Trait	P = Minimal HC = Minimal	P = 114 D = NA	Exc	Pain corr dep	ns	ns	MRI	N
Mountz 1995 [100]	P = 10	P = 44	FM	P = Mild	Trait	P = Mild	P = NR D = NA	Exc	Pain corr dep	ns	ns	SPECT	N
Nees 2019 [101]	P = 39 HC = 30	P = 45 HC = 41	CBP	P = Mild HC = Minimal	Trait	P = Mild HC = Minimal	P = 104 D = NA	Inc	Pain corr dep	ns	ns	Cortisol	N
Niddam 2018 [102]	P = 49 HC = 25	P = 35 HC = 33	H/M	P = Moderate HC = NR	Trait	P = Minimal HC = Minimal	P = 160 D = NA	Exc	Pain corr dep	Neg	ACC	MRS	N
Otti 2013 [103]	P = 21 HC = 19	P = 47 HC = 49	SomP	P = Moderate HC = NR	Trait	P = Mild HC = Minimal	P = NR D = NA	Inc	Pain corr dep	ns	ns	rs-fMRI	N
Qi 2016 [29]	P = 65 HC = 67	P = 34 HC = 31	IBS	P = Mild HC = NR	Trait	P = Minimal HC = Minimal	P = 42 D = NA	Exc	Pain corr dep	ns	ns	rs-fMRI	N
Robinson 2011 [104]	P = 14 HC = 11	P = 43 HC = 42	FM	P = MildHC = NR	Trait	P = Minimal HC = Minimal	P = NR D = NA	NR	Pain corr dep	ns	ns	MRI	N
Rosenberger 2013 [105]	P = 15 HC = 12	P = 42 HC = 31	IBS	P = Moderate HC = Mild	Trait	P = Minimal HC = Minimal	P = 12 D = NA	Exc	Pain corr dep	Pos	Cerebellum	task-fMRI	Y^a
Schweinhardt 2008 [42]	P = 20	P = 57	RA	P = Moderate	Trait	P = Minimal	P = NR D = NA	Exc	Pain corr dep	Pos	MPFC	task-fMRI	Y^a
Seifert 2011 [106]	P = 13	P = 44	H/M	P = Mild HC = NR	Trait	P = Mild	P = 2 D = NA	Inc	Pain corr dep	Pos	Insula	rs-fMRI	Y
Smit 2018 [30]	P = 14 HC = 12	P = 56 HC = 53	Cervical dystonia	P = Mild HC = NR	Trait	P = Minimal HC = Minimal	P = 144 D = NA	Exc	Pain corr dep	ns	ns	PET	N
Strigo 2008 [46]	D = 15 HC = 15	D = 25 HC = 24	Exp.	P = NR HC = NR	Dx	D = Moderate HC = NR	P = NA D = NA	Exc	Dep corr pain	Dep > HC Dep < HC	R amygdala L parahippocampal gyrus Visual cortexR ACC R DLPFC L DLPFC L SFG L MTG L precuneus R PAG R brainstem	task-fMRI	Y^a
Tan 2019 [31]	P = 26 HC = 27	P = 52 HC = 51	BMS	P = MildHC = NR	Trait	P = Minimal HC = Minimal	P = 9 D = NA	NR	Pain corr dep	ns	ns	MRI	N
Truini 2016 [107]	P = 20 HC = 15	P = 28–67 range HC = 26–65 range	FM	P = Moderate HC = NR	Trait	P = Minimal HC = NR	P = 93 D = NA	Exc	Pain corr dep	Neg	PAG^a Opercular cortex SFG Supramarginal gyrus	rs-fMRI	N
Vachon-Presseau 2016 [37]	P = 69 HC = 20	P = 43 HC = 37	BP	P = Moderate HC = NR	Trait	P = Minimal HC = NR	P = NR D = NR	Inc	Pain corr dep	Pos	Amygdala Nucleus accumbens MPFC	rs-fMRI	Y
Valdes 2010 [108]	P = 28 HC = 24	P = 43 HC = 44	FM	P = Moderate HC = NR	Trait	P = Mild HC = Minimal	P = 151 D = NA	NR	Pain corr dep	ns	ns	MRS	N
van Ettinger-Veenstra 2019 [109]	P = 38 HC = 37	P = 46 HC = 51	Unspecified CP	P = Moderate HC = None	Trait	P = Mild HC = Minimal	P = NR D = NA	Inc	Pain corr dep	ns	ns	rs-fMRI	N
Wagner 2009 [110]	HC = 40	HC = 25	Exp.	HC = Pain sensitivity +	Exp.	HC = NR	P = NA D = NA	NR	Pain/Dep	P-D > P	B Thalamus	task-fMRI	Y^a,b
Y. Wang 2017 [111]	P = 38 HC = 38	P = 56 HC = 56	NeuP	P = NR HC = NR	Trait	P = Minimal HC = Minimal	P = 85 D = NA	Exc	Pain corr dep	Neg	Insula^a ACC	rs-fMRI	Y
D. Wang 2017 [32]	P = 31 HC = 30	P = 44 HC = 43	IBS	P = Moderate HC = NR	Trait	P = Minimal HC = Minimal	P = 88 D = NA	NR	Pain corr dep	ns	ns	task-fMRI	N
Wingenfeld 2010 [112]	P = 21 HC = 26	P = 33 HC = 35	CPP	P = Minimal HC = Minimal	Trait	P = Mild HC = NR	P = 21 D = NA	Inc	Pain/Dep	P-D < P	HPA	Cortisol	N
Woldeamanuel 2019 [113]	P = 30 HC = 30	P = 40 HC = 40	H/M	P = Moderate HC = NR	Trait	P = Mild HC = Minimal	P = 312 D = NA	Inc	Pain corr dep	ns	ns	MRI	N
Q. Yang 2017 [114]	P = 49 HC = 49	P = 51 HC = 55	H/M, CBP	P = Moderate HC = NR	Trait	P = Minimal HC = Minimal	P = 168 D = NA	Inc	Pain corr dep	ns	ns	rs-fMRI	N
Yu 2013 [115]	P = 40 HC = 40	P = 36 HC = 33	H/M	P = Moderate HC = NR	Trait	P = Moderate HC = Minimal	P = 130 D = NA	Exc	Pain/Dep	P-D < P	Caudate	rs-fMRI	N
Zhang 2018 [38]	P = 29 HC = 34	P = 48 HC = 43	NeuP	P = Moderate HC = NR	Trait	P = Minimal HC = None	P = 72 D = NA	Exc	Pain corr dep	Pos	R amygdala^a Medial frontal gyrus	rs-fMRI	N
Zunhammer 2016 [116]	HC = 39	HC = 26	Exp.	HC = Pain sensitivity +	Trait	HC = Minimal	P = NA D = NA	Inc	Pain corr dep	Pos	ACC Insula	MRS	N
Details of 2 additional studies (3 analyses) (August 2020–September 2021 search) included in the systematic review
Hou 2021 [117]	HC = 25 P + D = 17 D = 19	HC = 23 P + D = 23 D = 22	Exp.	HC = Moderate P + D = Moderate D = Moderate	Dx	HC = Normal P + D = Moderate D = Moderate	P + D (D) = 17 D (D) = 14	Exc	Dep v HC Pain/Dep	D < HC P-D > D	L Rolandic operculum R temporal lobe R fusiform gyrus R insula L PCG L parietal inferior gyrus L temporal lobe	task-fMRI	Y^a
Kim 2020 [118]	HC = 18 P = 28	HC = 46 P = 41	Chronic musculoskeletal + FM	HC = Normal P = Mild	Trait	HC = Normal D = Normal-mild	P = NR D = NR	NR	Pain/Dep v HC	ns	ns	task-fMRI, PET	N

BMS Burning mouth syndrome, BP Back pain, CBP Chronic back pain, CD Crohn’s disease, CPP Chronic pelvic pain, CRPS Complex regional pain syndrome, D Depression sample, Dx Diagnosis, Exc Excluded at time of study, Exp Experimentally induced, FD Functional dyspepsia, FM Fibromyalgia, H/M Headache/migraine, HC Healthy control, Inc Included at time of study, IBS irritable bowel syndrome, NA Not applicable, NR Not reported, NeuP Neuropathic pain, P Pain sample, P + D Simultaneous pain and depression, PD Primary dysmenorrhea, PCG postcentral gyrus, PSPD Persistent somatic pain disorder, RA Rheumatoid arthritis, SomP Somatic pain disorder, Unspecified CP Unspecified chronic pain.
Comparison types:
Pain/Dep Simultaneous pain and depression comorbidity studies, Pain corr dep Pain correlated with concurrent depression, Pain v HC Pain contrasted with HC, with depression as covariate, Dep corr pain Depression correlated with concurrent pain, Dep v HC Depression contrasted with HC, with pain as covariate, or in pain-related brain activation; ns non-significant.
Neuroimaging:
task-fMRI task functional magnetic resonance imaging, PET positron emission tomography, MRI magnetic resonance imaging, SPECT single-photon emission computed tomography, MRS magnetic resonance spectroscopy, rs-fMRI resting-state functional magnetic resonance imaging.
ALE legends:
N Study not included in ALE analysis, Y Study included in ALE analysis, ^aExperimentally induced pain, ^bExperimentally induced depression/sad mood

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Table 1 Details of all 70 (68 + 2 corresponding to 2 search periods) studies included in the systematic review.

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