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"Pudendal Neuralgia" OR "Raynaud's Disease" OR "Restless Leg ... OR "Spinal Cord Injury" OR "Spinal Stenosis" OR " Syringomyelia" OR "Tarlov Cysts" OR.

SUPPLEMENTARY MATERIALS

Strategy used for literature search and data extraction from primary studies A. LITERATURE SEARCH STRATEGY

In order to identify relevant studies across the online Medline database we used a comprehensive PubMed literature search strategy (http://www.ncbi.nlm.nih.gov/pubmed) involving the following terms: “voxel-based morphometry" OR "VBM” and “chronic pain” OR each disorder listed by the American Chronic Pain Association as related to chronic pain. The SEARCH ALGORITHM was constructed as follows: ("voxel-based morphometry" [ALL] OR "VBM" [ALL]) AND (“chronic pain” OR # each disorder indicated by the American Chronic Pain Association (https://www.theacpa.org/conditions) as part of the spectrum of chronic pain [ALL]) ("voxel-based morphometry" [ALL] OR "VBM" [ALL]) AND ("Chronic Pain" OR "Addiction" OR "Advanced Prostate Cancer" OR "AIDS-Related Pain" OR "Ankylosing Spondylitis" OR "Arachnoiditis" OR "Arthritis" OR "Arthrofibrosis" OR "Ataxic Cerebral Palsy" OR "Autoimmune Diseases" OR "Avascular Necrosis" OR "Back Pain" OR "Breakthrough Pain" OR "Burning Mouth Syndrome" OR "Bursitis" OR "CADASIL" OR "Cancer Pain" OR "Carpal Tunnel" OR "Cauda Equina Syndrome" OR "Central Pain Syndrome" OR "Cerebral Palsy" OR "Cerebrospinal Fluid Leaks" OR "Cervical Stenosis" OR "Charcot-Marie-Tooth Disease" OR "Chronic Fatigue Syndrome" OR "Chronic Functional Abdominal Pain" OR "Chronic Pancreatitis" OR "Coccyx Collapsed Lung" OR "Complex Regional Pain Syndrome" OR "Corneal Neuropathic Pain" OR "Crohn's Disease" OR "Degenerative Disc Disease" OR "Dependence" OR "Dercum's Disease" OR "Dermatomyositis" OR "Diabetic Peripheral Neuropathy" OR "Dystonia" OR "Ehlers-Danlos Syndrome" OR "Endometriosis" OR "Erythromelalgia" OR "Failed Back Surgery Syndrome" OR "Fibromyalgia" OR "Gout Growing Pains" OR "Headaches" OR "Herniated disc" OR "Hydrocephalus" OR "Intercostal Neuraligia" OR "Interstitial Cystitis" OR "Irritable Bowel syndrome" OR "Juvenile Dermatomyositis" OR "Knee Injury" OR "Leg Pain" OR "Loin Pain-Haematuria Syndrome" OR "Lupus Lyme Disease" OR "Medullary Sponge Kidney" OR "Meralgia Paresthetica" OR "Migraine" OR "Mitochondrial Disorders" OR "Multiple Sclerosis" OR "Musculoskeletal pain" OR "Myofascial Pain" OR "Myositis" OR "Neck Pain" OR "Neuropathic Pain" OR "Occipital Neuralgia" OR "Osteoarthritis" OR "Paget's Disease" OR "Pelvic Pain" OR "Peripheral Neuropathy" OR "Phantom Limb Pain" OR "Pinched Nerve" OR "Polymyalgia Rheumatica" OR "Polymyositis" OR "Post Herniorraphy Pain Syndrome" OR "Post Mastectomy Pain Syndrome" OR "Post Stroke Pain" OR "Post Thorocotomy Pain Syndrome" OR "Postherpetic Neuralgia" OR "PostPolio Syndrome" OR "Post-Traumatic Stress Disorder" OR "Primary Lateral Sclerosis" OR "Psoriatic Arthritis" OR

"Pudendal Neuralgia" OR "Raynaud's Disease" OR "Restless Leg Syndrome" OR "Rheumatoid Arthritis" OR "Sacroiliac Joint Dysfunction" OR "Sarcoidosis" OR "Sciatica" OR "Scoliosis" OR "Shingles" OR "Herpes Zoster" OR "Sickle Cell" OR "Sjogren's Syndrome" OR "Sleep apnea" OR "Spasmodic Torticollis" OR "Sphincter of Oddi Dysfunction" OR "Spinal Cerebellum Ataxia" OR "Spinal Cord Injury" OR "Spinal Stenosis" OR " Syringomyelia" OR "Tarlov Cysts" OR "Thoracic Outlet Syndrome" OR "TMJ" OR "Tolerance" OR "Transverse Myelitis" OR "Trigeminal Neuralgia" OR "Ulcerative Colitis" OR "Vascular Pain" OR "Vulvodynia" OR "Whiplash"[ALL])

B. ASSESSMET OF ELIGIBILITY OF STUDIES

All the studies identified by our search strategy were assessed in order to ensure that they comply with our eligibility criteria. Studies were excludes if: a. they were non-original studies; b. the location of gray matter alterations was not reported in Talairach/Tournoux or in MNI coordinate space; c. the field of view was confined to a restricted region of the cortex (ROI analysis); d. they reported unspecified VBM analysis; e. they did not report the results of a comparison between chronic pain patients and healthy controls; f. they were published in languages other than English; g. they were not related to the clinical condition of interest (i.e., not chronic pain); h. they were not full publications; i. they were animal models; j. they have duplicated data or sample. The strategy used for the selection of studies is shown in Fig. S1 (PRISMA flow diagram).   C. EXTRACTING THE DATA FROM THE STUDIES

We used the BrainMap database in order to extract the coordinates from the original studies. The strategy used for the extraction of coordinates from the original studies is illustrated in Fig. S1 (PRISMA flow diagram).

Identification

Records identified through database searching (n = 322)

Additional records identified through other sources (n = 0)

Screening

Records after duplicates removed (n = 322)

Eligibility

Full-text articles assessed for eligibility (n = 118 )

Included

Records screened (n = 322)

Papers included in Meta-analysis (n = 51) (55 samples)

Records excluded (n = 204 )

Full-text articles excluded (n = 67 ) Not adhering to eligibility criteria

Extracting  the  coordinates

Are the studies included in BrainMap database?

YES 29 papers

NO 22 papers

Extract coordinates from BrainMap database in Talairach space

Extract coordinates from published studies and include them in BrainMap database  

Fig. S1 PRISMA (2009) flow diagram of paper selection and data extraction.

Table S1. Selected studies for the meta-analysis. PAPERS SELECTION Paper ID

Year

First author

1

2014

Pleger, B.

2

2013

Agostini, A.

3

2013

Barad, M.J.

4

2013

Ceko, M.

Fibromyalgia interacts with age to change the brain

5

2013

Fallon, N.

Structural alterations in brainstem of fibromyalgia syndrome patients correlate with sensitivity to mechanical pressure

6

2013

Ivo, R.

Brain structural and psychometric alterations in chronic low back pain

7

2013

Maeda, Y.

Altered brain morphometry in carpal tunnel syndrome is associated with median nerve pathology

8

2013

Martikainen, I.K.

Alterations in Endogenous Opioid Functional Measures in Chronic Back Pain

9

2013

Obermann, M.

10

2013

Prell, T.

11

2013

RodriguezRaecke, R.

12

2013

Yang, F.C.

13

2013

Yoon, E.J.

14

2012

As-Sanie, S.

15

2012

Mordasini, L.

16

2012

Riederer, F.

17

2012

Ung, H.

Multivariate Classification of Structural MRI Data Detects Chronic Low Back Pain

18

2011

Barnden, L.R.

A brain MRI study of chronic fatigue synfrome: evidence of brainsteam dysfunction and altered homeostasis

19

2011

Gerstner, G.

Changes in regional gray and white matter volume in patients with myiofascial-type temporomandibular disorders: a voxel-based morphometry study

20

2011

Gustin, S.M.

Different pain, different brain: thalamic anatomy in neuropathic and nonneuropathic chronic pain syndromes

21

2011

Pantano, P.

A transverse and longitudinal MR imaging voxel-based morphometry study in patients with primary cervical dystonia

22

2010

Gwilym, S.E.

23

2010

24

2010

25

2010

SchmidtWilcke, T Seminowicz, D.A. Tu, C.H.

26

2010

Younger, J.W.

27

2009

Obermann, M.

28

2009

RodriguezRaecke, R.

Paper Title Complex Regional Pain Syndrome Type I Affects Brain Structure in Prefrontal and Motor Cortex New insights into the brain involvement in patients with Crohn’s disease: a voxel-based morphometry study Complex Regional Pain Syndrome is associated with structural abnormalities in pain-related regions of the human brain

Gray matter volume reduction reflects chronic pain in trigeminal neuralgia Structural brain abnormalities in cervical dystonia Structural Brain Changes in Chronic Pain Reflect Probably Neither Damage Nor Atrophy Altered gray matter volume in the frontal pain modulation network in patients with cluster headache Cortical and white matter alterations in patients with neuropathic pain after spinal cord injury Changes in regional gray matter volume in women with chronic pelvic pain:A voxel-based morphometry study Chronic Pelvic Pain Syndrome in Men is Associated with Reduction of Relative Gray Matter Volume in the Anterior Cingulate Cortex Compared to Healthy Controls Grey matter changes associated with medication-overuse headache: Correlations with disease related disability and anxiety

Thalamic atrophy associated with painful osteoarthritis of the hip is reversible after arthroplasty Altered regional brain morphology in patients with chronic facial pain Regional gray matter density changes in brains of patients with irritable bowel syndrome Brain morphological changes associated with cyclic menstrual pain Chronic myofascial temporomandibular pain is associated with neural abnormalities in the trigeminal and limbic systems Gray matter changes related to chronic posttraumatic headache Brain gray matter decrease in chronic pain is the consequence and not the cause of pain

Journal PLOS ONE 9(1):e85372

Neurogastroenterol. Motil. 25, 147–e82 Journal of Pain, 15(2):197-203 NeuroImage Clin 3:249-60 NeuroImage Clin 3:163-70 Eur Spine J 22(9):1958-64 NeuroImage Clin 2:313-319 The Journal of Neuroscience 33(37):14729-37 NeuroImage 74:352-8 BMC Neuroscience 14:123 PLOS ONE 8(2):e54475 Pain 154(6):801-7 Brain Research 1540:64-73 Pain 153(5):100614 The Journal of Urology 188(6):2233-7 World J Biol Psychiatry. 13(7):517-25 Cerebral Cortex 24(4):1037-44 NMR in Biomedicine 24(10):1302-12 Journal of orofacial pain 25(2):99-106 The Journal of Neuroscience 31(16):5956-64 AJNR Am J Neuroradiol 32(1):81-4 Arthritis & Rheumatism 62(10):2930-40 Headache 50(8):1278-85. Gastroenterology 139(1):48-57.e2 Pain 150(3):462-8 Pain, 149(2):222-8. Neurology 73(12):978-83 The Journal of Neuroscience

29(44):13746-50

 

Patients with pain disorder show gray-matter loss in pain-processing structures: a voxel-based morphometric study

29

2009

Valet, M.

30

2009

Vartiainen, N.

31

2009

Wood, P.B.

32

2008

Buckalew, N.

33

2008

Davis, K.D.

34

2008

Geha, P.Y.

35

2008

Kim, J.H.

36

2008

Schweinhardt, P.

Increased gray matter density in young women with chronic vulvar pain

37

2008

Valfrè, W.

Voxel-based morphometry reveals gray matter abnormalities in migraine

38

2007

Kuchinad, A.

Accelered brain gray matter loss in fibromyalgia patients: prematur aging of the brain?

39

2007

Obermann, M.

Morphometric changes of sensorimotor structures in focal dystonia

40

2007

SchmidtWilcke, T.

41

2007

Unrath, A.

42

2006

Draganski, B.

43

2006

Etgen, T.

44

2006

Rocca, M.A.

45

2006

SchimdtWilcke, T.

46

2005

Etgen, T.

47

2005

SchimdtWilcke, T.

Gray matter decrease in patients with chronic tension type headache

48

2004

Apkarian, A.V.

Chronic back pain is associated with decreased prefrontal and thalamic gray matter density

49

2004

Garraux, G.

50

2004

Okada, T.

51

1999

May, A.

Changes in brain function and morphology in patients with recurring herpes simplex virus infections and chronic pain Changes in gray matter density in fibromyalgia: correlation with dopamine metabolism Chronic pain is associated with brain volume loss in older adults: preliminary evidence Cortical thinning in IBS: implications for homeostatic, attention, and pain processing The brain in chronic CRPS pain: abnormal gray-white matter interactions in emotional and automatic regions Regional gray matter density changes in patients with migraine: a voxelbased morphometry study

Striatal grey matter increase in patients suffering from fibromyalgia - a voxel-based morphometry study Cortical gray matter alterations in idiopathic restless legs syndrome: an optimized vocel-based morphometry study Decrease of thalamic gray matter following limb amputation Bilateral gray matter increase in the putamen in primary blepharospasm Bray gray matter changes in migraine patients with T2-visible lesions: a 3T MRI study Affective components and intensity of pain correlate with structural differences in gray matter in chronic back pain patients Bilateral thalamic gray matter change in patients with restless legs syndrome

Changes in brain anatomy in focal hand dystonia Mechanisms underlying fatigue: a voxel-based morphometric study of chronic fatigue syndrome Correlation between structural and functional changes in brain in an idiopathic headache syndrome

Psychosomatic Medicine 71(1):4956 Pain 144(1-2):200-8 The Journal of Pain 10(6):609-18 Pain Medicine 9(2):240-8 Neurology 70(2):153-4 Neuron 60(4):57081 Cephalalgia 28(6):598-604 Pain 140(3):411-9 Headache 48(1):109-17 The Journal of Neuroscience 27(15):4004-7 Movement Disorder 22(8):1117-23 Pain 132 Suppl 1:S109-16 Movement Disorder 22(12):1751-6 NeuroImage 31(3):951-7 J Neurol Neurosurg Psichiatry 77(9):1017-20 Stroke 37(7):176570 Pain 125(1-2):89-97 NeuroImage 24(4):1242-7 Neurology 65(9):1483-6 The Journal of Neuroscience 24(46):10410-5 Ann Neurol 55(5):736-9 BMC Neurology 4(1):14 Nature Medicine 5(7):836-8

Table S2. Clinical and demographic aspects of the studies included in the meta-analysis. PAPER Paper ID

CHRONIC PAIN SAMPLE

First author

Sample ID

N

Age (years)

M

F

1

Pleger, B.

1

20

41.8±9.8

11

9

Agostini, A.

2

18

32.8±7.22

8

10

3

Barad, M.J.

3

15

44

0

15

4

Ceko, M.(a)

4

14

42.4±5.9

0

14

CRPS type I (whole hand including all digits; peripheral nerve injury excluded) Crohn’s disease (CD) right upper extremity Complex Regional Pain Syndrome (CRPS) fibromyalgia (younger patients)

2

4

Ceko, M.(b)

5

14

55±2.9

0

14

fibromyalgia (older patients)

12.1±0.9 y

5

Fallon, N.

6

16

38.5±8.45

0

16

fibromyalgia

9.1 ± 6.8 y

6

Ivo, R.

7

14

54

6

8

chronic low back pain

>1y

7

Maeda, Y.

8

28

48.1±9.6

8

20

8.5± 9.1 y

8

Martikainen, I.K.

9

16

38±11

8

8

carpal tunnel syndrome chronic nonspecific back pain (CNBP): low back 4, neck 4, larger areas 8

10

60

62±13.2

24

36

trigeminal neuralgia

8.3±6.7 y

11

24

52

6

18

idiopathic cervical dystonia

13.9±10.4 y

12

20

9 10 11

Obermann, M. Prell, T. RodriguezRaecke, R.

63.25±9.46 10

10 unilateral primary hip osteoarthritis

12

Yang, F.C.

13

49

35.7

38

11

13

Yoon, E.J.

14

10

39.8±2.04

7

3

15

17

26.1±1.5

0

17

16

6

24.2±1.9

0

6

14 14

As-Sanie, S.(a) As-Sanie, S. (b)

Diagnosis

15

Mordasini, L.

17

20

40±14

20

0

16

Riederer, F.

18

29

41.4±12.7

7

22

17

Ung, H.

19

47

37.3±12.2

25

22

18

Barnden, L.R.

20

25

32

6

19

19

Gerstner, G.

21

9

25.5±2.5

0

9

20

Gustin, S.M.

22

21

45.7 ± 2.9

4

17

21

Pantano, P.

23

19

53.2 ±11.2

4

15

22

Gwilym, S.E. SchmidtWilcke, T Seminowicz, D.A. Tu, C.H. Younger, J.W. Obermann, M. RodriguezRaecke, R.

24

16

68

8

8

25

8

52.2±8.9

1

7

26

56

32.2 ± 12.3

0

27

32

23.84±2.99

28

14

29

29

episodic cluster headache (CH) (in bout period) chronic neuropathic pain after traumatic spinal cord injury (SCI) endometriosis-associated chronic pelvic pain (CPP) chronic pelvic pain (CPP) but no evidence of endometriosis refractory chronic pelvic pain syndrome (CPPS) Medication-overuse headache (MOH) and migraine(as the underlying primary headache) chronic low back pain chronic fatigue syndrome (CFS) myofascial temporomandibular disease (M-TMD) 13 trigeminal neuropathy; 8 trigeminal neuralgia prymary cervical dystonia (CD)

Disease Duration 11.95 m 10.33±5.94 y 2 m - 17.16 y 8.8±7.1y

5.0±3.8 y (me)

7.35 y 8.6±6.9 y 1.5 y 5.5 y 3.75 y >3m 15.14±11.0 y 8.55±7.81 y 7.4±3.5 y 2.5±2.1 y 8.5 ± 2.1 y 12.7±6.5 y

primary osteoarthritis (OA) persistent idiopathic facial pain (PIFP)

unknown

56

irritable Bowel Syndrome (IBS)

11.1 ± 7.7 y

0

32

10.19±3.25 y

38±13.7

0

14

primary dysmennorrhea (PDM) myofascial temporomandibular disease (M-TMD)

7

39.6±15.1

0

7

chronic posttraumatic headache

118.1±51.4 d

30

32

66.8±9

13

19

primary osteoarthritis (OA)

7.35 y

Valet, M.

31

14

51.1

0

14

30

Vartiainen, N.

32

8

47

1

7

4 headache; 7 low back pain; 1 temporomandibular; 1 pelvic; 1 lower limbs labial or genital herpes

31

Wood, P.B.

33

30

42.03±8.43

0

30

fibromyalgia

unknown

32

Buckalew, N.

34

8

-

4

4

chronic back pain (CBP)

>3m

23 24 25 26 27 28

unknown

4.4±2.9 y

9.8±7.2 y 3-20 y

33

Davis, K.D.

35

9

-

3

6

irritable Bowel Syndrome (IBS)

>2y

34

Geha, P.Y.

36

22

40.7±2.3

3

19

complex regional pain syndrome

3m – 13.5 y

35

Kim, J.H. Schweinhardt, P. Valfrè, W.

37

20

33.7±11.3

3

17

9.8±6 y

38

14

25.7±5.1

0

14

39

11

38.9±6.4

2

9

5 aura vulvar vestibulitis syndrome (PVD) 6 aura

Kuchinad, A. Obermann, M.(a) Obermann, M.(b) SchmidtWilcke, T.

40

10

52

0

10

41

11

52.6

42

9

55.9

2

7

9 idiopathic cervical dystonia (CD)

10±6.8 y

43

20

53.6±7.7

1

19

fibromyalgia

173±86.5 m

41

Unrath, A.

44

63

63.7±11.4

18

45

42

Draganski, B.

45

28

41.9±13.8

20

43

Etgen, T.

46

16

67.4±4.3

44

Rocca, M.A. SchimdtWilcke, T.

47

16

42.7

48

18

46

Etgen, T.(a)

49

46

Etgen, T.(b)

47

SchimdtWilcke, T.

36 37 38 39 39 40

45

fibromyalgia 11 idiopathic blepharospasm (BEB)

unknown 5.5±4.3 y

8

119.3±140 m

4

12

prymary blepharospasm (BEB)

6.5±4.9 y

1

15

7 aura

24.8 y

50.4±6.8

9

9

chronic back pain (CBP)

176±87,60 m

28

53.3±8

7

21

50

23

59.3±10

6

17

51

40

50.85

12

28

52

26

-

10

16

53

36

53±9.7

21

15

idiopathic restless legs syndrome (RLS) idiopathic restless legs syndrome (RLS) 20 chronic tension type headache (CTTH); 20 medication-overuse headache 15 muscoloskeletal; 5 radiculopathy; 6 both focal hand dystonia (FHD)

49 50

Okada, T.

54

16

34

10

6

chronic fatigue syndrome (CFS)

51

May, A.

55

25

47

23

2

idiopathic headache

N: number of subjects; m: months; y: years; me: median.

                           

20.6±8.9 y

idiopathic restless legs syndrome (RLS) phantom limb pain

Apkarian, A.V. Garraux, G.

48

5±2.9 y

22.3±7.1 y

19±14 y 11.4±11 y unknown 11.3±11.4 y 13±7 y 10±244 m

Table S3. Methodological aspects of the studies included in the meta-analysis.   PAPER Paper Sample First author ID ID

VBM

1

Pleger, B.

1

SPM8

2

Agostini, A.

2

SPM5

3

Barad, M.J.

3

SPM8

4

Ceko, M.(a)

4

SPM8

4

Ceko, M.(b)

5

SPM8

5

Fallon, N.

6

SPM8

6

Ivo, R.

7

SPM8

7

Maeda, Y.

8

SPM8

9

SPM8

10

SPM8

8 9

Martikainen, I.K. Obermann, M.

10

Prell, T.

11

SPM2

11

RodriguezRaecke, R.

12

SPM2

12

Yang, F.C.

13

SPM8

13

Yoon, E.J.

14

SPM8

15

SPM5

16

SPM5

17

SPM5

14 14 15

As-Sanie, S.(a) As-Sanie, S. (b) Mordasini, L.

Gray Matter

VBM DATA VBM algorithm unified segmentation scheme VBM, modulated (volume) optimized VBM, modulated (volume) segmented, DARTEL VBM DARTEL VBM, modulated (volume) DARTEL VBM, modulated (volume) optimized VBM, modulated (volume) DARTEL VBM, modulated (volume) DARTEL VBM, modulated (volume) DARTEL VBM, modulated (volume) DARTEL VBM, modulated (volume) Optimized VBM, modulated (volume)

voxel size (mm)

smoothing Atlas (mm) Space

Scanner (Tesla)

↑↑ ↓↓

1x1x1

7

MNI

1.5T

1

0

1x1x1

12

MNI

3T

0

4

1.5x1.5x1.5

8

MNI

3T

3

6

1x1x1

8

MNI

3T

9

0

1x1x1

8

MNI

3T

0

14

1x1x1

10

MNI

3T

2

2

1x1x1

8

MNI

3T

0

16

1x1x1

10

MNI

3T

0

4

1x1x1

8

MNI

3T

0

3

1x1x1

8

MNI

1.5

0

14

0.97x0.97x 1.5

8

MNI

1.5T

10

5

optimized VBM

1x1x1

10

MNI

3T

2

11

DARTEL VBM, modulated (volume) DARTEL VBM, modulated (volume) VBM5.1, modulated (volume) VBM5.1, modulated (volume) VBM5, modulated (volume) VBM8, modulated (volume) unified segmentation scheme VBM

1.02x1.02x 1.05

8

MNI

1.5T

0

5

1 mm thick

12

MNI

3T

0

4

1x1x1.2

8

MNI

3T

1

6

1x1x1.2

8

MNI

3T

0

1

1x1x1

10

TAL

3T

0

3

8

MNI

3T

17

8

8

MNI

3T

2

1

0.86x0.86x 1.0 0.86x0.86x 1.5

16

Riederer, F.

18

SPM8

17

Ung, H.

19

SPM8

20

SPM5

Dartel VBM

0.94×0.94×1

8

MNI

1.5 T

0

0

21

SPM5

Segmentation

1×1×1.2

8

TAL

3T

0

7

19

Barnden, L.R. Gerstner, G.

20

Gustin, S.M.

22

SPM5

modulated (volume)



6

MNI

3T

1

6

21

Pantano, P. Gwilym, S.E. SchmidtWilcke, T

23

SPM5 FSLVBM

modulated (volume)

1mm-thick

12

MNI

1.5 T

0

8

modulated (volume)

1 isotropic

3

TAL

3T

11

2

VBM 5.1, modulated (volume)

1×1×1

8

TAL

1.5 T

0

9

Standard VBM (MNI template)

1×1×1

8

MNI

3T

7

18



8

TAL

1.5 T

7

9

1×1×1

8

MNI

3T

11

1

18

22 23 24 25 26 27 28 29 30

Seminowicz, D.A. Tu, C.H. Younger, J.W. Obermann, M. RodriguezRaecke, R. Valet, M. Vartiainen, N.

24 25

SPM5

27

CIVET pipeline 1.1.9 SPM8

28

SPM8

29

SPM2

Optimized VBM

1×1×1

12

TAL

1.5 T

5

0

30

SPM2

Optimized VBM

1mm-thick

10

MNI

3T

1

16

31

SPM2

Optimized VBM

1×1×1

8

MNI

1.5 T

0

13

32

SPM2

Optimized VBM

1×1×1

12

MNI

3T

0

7

26

Optimized VBM Standard VBM (MNI template)

31

Wood, P.B.

33

SPM2

Unmodulated (concentration)

0.94×0.94×1. 2

12

TAL

1.5 T

0

4

34

SPM2

Optimized VBM



12

TAL

3T

0

2

35

SPM2

modulated (volume)

1.5mm-thick 1.7×1.7×2 (18s); 2×2×2 (3s) 0.94×0.94× 1.25

10

TAL

1.5 T

0

2

9.2

MNI

3T

0

1

10

MNI

1.5 T

0

20

33

Buckalew, N. Davis, K.D.

34

Geha, P.Y.

36

FSL 4.0/IRTK

Optimized VBM

35

Kim, J.H.

37

SPM2

Optimized VBM

38

INSECT

39

32

1×1×1

10

MNI

1.5 T

5

0

SPM2

Standard VBM (MNI template) Optimized VBM

1.4mm-thick

12

MNI

1T

0

11

40



modulated (volume)

1×1×1

10

MNI

1.5 T

0

5

41

SPM2

Optimized VBM

1×1×1

12

TAL

1.5 T

5

4

42

SPM2

Optimized VBM

1×1×1

12

TAL

1.5 T

6

3

43

SPM2

Optimized VBM

1×1×1.08

10

MNI

1.5 T

4

2

44

SPM2

Optimized VBM

1×1×1

6

MNI

1.5 T

0

3

45

SPM2

Optimized VBM

1×1×1.08

10

MNI

1.5 T

0

14

46

SPM2

Optimized VBM

1×1×1

12

MNI

1.5 T

2

1

Rocca, M.A. SchimdtWilcke, T.

47

SPM2

Optimized VBM

12

TAL

3T

1

21

48

SPM99

Optimized VBM

1×1×1 0.97×0.97× 1.08

10

TAL

1.5 T

3

4

46

Etgen, T.(a)

49

Segmentation

1×1×1

8

TAL

1.5 T

2

2

46

Etgen, T.(b)

50

Segmentation

1×1×1

8

TAL

1.5 T

4

0

Segmentation



12

TAL

1.5 T

0

16

Optimized VBM

2mm-thick

12

TAL

1.5 T

0

4

Optimized VBM

1.3mm-thick

8

MNI

3T

7

0

Optimized VBM

1.2mm-thick

12

TAL

3T

0

1

Segmentation

1×1×1.5

10

TAL

2T

1

0

36 37 38 39 39 40 41 42 43 44 45

Schweinhard t, P. Valfrè, W. Kuchinad, A. Obermann, M.(a) Obermann, M.(b) SchmidtWilcke, T. Unrath, A. Draganski, B. Etgen, T.

49

SchimdtWilcke, T. Apkarian, A.V. Garraux, G.

50

Okada, T.

54

51

May, A.

55

47 48

51 52 53

SPM software SPM software SPM99 SPM99/S nPM SPM2 SPM2/Sn PM99 ─

↑↑ foci of gray matter increase; ↓↓ foci of gray matter decrease.

Table S4. Statistical aspects of the studies included in the meta-analysis. PAPER STATISTICS Paper Sample First author ID ID 1

Pleger, B.

2

Agostini, A.

1 2

3

Barad, M.J.

3

4

Ceko, M.(a)

4

4

Ceko, M.(b)

5

5

Fallon, N.

6

6

Ivo, R.

7

7

Maeda, Y.

8

8 9

Martikainen, I.K. Obermann, M.

9 10

10

Prell, T.

11

11

RodriguezRaecke, R.

12

12

Yang, F.C.

13

13

Yoon, E.J.

14

14 14 15

As-Sanie, S.(a) As-Sanie, S. (b) Mordasini, L.

15 16 17

16

Riederer, F.

18

17

Ung, H.

19

18

Barnden, L.R.

20

19

Gerstner, G.

21

20

Gustin, S.M.

22

21

Pantano, P.

23

22 23 24

Gwilym, S.E. SchmidtWilcke, T Seminowicz,

24 25 26

Significance level Initial p value p=0.001 (uncorrected) p