RUNNING HEAD

RUNNING HEAD: N-BACK. META-ANALYSIS OF fMRI STUDIES IN CHILDREN

SUPPLEMENTARY MATERIAL FOR:

N-back Working Memory Task: Meta-analyses of Normative fMRI Studies with Children Zachary Yaple1 Marie Arsalidou2,3, * 1

Centre for Cognition and Decision Making, National Research University Higher School of

Economics, Moscow, Russian Federation 2

Department of Psychology, National Research University Higher School of Economics, Moscow,

Russian Federation 3

Department of Psychology, York University, Toronto, Canada

Methods The key terms: ‘fMRI’ AND ‘n-back’, specifying language as English, and document type as article were searched (http://www.webofknowledge.com) on the 7th of August 2017. This search was set to look for articles published from January 1st, 2011 to August 7th, 2017; eligible articles published before 2011 were taken from previously published meta-analyses using the n-back (Rottschy et al., 2012). Our literature search yielded 328 articles, which underwent a series of selection criteria (Figure S1). Specifically, in order to be included in the analyses, articles had to (a) report healthy participants, (b) use fMRI, (c) report whole-brain, within-group results using randomeffects analysis, (d) report stereotaxic coordinates in Talairach or Montreal Neurological Institute


(MNI) space, and (e) include contrasts of the n-back task (e.g. 2 back > 1 back). Only those articles with adult participants (age range 18-65) were included in the analysis. Both examiners undertook this selection process separately, and then came to a final agreement. Data from 48 articles between 2012 and 2017 were included in the meta-analyses. Additional articles using the n-back task with adults were taken from a recent meta-analysis (Rottschy et al., 2012). Four articles, which included adults older than 65 years were not included (Wishart et al., 2006; Döhnel et al., 2008; Lim et al., 2008; McGeown et al., 2008), thus data from 46 articles from Rottschy et al. (2012) were included in our meta-analysis. The total number of articles was 94, with included data from 97 subject groups, 131 experiments (i.e., contrasts). Twenty-three articles reported more than one experiment (as indicated by a in Table S1) and three articles reported results for two separate subject groups (Goldstein et al., 2005; Schmidt et al., 2009; Yan et al., 2011 as indicated by b in Table S1). Table S1 shows article information, participant demographics and contrast included in the analysis. Activation likelihood Estimate (ALE) meta-analysis was computed using GingerALE 2.3.6 (http://brainmap.org/ale/; Eickhoff et al., 2017). All coordinates were transformed into the same space: MNI coordinates were converted to Talairach using the Lancaster et al., (2007) transformation algorithm. Resulting statistical maps were thresholded using a cluster level correction for multiple comparisons p = 0.05 at a cluster forming threshold set at p < 0.001 (Eickhoff et al., 2017). Single study and contrast study analyses were performed between adults and children. Contrast analyses are performed on images corrected for multiple comparisons, thus the threshold for contrasts between adults and children is set to p = 0.01 uncorrected, with 5000 permutations and minimum volume 50 mm3. Lastly, a Fisher-Freeman-Halton Exact Test was calculated to examine whether experiments were partial to task type (verbal, shape, visuospatial, etc.) or contrast type (e.g. 2-back minus baseline, 1-back minus baseline).


Results N-back tasks for adults between 18 and 65 years, with an average age of 29.83 ±6.56 years (55.85% male; 85.45% right handed), yielded a total of 1648 foci. The Fisher-Freeman-Halton Exact Test (2x3) revealed no statistical significance in frequency across task modality (Verbal and Visuospatial n-back) and contrast type (2 back, 1-back, Linear Trend of load; p = 0.353, FisherFreeman-Halton Exact Test), indicating that the results were not biased towards a contrast type or task modality.

N-back: Adults N-back tasks in adults showed significant ALE scores mainly in large bilateral clusters in the prefrontal and parietal cortex (Table S2). Other regions included the insula, claustrum and cerebellum.

Contrast: Adults vs Children Table S3 shows a complete list of significant coordinates from the conjunction analysis and contrast between children and adults. A conjunction analysis shows significant ALE values in the superior and medial frontal gyri (Brodmann Area, BA 6) and in superior and parietal lobules (BA 7, 40). Other common regions include the insula and the cerebellum. Children did not have any suprathreshold clusters compared to adults. Compared to children, adults showed increased ALE values mainly in prefrontal regions (BA 9, 46, 10), the claustrum and parietal cortex (BA 7, 40).


Keywords: TOPIC: fMRI AND “n back” AND LANGUAGE: (English) AND DOCUMENT TYPES (Article); TIMESPAN: 2011-‐Present; n = 328

Identification

Screening

No healthy contrasts n = 4

Age < 18: n = 14

No fMRI n = 35 No whole-‐brain coordinates n = 58

No n back contrast n = 10

No control group or within group contrast n = 65

Age > 65: n = 14

Eligibility

Removed n = 200

Eligible articles from previous meta-‐analysis (Rottschy et al., 2012) + n = 46

Eligible articles n = 128

No foci reported n = 80

Eligible articles n = 48

Included

Adults (18-‐65 yrs) n = 94; experiments = 131; foci = 1648

Figure S1. PRISMA flowchart for eligibility of articles included in the adult meta-analysis.


Table S1. Information on source datasets included in the meta-analysis of adults Gender

Hand

Age range/ Mean,

Article

n

(M)

(R)

(STD)

Foci

Task Modality

Contrast

Allen et al., 2006

10

8

All

23-35

6

Verbal n-back

2-back > 0-back

Alonso-Lana et al., 2016 a

28

12

All

44.01(6.03)

1

Verbal n-back

2-back > 1-back

1

Verbal n-back

2-back > rest

3

Verbal n-back

1-back > rest

Beneventi et al., 2007

12

6

All

21-29

24

Face n-back

Linear trend of WM load

Binder & Urbanik, 2005 a c

12

7

All

20-29

19

Verbal n-back

2-back > 0-back

17

Shape n-back

2-back > 0-back

8

Verbal n-back

2-back and 1-back > 0-back

8

Verbal n-back


18

Visuospatial n-back


Cader et al., 2006 a

Callicott et al., 1999

16

9

6

6

All

NA

23-51

18-39


Campanella et al., 2013

32

14

All

21.2 (~2.2)

6

Digit n-back

2-back > 0-back

Caseras et al., 2006

12

4

All

24-45

10

Verbal n-back


Cerasa et al., 2008

30

30

All

18-43

16

Visuospatial n-back

2-back > 0-back

Choo et al., 2005

14

9

All

21.8 (0.8)

8

Verbal n-back


Ciesielski et al., 2006

10

5

All

20.4-27.6

15

Categorical n-back

2-back > 0-back

Cohen et al., 1997

10

5

NA

18-34

9

Verbal n-back


D’Aiuto et al., 2015 a

17

10

NA

26.38 (6.78)

3

Verbal n-back

2-back > 0-back

1

Verbal n-back

1-back > 0-back

Deckersbach et al., 2008

17

17

All

25.6 (5.9)

12

Verbal n-back

2-back > rest

Dima et al., 2014 a

40

20

All

31.5 (10.4)

10

Verbal n-back

3-back > 0-back

8

Verbal n-back

2-back > 0-back

5

Verbal n-back

1-back > 0-back

Dores et al., 2014

10

6

All

27.1 (2.27)

20

Visuospatial n-back

2-back > rest

Drapier et al., 2008 a

20

10

NA

26-63

4

Verbal n-back

1-back > rest

6

Verbal n-back

2-back > rest

7

Verbal n-back

3-back > rest


Druzgal & D’Esposito, 2001

9

5

All

21-27

12

Face n-back


Duggirala et al., 2016 a c

50

28

All

23.62 (3.17)

13

Categorical n-back

2-back > 0-back

15

Face n-back

2-back > 0-back

18

Verbal n-back

2-back > 0-back

El-Hage et al., 2011

90

45

All

19-56

5

Verbal n-back


Elzinga et al., 2007

14

14

NA

34.6 (10.9)

21

Verbal n-back

3, 2, 1-back > rest

Falkenberg et al., 2015

15

10

All

19-35

9

Verbal n-back

2, 1-back > 0 back

2013

41

24

All

40.27 (9.8)

2

Verbal n-back

2-back > rest

Forn et al., 2007

10

5

NA

NA

10

Verbal n-back

2-back > 0-back

Frangou et al., 2008 a

7

2

All

39 (5.88)

11

Verbal n-back

2-back > 0-back

5

Verbal n-back


Fernández-Corcuera et al.,

Fusar-Poli et al., 2011

15

9

All

25.18 (5.07)

8

Verbal n-back


Garrett et al., 2011

19

13

17

34.85 (12.54)

12

Verbal n-back

1-back > 0-back

Gillis et al., 2016

15

15

All

18-36

34

Categorical n-back

2-back > 0-back

Göbel et al., 2016

21

21

All

21-49

65

Verbal n-back



Goldstein et al., 2005 b

7

7

All

32.1 (6.6)

9

Verbal n-back

3-back > 1-back

Goldstein et al., 2005 b

7

0

All

34.1 (12.2)

16

Verbal n-back

3-back > 1-back

Gropman et al., 2011

21

7

17

31.8 (2.7)

43

Verbal n-back


Harvey et al., 2005

10

5

All

18-42

10

Verbal n-back

3, 2, 1-back > rest

Honey et al., 2000

20

20

All

19-64

10

Verbal n-back


Honey et al., 2003

27

21

All

35.1 (9.9)

11

Verbal n-back

2-back > 0-back

Huang et al., 2015 a

18

6

All

36-55

10

Visuospatial n-back

2-back > 1-back

5

Visuospatial n-back

1-back > 0-back

Jogia et al., 2012

37

21

NA

18-63

5

Verbal n-back

3, 2, 1-back > rest

Johannsen et al., 2013

12

4

All

21.7-37.8

14

Verbal n-back

2-back > 0-back

Kasahara et al., 2011

9

4

All

19-53

9

Verbal n-back


Kim et al., 2006

12

9

11

21-46

8

Verbal n-back

2-back > rest

Koppelstaetter et al., 2008

15

15

All

25-47

16

Verbal n-back

2-back > 0-back

Korsnes et al., 2013

11

0

NA

18-45

9

Digit n-back

2-back > 1-back

Koshino et al., 2008

11

10

10

28.7 (10.9)

15

Face n-back

2, 1, 0-back > rest

Kumari et al., 2003

12

12

All

20-40

8

Digit n-back

2, 1-back > 0-back


Kumari et al., 2006 a

13

13

All

18-55

16

Visuospatial n-back

0-back > rest

22

Visuospatial n-back

1-back > 0-back

18

Visuospatial n-back

2-back > 0-back

Lamp et al., 2016

16

5

All

18-27

17

Shape n-back

1-back > rest

Leung & Alain, 2011 a c

16

5

All

18-30

13

Categorical n-back

2-back > 1-back

13

Visuospatial n-back

2-back > 1-back

18

Verbal n-back

2-back > rest

10

Verbal n-back

1-back > rest

7

Verbal n-back

0-back > rest

Li et al., 2014 a

15

0

All

19-22

Loughead et al., 2009

33

18

All

33 (10.55)

13

Shape n-back


Luo et al., 2014

25

25

All

20-28

12

Face n-back

2-back > 0-back

Lythe et al., 2012

20

20

26.7 (6.7)

2

Verbal n-back


Manelis & Reder, 2014

16

5

All

24

18

Verbal n-back


Manktelow et al., 2014

21

13

All

18-60

22

Verbal n-back

2-back > 0-back

Marquand et al., 2008

20

7

All

43.7 (8.6)

19

Verbal n-back

2-back > 0-back

Matsuo et al., 2007 a

15

6

12

37.7 (12.1)

2

Visuospatial n-back

2-back > 0-back


4

Visuospatial n-back

1-back > 0-back

Mattfeld et al., 2016

17

11

NA

28.7 (4.0)

6

Verbal n-back


McAllister et al., 1999 a

11

4

All

30.6 (11.2)

2

Verbal n-back

2-back > 0-back

5

Verbal n-back

1-back > 0-back

Monks et al., 2004

12

12

All

45.6 (3.52)

14

Verbal n-back

2-back > 0-back

Nebel et al., 2005 a

19

12

All

26-37

30

Verbal n-back

2-back > rest

10

Verbal n-back

1-back > rest

Nichols et al., 2017

41

88

All

30.8 (7.9)

7

Verbal n-back

3-back > 0-back

Norbury et al., 2014

15

10

All

23-61

6

Verbal n-back

3, 2, 1-back > 0-back

Oren et al., 2017

24

16

All

22-35

5

Digit n-back


Park et al., 2016

45

22

All

22.87 (~2.205)

41

Shape n-back

2-back > 0-back

Pomarol-Clortet et al., 2012

46

27

All

20-62

2

Verbal n-back

2-back > rest

Qin et al., 2009

27

27

All

18-25

14

Digit n-back

2-back > 0-back

Ragland et al., 2002 a c

11

6

All

21-53

10

Verbal n-back

2-back > 1-back

7

Verbal n-back

2-back > 0-back

6

Verbal n-back

1-back > 0-back


Rama et al., 2001 a

8

0

All

21-25

6

Shape n-back

2-back > 1-back

9

Shape n-back

2-back > 0-back

5

Shape n-back

1-back > 0-back

32

Verbal n-back

2-back > 0-back

24

Verbal n-back

1-back > 0-back

Richter et al., 2013

34

26

NA

23.8 (~2.15)

25

Face n-back

2-back > 0-back

Reynolds et al., 2009

18

7

All

19-29

5

Verbal n-back

3-back > 1-back

Riccaiardi et al., 2006 a c

6

6

All

28 (1)

36

Tactile n-back

1-back > 0-back

28

Visuospatial n-back

1-back > 0-back

Rocca et al., 2014

52

24

All

22-52

16

Verbal n-back


Sabri et al., 2014

20

10

All

25 (5)

16

Verbal n-back

2-back > 1-back

Sánchez-Carrión et al., 2008 a

14

NA

All

24.2 (4.7)

18

Digit n-back

3-back > 0-back

16

Digit n-back

2-back > 0-back

Savini et al., 2012

12

12

All

19-32

9

Shape n-back


Scheuerecker et al., 2008 a

23

19

All

32.6 (9.9)

8

Verbal n-back

2-back > 0-back

15

Verbal n-back

2-back deg. > 0-back deg.


18-58/34.36 Schmidt et al., 2009 b

25

25

All

(13.24)

8

Verbal n-back


18-58/33.13 Schmidt et al., 2009 b

25

0

All

(12.31)

6

Verbal n-back


Schmidt et al., 2012 a

32

NA

NA

24.6 (~3.6)

1

Verbal n-back

3-back > 2-back

16

Verbal n-back

3-back > 0-back

12

Verbal n-back

2-back > 0-back

Schneiders et al., 2011

48

22

All

19-31

22

Shape n-back

2-back > 0-back

Seo et al., 2011

22

0

All

38.27 (8.48)

18

Verbal n-back

2-back > 0-back

Shen et al., 1999

9

6

All

20-40

24

Visuospatial n-back

2-back > rest

Spreng et al., 2014

36

17

NA

22.3 (3.8)

18

Face n-back

2-back > rest

Stretton et al., 2012 a

15

4

11

19-58

5

Visuospatial n-back

2-back > 0-back

4

Visuospatial n-back

1-back > 0-back

Takeuchi et al., 2012

248 126

All

21.1 (1.8)

11

Verbal n-back

2-back > 0-back

Thomas et al., 2005

16

5

NA

21-50

9

Verbal n-back

2-back > 0-back

Thornton & Conway, 2013

16

6

All

22 (2.3)

16

Face n-back



Veltman et al., 2003

21

7

NA

22.7 (3.6)

11

Verbal n-back


Veltman et al., 2005

10

3

All

22.9 (1.27)

20

Verbal n-back


Wesley et al., 2016

11

4

NA

28.8 (7.8)

3

Verbal n-back

1-back > 0-back

Winston et al., 2013

28

11

25

19-64

3

Visuospatial n-back


Wu et al., 2017

45

24

All

24.07 (4.83)

4

Digit n-back

2-back > 0-back

Yan et al., 2011 b

28

12

All

20.4 (1.4)

6

Visuospatial n-back

2-back > 0-back

Yan et al., 2011 b

28

12

All

20.9 (1.5)

8

Visuospatial n-back

2-back > 0-back

Verbal Yoo et al., 2004 a c

14

9

All

21-34

16

n-back

(visual) Verbal

2-back > 1-back n-back

23

(auditory)

2-back > 1-back

Yoo & Choi, 2005

10

8

All

20-30

22

Face n-back

2-back > rest

Zhou et al., 2014

18

9

All

24.94 (7.29)

5

Verbal n-back

2-back > 0-back

Ziemus et al., 2007

9

6

All

35-63

15

Verbal n-back

2-back > 0-back


Note: n = sample size; M = Male; R = Right handed; STD = Standard deviation; NA = not available; a = for each experiment with within-group contrasts, foci was compiled into one experiment; b = experiment contained more than one group with a different set of foci; c = study includes multiple task modalities


Table S2: Concordant brain regions related to the n-back task in adults

Cluster # Volume mm3 ALE Value x 1

2

3

4

27152

14560

13856

12824

y

z

Label

0.143 -30

20

4 L Insula BA 13

0.114 -42

2

0.084 -44

20

32 L Middle Frontal Gyrus BA 9

0.082 -30

-6


0.072 -34

46


0.036 -44

12

34 L Precentral Gyrus BA 6

8 L Precentral Gyrus BA 44

0.123 -34 -54

40 L Inferior Parietal Lobule BA 40

0.055 -12 -70

48 L Precuneus BA 7

0.133

38 -48

40 R Inferior Parietal Lobule BA 40

0.082

30 -58

42 R Superior Parietal Lobule BA 7

0.057

14 -70

50 R Precuneus BA 7

0.031

48 -38


0.103

40

34

30 R Superior Frontal Gyrus BA 9

0.042

48

10

36 R Middle Frontal Gyrus BA 9

0.041

48

14

24 R Inferior Frontal Gyrus BA 9 48 L Superior Frontal Gyrus BA 6

5

11488

0.129

0

12

6

6808

0.114

26

0

7

5416

0.153

30

20

8

3256

0.062

32 -58 -30 R Cerebellum Tuber

0.048

32 -62 -20 R Cerebellum Declive

56 R Sub-Gyral BA 6 4 R Claustrum


9

3240

0.075 -30 -56 -32 L Cerebellar Tonsil

10

2848

0.068 -16

11

1136

0.042

10

2 -4

14 L Caudate Body 8 R Thalamus Ventral Anterior Nucleus

Note: L = Left; R = Right; BA = Brodmann area; Coordinates are reported in Talairach and all results are thresholded with cluster-level threshold was set to p = 0.05 whereas the cluster-forming threshold was set to p < 0.001.


Table S3: Concordant brain regions related to the n-back task in adults versus children Conjunction: Adults AND Children Cluster # Volume mm3 1

2

4088

1488

ALE Value

x

y

z

Label

0.027

-2

14

48 L Superior Frontal Gyrus BA 6

0.023

-8

6

0.018

24

-62

42 R Superior Parietal Lobule BA 7

0.015

48

-44


0.014

32

-50


0.013

36

-52


0.012

42

-48

48 R Inferior Parietal Lobule BA 40 40 L Superior Parietal Lobule BA 7

50 L Medial Frontal Gyrus BA 6

3

1320

0.022

-30

-54

4

936

0.021

-24

-2

5

856

0.023

-38

0

6

648

0.021

30

18

7

520

0.016

-34

-60

-34 L Cerebellar Tonsil

0.014

-28

-64

-26 L Cerebellum Uvula

56 L Sub-Gyral BA 6 38 L Precentral Gyrus BA 6 10 R Insula BA 13

Adults > Children Cluster # Volume mm3

ALE Value

x

y

3.719 43.2

z

Label

1

4928

34.4 27.2 R Middle Frontal Gyrus BA 46

2

480

2.848

-28

14

3

368

2.948

-50

14


2.794

-44

12


2 L Claustrum


4

272

2.605

-33

42


5

208

2.576

34

-4

52 R Middle Frontal Gyrus BA 6

6

136

2.652

38

-46

7

120

2.687

34

8

8

72

2.478

34

-66

38 R Inferior Parietal Lobule BA 40 48 R Middle Frontal Gyrus BA 6 48 R Superior Parietal Lobule BA 7

Children > Adults No suprathreshold cluster Note: L = Left; R = Right; BA = Brodmann area; Coordinates are reported in Talairach and all results are thresholded with cluster-level threshold was set to p = 0.05 whereas the cluster-forming threshold was set to p < 0.001.


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