Table 1 Summary of included articles analysing resting-state functional connectivity in patients with manifest cerebral small vessel disease (CSVD). We report imaging and clinical characteristics of patients included in each study, key steps in the acquisition and pre-processing of BOLD data, analysis of functional connectivity, and FC patterns found to be associated with CSVD. Descriptive statistics as extracted from articles are reported as mean ± standard deviation. Missing information is indicted by empty brackets ([]). Arrows indicate increased (↑) or reduced (↓) values, as well as positive (↗) and negative (↘) associations

[28]

18 CSVD-CN

16 CSVD-MCI

WMH and lacunes (clinical diagnosis)

MMSE

CN 28.9 ± 1.3

MCI 28.1 ± 1.4

Philips Achieva, 3 T

TR 2000 ms, TE 30 ms

64 × 64 × []

3.6 × 3.6 × 4 mm³

220 volumes

eyes open

DPARSF v2.0, SPM 5, REST

[Confound regression]

Motion scrubbing

- Max motion > 1 mm/1°

PCC from external template

SCA to define DMN

Pearson correlation

↓ FC in DMN in the left middle temporal gyrus, left ant. cingulate/left middle frontal gyrus, right caudate, right middle frontal gyrus, and left medial frontal gyrus/paracentral lobule

↑ FC in DMN in the right inf. temporal gyrus, left middle temporal gyrus, left precentral gyrus, and left sup. parietal lobule

High (2)

[29]

29 CSVD

WMH (clinical diagnosis)

WMH volume

VRF 0, 20.4 ± 19.3

VRF 1, 27.3 ± 21.5

VRF 3, 17.4 ± 19.5

MoCA

VRF 0, 25.8 ± 3.5

VRF 1, 22.0 ± 6.2

VRF 3, 21.0 ± 5.4

Philips Achieva, 3 T

TR 2000 ms, TE 30 ms

64 × 64 × 40

3.6 × 2.9 × 3 mm³

184–259 volumes, [eyes]

FSL v4.1

Confound regression

- ICA

Motion scrubbing

- ‘relative motion’ > 1.5 mm

ICA to define DMN, SMN, medial-visual RSN

Pearson correlation

FC in DMN ↗ cardiovascular reactivity

Moderate (4)

[30]

21 CSVD-CN

16 CSVD-MCI

13 SVaD

WMH (clinical diagnosis)

MMSE

CN 28.9 ± 0.7

MCI 26.3 ± 1.0

SVaD 20.5 ± 2.3

MoCA

CN 24.6 ± 2.9

MCI 20.6 ± 2.8

SVaD 15.1 ± 3.6

Siemens, 3 T

TR 2480 ms, TE 30 ms

64 × 64 × 36, 3 × 3 × 4 mm³

240 volumes

eyes closed

SPM 8

[Confound regression]

Motion scrubbing

- Head motion > 2 mm/2°

AAL atlas

Pearson correlation, (extended) maximal information coefficient

SVM classification

None

High (3)

[31]

46 CSVD

41 CADASIL

WMH volume

0.3% [0.03, 3.1]% of intracranial volume

Lacunes

0 (0) [0–20]

MMSE median 29, IQR [26, 32]

Siemens Skyra/Prisma, 3 T, 64-/32-channel head coils, multi-band × 8

TR 700 ms, TE 39 ms

[matrix]

3 × 3 × 3 mm³

2.4 × 2.4 × 2.4 mm³

675–700 volumes

eyes closed

FSL, ANTs, BRAMILA v2.0

Confound regression

- ICA-AROMA non-aggressive

- Linear trend, 6 motion params

- GSR: CSF, WM

Motion scrubbing

- Volume censoring (FD > 0.5 mm, total time < 5 min)

Power atlas to define DMN, FPCN, hand-SMN, VN

Pearson correlation

graph theory

No association between WMH and FC

Poor reproducibility of network measures in CSVD

Moderate (6)

[33]

33 MCI with confluent (C) WMH

30 MCI with non-confluent (NC) WMH

Fazekas

C-WMH 8.0 ± 2.4

NC-WMH 3.2 ± 1.2

WMH volume

C-WMH 8.7 ± 9.2 ml

NC-WMH 1.9 ± 1.5 ml

MMSE

C-WMH 27.6 ± 1.5

NC-WMH 27.8 ± 1.7

Siemens Trio, 3 T

TR 2000 ms, TE 30 ms

[] × []× 36, 3 × 3 × 3 mm³

240 volumes

[eyes]

CONN 18b

Confound regression

- GSR: WM, CSF

- Motion parameters

Motion correction

- Artefact Detection Tools

- Spike regression (FD > 0.5 mm)

CONN atlas with 138 ROIs to define DMN, SMN, VN, DAN, FPCN language, and cerebellar networks

Bivariate correlation coefficients

↑ Interregional FC (C-WMH > NC-WMH)

↑ Intra-regional FC (C-WMH > NC-WMH)

Few ↓ interregional FC (C-WMH < NC-WMH)

High (2)

[34]

29 CSVD with gait disorder (GD+)

29 CSVD without gait disorder (GD−)

Fazekas ≥2

WMH volume

GD+, 6.12 mm³

GD−, 3.53 mm³

Lacunes

GD+, 7.45 ± 4.01

GD−, 5.62 ± 3.35

MMSE

GD+, 25.14 ± 3.24

GD−, 25.69 ± 3.32

GE Signa, 3 T, 8-channel head coil

TR 2000 ms, TE 30 ms

64 × 64 × []

3.75 × 3.75 × 4.6 mm³

240 volumes

eyes closed

DPABI, SPM 8

Confound regression

- Linear trend, 24p

- GSR: CSF, WM

Motion scrubbing

- ‘displacement’ > 2.5 mm /2.5°

fALFF

Pearson correlation

VBM

↓ FC between left SMA and temporal lobe (GC+ < GD−) ↗ gait speed

fALFF in left SMA ↗ cadence

Moderate (4)

 [35]

12 CSVD

21 HC

Wahlund 8.3 ± 4.0

Lacunes 1.9 ± 2.4

MMSE 27.6 ± 1.5

[Scanner, field str.]

TR 2300 ms, [TE]

[matrix], 3 × 3 × 4 mm³

300 volumes

[eyes]

FSL, AFNI, SPM

B₀ field map correction

Confound regression

- Linear/quadratic trend

- 6 motion parameters

- GSR: WM, CSF signal

[Motion scrubbing]

Eigenvector centrality

↓ FC in ventromedial PFC, MCC, and sup. parietal lobe

↑ FC in the cerebellar regions I–VI

FC ↗ WMH in the middle temporal sulcus, inf. temporal gyrus, cerebellar lobules Crus II, VIIb, VIII

FC ↘ WMH in ventromedial PFC, SMA, PCC, and sup. parietal lobe

High (1)

 [36]

30 CSVD

26 HC

Fazekas 1–3

Lacunes excluded

MoCA 22.9 ± 3.4 (pooled)

Siemens, 3 T

TR 2480 ms, TE 30 ms

64 × 64 × 36, 3 × 3 × 4 mm³

240 volumes, eyes closed

SPM 8

[Confound regression]

Motion scrubbing

- Head movement > 2 mm/2°

ICA to define SMN

voxel-wise two-sample t test

↓ FC in the right cingulate motor area, left posterior insula, and left ventral premotor area

High (2)

 [37]

28 CSVD

30 HC

Fazekas 2.9 ± 1.2

MMSE 27.9 ± 1.6

MoCA 25.7 ± 2.0

Siemens Trio, 3 T

TR 2000 ms, TE 30 ms

64 × 64 × []

3.5 × 3.5 × 3 mm³

240 volumes

[eyes]

SPM 8, DPABI, REST

[Confound regression]

Motion scrubbing

- Head movement > 2 mm/2°

ALFF, SCA

↓ ALFF in the left parahippocampus

↑ ALFF in the left inf. semi-lunar lobule and right frontal sup. orbital gyrus

↑ FC between right insula–right sup. orbitofrontal gyrus and right calcarine–left parahippoca. gyrus

High (2)

 [38]

16 CSVD

13 HC

WMH (clinical diagnosis, Fazekas)

MMSE 23.7 ± 3.9

MoCA 18.3 ± 4.1

Siemens, 3 T

TR 2000 ms, TE 30 ms

64 × 64 × 35

3 × 3 × 3 mm³

230 volumes

eyes closed

SPM 8

Confound regression

- Linear trend

Motion scrubbing

- Head movement > 2 mm/2°

Regional homogeneity

↓ ReHo in the left insula, right sup. temporal gyrus, Rolandic operculum, precentral gyrus, and cerebellum; bilateral ant. cingulate gyrus, ant. MCC, PFC, and SMA

↑ ReHo values in the left middle temporal gyrus, cuneus and sup. occipital gyrus, and the bilateral angular gyrus, precuneus, postcentral gyrus, inf. and sup. parietal gyrus

Moderate (5)

 [39]

15 CSVD

15 HC

WMH (clinical diagnosis, Fazekas)

MMSE 23.7 ± 4.0

MoCA 18.6 ± 4.1

Siemens, 3 T

TR 2000 ms, TE 30 ms

64 × 64 × []

3 × 3 × 4 mm³

230 volumes

eyes closed

DPABI v2.1

Confound regression

- Linear trend

- 24p [40]

- GSR: WM, CSF

- Spike regressor (FD > 0.2 mm)

Motion scrubbing

- Mean FD > group mean + 2*SD

36 ROIs representing DMN, DAN, FPCN, SMN, VN

Pearson correlation

Network-based statistics (NBS) [41]

↓ AN-SMN network FC

↑ DAN-FPCN network FC

↓ Edge FC SMN-AN, SMN-VN, FPCN-AN and DAN-VN pairs, and within AN and VN

↑ Edge FC in DMN-AN, DMN-FPCN, and DAN-FPCN pairs

High (3)

 [42]

26 lacunar stroke patients

19 HC

Fazekas ≥2

Lacunes 1–17 (6)

WMH 33 ± 34 ml

History of lacunar stroke syndrome

Siemens Verio, 3 T, 32-channel head coil

TR 2430 ms

TE 1/2/3 13/31/48 ms

64 × 64 × 34

3.75 × 3.75 × 4.18 mm³

269 volumes, eyes open

SPM, CONN

Confound regression

- Motion parameters [details]

- GSR: WM, CSF

[Motion scrubbing]

Desikan–Killiany parcellation

Pearson correlation

Probab. tractography

Graph theory

No difference in FC or brain network topology

Moderate (6)

 [43]

36 CSVD

31 HC

Fazekas ≥2

MMSE

HC 28.4 ± 1.8

CSVD 26.4 ± 3.7

Siemens Verio, 3 T, 12-channel head coil

TR 2000 ms, TE 25 ms

64 × 64 × [z]

3.75 × 3.75 × 4 mm³

[volumes], [eyes]

DPARSF, SPM 8

Confound regression

- 6 head motions params

- GSR: global, WM, CSF

Motion scrubbing

- Head movement > 2 mm/2°

AAL 90

Pearson correlation

Graph theory

NBS

↓ Global FC

↑ Characteristic path length

↓ Global efficiency

High (0)

 [44]

26 svMCI

28 HC

Wahlund ≥ 2

± lacunes

Subjective complaints

MMSE 25.7 ± 2.7

Siemens, 3 T

TR 2000 ms, TE 40 ms

64 × 64 × 28

4 × 4 × 5 mm³

239 volumes

eyes closed

SPM 5

Confound regression

- Linear trend

- 6 motion profiles

- GSR: WM, CSF

Motion scrubbing

- Head movement > 3 mm/3°

ALFF, SCA, FC density

Pearson correlation (only positive)

↓ ALFF in bilateral medial PFC

↑ ALFF in right PCC, precuneus, right hippocampus, right thalamus

↓ FC in DMN (PCC/precuneus, medial PFC, sup. frontal gyrus, inf. parietal lobule and hippocampus) and inferior/middle frontal gyrus

High (2)

 [45]

21 svMCI

26 HC

Wahlund ≥ 2

± lacunes

Subjective complaints

MMSE 25.5 ± 2.7

Siemens, 3 T

TR 2000 ms, TE 40 ms

64 × 64 × 28

4 × 4 × 5 mm³

239 volumes

eyes closed

SPM 5 and 8, REST, DARTEL

Confound regression

- Linear trend

- 6 motion profiles

- GSR: WM, CSF

Motion scrubbing

- Head movement > 3 mm/3°

- Volume censoring (FD > 0.3 mm, <  3 min)

H-1024 parcellation

Pearson correlation

Graph theory

↑ Characteristic path length, ↑ modularity

↑ Within-module degree in the medial PFC, left insula, and cuneus

↓ Within-module degree in the middle cingulate gyrus

↑ Participation coefficient in the left inferior/superior parietal cortex

High (1)

 [46]

37 PiB+ AD

37 PiB− SVaD

13 mixed dementia

65 HC

Fazekas (severe)

MMSE

PiB+ AD, 18.1 ± 4.2

PiB− SVaD, 21.5 ± 4.3

MD, 17.9 ± 4.9

HC, 28.9 ± 1.2

Philips Achieva, 3 T, 8-channel head coil

TR 3000 ms, TE 35 ms

[matrix], 1.7 × 1.7 × 4 mm³

100 volumes, eyes open

AFNI

Despiking

[Confound regression]

Motion scrubbing

- Max FD > 0.3 mm

- Head movement > 2 mm/2°

ICA to define DMN and FPCN

W-score maps

↓ FC in DMN in the left superior frontal gyrus

↓ FC in FPCN in the left insula

Moderate (5)

 [47]

32 CSVD-CI

23 HC

Fazekas 2–3

± lacunes

MMSE 23.8 ± 2.7

GE Signa, 3 T

TR 2000 ms, TE 30 ms

64 × 64 × []

3.75 × 3.75 × 4.6 mm³

240 volumes

eyes closed

SPM 8, DPARSF, CONN

Confound regression

- compCor

- GSR: global signal

[Motion scrubbing]

Medial PFC and thalamus from ext. template

SCA

Pearson correlation

↓ FC between the left thalamus and right sup. temporal gyrus, left sup. frontal gyrus, left and putamen

↓ FC between the right thalamus and left inferior temporal gyrus

↑ FC between the bilateral thalamus and right inferior/middle frontal gyri

↓ FC between the med. PFC and bilateral SMA, thalamus, left sup. frontal gyrus, ACC, sup. parietal lobe, and hippocampus

High (2)

 [48]

14 CSVD-CN

27 CSVD-MCI

12 SVaD

30 HC

Fazekas (cut-off not specified)

MMSE

CSVD-CN 29.1 ± 1.0

CSVD-MCI 27.2 ± 2.4

SVaD 23.3 ± 3.4

Siemens, 3 T

TR 2000 ms, TE 30 ms

64 × 64 × 32, 4 × 4 × 3.7 mm³

[volumes], eyes closed

SPM 8

[Confound regression]

Motion scrubbing

- Head movement > 2 mm/2°

ICA to define DMN, SN, FPCN

SCA from the right fronto-insular cortex

↓ FC between SN-DMN

↑ FC between SN-FPCN and within SN

High (3)

 [49]

36 CSVD

50 AD

55 HC

WMH volume

svMCI 22.6 ± 6.1 ml

SVaD 44.8 ± 10.1 ml

Lacunes

svMCI 6.5 ± 7.5

SVaD 7.4 ± 7.2

Microbleeds

svMCI 13.4 ± 18.7

SVaD 26.0 ± 49.2

MMSE

svMCI 25.4 ± 3.7

SVaD 17.4 ± 4.2

Siemens, 3 T

TR 3000 ms, TE 35 ms

[matrix]

3.4 × 3.4 × 3.4 mm³

200 volumes

[eyes]

SPM 12

No smoothing

Confound regression

- Motion parameters

- Linear trend

- GSR: WM, CSF

Motion scrubbing

- Volume censoring (FD > 1 mm, >  30%)

Schaefer 400 atlas

Pearson correlation

AV1451 tau-PET

FC ↗ tau covariance, no associations with WMH

Moderate (7)

 [50]

25 CSVD-CN

24 CSVD-MCI

36 HC

Fazekas ≥2

± lacunes

WMH

CN 3.0 (0.76, 4.0) ml

MCI 4.8 (0.76, 5.6) ml

MMSE

CN 28.4 ± 1.3

MCI 27.8 ± 2.1

MoCA

CN 26.1 ± 0.5

MCI 21.4 ± 0.5

Philips, 3 T

TR 2000 ms, TE 30 ms

64 × 64 × 35

3.75 × 3.75 × 4 mm³

230 volumes

eyes closed

GRETNA v2.0, SPM 8

Confound regression

- Linear trend, 24p

- GSR: GS, WM, CSF

Motion scrubbing

- Head movement > 2 mm/2°

H-1024 parcellation

Pearson correlation

Graph theory to define DMN, FPCN, SMN, and VN

No robust associations

Moderate (4)

 [51]

21 CSVD-CN

20 CSVD-MCI

25 HC

WMH volume

CN 3.2 ± 3.0 ml

CI 3.4 ± 4.1 ml

± lacunes

MMSE

CN 28.5 ± 1.3

MCI 28.1 ± 1.3

MoCA

CN 25.6 ± 1.9

MCI 22.2 ± 2.9

Philips, 3 T, 32-channel head coil

TR 2000 ms, TE 30 ms

64 × 64 × 35

3.75 × 3.75 × 4 mm³

230 volumes

Eyes closed

DPABI

Confound regression

- 24p

- GSR: GS, WM, CSF

Motion scrubbing

- Head movement > 3 mm/3°

PCC, dlPFC, IPS from external template

SCA to define DMN, FPCN, and DAN

↓ FC in DMN in the right thalamus, hippocampus, and precuneus

↑ FC in FPCN in the right inf. parietal lobule

↓ FC between PCC-FPCN in the left precentral gyrus and bilateral middle cingulate gyri

↓ FC between PCC-DAN in the bilateral paracentral lobule and precuneus

↓ FC between PCC-DAN in the bilateral PCC and right precuneus

Moderate (6)

 [52]

14 CSVD + THA LAC

27 CSVD − THA LAC

34 HC

Fazekas 3–6

Lacunes

LAC+, 5.6 ± 3.9

LAC−, 2.0 ± 1.4

MMSE

LAC+, 26.3 ± 2.8

LAC−, 28.1 ± 2.0

GE Discovery, 3 T

TR 2000 ms, TE 35 ms

64 × 64 × 36

3.4 × 3.4 × 4 mm³

210 volumes

eyes closed

SPM 8

Confound regression

- 6 motion parameters

- GSR: WM, CSF

Motion scrubbing

- Head movement > 2 mm/2°

AAL 90

Pearson correlation

Graph theory, Network-based statistics

↓ FC in para-/limbic and subcortical regions

Moderate (5)

 [53]

32 CSVD-MCI

20 SVaD

35 HC

Fazekas ≥1

MMSE

MCI 25.5 ± 1.8

SVaD 22.0 ± 2.0

MoCA

MCI 22.2 ± 1.

SVaD 17.4 ± 2.9

Siemens Verio, 3 T

TR 2000 ms, TE 30 ms

64 × 64 × 32

4 × 4 × 4.2 mm³

240 volumes

eyes closed

DPARSF

Confound regression

- Linear/quadratic, 24p

- GSR: WM, CSF

Motion scrubbing

- Head movement > 3 mm/3°

AAL atlas

Pearson correlation

Graph theory

↓ Global FC

↓ Small-worldness

Moderate (4)

 [54]

20 LA-VAD

32 LA-VCIND

35 HC

Not reported

MMSE

HC 29.4 ± 1.1

LA-VCIND 27.9 ± 1.8

LA-VaD 23.0 ± 3.8

MoCA

HC 26.0 ± 2.5

LA-VCIND 25.8 ± 2.0

LA-VaD 23.2 ± 2.8

Siemens, 3 T

TR 2000 ms, TE 30 ms

64 × 64 × 20

4 × 4 × 6 mm

250 volumes

eyes closed

DPARSF

Confound regression

- 24p

- GSR: WM, CSF

Motion scrubbing

- Head movement > 3 mm/3°

Group ICA (GIFT)

Granger causality

Unclear; text and figures not consistent

High (2)