Table 1.
Studies Investigating fMRI Functional Connectivity Differences Between ADHD and Typical Development Grouped by Cognitive Domain
| Study | Analysis Method | Task (Contrast) | NADHD (% Male) | AgeADHD, Years, Mean (SD) | Medication History | Medication Washout | ADHD Comorbidities | NControl (% Male) | AgeControl, Years, Mean (SD) | Control > ADHD | ADHD > Control |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Attention | |||||||||||
| Li et al., 2012 (39) | SBC | CPT (unspecified) | 22 (55%) | 11.6 (2.86) | Current MPH use (41%); medication-free (59%) | 48 hours | None | 22 (45%) | 12.1 (2.23) | L pulvinar nuclei ↔ R IFC, MFG; R pulvinar nuclei ↔ R PFC | R pulvinar nuclei ↔ BIL occipital lobe |
| Luo et al., 2018 (40) | GTTs | Cued attention task (cues) | 17 (77%) | 24.69 (2.1) | Current stimulant use (12%); past stimulant use (unspecified) | 48 hours | None | 33 (85%) | 24.27 (2.2) | Acting network hubs in BIL IPL; L IPL ↔ L SFG; degree in R MFG; betweenness centrality in L SFG, MFG, precentral, R IFC | Acting network hubs in L MFG and precentral |
| Rubia et al., 2009 (41) | SBC | CPT (targets > nontargets) | 13 (100%) | 12.5 (1.3) | Medication-naïve (100%) | – | ODD/CD (8%) | 13 (100%) | 13 (1.7) | L IFC ↔ striatum, cerebellum; R IFC ↔ striatum, BIL cerebellum; BIL thalamus/striatum ↔ striatum, R cerebellum; L striatum ↔ BIL cerebellum, R striatum; ACC ↔ cerebellum, cerebellar vermis; R IPL ↔ cerebellum, L IPL; cerebellar vermis ↔ PCC; R cerebellum ↔ PCC, L IPL; L cerebellum ↔ L IPL | None |
| Xia et al., 2014 (42) |
GTTs |
CPT (unspecified) |
22 (55%) |
11.6 (2.86) |
Current MPH use (41%); medication-free (59%) |
48 hours |
None |
22 (45%) |
12.1 (2.23) |
Nodal efficiency in L superior OFG and R SOG; degree and betweenness centrality in BIL occipital lobes, R temporal lobe, L paracentral, SMG |
Nodal efficiency in L cuneus; degree and betweenness centrality in ACC |
| Cognitive Control | |||||||||||
| Cubillo et al., 2010 (15) | SBC | Switch task (unspecified) | 11 (100%) | 29 (1) | Medication-naïve (100%) | – | Anxiety disorder (9%), mood disorder (27%), CD (9%), substance use disorder (18%) | 13 (100%) | 28 (1) | None | None |
| Hwang et al., 2015 (43) | gPPIAFNI | Affective Stroop task (incongruent > congruent stimuli) | 26 (65%) | 14.53 (unspecified) | Current stimulant use (42%); medication-free (58%) | >24 hours | ODD (4%), substance use disorder (8%) | 35 (51%) | 13.91 (unspecified) | L DMFG ↔ R lateral frontal, claustruma | L DMFG ↔ L posterior insula |
| Querne et al., 2017 (44) | ICA | Flanker task (unspecified) | 11 (unspecified) | 9.8 (1.7) | Medication-naïve (100%) | – | None | 11 (unspecified) | 10.8 (1.7) | Anticorrelation between DMN and frontotemporoparietal regions (direct group comparison not reported) | None |
| Plessen et al., 2016 (45) | ICA | Flanker task (post-error > post-correct trials) | 25 (68%) | 10.75 (1.09) | Medication-naïve (100%) | – | ODD (40%), ODD+CD (8%), phobia (16%), tics (4%), separation anxiety disorder (4%), elimination disorder (4%) | 29 (52%) | 10.15 (1.04) | None | Cingulo-opercular network ↔ VANa |
| Vloet et al., 2010 (46) | PPISPM | Time discrimination + stimulus-response compatibility task (stimulus-response compatibility) | 14 (100%) | 11.3 (2) | Past or current stimulant use (100%) | >48 hours | None | 14 (100%) | 11.9 (1.4) | L IFC ↔ L SPG; R IFC ↔ R SPG | None |
| Zamorano et al., 2017 (47) |
PPIFSL |
MSIT (incongruent > congruent conditions) |
17 (100%) |
11.6 (0.86) |
Current MPH use (100%) |
Medication not taken on study day |
None |
17 (100%) |
11.7 (0.67) |
Not reported |
R MFG + R IFC ↔ BIL OFC, striatum |
| Emotion Processing | |||||||||||
| Hafeman et al., 2017 (61) | gPPISPM | Emotional dynamic faces task (emotional faces > shapes) | 30 (67%) | 14.1 (1.8) | Current use of stimulants (43%), antipsychotics (10%), antidepressants (10%) | Unspecified | ODD (53%), CD (3%), depressive disorder (53%), anxiety disorder (3%) | 26 (46%) | 13.2 (2.2) | None | BIL amygdala ↔ subgenual cingulate; BIL amygdala ↔ R SFG |
| Hwang et al., 2015 (43) | gPPISPM | Affective Stroop task: 1) positive > neutral stimuli; 2) positive > neutral incongruent stimuli; 3) negative > neutral stimuli) | 26 (65%) | 14.53 (unspecified) | Current stimulant use (42%); medication-free (58%) | >24 hours | ODD (4%), substance use disorder (8%) | 35 (51%) | 13.91 (unspecified) | 1) R amygdala ↔ R MOG, L lentiform nucleus; 2) R amygdala ↔ BIL postcentrala; 3) none | None |
| Park et al., 2016 (55) | GTTsb | Emotive faces task (unspecified) | 34 (59%) | 27.88 (3.37) | Unspecified | Unspecified | Unspecified | 34 (62%) | 29.44 (3.57) | Degree in BIL medial frontal, L ACC, L postcentral, R caudate, L insula | Degree in L MFG, R SMG, R IPL, L MOG, L IOG, R cerebellum |
| Posner et al., 2011 (62) | DCM | Fearful faces task with priming (fearful faces) | 15 (87%) | 13.5 (1.2) | Current stimulant use (100%) | >48 hours | ODD/CD (% unspecified) | 15 (87%) | 13.4 (1.2) | None | R amygdala ↔ R lateral PFC |
| Schulz et al., 2014 (63) | PPISPM | Face emotion GNG (correct no-go > go) | 14 (100%) | 23.3 (2.3) | Medication-naïve (29%); past stimulant use but medication-free at time of study (71%) | – | Mood disorder (14%), anxiety disorder (14%), substance use disorder (36%) | 14 (100%) | 22.8 (2.7) | R DLPFC ↔ L IFC, putamen, BIL subgenual cingulate | None |
| Stoddard et al., 2017 (64) |
gPPIAFNI |
Implicit face emotion processing task (150% intensity across emotions) |
24 (75%) |
13.5 (2.9) |
Unspecified |
Unspecified |
Unspecified |
22 (41%) |
14.2 (2.1) |
None |
L amygdala ↔ L insula |
| Response Inhibition | |||||||||||
| Cai et al., 2021 (48) | gPPISPM | GNG (correct no-go) | 27 (78%) | 13.95 (2.62) | Medication-free during testing (100%) | >5 half-lives of drug | Unspecified | 30 (73%) | 13.65 (2.47) | R DLPFC ↔ R posterior parietal | None |
| Cubillo et al., 2010 (15) | SBC | SST (unspecified) | 10 (100%) | 28 (1) | Medication-naïve (100%) | – | Anxiety disorder (10%), mood disorder (30%), CD (10%), substance use disorder (20%) | 14 (100%) | 28 (2) | R IFC ↔ L IFC, R MFG, ACC, PCC, SMA, thalamus, striatum, BIL parietal/temporal/occipital; R ACC/PCC/SMA ↔ R thalamus, striatum | None |
| Massat et al., 2018 (49) | PPISPM | SST (successful > failed stop) | 18 (44%) | 10.6 (1.13) | Medication-naïve (100%) | – | None | 19 (47%) | 10 (1.35) | R IFC ↔ R OFC, L MFG, IFC | R dorsal caudate ↔ R IPL, SPG, L MFG, middle cingulate, precentral, postcentral |
| Mulder et al., 2011 (50) | SBC | GNG (unspecified) | Sample 1: 11 (100%) Sample 2: 12 (100%) |
Sample 1: 13.97 (3.14) Sample 2: 14.9 (2.3) | Sample 1: current stimulant use (55%); medication-free (45%) Sample 2: current stimulant use (58%); medication-free (42%) |
>24 hours | Sample 1: ODD (27%) Sample 2: ODD (33%) |
Sample 1: 11 (100%) Sample 2: 12 (100%) | Sample 1: 15.27 (1.92) Sample 2: 15 (2.1) | Samples 1 and 2: ACC ↔ cerebellum Sample 1: motor cortex ↔ striatuma Sample 2: not reported |
None |
| van Rooij et al., 2015 (51) |
PPIFSLb,c |
SST: 1) successful stop > go; 2) failed stop > go) |
185 (70%) |
17.3 (3.2) |
Current medication use, class unspecified (77%); medication-free (23%) |
Unspecified |
ODD (30%), CD (7%), reading disability (18%) |
125 (44%) |
16.5 (3.3) |
1) L IFC ↔ R putamen; L SFG ↔ L thalamus, operculum; 2) L IFC ↔ R IFC, BIL SFG/preSMA, L occipital cortex, MTG; L SFG ↔ L IFC |
1) L IFC ↔ L MTG, cerebellum; L SFG ↔ R ACC, frontal pole, BIL precuneus, L precentral, R cerebellum; 2) L IFC ↔ BIL temporal pole, L cerebellum, R SMG; L SFG ↔ L MTG |
| Reward Processing | |||||||||||
| Ceceli et al., 2020 (52) | PPIFSL | Free operant task with food rewards (late > early phase) | 25 (56%) | 22.31 (4.69) | Current or previous stimulant use (72%); past stimulant use but medication-free at time of study (16%); medication-naïve (12%) | 36 hours | None | 25 (56%) | 21.48 (2.92) | L posterior putamen ↔ dorsal ACC, medial frontal | None |
| Ma et al., 2016 (53) | gPPISPM | Rewarded Stroop task (rewarded > neutral Stroop) | 25 (76%) | 15.36 (1.08) | Current MPH use (60%); medication-free (40%) | 24 hours | ODD and CD (% unspecified) | 33 (67%) | 15.3 (1.05) | None | L ventral striatum ↔ R precentral |
| Mowinckel et al., 2017 (54) | Bayesian hierarchical mixed model | Value-based decision-making task (unspecified) | 20 (35%) | 29.9 (1.41) | Current stimulant use (100%) | >20 hours | None | 27 (30%) | 27.42 (1.23) | Within VIS, FPN, ECN, subcortical network, L VAN; ECN ↔ FPN ↔ sensorimotor network; DAN ↔ sensorimotor network; DAN ↔ VIS | VAN ↔ DMN; VAN ↔ ECN; DMN ↔ ECN |
| Park et al., 2016 (55) | GTTsb | Gambling task: 1) gambling reward; 2) gambling punishment | 34 (59%) | 27.88 (3.37) | Unspecified | Unspecified | Unspecified | 34 (62%) | 29.44 (3.57) | 1) Degree in BIL SFG, MTG; 2) degree in R medial frontal, MFG, insula, BIL SFG, L IPL, thalamus, parahippocampal | 1) Degree in R ACC, L PCC, lingual, thalamus, BIL insula, cerebellum; 2) R precentral, MTG, L postcentral, STG, BIL cerebellum |
| von Rhein et al., 2017 (56) |
ICA |
MID task (unspecified) |
150 (70%) |
17.7 (3) |
Unspecified |
>48 hours |
ODD (23%), CD (5%) |
48 (69%) |
16.9 (3.2) |
Within SAL (R ITG), ECN (R IFC, L cerebellum) |
Within SAL (R cerebellum) |
| Working Memory | |||||||||||
| Bédard et al., 2014 (57) | PPISPM | Visuospatial n-back task: 1) 1-back > 0-back; 2) 2-back > 0-back | 24 (88%) | 13.07 (1.93) | Current stimulant use (4%); current nonstimulant use (4%); past stimulant/nonstimulant use but medication-free at time of study (29%); medication-naïve (63%) | 2 weeks | ODD (8%), CD (4%), anxiety disorder (17%) | 21 (76%) | 12.44 (1.95) | 1) L DLPFC ↔ L PCC; 2) L DLPFC ↔ L midcingulate, PCC | 1) L DLPFC ↔ BIL posterior insula, R temporal cortex; 2) L DLPFC ↔ L intraparietal sulcus, cerebellum |
| Massat et al., 2012 (58) | gPPISPM | Verbal n-back task (2-back > 0-back) | 19 (47%) | 10.75 (1.31) | Medication-naïve (100%) | – | None | 14 (57%) | 10.05 (1.28) | None | R cerebellum ↔ red nucleus, R amygdalaa, hippocampusa, linguala, precuneusa, L IFCa, MFGa, postcentrala, cerebelluma; L occipital ↔ BIL MFGa, R MTGa, STGa, fusiforma, putamena, L cerebelluma; L IPL ↔ BIL IFCa, MFGa, STGa, L ACCa, SMAa; R caudate ↔ BIL MFGa, R SFGa, putamena, insulaa |
| Park et al., 2016 (55) | GTTsb | Visuospatial n-back task (unspecified) | 34 (59%) | 27.88 (3.37) | Unspecified | Unspecified | Unspecified | 34 (62%) | 29.44 (3.57) | Degree in L precuneus, MTG, cuneus, insula | Degree in L precentral, IPL, cerebellum, R MFG, IFC, STG, BIL SFG, caudate |
| Wolf et al., 2009 (59) | ICA | Verbal working memory task (unspecified) | 12 (100%) | 22.2 (4.4) | Current MPH use (50%); past MPH use but medication-free at time of study (50%) | 72 hours | None | 12 (100%) | 21.6 (4.7) | Within BIL IFC, SFG, SPG, cerebellum, L ACC, medial frontal | Within L dorsal cingulate, cuneus, R IFC, SFG |
| Wu et al., 2017 (60) |
ICA |
Verbal n-back task (2-back > 0-back) |
22 (100%) |
12.71 (1.55) |
Past stimulant use but medication-free at time of study (23%); medication-naïve (77%) |
>4 weeks |
ODD (18%) |
30 (100%) |
11.96 (1.72) |
Within ECN (L SMG, insula) |
Within FPN (L postcentral, SPG), auditory network (R cuneus, occipital pole, supracalcarine, intracalcarine, lateral SOG, precuneus) |
| Other Cognitive Functions | |||||||||||
| Chevrier et al., 2019 (65) | SBC | SST: 1) error detection; 2) post-error slowing | 14 (50%) | 13.7 (2.1) | Current stimulant use (43%); medication-free (57%) | 24 hours | ODD (14%) | 14 (64%) | 15.4 (1.6) | 1) SN ↔ medial septal; 2) LC ↔ L amygdala, L hypothalamus; medial septal nuclei ↔ R amygdala, LC, R hypothalamus; raphe nucleus ↔ R SN/parahippocampal | 1) Dorsal striatum ↔ R IPL; SN ↔ R hypothalamus; SN ↔ L amygdala, LC, raphe nucleus; 2) ventral pallidum ↔ SN/parahippocampal, R dorsal pallidum, L amygdala; SN ↔ L hypothalamus; LC ↔ R IFC; medial septal nuclei ↔ BIL amygdala, L SN, BIL basal forebrain; raphe nucleus ↔ BIL amygdala, R SN, BIL hypothalamus |
| Clerkin et al., 2013 (66) | PPISPM | Cued reaction time task (cues > noncues) | 35 (83%) | 24.6 (2.04) | Current stimulant use (6%); past stimulant use but medication-free at time of study (71%) | >48 hours | Mood disorder (23%), anxiety disorder (23%), substance use disorder (43%) | 32 (84%) | 24.38 (2.4) | R thalamus ↔ pons | None |
| Park et al., 2016 (55) | GTTsb | Motor task (unspecified) | 34 (59%) | 27.88 (3.37) | Unspecified | Unspecified | Unspecified | 34 (62%) | 29.44 (3.57) | Degree in R precentral, medial frontal, SMG, L MFG, precuneus, cuneus, parahippocampal, cerebellum, BIL MTG, MOG | Degree in BIL SFG, PCC, R MFG, ACC, L postcentral |
| GTTsb | Relational processing task (unspecified) | 34 (59%) | 27.88 (3.37) | Unspecified | Unspecified | Unspecified | 34 (62%) | 29.44 (3.57) | Degree in R medial frontal, SFG, BIL ACC, L lingual, cerebellum | Degree in R PCC, cuneus, BIL IPL, STG, L MTG | |
| GTTsb | Social cognition task (unspecified) | 35 (59%) | 27.88 (3.37) | Unspecified | Unspecified | Unspecified | 34 (62%) | 29.44 (3.57) | Degree in BIL SFG, R PCC, L cuneus | Degree in L precentral, postcentral, cerebellum, BIL precuneus, R MTG | |
| Vloet et al., 2010 (46) | PPISPM | Time discrimination + stimulus-response compatibility task (time discrimination) | 14 (100%) | 11.3 (2) | Past or current stimulant use (100%) | >48 hours | None | 14 (100%) | 11.9 (1.4) | R IFC ↔ R cerebellum | None |
ACC, anterior cingulate cortex; ADHD, attention-deficit/hyperactivity disorder; BIL, bilateral; CD, conduct disorder; CPT, continuous performance task; DAN, dorsal attention network; DCM, dynamic causal modeling; DLPFC, dorsolateral prefrontal cortex; DMFG, dorsomedial frontal gyrus; DMN, default mode network; ECN, executive control network; fMRI, functional magnetic resonance imaging; FPN, frontoparietal network; GNG, go/no-go; gPPI, generalized psychophysiological interaction; GTT, graph theoretic technique; ICA, independent component analysis; IFC, inferior frontal cortex; IOG, inferior occipital gyrus; IPL, inferior parietal lobule; ITG, inferior temporal gyrus; L, left; LC, locus coeruleus; MFG, middle frontal gyrus; MID, monetary incentive delay; MOG, middle occipital gyrus; MPH, methylphenidate; MSIT, multi-source interference task; MTG, middle temporal gyrus; ODD, oppositional defiant disorder; OFG, orbitofrontal gyrus; PCC, posterior cingulate cortex; PFC, prefrontal cortex; PPI, psychophysiological interaction; preSMA, pre–supplementary motor area; R, right; SAL, salience network; SBC, seed-based correlation; SFG, superior frontal gyrus; SMA, supplementary motor area; SMG, supramarginal gyrus; SN, substantia nigra; SOG, superior occipital gyrus; SPG, superior parietal gyrus; SST, stop signal task; STG, superior temporal gyrus; VAN, ventral attention network; VIS, visual network.
a
Correction for multiple comparisons not specified.
b
White matter and cerebrospinal fluid signal regressors included in the model in addition to standard motion parameters.
c
Scrubbing regressors included in the model for volumes with excessive motion in addition to standard motion parameters.