By analyzing the intrinsic functional connectivity of putative frontal control loci in unbiased whole brain comparisons, we confirmed that the negative relationship posited by Weissman et al. (11
) between control regions and the default-mode network is intrinsically represented in brain. Consistent with our hypothesis that ADHD is associated with abnormalities in fronto-default-mode interactions implicated in preventing attentional lapses, we found ADHD-related decreases in functional connectivity between a dorsal ACC seed and posterior components of the default-mode network (i.e., precuneus and PCC). Iteratively using the precuneus/PCC region as a ‘seed’ for an additional regression analysis revealed ADHD-related decreases in connectivity among components of the default-mode network, notably between precuneus/PCC and ventromedial prefrontal cortex. We did not find a specific relationship between functional connectivity measures and inattention symptoms within the ADHD group, perhaps because inattentive and hyperactive symptoms, both of which were significantly negatively correlated with the regression parameter estimates, were highly correlated in our combined-type ADHD sample (r=0.68). Of note, these novel results fit with the three unbiased voxel-based morphometric findings of diminished volume (30
) or decreased cortical thickness (32
) in precuneus and PCC in ADHD.
While not the primary focus of the present study, our finding of ADHD-related decreases in connectivity between anterior and posterior default mode components may suggest a novel locus of dysfunction for working memory deficits commonly observed in ADHD (33
). Better performance on a working memory task has been reported to be positively related to the strength of functional connectivity between anterior and posterior default-mode components (VMPFC and PCC) (34
). In this light, our findings of ADHD-related decreases in functional connectivity among default-mode components and abnormal connectivity with control regions suggest a potential neural basis for a linkage between working memory deficits and attentional fluctuations that will be addressed in future studies. Similarly, future studies combining pharmacological manipulations and electrophysiological methods or magnetoencephalography will be required to move beyond functional connectivity to effective connectivity
, the influence exerted by one neural system on another (8
Our results do not confirm a prior report of greater functional connectivity in adolescents with ADHD between dACC and widespread regions including thalamus, cerebellum, insula and pons (17
). There are several possible explanations for our divergent findings. First, ACC is functionally and structurally complex (35
); we ‘seeded’ an ACC subregion empirically linked to default-mode interactions, while the seed ROI used by Tian et al. comprised the entire dorsal ACC. Second, Tian et al. did not differentiate the anti-phase relationships (“anti-correlations”) (24
) that accounted for our findings. It is possible that undiagnosed learning disorders in the ADHD participants may have contributed to our finding, although the reasonably high level of educational attainment in all participants tends to diminish this concern. Finally, the samples differed with respect to age group (child, adult). In future studies we plan to examine age effects and directly assess cognitive measures such as attentional lapses (6
), working memory (33
), response variability (36
), and medication response.
In summary, we found strong evidence of disconnection between an anterior cingulate control region implicated in ADHD (32
) and posterior components of the default-mode network, i.e., precuneus and PCC. In the context of increasing awareness of the complex role of precuneus and PCC in “high-level integration between posterior association processes and anterior executive functions” (38
, p. 578), our findings suggest that structural and functional circuits linking the dACC to precuneus and PCC may represent ‘small-world network’ long-range connections (39
) that should be considered as a candidate locus of dysfunction in ADHD.