Table I.
Neuroimaging studies on structural and functional connectivity in subjects with ADHD
| Authors | Measures | Task | Subjects | Findings |
|---|---|---|---|---|
| Resting state | ||||
| Tian et al. (2006) | fMRI, ROI, LFF | Resting state | N = 8 subjects with ADHD compared to N = 8 controls (aged 11–15 years) | Compared to controls, ADHD patients exhibited more significant resting‐state functional connectivities with the dACC in thalamus, cerebellum, insula and pons, all bilaterally. No brain region in the controls was found to exhibit more significant resting‐state functional connectivity with the dACC |
| Cao et al. (2006) | fMRI, seed‐based correlation analyses, regional homogeneity | Resting state | N = 23 boys with ADHD compared to N = 21 controls (aged 11.00–16.5 years) | Boys with ADHD showed decreased regional homogeneity in the frontal‐striatal‐cerebellar circuits, but increased regional homogeneity mainly in the occipital cortex. |
| Zhu et al. (2005) | Multivariate pattern classification for ReHo values assessed by fMRI | Resting state | N = 9 subjects with ADHD (aged 11–15 years) compared to N = 11 controls | Initial experimental results show a successful classification rate of 85%, using leave‐one‐out cross validation. Compared with linear SVM and Batch Perceptron, the classifier outperformed the alternatives significantly. |
| Zang et al. (2006) | ALFF (0.01‐0.08Hz) | Resting‐state | N = 13 subjects with ADHD (aged 13 ± 1.4 ears) compared to N = 12 controls | Patients with ADHD had decreased ALFF in the right inferior frontal cortex, left sensorimotor cortex, and bilateral cerebellum and the vermis as well as increased ALFF in the right anterior cingulated cortex, left sensorimotor cortex, and bilateral brainstem. |
| Castellanos et al (2008) | fMRI, ROI | Resting state | N = 20 adults with ADHD compared to N = 20 controls | Examination of control subjects verified presence of an antiphasic or negative relationship between activity in dorsal anterior cingulate cortex and in default‐mode network components. Group analyses revealed ADHD‐related compromises in this relationship, with decreases in the functional connectivity between the anterior cingulate and precuneus/posterior cingulate cortex regions. Secondary analyses revealed an extensive pattern of ADHD‐related decreases in connectivity between precuneus and other default‐mode network components, includingventromedial prefrontal cortex and portions of posterior cingulate |
| Tian et al. (2008) | fMRI, ROI, RSAI | Resting state | Same dataset as Tian et al. (2006) | As compared to the controls, the ADHD patients exhibited more significant resting‐state activities in basic sensory and sensory‐related cortices. |
| Uddin et al. (2008) | fMRI, network homogeneity | Resting state | Same dataset as Castellanos et al. (2008) | Reduced network homogeneity within the default mode network in ADHD subjects compared to age‐matched controls, particularly between the precuneus and other default mode network regions |
| Helps et al (2008) | DC‐EEG, VLFO (<0.2 Hz) | Resting state | 13 young adults with high‐ compared to 11 adults with low self‐ratings of ADHD | A consistent and temporally stable pattern of VLFOs was observed across specific scalp regions in low‐ADHD participants. High‐ADHD participants had less VLFO power across these locations, especially where inattention self‐ratings were high. Inattention was not related to VLFO power in other locations |
| Wang et al. (2009) | Correlation matrix between 90 cortical and subcortical regions, further analyzed by applying graph theoretical approaches (small world network topology) | Resting state | N = 19 subjects with ADHD (aged 13.59 ± 1.52 years) compared to N = 20 controls (aged 13.32 ± 0.97 years) | Increased local efficiencies combined with a decreasing tendency in global efficiencies found in ADHD suggested a disorder‐related shift of the topology toward regular networks. Additionally, significant alterations in nodal efficiency were also found in ADHD, involving prefrontal, temporal, and occipital cortex regions |
| Cognitive Tasks | ||||
| Wolf et al. (2009) | fMRI, ICA | Working memory task | N = 12 adults with ADHD compared to N = 12 controls | In both groups, independent component analyses revealed a functional network comprising bilateral lateral prefrontal, striatal, and cingulate regions. ADHD adults had significantly lower connectivity in the bilateral VLPFC, the anterior cingulate cortex, the superior parietal lobule, and the cerebellum compared with healthy controls. Increased connectivity in ADHD adults was found in right prefrontal regions, the left dorsal cingulate cortex and the left cuneus |
| Rubia et al. (2009) | fMRI, correlation of averaged time‐series | Rewarded continuous performance test | N =13 treatment‐naive subjects with ADHD (aged 10–15 years) scanned twice (on and off medication) compared to N = 13 controls | Under placebo, patients with ADHD showed reduced activation and functional interconnectivity in bilateral fronto‐striato‐‐parieto‐cerebellar networks during sustained attention. MPH normalised differences during sustained attention in fronto‐striatal and fronto‐cerebellar connectivity. |
| Vloet et al. (in press) | fMRI, PPI | Combined interference and time discrimination task | N = 14 children with ADHD compared to 14 controls (aged 8–15 years) | Functional connectivity analyses revealed abnormal fronto‐parietal coupling during the interference task and reduced fronto‐cerebellar connectivity during the Time discrimination task in the ADHD group compared to controls. |
| DTI studies | ||||
| Ashtari et al. (2005) | DTI, FA | N = 18 children with ADHD compared to N = 15 controls | Decreased FA in right premotor, right striatal, right cerebral peduncle, left middle cerebellar peduncle, left cerebellum, and left parieto‐occipital areas | |
| Makris et al (2008) | DTI, FA | CB and SLF II | N = 12 adults with childhood ADHD compared to N = 17 controls | Significantly lower FA values in both regions of interest in the right hemisphere, in contrast to a control region (the fornix) in ADHD compared to control subjects |
| Casey et al. (2007) | DTI, FA | Automated fiber‐tracking algorithm was used to delineate white matter fibers adjacent to functionally defined regions as identified by a Go‐Nogo task | N = 20 parent–child dyads with ADHD and N = 10 dyads without ADHD | FA in right prefrontal fiber tracts correlated with both functional activity in the inferior frontal gyrus and caudate nucleus and performance of a go/nogo task in parent‐child dyads with ADHD, even after controlling for age. Prefrontal fiber tract measures were tightly associated between ADHD parents and their children. |
| Pavuluri et al. (2009) | DTI, FA, ADC, r‐FCI | Eight fiber tracts: ACR, ALIC, SRI, PLIC, SLF, ILF, CG, SP. | N = 13 PBD, N =13 ADHD compared to N = 15 controls | Significantly lower FA was observed in ACR in both PBD and ADHD relative to HC. In addition, FA and r‐FCI values were significantly lower in ADHD relative to PBD and HC in both the ALIC and the SRI. Further, ADC was significantly greater in ADHD relative to both the PBD and HC in ACR, ALIC, PLIC, SRI, CG, ILF, and SLF. |
| Hamilton et al. (2008) | DTI, FA within the cingulum, corpus callosum, corticospinal tract, fornix, optic radiations, superior longitudinal fasciculus, uncinate fasciculus, and the superior and inferior occipitofrontal fasciculi | N = 17 children and adolescents with ADHD compared to N = 16 age‐matched controls | ADHD patients had significantly lower FA in the corticospinal tract and the superior longitudinal fasciculus compared to controls. | |
| Silk et al. (2009) | DTI, FA and mean diffusity in ROIs of the basal ganglia | N = 15 male children and adolescents with ADHD compared to N = 15 age‐matched controls (aged 8–18 years) | In the caudate nucleus, developmental changes in FA with age were significantly different between subjects with ADHD and controls. | |
ROI, region of interest; LFF, low‐frequency fluctuations; dACC, dorsal anterior cingulate cortex; DMN, default‐mode network; ReHO, regional homogeneity; SVM, support vector machine; ALFF, amplitude of low‐frequency fluctuation; RSAI, resting state activity index; DC‐EEG, direct current electroencephalogram; VLFO, very low frequency oscillations; ICA, independent component analysis; VLPFC, ventrolateral prefrontal cortex; MPH, methylphenidate; PPI, psychophysiological interaction; DTI, diffusion tensor imaging; FA, fractional anisotropy; CB, cingulum bundle; SLF II, superior longitudinal fasciculi; ADC, apparent diffusion coefficient; r‐FCI, regional fiber coherence index; ACR, anterior corona radiata; ALIC, anterior limb of the internal capsule; SRI, superior region of the internal capsule; PLIC, posterior limb of the internal capsule; SLF, superior longitudinal fasciculus; ILF, inferior longitudinal fasciculus; CG, cingulum; SP, splenium; PBD, pediatric bipolar disorder; HC, healthy controls.