No support for white matter connectivity differences in the combined and inattentive ADHD presentations

Abstract

Evidence from functional neuroimaging studies support neural differences between the Attention Deficit Hyperactivity Disorder (ADHD) presentation types. It remains unclear if these neural deficits also manifest at the structural level. We have previously shown that the ADHD combined, and ADHD inattentive types demonstrate differences in graph properties of structural covariance suggesting an underlying difference in neuroanatomical organization. The goal of this study was to examine and validate white matter brain organization between the two subtypes using both scalar and connectivity measures of brain white matter. We used both tract-based spatial statistical (TBSS) and tractography analyses with network-based Statistics (NBS) and graph-theoretical analyses in a cohort of 35 ADHD participants (aged 8–17 years) defined using DSM-IV criteria as combined (ADHD-C) type (n = 19) or as predominantly inattentive (ADHD-I) type (n = 16), and 28 matched neurotypical controls. We performed TBSS analyses on scalar measures of fractional anisotropy (FA), mean (MD), radial (RD), and axial (AD) diffusivity to assess differences in WM between ADHD types and controls. NBS and graph theoretical analysis of whole brain inter-regional tractography examined connectomic differences and brain network organization, respectively. None of the scalar measures significantly differed between ADHD types or relative to controls. Similarly, there were no tractography connectivity differences between the two subtypes and relative to controls using NBS. Global and regional graph measures were also similar between the groups. A single significant finding was observed for nodal degree between the ADHD-C and controls, in the right insula (corrected p = .029). Our result of no white matter differences between the subtypes is consistent with most previous findings. These findings together might suggest that the white matter structural architecture is largely similar between the DSM-based ADHD presentations is similar to the extent of being undetectable with the current cohort size.

The structural connectome in ADHD

“…Notably, only three of these studies found significant between-group differences: two studies (Wu et al ., 2017 ; Ohta et al ., 2020 ) showed decreased FA and increased RD mostly overlapping in the genu and posterior of the CC after relatively rigorous head motion was controlled for (participants with heavy motion were excluded; no group differences in head motion were detected; and head motion was used as a covariate); one study reported higher FA in anterior thalamic radiations, bilateral inferior longitudinal fasciculus, and left CST for patients in the predominantly inattentive ADHD presentation and higher FA in the bilateral cingulum bundle in those in the combined ADHD presentation compared with healthy controls (Svatkova et al ., 2016 ). The other eight studies, which also accounted for head motion, reported negative results regarding group differences between ADHD patients and healthy controls in DTI parameters, such as FA and MD, while some of the studies showed significant correlations between FA/MD and symptoms/cognitive performance using a dimensional approach (Ercan et al ., 2016 ; Aoki et al ., 2017 ; Bos et al ., 2017 ; Bouziane et al ., 2018 ; Albaugh et al ., 2019 ; Bessette and Stevens, 2019 ; Albajara Saenz et al ., 2020 ; Saad et al ., 2021 ).…”

“…First, it is hard to ignore that many researchers have reported negative between-group differences in TBSS (Aoki et al ., 2017 ; Bos et al ., 2017 ; Albaugh et al ., 2019 ; Bessette and Stevens, 2019 ; Saad et al ., 2021 ), tractography (Lawrence et al ., 2013 ; de Luis-Garcia et al ., 2015 ; Damatac et al ., 2020 ), and network studies (Sidlauskaite et al ., 2015 ; Griffiths et al ., 2021 ; Qian et al ., 2021 ; Saad et al ., 2021 ). We assume that the lack of significant differences could be related to heterogeneity of both participants and ADHD per se, and the methodology used by most studies.…”

Altered White Matter Integrity in ADHD Revealed by Meta-analysis of Tract-based Spatial Statistics

“…So, this current study solely focused on TBSS findings to avoid the influence of various methodology. Moreover, after we reviewing TBSS studies in ADHD in recent 5 years, we found most literatures did not disclose any significant differences in FA between ADHD and HC group (Albajara Sáenz et al, 2020; Aoki et al, 2018; Bouziane et al, 2018; Saad et al, 2021; S. C. J. Wu et al, 2022).…”

“…Table 1 showed the demographic and methodological information of the included studies. Among them, four studies (Cortese et al, 2013; de Luis-García et al, 2015; Saad et al, 2021; S. C. J. Wu et al, 2022) comprised two subgroups, while another study (Ercan et al, 2016) included three subgroups.…”

“…A total of 317 full text articles were retrieved, of which 22 studies met the inclusion criteria (Albajara Sáenz et al, 2020;Aoki et al, 2018;Bode et al, 2015;Bouziane et al, 2018;Chuang et al, 2013;Cooper et al, 2014;Cortese et al, 2013;de Luis-García et al, 2015;Ercan et al, 2016;Nagel et al, 2011;O'Conaill et al, 2015;Ohta et al, 2020;Onnink et al, 2015;Saad et al, 2021;Silk et al, 2009;Ünsel-Bolat et al, 2020;van Ewijk et al, 2014;; S. C. J. Wu et al, 2022;Yoncheva et al, 2016;R.…”