Journal Pre-proof Common and Distinct Neural Patterns of Attention-Deficit/Hyperactivity Disorder and Borderline Personality Disorder: A Multimodal Functional and Structural Meta-analysis

32 Background: Attention-deficit/hyperactivity disorder (ADHD) and borderline 33 personality disorder (BPD) have partially overlapping symptom profiles and are 34 highly comorbid in adults. However, whether the behavioral similarities 35 correspond to shared neurobiological substrates is not known. 36 Methods: An overlapping meta-analysis of 58 ADHD and 66 BPD whole-brain 37 articles incorporating observations from 3401 adult patients and 3238 healthy 38 participants was performed by Seed-based d Mapping. Brain maps were 39 subjected to meta-analytic connectivity modeling and data-driven functional 40 decoding analyses to identify associated neural circuit alterations and relations 41 to behavioral dimensions. 42 Results: Both groups exhibited hypo-activated abnormalities in the left inferior 43 parietal lobule, and altered clusters of the bilateral superior temporal gyrus were 44 disjunctive in ADHD and BPD. No overlapping structural abnormalities were 45 found. Multimodal alterations of ADHD were located in the right putamen and 46 of BPD in the left orbitofrontal cortex. 47 Conclusions: The transdiagnostic neural bases of ADHD and BPD in temporo- 48 parietal circuitry may underlie overlapping problems of behavioral control, while 49 disorder-specific substrates in fronto-striatal circuitry may account for their 50 distinguishing features in motor and emotion domains respectively.

considering BPD samples (16). The other core area of symptomatic overlap is 77 emotional instability-hasty and inflated alterations in affective states (17), 78 centering on dysfunctional frontal-parietal-limbic systems (18,19). Though 79 sharing these similarities, individuals with BPD tend to have trouble controlling 80 emotions related to their inner experience (20), while the affective and motoric 81 hyper-reactivity of ADHD patients is often a response to external events (21,22). 82 The neuroimaging meta-analysis of ADHD has suggested that volumetric  Table S1). All included studies were evaluated for 129 quality and limitation to infer the importance of these findings with a 12-point 130 Imaging Methodology Quality Assessment Checklist (35), and for details see 131 Supplementary methods. 132 We extracted peak coordinates for brain functional or structural 133 abnormalities and corresponding t values from those articles. Then we coded 134 each study with sample size, mean age, and sex ratio, as well as for parameters 135 of scanner (i.e., Tesla and slice thickness), statistical approach (i.e.,   Table S2). 141 We pooled effect-size brain maps from all categories of fMRI experiments for 142 J o u r n a l P r e -p r o o f the following rationales (36-38). A task paradigm has the presumed association 143 with particular psychological processing that attributes to specific neural 144 substrates (36), while a brain region may underlie tasks of different categories 145 (39,40), indicating that not only one-to-many but also many-to-one theory 146 reflects the nature of the relationship between task paradigms and neural

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To investigate brain functional and structural abnormalities of individuals with 152 ADHD and BPD, we conducted a multimodal meta-analysis with Seed-based d 153 Mapping with Permutation of Subject Images toolbox (SDM-PSI, version 6.21, 154 https://www.sdmproject.com/). Voxel-wise effect-size brain maps were 155 reconstructed accommodating the peak coordinates and corresponding 156 statistical values in the pre-processing (30,42). We created mean effect-size approach could identify both common and distinct patterns of two disorders, 165 and it has the potential to inform the emergence of diagnostic biomarkers for 166 comorbid conditions (30,45). To avoid the likelihood that the false positive rate 167 is higher than a preferred degree in the worst-case scenario, the SDM adjusts

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Meta-analytic co-activation analysis examines regions that typically are co-176 active in prior imaging research with those found to be abnormal in a clinical or 177 psychophysiological study (46,47), allowing for a practical interpretation of the 178 interaction across the whole brain and adding complementary information to 179 task-related and resting-state functional connectivity studies (32,48,49). We 180 delineated the co-activated neural circuits of identified peaks by extracting the 181 peak coordinates and integrated findings of articles that reported activation in 182 2.5. Ancillary Analyses 209 We conducted separate disorder-and modality-specific analyses to supplement 210 with overlapping analysis. Meta-regression analysis was employed to examine 211 the potential role of demographic factors and medication status at the whole-212 brain level (23). Following the main meta-analyses, we extracted the Hedges'   Among 122 eligible studies in the meta-analysis, no statistical difference 226 between patient groups was noted in the sample size-weighted t tests in age 227 (fMRI, t91 = .510, p = .611; VBM, t25 = .052, p = .959), but BPD studies consisted t91 = 11.027, p < .001; VBM, t25 = 5.621, p < .001). The proportion of medicated 230 patients did not differ by diagnosis ( 2 1 = .020, p = .889) ( Table 1).  (Table 3).

Overlapping Analysis across Modalities
In ADHD, multimodal conjunction analysis revealed that the cluster in right  were found in either ADHD or BPD.  (Table 3). Co-activation patterns 273 in MACM analysis are shown in Supplementary Table S5 and Figure Table S6 and Figure S2). The top 10 278 psychophysical terms correlated with those brain abnormalities to infer its main 279 functioning were shown in Supplementary Table S7, as the left IPL of 280 overlapping analysis predominately correlated with "retention" and "execution", 281 left STG correlated with "music" and "speak", right STG correlated with "pain" 282 and "listening", and the right putamen of distinct multimodal analysis with 283 "sensation" and "motor" and left OFC with "decision" and "value".  Table S8). The modulatory effects of medication status on brain 292 structural patterns of ADHD and BPD overlapped in the right putamen/insula.

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The current multimodal meta-analysis provides a comprehensive delineation of

Potential role of medication status 422
The meta-regression analysis revealed that modulated brain structural   Acknowledgments 468 We deeply appreciate all the authors of the included studies who responded to 469 our requests for further information.