Hostname: page-component-848d4c4894-x5gtn Total loading time: 0 Render date: 2024-06-09T01:58:14.640Z Has data issue: false hasContentIssue false
  • English
  • Français

Shared intrinsic functional connectivity alterations as a familial risk marker for ADHD: a resting-state functional magnetic resonance imaging study with sibling design

Published online by Cambridge University Press:  13 October 2020

Huey-Ling Chiang Open the ORCID record for Huey-Ling Chiang [Opens in a new window] ,
Wen-Yih Isaac Tseng ,
Hsiao-Ying Wey  and
Susan Shur-Fen Gau Open the ORCID record for Susan Shur-Fen Gau [Opens in a new window]
Huey-Ling Chiang
Affiliation:
Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan Department of Psychiatry, Far Eastern Memorial Hospital, New Taipei City, Taiwan Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, USA
Wen-Yih Isaac Tseng
Affiliation:
Institute of Medical Device and Imaging, National Taiwan University College of Medicine, Taipei, Taiwan
Hsiao-Ying Wey*
Affiliation:
Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, USA
Susan Shur-Fen Gau*
Affiliation:
Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan Graduate Institute of Clinical Medicine, and Graduate Institute of Brain and Mind Sciences, National Taiwan University College of Medicine, Taipei, Taiwan
*
Author for correspondence: Susan Shur-Fen Gau, E-mail: gaushufe@ntu.edu.tw; Hsiao-Ying Wey, E-mail: hsiaoying.wey@mgh.harvard.edu
Author for correspondence: Susan Shur-Fen Gau, E-mail: gaushufe@ntu.edu.tw; Hsiao-Ying Wey, E-mail: hsiaoying.wey@mgh.harvard.edu
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Although aberrant intrinsic functional connectivity has been reported in attention-deficit/hyperactivity disorder (ADHD), we have a limited understanding of whether connectivity alterations are related to the familial risk of ADHD.

Methods

Fifty-three probands with ADHD, their unaffected siblings (n = 53) and typically developing controls (n = 53) underwent resting-state functional magnetic resonance imaging scans. A seed-based approach with the bilateral precuneus/posterior cingulate cortex (PCC) was used to derive a whole-brain functional connectivity map in each subject. The differences in functional connectivity among the three groups were tested with one-way ANOVA using randomized permutation. Comparisons between two groups were also performed to examine the increase or decrease in connectivity. The severity of ADHD symptoms was used to identify brain regions where symptom severity is correlated to the strength of intrinsic functional connectivity.

Results

When compared to controls, both probands and unaffected siblings showed increased functional connectivity in the left insula and left inferior frontal gyrus. The connectivity in these regions was linked to better performance in response inhibition in the control group but absent in other groups. Higher ADHD symptom severity was correlated with increased functional connectivity in bilateral fronto-parietal-temporal regions only noted in probands with ADHD.

Conclusions

Alterations in resting-state functional connectivities with the precuneus/PCC, hubs of default-mode network, account for the underlying familial risks of ADHD. Since the left insula and left inferior frontal gyri are key regions of the salience and frontoparietal network, respectively, future studies focusing on alterations of cross-network functional connectivity as the familial risk of ADHD are suggested.

Keywords

Attention-deficit/hyperactivity disorderfamilial riskintrinsic functional connectivityresting-state functional magnetic resonance imagingunaffected siblings
Type
Original Article
Information
Psychological Medicine , Volume 52 , Issue 9 , July 2022 , pp. 1736 - 1745
Check for updates
Copyright
Copyright © The Author(s) 2020. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Barber, A. D., Jacobson, L. A., Wexler, J. L., Nebel, M. B., Caffo, B. S., Pekar, J. J., Mostofsky, S. H. (2015). Connectivity supporting attention in children with attention deficit hyperactivity disorder. Neuroimage Clinical, 7, 68–81.CrossRefGoogle ScholarPubMed
Bonnelle, V., Ham, T. E., Leech, R., Kinnunen, K. M., Mehta, M. A., Greenwood, R. J., & Sharp, D. J. (2012). Salience network integrity predicts default mode network function after traumatic brain injury. Proceedings of the National Academy of Sciences of the USA, 109, 4690–4695.CrossRefGoogle ScholarPubMed
Bussing, R., Mason, D. M., Bell, L., Porter, P., & Garvan, C. (2010). Adolescent outcomes of childhood attention-deficit/hyperactivity disorder in a diverse community sample. American Academy of Child & Adolescent Psychiatry, 49, 595–605.Google Scholar
Castellanos, F. X., Margulies, D. S., Kelly, C., Uddin, L. Q., Ghaffari, M., Kirsch, A., … Milham, M. P. (2008). Cingulate-precuneus interactions: a new locus of dysfunction in adult attention-deficit/hyperactivity disorder. Biological Psychiatry, 63, 332–337CrossRefGoogle ScholarPubMed
Chang, L. R., Chiu, Y. N., Wu, Y. Y., & Gau, S. S. (2013). Father's parenting and father-child relationship among children and adolescents with attention-deficit/hyperactivity disorder. Comprehensive Psychiatry, 54, 128–140.CrossRefGoogle ScholarPubMed
Chiang, H. L., Chen, Y. J., Lo, Y. C., Tseng, W. Y., & Gau, S. S. (2015). Altered white matter tract property related to impaired focused attention, sustained attention, cognitive impulsivity and vigilance in attention-deficit/ hyperactivity disorder. Journal of Psychiatry & Neuroscience, 40, 325–335.CrossRefGoogle ScholarPubMed
Cockshott, F. C., Marsh, N. V., & Hine, D. W. (2006). Confirmatory factor analysis of the Wechsler Intelligence Scale for Children – Third Edition in an Australian clinical sample. Psychological Assessment, 18, 353–357.CrossRefGoogle Scholar
Conners, C. K., & MHS Staff. (2000) Conners’ continuous performance test II: Computer program for windows technical guide and software manual. North Tonwanda, NY: Multi-Health Systems.Google Scholar
Craig, A. D. (2002). How do you feel? Interoception: The sense of the physiological condition of the body. Nature Reviews Neuroscience, 3, 655–666.CrossRefGoogle Scholar
Fan, L. Y., Shang, C. Y., Tseng, W. I., Gau, S. S., & Chou, T. L. (2018). Visual processing as a potential endophenotype in youths with attention-deficit/hyperactivity disorder: A sibling study design using the counting Stroop functional MRI. Human Brain Mapping, 39, 3827–3835.CrossRefGoogle ScholarPubMed
Faraone, S. V., & Larsson, H. (2019). Genetics of attention deficit hyperactivity disorder. Molecular Psychiatry, 24, 562–575.CrossRefGoogle ScholarPubMed
Farrant, K., & Uddin, L. Q. (2015). Asymmetric development of dorsal and ventral attention networks in the human brain. Developmental Cognitive Neuroscience, 12, 165–174.CrossRefGoogle ScholarPubMed
Fox, M. D., Snyder, A. Z., Vincent, J. L., Corbetta, M., Van Essen, D. C., & Raichle, M. E. (2005). The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proceedings of the National Academy of Sciences of the USA, 102, 9673–9678.CrossRefGoogle ScholarPubMed
Francx, W., Oldehinkel, M., Oosterlaan, J., Heslenfeld, D., Hartman, C. A., Hoekstra, P. J., … Mennes, M. (2015). The executive control network and symptomatic improvement in attention-deficit/hyperactivity disorder. Cortex, 73, 62–72.CrossRefGoogle ScholarPubMed
Gau, S. S., Chong, M. Y., Chen, T. H., & Cheng, A. T. (2005). A 3-year panel study of mental disorders among adolescents in Taiwan. American Journal of Psychiatry, 162, 1344–1350.CrossRefGoogle ScholarPubMed
Gau, S. S., & Huang, W. L. (2014). Rapid visual information processing as a cognitive endophenotype of attention deficit hyperactivity disorder. Psychological Medicine, 44, 435–446.CrossRefGoogle ScholarPubMed
Gau, S. S., Lin, Y. J., Cheng, A. T., Chiu, Y. N., Tsai, W. C., & Soong, W. T. (2010). Psychopathology and symptom remission at adolescence among children with attention-deficit/hyperactivity disorder in Taiwan. Australian & New Zealand Journal of Psychiatry, 44, 323–332.Google Scholar
Glahn, D. C., Knowles, E. E., McKay, D. R., Sprooten, E., Raventos, H., Blangero, J, … Almasy, L. (2014). Arguments for the sake of endophenotypes: Examining common misconceptions about the use of endophenotypes in psychiatric genetics. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics, 165B, 122–130.CrossRefGoogle ScholarPubMed
Godinez, D. A., Willcutt, E. G., Burgess, G. C., Depue, B. E., Andrews-Hanna, J. R., & Banich, M. T. (2015). Familial risk and ADHD-specific neural activity revealed by case-control, discordant twin pair design. Psychiatry Research, 233, 458–465.CrossRefGoogle ScholarPubMed
Karam, R. G., Rovaris, D. L., Breda, V., Picon, F. A., Victor, M. M., Salgado, C. A. I., ... Bau, C. H. D. (2017). Trajectories of attention-deficit/hyperactivity disorder dimensions in adults. Acta Psychiatrica Scandinavica, 136, 210–219.CrossRefGoogle ScholarPubMed
Kelly, A. M., Uddin, L. Q., Biswal, B. B., Castellanos, F. X., & Milham, M. P. (2008). Competition between functional brain networks mediates behavioral variability. Neuroimage, 39, 527–537.CrossRefGoogle ScholarPubMed
Larsson, H., Chang, Z., D'Onofrio, B. M., & Lichtenstein, P. (2014). The heritability of clinically diagnosed attention deficit hyperactivity disorder across the lifespan. Psychological Medicine, 44, 2223–2229.CrossRefGoogle ScholarPubMed
Lin, Y. J., Yang, L. K., & Gau, S. S. (2016). Psychiatric comorbidities of adults with early- and late-onset attention-deficit/hyperactivity disorder. Australian & New Zealand Journal of Psychiatry, 50, 548–556.CrossRefGoogle ScholarPubMed
Marcus, D. S., Harms, M. P., Snyder, A. Z., Jenkinson, M., Wilson, J. A., Glasser, M. F., Van Essen, D. C. (2013). Human connectome project informatics: Quality control, database services, and data visualization. Neuroimage, 80, 202–219.CrossRefGoogle ScholarPubMed
McCarthy, H., Skokauskas, N., Mulligan, A., Donohoe, G., Mullins, D., Kelly, J., … Frodl, T. (2013). Attention network hypoconnectivity with default and affective network hyperconnectivity in adults diagnosed with attention-deficit/hyperactivity disorder in childhood. JAMA Psychiatry, 70, 1329–1337.CrossRefGoogle ScholarPubMed
Menon, V. (2011). Large-scale brain networks and psychopathology: A unifying triple network model. Trends in Cognitive Sciences, 15, 483–506.CrossRefGoogle ScholarPubMed
Murphy, K., Birn, R. M., Handwerker, D. A., Jones, T. B., & Bandettini, P. A. (2009). The impact of global signal regression on resting state correlations: Are anti-correlated networks introduced? Neuroimage, 44, 893–905.CrossRefGoogle ScholarPubMed
Pironti, V. A., Lai, M. C., Muller, U., Dodds, C. M., Suckling, J., Bullmore, E. T., & Sahakian, B. J. (2014). Neuroanatomical abnormalities and cognitive impairments are shared by adults with attention-deficit/hyperactivity disorder and their unaffected first-degree relatives. Biological Psychiatry, 76, 639–647.CrossRefGoogle ScholarPubMed
Rommelse, N. N., Oosterlaan, J., Buitelaar, J., Faraone, S. V., & Sergeant, J. A. (2007). Time reproduction in children with ADHD and their nonaffected siblings. American Academy of Child & Adolescent Psychiatry, 46, 582–590.CrossRefGoogle ScholarPubMed
Rubia, K. (2018). Cognitive neuroscience of attention deficit hyperactivity disorder (ADHD) and its clinical translation. Frontiers in Human Neuroscience, 12, 100.CrossRefGoogle ScholarPubMed
Shang, C. Y., Lin, H. Y., Tseng, W. Y., & Gau, S. S. (2018). A haplotype of the dopamine transporter gene modulates regional homogeneity, gray matter volume, and visual memory in children with attention-deficit/hyperactivity disorder. Psychological Medicine, 48, 2530–2540.CrossRefGoogle ScholarPubMed
Sheline, Y. I., Price, J. L., Yan, Z., & Mintun, M. A. (2010). Resting-state functional MRI in depression unmasks increased connectivity between networks via the dorsal nexus. Proceedings of the National Academy of Sciences of the USA, 107, 11020–11025.CrossRefGoogle ScholarPubMed
Smith, S. M., & Nichols, T. E. (2009). Threshold-free cluster enhancement: Addressing problems of smoothing, threshold dependence and localisation in cluster inference. Neuroimage, 44, 83–98.CrossRefGoogle ScholarPubMed
Sonuga-Barke, E. J., & Castellanos, F. X. (2007). Spontaneous attentional fluctuations in impaired states and pathological conditions: A neurobiological hypothesis. Neuroscience & Biobehavioral Reviews, 31, 977–986.CrossRefGoogle ScholarPubMed
Sridharan, D., Levitin, D. J., & Menon, V. (2008). A critical role for the right fronto-insular cortex in switching between central-executive and default-mode networks. Proceedings of the National Academy of Sciences of the USA, 105, 12569–12574.CrossRefGoogle ScholarPubMed
Sripada, C., Kessler, D., Fang, Y., Welsh, R. C., Prem Kumar, K., & Angstadt, M. (2014). Disrupted network architecture of the resting brain in attention-deficit/hyperactivity disorder. Human Brain Mapping, 35, 4693–4705.CrossRefGoogle ScholarPubMed
Sudre, G., Choudhuri, S., Szekely, E., Bonner, T., Goduni, E., Sharp, W., & Shaw, P. (2017). Estimating the heritability of structural and functional brain connectivity in families affected by attention-deficit/hyperactivity disorder. JAMA Psychiatry, 74, 76–84.CrossRefGoogle ScholarPubMed
Tops, M., & Boksem, M. A. (2011). A potential role of the inferior frontal gyrus and anterior insula in cognitive control, brain rhythms, and event-related potentials. Frontiers in Psychology, 2, 330.CrossRefGoogle ScholarPubMed
Tsai, F. J., Tseng, W. L., Yang, L. K., & Gau, S. S. (2019). Psychiatric comorbid patterns in adults with attention-deficit hyperactivity disorder: Treatment effect and subtypes. PLoS ONE, 14, e0211873.CrossRefGoogle ScholarPubMed
Uddin, L. Q. (2015). Salience processing and insular cortical function and dysfunction. Nature Reviews Neuroscience, 16, 55–61.CrossRefGoogle ScholarPubMed
Utevsky, A. V., Smith, D. V., & Huettel, S. A. (2014). Precuneus is a functional core of the default-mode network. Journal of Neuroscience, 34, 932–940.CrossRefGoogle ScholarPubMed
van Rooij, D., Hoekstra, P. J., Mennes, M., von Rhein, D., Thissen, A. J., Heslenfeld, D., … Hartman, C. A. (2015). Distinguishing adolescents with ADHD from their unaffected siblings and healthy comparison subjects by neural activation patterns during response inhibition. American Journal of Psychiatry, 172, 674–683.CrossRefGoogle ScholarPubMed
von Rhein, D., Cools, R., Zwiers, M. P., van der Schaaf, M., Franke, B., Luman, M., … Buitelaar, J. (2015). Increased neural responses to reward in adolescents and young adults with attention-deficit/hyperactivity disorder and their unaffected siblings. American Academy of Child & Adolescent Psychiatry, 54, 394–402.CrossRefGoogle Scholar
Wechsler, D. (1981). Manual for the Wechsler Adult Intelligence Scale – revised. New York: Psychological Corporation.Google Scholar
Winkler, A. M., Ridgway, G. R., Webster, M. A., Smith, S. M., & Nichols, T. E. (2014). Permutation inference for the general linear model. Neuroimage, 92, 381–397.CrossRefGoogle ScholarPubMed
Wittmann, M., Simmons, A. N., Aron, J. L., & Paulus, M. P. (2010). Accumulation of neural activity in the posterior insula encodes the passage of time. Neuropsychologia, 48, 3110–3120.CrossRefGoogle ScholarPubMed
Yeo, B. T., Krienen, F. M., Sepulcre, J., Sabuncu, M. R., Lashkari, D., Hollinshead, M., … Buckner, R. L. (2011). The organization of the human cerebral cortex estimated by intrinsic functional connectivity. Journal of Neurophysiology, 106, 1125–1165.Google ScholarPubMed
Zhao, Q., Li, H., Yu, X., Huang, F., Wang, Y., Liu, L., … Wang, Y. (2017). Abnormal resting-state functional connectivity of insular subregions and disrupted correlation with working memory in adults with attention deficit/hyperactivity disorder. Frontiers in Psychiatry, 8, 200.CrossRefGoogle ScholarPubMed
Supplementary material: Image

Chiang et al. Supplementary Materials

Chiang et al. Supplementary Materials 1

Download Chiang et al. Supplementary Materials(Image)
Image 309.8 KB
Supplementary material: File

Chiang et al. Supplementary Materials

Chiang et al. Supplementary Materials 2

Download Chiang et al. Supplementary Materials(File)
File 15.5 KB