Amygdala sub-regional functional connectivity predicts anxiety in children with reading disorder
Open accessAbstract
Pediatric reading disorder (RD) is associated with an increased risk of anxiety symptoms, yet understudied are the neurobiological factors that might underlie anxiety in children with RD. Given the role of the amygdala in anxiety, we assessed resting state functional connectivity of amygdalar subregions in children with RD to identify functional correlates of anxiety and reading impairment. We collected resting state functional MRI data from 22 children with RD and 21 typically developing (TD) children, ages 7 to 13 years. We assessed group differences in resting state functional connectivity (RSFC) from amygdalar subregions. Associations of amygdalar RSFC and volume with reading impairment, reading fluency scores, and anxiety symptoms were explored. Relative to TD children, those with RD showed increased RSFC from amygdalar nuclei to medial prefrontal cortex. Across all subjects, RSFC from right centromedial amygdala to left medial prefrontal cortex positively predicted both reading impairment and self‐reported anxiety, and anxiety mediated the relationship between RSFC and reading impairment. These findings are consistent with amygdalar functional abnormalities in pediatric anxiety disorders, suggesting a common neurobiological mechanism underlying anxiety and reading impairment in children. Thus, aberrant patterns of RSFC from amygdalar subregions may serve as potential targets for the treatment of anxiety symptoms that typically co‐occur with RD. Our dimensional approach to studying anxiety in RD revealed how amygdalar connectivity underlies anxiety and reading impairment across a continuum from normal to abnormal.
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Reading engages the prefrontal cortex and amygdala and also modulates other regions involved in emotional and cognitive processing, such as the hippocampus and the cingulate gyrus.
“Findings indicate that reading not only engages the prefrontal cortex and amygdala but also modulates other regions involved in emotional and cognitive processing, such as the hippocampus and the cingulate gyrus (93, 94).”
From Recent developments in bibliotherapy for adolescent depression (2025) · cites this paper as [93]
The Discussion links reading impairment in children with reading disorder to resting-state connectivity between the amygdala and medial prefrontal cortex. It does not establish that reading itself engages those regions: the authors call for future imaging during reading tasks. Our copy also provides no finding that reading modulates the hippocampus or cingulate gyrus. (LLM, conf=0.83)
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Cites
Using Neuroscience to Help Understand Fear and Anxiety: A Two-System Framework
LeDoux, J. E., & Pine, D. S. (2016) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2016.16030353 · Cited by 1,035 · see citing works
Neural Correlates of Positive and Negative Emotion Regulation
Kim, S. H., & Hamann, S. (2007) · Journal of Cognitive Neuroscience · doi:10.1162/jocn.2007.19.5.776 · Cited by 615 · cited 2× · see citing works
“…prefrontal circuits involved in emotion regulation (Brown et al., 2014; Etkin, 2010; Gee et al., 2013; Hahn et al., 2011; Hamm et al., 2014; S.H. Kim & Hamann, 2007; Liao et al., 2010; Prater et al., 2013; Qin et al., 2014; Roy et al., 2009, 2013; Sripada et al., 2012; Sylvester et al., 2013;…”
BackgroundAltered resting-state amygdala functional connectivity in men with posttraumatic stress disorder
Sripada, R. K., King, A. P., Garfinkel, S. N., Wang, X., Sripada, C. S., Welsh, R. C., & Liberzon, I. (2012) · Journal of Psychiatry and Neuroscience · doi:10.1503/jpn.110069 · Cited by 352 · see citing works
Qin, S., Young, C. B., Duan, X., Chen, T., Supekar, K., & Menon, V. (2014) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.10.006 · Cited by 249 · see citing works
Prater, K. E., Hosanagar, A., Klumpp, H., Angstadt, M., & Luan Phan, K. (2013) · Depression and Anxiety · doi:10.1002/da.22014 · Cited by 194 · see citing works
Remediation of childhood math anxiety and associated neural circuits through cognitive tutoring
Supekar, K., Iuculano, T., Chen, L., & Menon, V. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.0786-15.2015 · Cited by 187 · see citing works
Immature integration and segregation of emotion-related brain circuitry in young children
Qin, S., Young, C. B., Supekar, K., Uddin, L. Q., & Menon, V. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1120408109 · Cited by 130 · see citing works
Flagged first, then by citations
Research works printed but not linked: 40
- Baas D Aleman A Kahn RS 2004 Lateralization of amygdala activation: A systematic review of functional neuroimaging studies Brain Research Reviews 45 96 103 15145620
- Behzadi Y Restom K Liau J Liu TT 2007 A component based noise correction method (CompCor) for BOLD and perfusion based fMRI NeuroImage 37 90 101 17560126 PMC2214855
- Binder JR Frost JA Hammeke TA Cox RW Rao SM Prieto T 1997 Human brain language areas identified by functional magnetic resonance imaging Journal of Neuroscience 17 353 362 8987760 PMC6793702
- Brown VM LaBar KS Haswell CC Gold AL Beall SK Van Voorhees E … Morey RA 2014 Altered resting-state functional connectivity of basolateral and centromedial amygdala complexes in posttraumatic stress disorder Neuropsychopharmacology 39 351 359 23929546 PMC3870774
- Carroll JM Maughan B Goodman R Meltzer H 2005 Literacy difficulties and psychiatric disorders: Evidence for comorbidity Journal of Child Psychology and Psychiatry 46 524 532 15845132
- Ciric R Wolf DH Power JD Roalf DR Baum GL Ruparel K Satterthwaite TD 2017 Benchmarking of participant-level confound regression strategies for the control of motion artifact in studies of functional connectivity NeuroImage 154 174 187 28302591 PMC5483393
- de los Reyes A 2017 Inaugural editorial: Making the Journal of Clinical Child & Adolescent Psychology your “home journal” Journal of Clinical Child and Adolescent Psychology 46 1 10 28169578
- Diamond A 2013 Executive functions Annual Review of Psychology 64 135 168 PMC4084861 23020641
- Eickhoff SB Stephan KE Mohlberg H Grefkes C Fink GR Amunts K Zilles K 2005 A new SPM toolbox for combining probabilistic cytoarchitectonic maps and functional imaging data NeuroImage 25 1325 1335 15850749
- Etkin A 2010 Functional neuroanatomy of anxiety: A neural circuit perspective Current Topics in Behavioral Neurosciences 2 251 277 21309113
- Etkin A Prater KE Schatzberg AF Menon V Greicius MD 2009 Disrupted amygdalar subregion functional connectivity and evidence of a compensatory network in generalized anxiety disorder Archives of General Psychiatry 66 1361 1372 19996041 PMC12553334
- Gabrieli JDE Poldrack RA Desmond JE 1998 The role of left prefrontal cortex in language and memory Proceedings of the National Academy of Sciences, USA 95 906 913 PMC33815 9448258
- Gee DG Humphreys KL Flannery J Goff B Telzer EH Shapiro M … Tottenham N 2013 A developmental shift from positive to negative connectivity in human amygdala–prefrontal circuitry Journal of Neuroscience 33 4584 4593 23467374 PMC3670947
- Greenham SL 1999 Learning disabilities and psychosocial adjustment: A critical review Child Neuropsychology 5 171 196
- Grills-Taquechel AE Fletcher JM Vaughn SR Stuebing KK 2012 Anxiety and reading difficulties in early elementary school: Evidence for unidirectional- or bi-directional relations? Child Psychiatry and Human Development 43 35 47 21822734 PMC3360892
- Hagoort P Indefrey P 2014 The neurobiology of language beyond single words Annual Review of Neuroscience 37 347 362 24905595
- Hahn A Stein P Windischberger C Weissenbacher A Spindelegger C Moser E … Lanzenberger R 2011 Reduced resting-state functional connectivity between amygdala and orbitofrontal cortex in social anxiety disorder NeuroImage 56 881 889 21356318
- Hamm LL Jacobs RH Johnson MW Fitzgerald DA Fitzgerald KD Langenecker SA … Phan KL 2014 Aberrant amygdala functional connectivity at rest in pediatric anxiety disorders Biology of Mood and Anxiety Disorders 4 15 25530842 PMC4272798
- Hudziak JJ Achenbach TM Althoff RR Pine DS 2007 A dimensional approach to developmental psychopathology International Journal of Methods in Psychiatric Research 16 S16 S23 17623391 PMC6879082
- Insel T Cuthbert B Garvey M Heinssen R Pine DS Quinn K … Wang P 2010 Research domain criteria (RDoC): Toward a new classification framework for research on mental disorders American Journal of Psychiatry 167 748 751 20595427
- Kim MJ Loucks RA Palmer AL Brown AC Solomon KM Marchante AN Whalen PJ 2011 The structural and functional connectivity of the amygdala: From normal emotion to pathological anxiety Behavioural Brain Research 223 403 410 21536077 PMC3119771
- Koyama MS Di Martino A Kelly C Jutagir DR Sunshine J Schwartz SJ … Milham MP 2013 Cortical signatures of dyslexia and remediation: An intrinsic functional connectivity approach PLoS ONE 8 e55454 23408984 PMC3569450
- Koyama MS Di Martino A Zuo XN Kelly C Mennes M Jutagir DR … Milham MP 2011 Resting-state functional connectivity indexes reading competence in children and adults Journal of Neuroscience 31 8617 8624 21653865 PMC3893355
- LeDoux JE 2003 The emotional brain, fear, and the amygdala Cellular and Molecular Neurobiology 23 727 738 14514027 PMC11530156
- Li Y Qin W Jiang T Zhang Y Yu C 2012 Sex-dependent correlations between the personality dimension of harm avoidance and the resting-state functional connectivity of amygdala subregions PLoS ONE 7 e35925 22558274 PMC3338761
- Liao W Qiu C Gentili C Walter M Pan Z Ding J … Chen H 2010 Altered effective connectivity network of the amygdala in social anxiety disorder: A resting-state fMRI study PLoS ONE 5 e15238 21203551 PMC3008679
- Lyon GR 1996 Learning disabilities The Future of Children 6 54 76 8689262
- Margari L Buttiglione M Craig F Cristella A de Giambattista C Matera E … Simone M 2013 Neuropsychopathological comorbidities in learning disorders BMC Neurology 13 198 24330722 PMC3878726
- Murphy K Birn RM Handwerker DA Jones TB Bandettini PA 2009 The impact of global signal regression on resting state correlations: Are anti-correlated networks introduced? NeuroImage 44 893 905 18976716 PMC2750906
- Ochsner KN Gross JJ 2005 The cognitive control of emotion Trends in Cognitive Sciences 9 242 249 15866151
- Rigoux L Daunizeau J 2015 Dynamic causal modelling of brain–behaviour relationships NeuroImage 117 202 221 26008885
- Roy AK Fudge JL Kelly C Perry JSA Daniele T Carlisi C … Ernst M 2013 Intrinsic functional connectivity of amygdala-based networks in adolescent generalized anxiety disorder Journal of the American Academy of Child and Adolescent Psychiatry 52 290 299 e2 23452685 PMC3760686
- Roy AK Shehzad Z Margulies DS Kelly AMC Uddin LQ Gotimer K … Milham MP 2009 Functional connectivity of the human amygdala using resting state fMRI NeuroImage 45 614 626 19110061 PMC2735022
- Smallwood J Gorgolewski KJ Golchert J Ruby FJM Engen H Baird B … Margulies DS 2013 The default modes of reading: Modulation of posterior cingulate and medial prefrontal cortex connectivity associated with comprehension and task focus while reading Frontiers in Human Neuroscience 7 734 24282397 PMC3825257
- Sylvester CM Barch DM Corbetta M Power JD Schlaggar BL Luby JL 2013 Resting state functional connectivity of the ventral attention network in children with a history of depression or anxiety Journal of the American Academy of Child and Adolescent Psychiatry 52 1326 1336 e5 24290465 PMC3918493
- Taylor JM Whalen PJ 2015 Neuroimaging and anxiety: The neural substrates of pathological and non-pathological anxiety Current Psychiatry Reports 17 49 25957101
- Thomason ME Burrows BE Gabrieli JDE Glover GH 2005 Breath holding reveals differences in fMRI BOLD signal in children and adults NeuroImage 25 824 837 15808983
- Toazza R Franco AR Buchweitz A Molle RD Rodrigues DM Reis RS … Manfro GG 2016 Amygdala-based intrinsic functional connectivity and anxiety disorders in adolescents and young adults Psychiatry Research: Neuroimaging 257 11 16 27716544
- Wu SS Willcutt EG Escovar E Menon V 2014 Mathematics achievement and anxiety and their relation to internalizing and externalizing behaviors Journal of Learning Disabilities 47 503 514 23313869 PMC3883980
- Young CB Wu SS Menon V 2012 The neurodevelopmental basis of math anxiety Psychological Science 23 492 501 22434239 PMC3462591
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Recent developments in bibliotherapy for adolescent depression
Liao, F., Liang, J., Zhang, M., Liang, W., Zhang, C., & Yun, X. (2025) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2025.1681462 · Cited by 4 · see citing works
- Authors
- Davis, K., Margolis, A. E., Thomas, L., Huo, Z., & Marsh, R.
- Affiliations
- New York State Psychiatric Institute (US)
- Corresponding author
- Davis, Katie
- Margolis, Amy E.
- Venue
- Developmental Science
- Publisher
- Wiley
- Published
- 2017-11-15
- Volume
- 21
- Issue
- 5
- Pages
- e12631-e12631
- ISSN
- 1363-755X (ISSN-L)
- 1467-7687
- PMC
- PMC6042207
- OpenAlex
- W2768714760
- Cited by
- 25
- References
- 7
- Citations by year
- 2025: 4 · 2024: 3 · 2023: 4 · 2022: 1 · 2021: 5 · 2020: 5 · 2019: 1 · 2018: 2
- FWCI
- 4.43
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Developmental Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Environmental Health Sciences (K23ES026239)
- Topics
- Social Sciences › Psychology › Developmental and Educational Psychology › Reading and Literacy Development
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Social Sciences › Psychology › Neuropsychology and Physiological Psychology › Developmental and Educational Neuropsychology
- Keywords
- dyslexia, anxiety, amygdala, resting-state functional connectivity, amygdala subregions, centromedial amygdala, medial prefrontal cortex, reading disorders, reading fluency, children
- MeSH terms
- Adolescent, Amygdala, Anxiety, Anxiety Disorders, Brain Mapping, Child, Child Development, Dyslexia, Female, Humans, Magnetic Resonance Imaging, Male, Prefrontal Cortex
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