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  • Review Article
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Clinical implications of brain asymmetries

Abstract

No two human brains are alike, and with the rise of precision medicine in neurology, we are seeing an increased emphasis on understanding the individual variability in brain structure and function that renders every brain unique. Functional and structural brain asymmetries are a fundamental principle of brain organization, and recent research suggests substantial individual variability in these asymmetries that needs to be considered in clinical practice. In this Review, we provide an overview of brain asymmetries, variations in such asymmetries and their relevance in the clinical context. We review recent findings on brain asymmetries in neuropsychiatric and neurodevelopmental disorders, as well as in specific learning disabilities, with an emphasis on large-scale database studies and meta-analyses. We also highlight the relevance of asymmetries for disease symptom onset in neurodegenerative diseases and their implications for lateralized treatments, including brain stimulation. We conclude that alterations in brain asymmetry are not sufficiently specific to act as diagnostic biomarkers but can serve as meaningful symptom or treatment response biomarkers in certain contexts. On the basis of these insights, we provide several recommendations for neurological clinical practice.

Key points

  • Brain asymmetries — that is, structural and functional differences between the left and the right hemispheres — are a major source of interindividual brain variability.

  • The substantial interindividual variability in brain asymmetry currently precludes its use as a diagnostic biomarker.

  • Individual variability in brain asymmetry needs to be considered in the assessment of symptoms and treatment of various disorders.

  • Altered brain asymmetries are observed in a number of neurological, neuropsychiatric and neurodevelopmental disorders.

  • Brain asymmetries can act as meaningful symptom or treatment response biomarkers in a range of neurological contexts.

  • Advancement of patient-tailored medicine will require clinical trials to elucidate how individual brain asymmetry influences the efficacy of lateralized interventions.

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Fig. 1: The three main forms of brain asymmetries.
Fig. 2: Variability in hemisphere organization in the general population.
Fig. 3: Hemisphere crowding and cognitive impairment comorbidity.

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References

  1. Genon, S., Eickhoff, S. B. & Kharabian, S. Linking interindividual variability in brain structure to behaviour. Nat. Rev. Neurosci. 23, 307–318 (2022).

    Article  CAS  PubMed  Google Scholar 

  2. Johnson, K. B. et al. Precision medicine, AI, and the future of personalized health care. Clin. Transl. Sci. 14, 86–93 (2021).

    Article  PubMed  Google Scholar 

  3. Ashina, M. et al. Migraine: disease characterisation, biomarkers, and precision medicine. Lancet 397, 1496–1504 (2021).

    Article  CAS  PubMed  Google Scholar 

  4. Isaacson, R. S. et al. The clinical practice of risk reduction for Alzheimer’s disease: a precision medicine approach. Alzheimers Dement. 14, 1663–1673 (2018).

    Article  PubMed  Google Scholar 

  5. Striano, P. & Minassian, B. A. From genetic testing to precision medicine in epilepsy. Neurotherapeutics 17, 609–615 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  6. Corballis, M. C. Evolution of cerebral asymmetry. Prog. Brain Res. 250, 153–178 (2019).

    Article  PubMed  Google Scholar 

  7. McManus, C. Half a century of handedness research: myths, truths; fictions, facts; backwards, but mostly forwards. Brain Neurosci. Adv. 3, 2398212818820513 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  8. Vallortigara, G. & Rogers, L. J. A function for the bicameral mind. Cortex 124, 274–285 (2020).

    Article  PubMed  Google Scholar 

  9. Guadalupe, T. et al. Human subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex. Brain Imaging Behav. 11, 1497–1514 (2017).

    Article  PubMed  Google Scholar 

  10. Kong, X.-Z. et al. Mapping brain asymmetry in health and disease through the ENIGMA consortium. Hum. Brain Mapp. 43, 167–181 (2022).

    Article  PubMed  Google Scholar 

  11. Kuo, F. & Massoud, T. F. Structural asymmetries in normal brain anatomy: a brief overview. Ann. Anat. 241, 151894 (2022).

    Article  PubMed  Google Scholar 

  12. Malik-Moraleda, S. et al. An investigation across 45 languages and 12 language families reveals a universal language network. Nat. Neurosci. 25, 1014–1019 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Papadatou-Pastou, M. et al. Human handedness: a meta-analysis. Psychol. Bull. 146, 481–524 (2020).

    Article  PubMed  Google Scholar 

  14. Vingerhoets, G. Phenotypes in hemispheric functional segregation? Perspectives and challenges. Phys. Life Rev. 30, 1–18 (2019).

    Article  PubMed  Google Scholar 

  15. Vallortigara, G. & Rogers, L. J. Survival with an asymmetrical brain: advantages and disadvantages of cerebral lateralization. Behav. Brain Sci. 28, 575–589 (2005).

    Article  PubMed  Google Scholar 

  16. Ocklenburg, S. & Güntürkün, O. The Lateralized Brain. The Neuroscience and Evolution of Hemispheric Asymmetries (Elsevier Science & Technology, 2024).

  17. Oldfield, R. C. The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 9, 97–113 (1971).

    Article  CAS  PubMed  Google Scholar 

  18. Scerri, T. S. et al. PCSK6 is associated with handedness in individuals with dyslexia. Hum. Mol. Genet. 20, 608–614 (2011).

    Article  CAS  PubMed  Google Scholar 

  19. Vingerhoets, G. et al. Laterality Indices Consensus Initiative (LICI): a Delphi expert survey report on recommendations to record, assess, and report asymmetry in human behavioural and brain research. Laterality 28, 122–191 (2023).

    Article  PubMed  Google Scholar 

  20. Westerhausen, R. A primer on dichotic listening as a paradigm for the assessment of hemispheric asymmetry. Laterality 24, 740–771 (2019).

    Article  PubMed  Google Scholar 

  21. Bourne, V. J. The divided visual field paradigm: methodological considerations. Laterality 11, 373–393 (2006).

    Article  PubMed  Google Scholar 

  22. Smith, E. E., Reznik, S. J., Stewart, J. L. & Allen, J. J. B. Assessing and conceptualizing frontal EEG asymmetry: an updated primer on recording, processing, analyzing, and interpreting frontal alpha asymmetry. Int. J. Psychophysiol. 111, 98–114 (2017).

    Article  PubMed  Google Scholar 

  23. Hugdahl, K. & Westerhausen, R. Speech processing asymmetry revealed by dichotic listening and functional brain imaging. Neuropsychologia 93, 466–481 (2016).

    Article  PubMed  Google Scholar 

  24. Hage, B. D., Truemper, E. J. & Bashford, G. R. Functional transcranial Doppler ultrasound for monitoring cerebral blood flow. J. Vis. Exp. https://doi.org/10.3791/62048 (2021).

    Article  PubMed  Google Scholar 

  25. Büchel, C. et al. White matter asymmetry in the human brain: a diffusion tensor MRI study. Cereb. Cortex 14, 945–951 (2004).

    Article  PubMed  Google Scholar 

  26. Ocklenburg, S. et al. Neurite architecture of the planum temporale predicts neurophysiological processing of auditory speech. Sci. Adv. 4, eaar6830 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  27. Amunts, K. in Two Halves of the Brain: Information Processing in the Cerebral Hemispheres (eds Hugdahl, K. & Westerhausen, R.) 145–176 (MIT Press, 2010).

  28. Carey, D. P. & Johnstone, L. T. Quantifying cerebral asymmetries for language in dextrals and adextrals with random-effects meta analysis. Front. Psychol. 5, 1128 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  29. Karlsson, E. M., Hugdahl, K., Hirnstein, M. & Carey, D. P. Analysis of distributions reveals real differences on dichotic listening scores between left- and right-handers. Cereb. Cortex Commun. 4, tgad009 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  30. Badzakova-Trajkov, G., Corballis, M. C. & Häberling, I. S. Complementarity or independence of hemispheric specializations? A brief review. Neuropsychologia 93, 386–393 (2016).

    Article  CAS  PubMed  Google Scholar 

  31. Badzakova-Trajkov, G., Häberling, I. S., Roberts, R. P. & Corballis, M. C. Cerebral asymmetries: complementary and independent processes. PLoS ONE 5, e9682 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  32. Gerrits, R. Variability in hemispheric functional segregation phenotypes: a review and general mechanistic model. Neuropsychol. Rev. 34, 27–40 (2022).

    Article  PubMed  Google Scholar 

  33. Zago, L. et al. The association between hemispheric specialization for language production and for spatial attention depends on left-hand preference strength. Neuropsychologia 93, 394–406 (2016).

    Article  PubMed  Google Scholar 

  34. Gerrits, R., Verhelst, H. & Vingerhoets, G. Mirrored brain organization: statistical anomaly or reversal of hemispheric functional segregation bias? Proc. Natl Acad. Sci. USA 117, 14057–14065 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Kroliczak, G. et al. Manual praxis and language-production networks, and their links to handedness. Cortex 140, 110–127 (2021).

    Article  PubMed  Google Scholar 

  36. Karlsson, E. M., Johnstone, L. T. & Carey, D. P. Reciprocal or independent hemispheric specializations: evidence from cerebral dominance for fluency, faces, and bodies in right- and left-handers. Psychol. Neurosci. 15, 89–104 (2022).

    Article  Google Scholar 

  37. Marie, D., Maingault, S., Crivello, F., Mazoyer, B. & Tzourio-Mazoyer, N. Surface-based morphometry of cortical thickness and surface area associated with Heschl’s gyri duplications in 430 healthy volunteers. Front. Hum. Neurosci. 10, 69 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  38. Tzourio-Mazoyer, N., Crivello, F. & Mazoyer, B. Is the planum temporale surface area a marker of hemispheric or regional language lateralization? Brain Struct. Funct. 223, 1217–1228 (2018).

    PubMed  Google Scholar 

  39. Califf, R. M. Biomarker definitions and their applications. Exp. Biol. Med. 243, 213–221 (2018).

    Article  CAS  Google Scholar 

  40. Mundorf, A., Peterburs, J. & Ocklenburg, S. Asymmetry in the central nervous system: a clinical neuroscience perspective. Front. Syst. Neurosci. 15, 733898 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  41. Oertel-Knochel, V., Knochel, C., Stablein, M. & Linden, D. E. J. Abnormal functional and structural asymmetry as biomarker for schizophrenia. Curr. Top. Med. Chem. 12, 2434–2451 (2012).

    Article  CAS  PubMed  Google Scholar 

  42. Dharmadhikari, A. S. et al. Frontal theta asymmetry as a biomarker of depression. East Asian Arch. Psychiatry 28, 17–22 (2018).

    CAS  PubMed  Google Scholar 

  43. Li, D. et al. Reduced hemispheric asymmetry of brain anatomical networks in attention deficit hyperactivity disorder. Brain Imaging Behav. 13, 669–684 (2019).

    Article  PubMed  Google Scholar 

  44. Mundorf, A. & Ocklenburg, S. The Clinical Neuroscience of Lateralization (Routledge, 2021).

  45. Hirnstein, M. & Hugdahl, K. Excess of non-right-handedness in schizophrenia: meta-analysis of gender effects and potential biases in handedness assessment. Br. J. Psychiatry 205, 260–267 (2014).

    Article  PubMed  Google Scholar 

  46. Mallet, J. et al. Handedness as a neurodevelopmental marker in schizophrenia: results from the FACE-SZ cohort. World J. Biol. Psychiatry 23, 525–536 (2022).

    Article  CAS  PubMed  Google Scholar 

  47. Ocklenburg, S., Westerhausen, R., Hirnstein, M. & Hugdahl, K. Auditory hallucinations and reduced language lateralization in schizophrenia: a meta-analysis of dichotic listening studies. J. Int. Neuropsychol. Soc. 19, 410–418 (2013).

    Article  PubMed  Google Scholar 

  48. Schijven, D. et al. Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium. Proc. Natl Acad. Sci. USA 120, e2213880120 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Packheiser, J. et al. Handedness and depression: a meta-analysis across 87 studies. J. Affect. Disord. 294, 200–209 (2021).

    Article  PubMed  Google Scholar 

  50. van der Vinne, N., Vollebregt, M. A., van Putten, M. J. A. M. & Arns, M. Frontal alpha asymmetry as a diagnostic marker in depression: fact or fiction? A meta-analysis. NeuroImage Clin. 16, 79–87 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  51. de Kovel, C. G. et al. No alterations of brain structural asymmetry in major depressive disorder: an ENIGMA Consortium analysis. Am. J. Psychiatry 176, 1039–1049 (2019).

    Article  PubMed  Google Scholar 

  52. Borawski, J., Papadatou-Pastou, M., Packheiser, J. & Ocklenburg, S. Handedness in post-traumatic stress disorder: a meta-analysis. Neurosci. Biobehav. Rev. 145, 105009 (2023).

    Article  PubMed  Google Scholar 

  53. Goetz, J. M., Pitman, S. R., Tanev, K. S., Pitman, R. K. & Chemtob, C. M. Mixed-handedness in identical twins discordant for combat exposure in Vietnam: relationship to posttraumatic stress disorder. J. Neuropsychiatry Clin. Neurosci. 28, 45–48 (2016).

    Article  PubMed  Google Scholar 

  54. Irani, Z. A., Sheridan, A. M. C., Badcock, N. A. & Fox, A. Assessing non-right-handedness and atypical cerebral lateralisation as predictors of paediatric mental health difficulties. Eur. J. Neurosci. 58, 4195–4210 (2023).

    Article  CAS  PubMed  Google Scholar 

  55. Rodriguez, A. et al. Mixed-handedness is linked to mental health problems in children and adolescents. Pediatrics 125, e340–e348 (2010).

    Article  PubMed  Google Scholar 

  56. Odintsova, V. V. et al. Handedness and 23 early life characteristics in 37,495 Dutch twins. Twin Res. Hum. Genet. 26, 199–208 (2023).

    Article  PubMed  Google Scholar 

  57. Li, Q., Zhao, W., Palaniyappan, L. & Guo, S. Atypical hemispheric lateralization of brain function and structure in autism: a comprehensive meta-analysis study. Psychol. Med. https://doi.org/10.1017/S0033291723000181 (2023).

  58. Markou, P., Ahtam, B. & Papadatou-Pastou, M. Elevated levels of atypical handedness in autism: meta-analyses. Neuropsychol. Rev. 27, 258–283 (2017).

    Article  PubMed  Google Scholar 

  59. He, N., Palaniyappan, L., Linli, Z. & Guo, S. Abnormal hemispheric asymmetry of both brain function and structure in attention deficit/hyperactivity disorder: a meta-analysis of individual participant data. Brain Imaging Behav. 16, 54–68 (2022).

    Article  PubMed  Google Scholar 

  60. Nastou, E., Ocklenburg, S., Hoogman, M. & Papadatou-Pastou, M. Handedness in ADHD: meta-analyses. Neuropsychol. Rev. 32, 877–892 (2022).

    Article  PubMed  Google Scholar 

  61. Floris, D. L. et al. Atypical brain asymmetry in autism — a candidate for clinically meaningful stratification. Biol. Psychiatry Cogn. Neurosci. Neuroimaging 6, 802–812 (2021).

    PubMed  Google Scholar 

  62. Charman, T. et al. The EU-AIMS Longitudinal European Autism Project (LEAP): clinical characterisation. Mol. Autism 8, 27 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  63. Sha, Z. et al. Subtly altered topological asymmetry of brain structural covariance networks in autism spectrum disorder across 43 datasets from the ENIGMA consortium. Mol. Psychiatry 27, 2114–2125 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Postema, M. C. et al. Altered structural brain asymmetry in autism spectrum disorder in a study of 54 datasets. Nat. Commun. 10, 4958 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Postema, M. C. et al. Analysis of structural brain asymmetries in attention-deficit/hyperactivity disorder in 39 datasets. J. Child. Psychol. Psychiatry 62, 1202–1219 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  66. Papadatou-Pastou, M. et al. Hand preference in stuttering: meta-analyses. Neuropsychol. Rev. https://doi.org/10.1007/s11065-023-09617-z (2023).

  67. Wilson, A. C. & Bishop, D. V. M. Resounding failure to replicate links between developmental language disorder and cerebral lateralisation. PeerJ 6, e4217 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  68. Bradshaw, A. R., Woodhead, Z. V. J., Thompson, P. A. & Bishop, D. V. M. Investigation into inconsistent lateralisation of language functions as a potential risk factor for language impairment. Eur. J. Neurosci. 51, 1106–1121 (2020).

    Article  PubMed  Google Scholar 

  69. APA. Diagnostic and Statistical Manual of Mental Disorders. DSM-5 (American Psychiatric Publishing, 2013).

  70. Martinez-Lincoln, A., Fotidzis, T. S., Cutting, L. E., Price, G. R. & Barquero, L. A. Examination of common and unique brain regions for atypical reading and math: a meta-analysis. Cereb. Cortex 33, 6959–6989 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  71. Tablante, J., Krossa, L., Azimi, T. & Chen, L. Dysfunctions associated with the intraparietal sulcus and a distributed network in individuals with math learning difficulties: an ALE meta-analysis. Hum. Brain Mapp. 44, 2726–2740 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  72. Kwok, F. Y. et al. Developmental dyscalculia is not associated with atypical brain activation: a univariate fMRI study of arithmetic, magnitude processing, and visuospatial working memory. Hum. Brain Mapp. 44, 6308–6325 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  73. Papadatou-Pastou, M. et al. Hand preference and mathematical learning difficulties: new data from Greece, the United Kingdom, and Germany and two meta-analyses of the literature. Laterality 26, 485–538 (2021).

    Article  PubMed  Google Scholar 

  74. Li, Y. & Bi, H.-Y. Comparative research on neural dysfunction in children with dyslexia under different writing systems: a meta-analysis study. Neurosci. Biobehav. Rev. 137, 104650 (2022).

    Article  PubMed  Google Scholar 

  75. Richlan, F. The functional neuroanatomy of developmental dyslexia across languages and writing systems. Front. Psychol. 11, 155 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  76. Cainelli, E., Vedovelli, L., Carretti, B. & Bisiacchi, P. EEG correlates of developmental dyslexia: a systematic review. Ann. Dyslexia 73, 184–213 (2023).

    Article  PubMed  Google Scholar 

  77. Yan, X. et al. Convergent and divergent brain structural and functional abnormalities associated with developmental dyslexia. eLife 10, e69523 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Moreau, D., Stonyer, J. E., McKay, N. S. & Waldie, K. E. No evidence for systematic white matter correlates of dyslexia: an activation likelihood estimation meta-analysis. Brain Res. 1683, 36–47 (2018).

    Article  CAS  PubMed  Google Scholar 

  79. Cummine, J., Ngo, T. & Nisbet, K. Characterization of cortical and subcortical structural brain asymmetry in adults with and without dyslexia. Brain Sci. 13, 1622 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  80. Packheiser, J. et al. Elevated levels of mixed-hand preference in dyslexia: meta-analyses of 68 studies. Neurosci. Biobehav. Rev. 154, 105420 (2023).

    Article  PubMed  Google Scholar 

  81. Mallet, J. et al. Handedness in bipolar disorders is associated with specific neurodevelopmental features: results of the BD-FACE cohort. Eur. Arch. Psychiatry Clin. Neurosci. 272, 827–838 (2022).

    Article  PubMed  Google Scholar 

  82. Goldenberg, G. Apraxia in left-handers. Brain 136, 2592–2601 (2013).

    Article  PubMed  Google Scholar 

  83. Bryden, M. P., Hécaen, H. & DeAgostini, M. Patterns of cerebral organization. Brain Lang. 20, 249–262 (1983).

    Article  CAS  PubMed  Google Scholar 

  84. Coppens, P., Hungerford, S., Yamaguchi, S. & Yamadori, A. Crossed aphasia: an analysis of the symptoms, their frequency, and a comparison with left-hemisphere aphasia symptomatology. Brain Lang. 83, 425–463 (2002).

    Article  PubMed  Google Scholar 

  85. Suchan, J. & Karnath, H.-O. Spatial orienting by left hemisphere language areas: a relict from the past? Brain 134, 3059–3070 (2011).

    Article  PubMed  Google Scholar 

  86. Ubben, S. D. et al. Deficient allo-centric visuospatial processing contributes to apraxic deficits in sub-acute right hemisphere stroke. J. Neuropsychol. 14, 242–259 (2020).

    Article  PubMed  Google Scholar 

  87. van der Hoorn, A., Burger, H., Leenders, K. L. & de Jong, B. M. Handedness correlates with the dominant Parkinson side: a systematic review and meta-analysis. Mov. Disord. 27, 206–210 (2012).

    Article  PubMed  Google Scholar 

  88. Verreyt, N., Nys, G. M. S., Santens, P. & Vingerhoets, G. Cognitive differences between patients with left-sided and right-sided Parkinson’s disease. A review. Neuropsychol. Rev. 21, 405–424 (2011).

    Article  PubMed  Google Scholar 

  89. Voruz, P., Constantin, I. M. & Péron, J. A. Biomarkers and non-motor symptoms as a function of motor symptom asymmetry in early Parkinson’s disease. Neuropsychologia 177, 108419 (2022).

    Article  PubMed  Google Scholar 

  90. Cubo, E., Martín, P. M., Martin-Gonzalez, J. A., Rodríguez-Blázquez, C. & Kulisevsky, J. Motor laterality asymmetry and nonmotor symptoms in Parkinson’s disease. Mov. Disord. 25, 70–75 (2010).

    Article  PubMed  Google Scholar 

  91. Rodríguez-Violante, M., Cervantes-Arriaga, A., Villar-Velarde, A. & Corona, T. Relationship between the type and side of motor symptoms with the prevalence of non-motor symptoms in Parkinson’s disease. Neurologia 26, 319–324 (2011).

    Article  PubMed  Google Scholar 

  92. Fiorenzato, E., Antonini, A., Bisiacchi, P., Weis, L. & Biundo, R. Asymmetric dopamine transporter loss affects cognitive and motor progression in Parkinson’s disease. Mov. Disord. 36, 2303–2313 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Zhu, Y. et al. Study of the relationship between onset lateralization and hemispheric white matter asymmetry in Parkinson’s disease. J. Neurol. 270, 5004–5016 (2023).

    Article  PubMed  Google Scholar 

  94. Lubben, N., Ensink, E., Coetzee, G. A. & Labrie, V. The enigma and implications of brain hemispheric asymmetry in neurodegenerative diseases. Brain Commun. 3, fcab211 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  95. Roe, J. M. et al. Asymmetric thinning of the cerebral cortex across the adult lifespan is accelerated in Alzheimer’s disease. Nat. Commun. 12, 721 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Lu, J. et al. The heterogeneity of asymmetric tau distribution is associated with an early age at onset and poor prognosis in Alzheimer’s disease. NeuroImage Clin. 38, 103416 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  97. McManus, I. C. Compellingly negative: Bayesian analysis shows handedness and dementia are not associated. Brain Commun. 5, fcad162 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Larson, R. D., McCully, K. K., Larson, D. J., Pryor, W. M. & White, L. J. Bilateral differences in lower-limb performance in individuals with multiple sclerosis. J. Rehabil. Res. Dev. 50, 215–222 (2013).

    Article  PubMed  Google Scholar 

  99. Chaves, A. R. et al. Asymmetry of brain excitability: a new biomarker that predicts objective and subjective symptoms in multiple sclerosis. Behav. Brain Res. 359, 281–291 (2019).

    Article  CAS  PubMed  Google Scholar 

  100. Turner, M. R. et al. Concordance between site of onset and limb dominance in amyotrophic lateral sclerosis. J. Neurol. Neurosurg. Psychiatry 82, 853–854 (2011).

    Article  CAS  PubMed  Google Scholar 

  101. Suzuki, Y.-I. et al. Fasciculation intensity and limb dominance in amyotrophic lateral sclerosis: a muscle ultrasonographic study. BMC Neurol. 22, 85 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Minkova, L. et al. Gray matter asymmetries in aging and neurodegeneration: a review and meta-analysis. Hum. Brain Mapp. 38, 5890–5904 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  103. Denison, T. & Morrell, M. J. Neuromodulation in 2035: the neurology future forecasting series. Neurology 98, 65–72 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  104. Sharma, V. D., Patel, M. & Miocinovic, S. Surgical treatment of Parkinson’s disease: devices and lesion approaches. Neurotherapeutics 17, 1525–1538 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  105. Bruder, G. E., Stewart, J. W. & McGrath, P. J. Right brain, left brain in depressive disorders: clinical and theoretical implications of behavioral, electrophysiological and neuroimaging findings. Neurosci. Biobehav. Rev. 78, 178–191 (2017).

    Article  PubMed  Google Scholar 

  106. Cole, E. J. et al. Stanford neuromodulation therapy (SNT): a double-blind randomized controlled trial. Am. J. Psychiatry 179, 132–141 (2022).

    Article  PubMed  Google Scholar 

  107. Caciagli, L. et al. Disorganization of language and working memory systems in frontal versus temporal lobe epilepsy. Brain 146, 935–953 (2023).

    Article  PubMed  Google Scholar 

  108. Foesleitner, O. et al. Language network reorganization before and after temporal lobe epilepsy surgery. J. Neurosurg. 134, 1694–1702 (2020).

    Article  PubMed  Google Scholar 

  109. Powell, H. W. R. et al. Abnormalities of language networks in temporal lobe epilepsy. NeuroImage 36, 209–221 (2007).

    Article  PubMed  Google Scholar 

  110. Sideman, N. et al. Task activation and functional connectivity show concordant memory laterality in temporal lobe epilepsy. Epilepsy Behav. 81, 70–78 (2018).

    Article  PubMed  Google Scholar 

  111. Tracy, J. I. et al. Hemispheric lateralization and language skill coherence in temporal lobe epilepsy. Cortex 45, 1178–1189 (2009).

    Article  PubMed  Google Scholar 

  112. Woodhead, Z. V. J., Thompson, P. A., Karlsson, E. M. & Bishop, D. V. M. An updated investigation of the multidimensional structure of language lateralization in left- and right-handed adults: a test–retest functional transcranial Doppler sonography study with six language tasks. R. Soc. Open Sci. 8, 200696 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Elger, C. E., Helmstaedter, C. & Kurthen, M. Chronic epilepsy and cognition. Lancet Neurol. 3, 663–672 (2004).

    Article  PubMed  Google Scholar 

  114. Stretton, J. & Thompson, P. J. Frontal lobe function in temporal lobe epilepsy. Epilepsy Res. 98, 1–13 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Oyegbile, T. O. et al. The nature and course of neuropsychological morbidity in chronic temporal lobe epilepsy. Neurology 62, 1736–1742 (2004).

    Article  CAS  PubMed  Google Scholar 

  116. Dossani, R. H., Missios, S. & Nanda, A. The legacy of Henry Molaison (1926–2008) and the impact of his bilateral mesial temporal lobe surgery on the study of human memory. World Neurosurg. 84, 1127–1135 (2015).

    Article  PubMed  Google Scholar 

  117. Branch, C., Milner, B. & Rasmussen, T. Intracarotid sodium amytal for the lateralization of cerebral speech dominance; observations in 123 patients. J. Neurosurg. 21, 399–405 (1964).

    Article  CAS  PubMed  Google Scholar 

  118. Wada, J. & Rasmussen, T. Intracarotid injection of sodium amytal for the lateralization of cerebral speech dominance. J. Neurosurg. 17, 266–282 (1960).

    Article  Google Scholar 

  119. Helmstaedter, C. et al. Differential effects of temporal pole resection with amygdalohippocampectomy versus selective amygdalohippocampectomy on material-specific memory in patients with mesial temporal lobe epilepsy. Epilepsia 49, 88–97 (2008).

    Article  PubMed  Google Scholar 

  120. Qadri, S., Dave, H., Das, R. & Alick-Lindstrom, S. Beyond the Wada: an updated approach to pre-surgical language and memory testing: an updated review of available evaluation techniques and recommended workflow to limit Wada test use to essential clinical cases. Epilepsy Res. 174, 106673 (2021).

    Article  PubMed  Google Scholar 

  121. Balter, S., Lin, G., Leyden, K. M., Paul, B. M. & McDonald, C. R. Neuroimaging correlates of language network impairment and reorganization in temporal lobe epilepsy. Brain Lang. 193, 31–44 (2019).

    Article  CAS  PubMed  Google Scholar 

  122. Annett, M. Handedness and Brain Asymmetry. The Right Shift Theory (Taylor and Francis, 2013).

  123. McManus, I. C. Handedness, language dominance and aphasia: a genetic model. Psychol. Med. Monogr. Suppl. 8, 1–40 (1985).

    Article  CAS  PubMed  Google Scholar 

  124. Armour, J. A. L., Davison, A. & McManus, I. C. Genome-wide association study of handedness excludes simple genetic models. Heredity 112, 221–225 (2014).

    Article  CAS  PubMed  Google Scholar 

  125. Cuellar-Partida, G. et al. Genome-wide association study identifies 48 common genetic variants associated with handedness. Nat. Hum. Behav. 5, 59–70 (2021).

    Article  PubMed  Google Scholar 

  126. McManus, C. Cerebral polymorphisms for lateralisation: modelling the genetic and phenotypic architectures of multiple functional modules. Symmetry 14, 814 (2022).

    Article  Google Scholar 

  127. Medland, S. E. et al. Genetic influences on handedness: data from 25,732 Australian and Dutch twin families. Neuropsychologia 47, 330–337 (2009).

    Article  PubMed  Google Scholar 

  128. de Kovel, C. G. F., Carrión-Castillo, A. & Francks, C. A large-scale population study of early life factors influencing left-handedness. Sci. Rep. 9, 584 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  129. Schmitz, J., Lor, S., Klose, R., Güntürkün, O. & Ocklenburg, S. The functional genetics of handedness and language lateralization: insights from gene ontology, pathway and disease association analyses. Front. Psychol. 8, 1144 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  130. Bisiacchi, P. & Cainelli, E. Structural and functional brain asymmetries in the early phases of life: a scoping review. Brain Struct. Funct. 227, 479–496 (2022).

    Article  PubMed  Google Scholar 

  131. Kumpulainen, V. et al. Sex differences, asymmetry, and age-related white matter development in infants and 5-year-olds as assessed with tract-based spatial statistics. Hum. Brain Mapp. 44, 2712–2725 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  132. Williams, L. Z. J. et al. Structural and functional asymmetry of the neonatal cerebral cortex. Nat. Hum. Behav. 7, 942–955 (2023).

    Article  PubMed  Google Scholar 

  133. Ford, A., Ammar, Z., Li, L. & Shultz, S. Lateralization of major white matter tracts during infancy is time-varying and tract-specific. Cereb. Cortex 33, 10221–10233 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  134. Olulade, O. A. et al. The neural basis of language development: changes in lateralization over age. Proc. Natl Acad. Sci. USA 117, 23477–23483 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Behrmann, M. & Plaut, D. C. A vision of graded hemispheric specialization. Ann. N. Y. Acad. Sci. 1359, 30–46 (2015).

    Article  PubMed  Google Scholar 

  136. Roe, J. M. et al. Tracing the development and lifespan change of population-level structural asymmetry in the cerebral cortex. eLife 12, e84685 (2023).

    Google Scholar 

  137. Brown, J. W. & Jaffe, J. Hypothesis on cerebral dominance. Neuropsychologia 13, 107–110 (1975).

    Article  CAS  PubMed  Google Scholar 

  138. Cabeza, R. Hemispheric asymmetry reduction in older adults: the HAROLD model. Psychol. Aging 17, 85–100 (2002).

    Article  PubMed  Google Scholar 

  139. Kosslyn, S. M. Seeing and imagining in the cerebral hemispheres: a computational approach. Psychol. Rev. 94, 148–175 (1987).

    Article  CAS  PubMed  Google Scholar 

  140. Vingerhoets, G., Gerrits, R. & Verhelst, H. Atypical brain asymmetry in human situs inversus: gut feeling or real evidence? Symmetry 13, 695 (2021).

    Article  Google Scholar 

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Acknowledgements

R.G. is currently employed on a postdoctoral fellowship by the Research Foundation — Flanders (FWO), grant no. 12A6322N. The authors thank J. Borawski for help with Fig. 1.

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S.O. conceptualized the article. S.O. conceptualized one figure, R.G. created two figures and G.V. and E.M.K. created the boxes. All authors researched data for the article, contributed substantially to discussion of the content, wrote the article and reviewed and/or edited the manuscript before submission.

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Ocklenburg, S., Mundorf, A., Gerrits, R. et al. Clinical implications of brain asymmetries. Nat Rev Neurol (2024). https://doi.org/10.1038/s41582-024-00974-8

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