Non-right-handedness, male sex, and regional, network-specific, ventral occipito-temporal anomalous lateralization in adults with a history of reading disability

Zachary A Miller; Leighton B N Hinkley; Valentina Borghesani; Ezra Mauer; Wendy Shwe; Danielle Mizuiri; Rian Bogley; Maria Luisa Mandelli; Jessica de Leon; Christa Watson Pereira; Isabel Allen; John Houde; Joel Kramer; Bruce L Miller; Srikantan S Nagarajan; Maria Luisa Gorno-Tempini

doi:10.1016/j.cortex.2024.09.018

Non-right-handedness, male sex, and regional, network-specific, ventral occipito-temporal anomalous lateralization in adults with a history of reading disability

Cortex. 2024 Nov 19:183:116-130. doi: 10.1016/j.cortex.2024.09.018. Online ahead of print.

Authors

Zachary A Miller¹, Leighton B N Hinkley², Valentina Borghesani³, Ezra Mauer⁴, Wendy Shwe⁵, Danielle Mizuiri⁶, Rian Bogley⁷, Maria Luisa Mandelli⁸, Jessica de Leon⁹, Christa Watson Pereira¹⁰, Isabel Allen¹¹, John Houde¹², Joel Kramer¹³, Bruce L Miller¹⁴, Srikantan S Nagarajan¹⁵, Maria Luisa Gorno-Tempini¹⁶

Affiliations

¹ Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA; Dyslexia Center, Department of Neurology and Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, USA. Electronic address: [email protected].
² Department of Radiology, University of California, San Francisco, San Francisco, CA, USA. Electronic address: [email protected].
³ University of Geneva, Swiss National Centre of Competence in Research, Geneva, Switzerland. Electronic address: [email protected].
⁴ Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA; Dyslexia Center, Department of Neurology and Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, USA; Department of Psychology, University of California, Berkeley, Berkeley, CA, USA. Electronic address: [email protected].
⁵ George Washington University, School of Medicine, Washington, DC, USA. Electronic address: [email protected].
⁶ Department of Radiology, University of California, San Francisco, San Francisco, CA, USA. Electronic address: [email protected].
⁷ Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA; Dyslexia Center, Department of Neurology and Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, USA. Electronic address: [email protected].
⁸ Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA; Dyslexia Center, Department of Neurology and Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, USA. Electronic address: [email protected].
⁹ Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA; Dyslexia Center, Department of Neurology and Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, USA. Electronic address: [email protected].
¹⁰ Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA; Dyslexia Center, Department of Neurology and Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, USA. Electronic address: [email protected].
¹¹ Department of Biostatistics, University of California, San Francisco, San Francisco, CA, USA. Electronic address: [email protected].
¹² Department of Radiology, University of California, San Francisco, San Francisco, CA, USA. Electronic address: [email protected].
¹³ Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA. Electronic address: [email protected].
¹⁴ Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA; Dyslexia Center, Department of Neurology and Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, USA. Electronic address: [email protected].
¹⁵ Department of Radiology, University of California, San Francisco, San Francisco, CA, USA. Electronic address: [email protected].
¹⁶ Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA; Dyslexia Center, Department of Neurology and Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, USA. Electronic address: [email protected].

PMID: 39631179
DOI: 10.1016/j.cortex.2024.09.018

Abstract

Based on historic observations that children with reading disabilities were disproportionately both male and non-right-handed, and that early life insults of the left hemisphere were more frequent in boys and non-right-handed children, it was proposed that early focal neuronal injury disrupts typical patterns of motor hand and language dominance and in the process produces developmental dyslexia. To date, these theories remain controversial. We revisited these earliest theories in a contemporary manner, investigating demographics associated with reading disability, and in a subgroup with and without reading disability, compared structural imaging as well as patterns of activity during tasks of verb generation and non-word repetition using magnetoencephalography source imaging. In a large group of healthy aging adults (n = 282; average age 72.3), we assessed reading ability via the Adult Reading History Questionnaire and found that non-right-handedness and male sex significantly predicted endorsed reading disability. In a subset of participants from the larger cohort who endorsed reading disability (n = 14) and a group who denied reading disability (n = 22), we compared structural and functional imaging data. We failed to detect structural differences in volumetric brain morphometry analyses, however we observed decreased neural activity on magnetoencephalography within the reading disability group. The detected differences were largely restricted to left hemisphere ventral occipito-temporal and posterior-lateral temporal cortices, the visual word form area and middle temporal gyrus, regions implicated in developmental dyslexia. Moreover, these observed disruptions occurred in a focal, network-specific manner, preferentially disturbing the ventral/sight reading recognition pathway, resulting in a pattern of regional anomalous lateralization of function that distinguished the reading disability cohort from normal readers. Collectively, the results presented here align with old theories regarding the etiology of developmental dyslexia and highlight how results from investigating neurodevelopmental differences in healthy aging individuals can powerfully contribute towards our overall understanding of neurodevelopment and neurodiversity.

Keywords: Anomalous language lateralization; Dyslexia; Magnetoencephalography; Neurodiversity; Non-right-handedness.