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Sex Differences in the Functional Neuroanatomy of Working Memory in Adults With ADHD
Open accessAbstract
OBJECTIVE: Although attention deficit hyperactivity disorder (ADHD) in adults is associated with significant morbidity and dysfunction and afflicts both sexes, relatively few imaging studies have examined female subjects and none have had sufficient power to adequately examine sex differences. The authors examined sex differences in the neural functioning of adults with ADHD during performance of a verbal working memory task. METHOD: The participants were 44 adults with ADHD matched on age, sex, and estimated IQ to 49 comparison subjects. Accuracy and reaction time on an N-back task were measured to assess working memory. The blood-oxygen-level-dependent functional MRI response was used as a measure of neural activity. RESULTS: A group-by-sex analysis of variance showed no between-group differences in either reaction time or percent correct for the working memory task. For both sexes combined, the adults with ADHD showed less activity than comparison subjects in prefrontal regions. However, sex-by-group analyses revealed an interaction, such that male ADHD subjects showed significantly less activity in right frontal, temporal, and subcortical regions and left occipital and cerebellar regions relative to male comparison subjects, whereas female ADHD subjects showed no differences from female comparison subjects. Exploratory correlation analyses revealed negative associations between working-memory-related activation and number of hyperactive symptoms for men and number of inattentive symptoms for women. CONCLUSIONS: Male but not female adults with ADHD showed significantly altered patterns of neural activity during a verbal working memory task. Men and women showed different associations between neural activity and ADHD symptoms.
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“A study in adults with ADHD found that 23 males had significant underactivation in widespread networks of frontal, temporal, cerebellar, occipital and subcortical regions during WM, whereas 21 females with ADHD showed no impairment relative to control females (Valera et al., 2010).”
From Cognitive Neuroscience of Attention Deficit Hyperactivity Disorder (ADHD) and Its Clinical Translation (2018) · cites this paper as Valera et al., 2010
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Items 101–137 of 137
Assari, S. (2021) · Journal of Neurology and Neuromedicine · doi:10.29245/2572.942x/2021/1.1278 · Cited by 14
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“Previous neuroimaging studies comparing the functional brain activation of aADHD patients to healthy controls during working memory tasks show alterations on the neuronal level with less prefrontal activation in the aADHD group than in a healthy control group (Ehlis et al., 2008; Valera et al., 2010; Schecklmann et al…”
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“Gender-related differences in neural activity and their associations with behavioral deficits have been discussed in a previous ADHD study [23].”
Working Memory and Neurodevelopmental Disorders
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“Furthermore, fMRI studies of adult patients with ADHD showed decreased activity in the temporo-occipital and prefrontal cortices [36, 37], which are responsible for Time Reproduction in Adult ADHD”
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“As WM is correlated with age, sex, and IQ (38,39), we included them as covariates.”
MethodAgoalikum, E., Klugah‐Brown, B., Wu, H., Jing, J., & Biswal, B. B. (2023) · Brain Connectivity · doi:10.1089/brain.2022.0069 · Cited by 8
“Moreover, in an fMRI study, Valera et al (2010) investigated the brain activity of adult ADHD patients as they completed working memory tasks.”
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Sex and estrous cycle in memory for sequences of events in rats.
Jayachandran, M., Langius, P., Rego, F., Vertes, R. P., & Allen, T. A. (2022) · Behavioral Neuroscience · doi:10.1037/bne0000508 · Cited by 7
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“Importantly, sex differences may further modulate these outcomes; for example, males with ADHD are at higher risk for academic underachievement and conduct-related problems compared to females (12, 13).”
Bloch, Y., Aviram, S., Ne'eman, R., Braw, Y., Nitzan, U., Maoz, H., & Mimouni-Bloch, A. (2015) · The World Journal of Biological Psychiatry · doi:10.3109/15622975.2015.1036115 · Cited by 8
“…during performance on a verbal working memory task. males and females showed different associations between neural activity and aDhD symptoms (valera et al. 2010). the results of the presented study support the use of the fundamental frequency as a putative marker in female but not in male…”
ResultSex differences in neural correlates of common psychopathological symptoms in early adolescence
Biondo, F., Nymberg, C., Xu, B., Chu, C., Jia, T., Ing, A., Quinlan, E. B., Tay, N., Banaschewski, T., Bokde, A. L. W., et al. (2021) · Psychological Medicine · doi:10.1017/s0033291720005140 · Cited by 9
“…clusters fall within a subset of brain regions that have been previously associated with ADHD studies, which did not test for sex differences possibly because most participants in these studies were male (Frodl & Skokauskas, 2012; Kaczkurkin et al., 2019; Kumar et al., 2017; Valera et al., 2010).”
BackgroundResultGender dynamics in ADHD: understanding ADHD in females from childhood to adulthood
Oroian, B. A., Nechita, P., Costandache, G., Marusic, R.-I., Pătrașcu, C., & Szalontay, A. S. (2023) · Bulletin of Integrative Psychiatry · doi:10.36219/bpi.2023.4.09 · Cited by 11
Aiming for remission in adults with attention-deficit/hyperactivity disorder: The primary care goal
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“Lifelong involvement is consistent with the fact that ADHD is not just a psychological disorder but also a neurobiological condition with a familial incidence pattern linked to genetic abnormalities and alterations in brain structure and function causing impairments in planning, response inhibition, and other executiv…”
BackgroundHupalo, S., Spencer, R. C., & Berridge, C. W. (2021) · European Journal of Neuroscience · doi:10.1111/ejn.15260 · Cited by 6
“However, evidence indicates that females display differential sensitivity to certain behavioral and cellular actions of CRF in subcortical regions (Howerton et al., 2014; Hupalo, Bryce, et al., 2019; Valentino et al., 2012; Valera et al., 2010).”
BackgroundLiang, H.-Y., & Kelsen, B. A. (2017) · Electronic Journal of Research in Educational Psychology · doi:10.25115/ejrep.41.16017 · Cited by 6
“This corresponds with more recent inquiries in the field of ADHD research (Simon et al., 2009; Valera et al., 2010; Wang et al., 2015) and indicates the potential existence of a moderating gender effect insufficiently researched in previous studies examining the effect of ADHD symptoms on EFL…”
BackgroundMethodResultInfluentialJung, M., Woo, J., Kim, S. J., Lim, Y. B., Kim, Y., Kang, D., Min, J., & Kim, B.-N. (2025) · JMIR Human Factors · doi:10.2196/70479 · Cited by 4
“Multitasking n-back training strengthens the right inferior frontal gyrus, an area exhibiting structural [30,31] and functional deficits in children with ADHD [32,33].”
Taddei, M., Bulgheroni, S., Riva, D., & Erbetta, A. (2022) · Journal of Neuroscience Research · doi:10.1002/jnr.25143 · Cited by 4
“Interestingly, executive tasks seem to more easily elicit altered brain activation in males than females also in clinical ADHD population when compared to the same s/g control subjects (Sheridan et al., 2007; Valera et al., 2010).”
ResultRamos‐Quiroga, J. A., Picado, M., Mallorquí‐Bagué, N., Vilarroya, Ó., Gloria Palomar, A., Vanesa Richarte, B., Vidal, R., & Casas, M. (2013) · Revista de Neurología · doi:10.33588/rn.56s01.2012659 · Cited by 6
“Este estudio [80] es importante, ya que no sólo comparó el grupo con TDAH con el control, sino que también estudió las diferencias en cuanto al gé-”
BackgroundClinical Practice Guideline for Patients with Attention Deficit/Hyperactivity Disorder
Carlton, T. G., Donachie, N., Frampton, K. K., Henschen, G., Kumar, P. E., Parrot, L. A., Smith, C. A., Tamil, F. A., Valenti, A. M., & Waxenberg, F. (2014) · Cited by 2
Assessing the Impact of White Noise on Cognition in Individuals with and without ADHD
Roye, S. (2017) · Louisiana State University · doi:10.31390/gradschool_theses.4323 · Cited by 2
“reduction within the dorsolateral prefrontal cortex (dlPFC; Biehl et al., 2016; Ehlis et al., 2008; Shecklmann et al., 2013; Valera et al., 2010) and the anterior cingulate cortex”
BackgroundBrain imaging of the neural systems affected in adults with attention-deficit/hyperactivity disorder
Banich, M. T. (2010) · Expert Review of Neurotherapeutics · doi:10.1586/ern.10.137 · Cited by 1
Salavert, J. (2015) · TDX (Tesis Doctorals en Xarxa) · Cited by 1
The EEG activity of girls with attention-deficit/hyperactivity disorder
Dupuy, F. E. (2014) · Research Online (University of Wollongong)
Villemonteix, T. (2015) · theses.fr (ABES) · doi:10.70675/84304c2az6a4fz488czbda7z8935968796d4 · Cited by 1
Is er een typisch neuropsychologisch profiel bij volwassenen met ADHD? Een ontwikkelingsperspectief
Tamminga, H. G. H., & Geurts, H. M. (2016) · Neuropraxis · doi:10.1007/s12474-015-0110-3 · Cited by 1
Die Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung (ADHS) im Erwachsenenalter: Aktueller Stand
Mette, C. (2019) · Springer eBooks · doi:10.1007/978-3-662-45995-9_17-1
Η νευροψυχολογική αξιολόγηση στη διαφοροδιάγνωση διπολικής διαταραχής και ΔΕΠΥ σε ενήλικες
Τζιράκη, Σ. Χ. (2020) · Psychology the Journal of the Hellenic Psychological Society · doi:10.12681/psy_hps.22422
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Ludolph, A. G. (2011) · Springer eBooks · doi:10.1007/978-3-642-19844-1_38
Insular-striatal activation during COVID-19 predicts stress reactivity in high-trait anxiety
Lee, S.-H., & Chou, T. (2025) · Biological Psychology · doi:10.1016/j.biopsycho.2025.108998
Littleton, A. C. (2011) · University Microfilms International eBooks
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“…with the literature reporting gender differences in ADHD (Stibbe et al., 2020), especially the functional connectivity during resting-state (Park & Park, 2016 ) and working memory tasks (Valera et al., 2010 ) which are related to frequent mind wandering (He et al., 2021 ; McVay & Kane, 2009).”
Metadata
- Authors
- Valera, E. M., Brown, A., Biederman, J., Faraone, S. V., Makris, N., Monuteaux, M. C., Whitfield-Gabrieli, S., Vitulano, M., Schiller, M., & Seidman, L. J.
- Affiliations
- Harvard University (US)
- Boston University (US)
- SUNY Upstate Medical University (US)
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Valera, Eve M
- ORCID
- Venue
- American Journal of Psychiatry
- Published
- 2010-01-01
- Volume
- 167
- Issue
- 1
- Pages
- 86-94
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- PMC
- PMC3777217
- OpenAlex
- W2151036885
- Cited by
- 138
- References
- 40
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 1 · 2023: 6 · 2022: 9 · 2021: 10 · 2020: 9 · 2019: 9 · 2018: 4 · 2017: 8 · 2016: 7 · 2015: 19 · 2014: 9 · 2013: 13 · 2012: 9
- FWCI
- 5.98
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- March of Dimes Foundation
- Eli Lilly and Company
- Pfizer
- Massachusetts General Hospital (P41RR14075, 071535)
- National Alliance for Research on Schizophrenia and Depression
- Shire
- National Institutes of Health (071535, 1f32mh065040-01a1)
- National Institute of Mental Health (MH-084041, MH 16259, F32 MH065040, MH-62152, K23MH071535, MH-071535, R01MH057934, MH-57934, R01MH062152, R21MH084041, T32MH016259)
- National Center for Research Resources (071535, P41-RR-14075, P41RR014075)
- National Center for Complementary and Integrative Health (1P01 AT-002048-06, P01AT002048)
- Janssen Pharmaceuticals
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Social Sciences › Psychology › Neuropsychology and Physiological Psychology › Developmental and Educational Neuropsychology
- Keywords
- adult ADHD, sex differences, working memory, functional neuroanatomy, n-back task, prefrontal cortex, inattentive symptoms, neuronal activation, cerebellum, temporal lobe
- MeSH terms
- Adolescent, Adult, Attention, Attention Deficit Disorder with Hyperactivity, Brain, Brain Mapping, Female, Humans, Intelligence Tests, Functional Laterality, Magnetic Resonance Imaging, Male, Memory, Short-Term, Neuropsychological Tests, Oxygen, Psychiatric Status Rating Scales, Reaction Time, Sex Factors, Prefrontal Cortex, Sex Distribution
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