The review is relevant to an estimated 44% to 60% of perimenopausal women who report cognitive changes such as forgetfulness and trouble concentrating, commonly described as brain fog. These symptoms can affect productivity, work, daily routines and quality of life, and no FDA-approved pharmacological intervention is currently available specifically for them. Researchers who conducted the review cautioned that the evidence is too limited to recommend either ADHD medication for menopausal brain fog.

Larger studies would be needed first to establish whether the drugs are safe and effective for this use, and the review does not establish that the benefits reported by participants were caused by changes in their underlying cognitive ability. To assess the potential role of existing ADHD treatments, the researchers conducted a scoping review of original research involving lisdexamfetamine, a stimulant, and atomoxetine, a non-stimulant. The eligible population consisted of biological women aged 45 to 60 whose last menstrual period had occurred less than 10 years earlier.

Studies were excluded if they involved transgender women, disordered sleep, surgical menopause, primary ovarian insufficiency, premature or early menopause, or a previous or current cancer diagnosis. These criteria were intended to focus the evidence on women experiencing the natural menopause transition, but they also restricted the size and composition of the evidence base and limit how widely its findings can be generalized. The biological rationale proposed by the researchers centers on the substantial decline and fluctuation in estrogen during menopause.

The menopause transition is associated with quantifiable deficits in working memory, attentional control and processing speed, and these domains overlap with core symptoms of ADHD. The authors suggested that ADHD medications may influence signaling pathways disrupted during the transition in a way that improves subjective executive function. Neuroimaging findings from a subset of women taking lisdexamfetamine were described as further supporting this interpretation, although the research release did not provide the sample size or detailed methods of that imaging analysis.

Evidence linking ADHD symptoms with menopausal experiences remains incomplete. Cross-sectional data showed a positive correlation between ADHD symptom severity and the intensity of menopause symptoms, indicating an association in the populations studied rather than proof of a causal relationship. Findings were inconsistent about whether a formal ADHD diagnosis was associated with somatic or psychological complaints.

Those limitations, together with the minimal or nonsignificant effects of both medications on objective cognitive measures, mean the review cannot demonstrate that lisdexamfetamine or atomoxetine improves cognition during menopause.

Subject of Research: Scoping review of ADHD medications for self-reported executive dysfunction during the menopause transition

Article Title: ADHD medications offer promise in managing menopausal brain fog

Article References: ADHD medications offer promise in managing menopausal brain fog. Original publication (Bibliographic details unavailable.)

Image Credits: AI Generated

DOI: Not provided

Keywords: menopause, brain fog, ADHD, lisdexamfetamine, atomoxetine, executive function, cognition, perimenopause, scoping review, medications, offer, promise

The research, led by Xiaoyu Xu and Zaixu Cui of the Chinese Institute for Brain Research in Beijing, together with colleagues at Peking University Sixth Hospital, Stanford University and other institutions, took aim at a fundamental problem in pediatric psychiatry. ADHD affects a substantial share of school-age children worldwide, yet no validated biomarkers exist for tracking symptom trajectories or guiding treatment selection in youth. Clinicians must largely rely on trial and error when choosing between medications, and families often wait weeks or months to learn whether a prescription is working. The team asked whether the developing brain’s structural connections could supply the missing prognostic information.

Their approach rested on the idea of normative growth charts, familiar from pediatrics, where a child’s height and weight are compared against population curves to flag unusual development. The researchers applied the same logic to the brain’s wiring diagram. Using diffusion magnetic resonance imaging, which traces the bundles of nerve fibers that connect distant brain regions, they built normative age-related trajectories of white-matter structural connectivity from a large longitudinal developmental cohort comprising 6,687 scans from typically developing youths and 1,114 scans from youths with ADHD. They then quantified, for every individual with ADHD, how much each connection deviated from the trajectory expected for that person’s age. An independent replication cohort of 355 typically developing and 477 ADHD participants allowed the team to confirm that their findings were not an artifact of a single dataset.

The first major result was that youths with ADHD showed pronounced deviations in structural connectivity, and those deviations were not distributed randomly across the brain. Instead, they clustered overwhelmingly at the association end of what neuroscientists call the sensorimotor–association connectional axis, a gradient that runs from regions devoted to basic sensation and movement to the higher-order association cortices that support attention, executive control and self-regulation. These association networks are precisely the circuits implicated in ADHD symptoms, and they are also the slowest-maturing parts of the brain, continuing to develop well into adolescence and early adulthood. The findings echo an influential earlier report that ADHD involves a delay in cortical maturation, but extend it from the gray matter of the cortex to the white-matter highways that link cortical networks together.

The study then probed how these deviations evolve. A subset of higher-order association connections showed ADHD-specific reductions in deviation with age, changes that went beyond typical developmental patterns and could not be explained by ordinary maturation. Critically, these converging trajectories statistically mediated the age-related decline in ADHD symptoms observed across development, suggesting a mechanistic account of why many children appear to grow out of the disorder. When the researchers followed individuals across two years, they found that within-person decreases in deviation tracked symptom improvement over the same interval, linking individual brain maturation to individual clinical course in a way that cross-sectional group comparisons never could.

The most clinically provocative findings concerned treatment. Using data from youths treated with either atomoxetine or methylphenidate, the two most widely prescribed ADHD medications, the team tested whether baseline structural connectivity deviations could predict response to a 12-week course of treatment. The answer was strikingly specific. Deviations predicted response to atomoxetine, a norepinephrine reuptake inhibitor whose effects are concentrated in prefrontal association circuits, but not to methylphenidate, a stimulant whose primary mechanism centers on dopamine signaling in striatal reward pathways. Follow-up imaging further revealed that treatment itself was associated with reductions in deviation, hinting that effective medication may nudge wayward white-matter development back toward the normative curve. Together, these results identify structural connectivity deviation as a developmental biomarker with prognostic relevance, supporting precision care through symptom monitoring and treatment stratification.

Technically, the study represents a synthesis of several modern neuroimaging and statistical methods. Diffusion MRI data were preprocessed and reconstructed with tools including QSIPrep and MRtrix3, with anatomically constrained tractography and multi-tissue constrained spherical deconvolution used to estimate the strength of each white-matter connection. Cortical parcellations derived from functional connectivity provided a common map of brain regions organized along the sensorimotor–association axis. Normative trajectories were modeled with generalized additive models for location, scale and shape, the same statistical machinery used to construct World Health Organization child growth standards, and deviation was quantified as the distance between an individual’s connectivity and the population curve. Longitudinal scanner effects were harmonized with longitudinal ComBat, and mediation analysis, mixed-effects models and structural equation modeling tied the deviations to symptom change.

The scale of the evidence base deserves emphasis. Prior studies of white matter in ADHD have often compared groups of a few dozen participants and produced inconsistent results, a pattern documented in meta-analyses of more than one hundred diffusion imaging studies. By anchoring deviation estimates in a normative cohort of thousands and replicating them in an independent cohort, the researchers sidestepped the case-control designs that have long limited interpretation. The normative modeling framework they used was developed specifically to understand heterogeneity in clinical cohorts, recognizing that each patient’s brain tells an individual story that average group differences obscure. The method also parallels the construction of lifespan brain charts published in recent years, extending that approach from brain volume to the connectome and from typically developing populations to clinical prediction.

The implications reach beyond ADHD. The sensorimotor–association axis has emerged in recent work as a general organizing principle of cortical development and function, and deviations along this axis have been linked to autism and other neurodevelopmental conditions. If individual deviation from normative development can forecast symptoms and treatment response in ADHD, the same logic may apply to other childhood psychiatric disorders that similarly lack biomarkers. The researchers have released their analysis code publicly, and the ABCD dataset underlying much of the work is available to qualified investigators, which should accelerate independent validation. Limitations remain: the medication analyses were observational, deviations were measured from diffusion imaging with inherent biases in tractography, and clinical deployment would require streamlined acquisition and standardized norms across scanner platforms.

Still, the study sketches a plausible near future in which a child newly diagnosed with ADHD undergoes a brief MRI session, their white-matter wiring is compared against a growth chart of the developing connectome, and the resulting deviation profile informs whether atomoxetine is likely to succeed, how their symptoms are likely to evolve over adolescence, and whether their brain is already converging toward the normative trajectory. For a disorder that has been defined almost entirely by behavior since it was first described more than a century ago, the prospect of a measurable, mechanistic, individualized biomarker drawn from the brain’s structural wiring marks a genuine turning point, one that could move pediatric psychiatry from reactive adjustment of prescriptions toward genuinely predictive, precision-guided care.

Subject of Research: Developmental deviations of association-network structural connectivity as predictive biomarkers of ADHD symptoms and treatment response in youth

Article Title: Developmental deviations of association-network structural connectivity in youths with ADHD predict symptom and treatment outcomes

Article References: Xu, X., Fu, Z., Xu, H., Zhang, K., Cong, J., Yang, H., Li, Y., Zhao, Y., Zheng, X., Keller, A. S., Xu, T., Chen, R., Cai, W., Cao, Q., Yang, L., & Cui, Z. (2026). Developmental deviations of association-network structural connectivity in youths with ADHD predict symptom and treatment outcomes. Nature Biomedical Engineering. https://doi.org/10.1038/s41551-026-01779-4

Image Credits: AI Generated

DOI: 10.1038/s41551-026-01779-4

Keywords: ADHD, structural connectivity, white matter, diffusion MRI, normative modeling, brain development, association networks, atomoxetine, methylphenidate, biomarkers, precision medicine, pediatric psychiatry