We introduce ComBatLS, a new harmonization method that preserves the effects of biological covariates like sex and age on brain feature distributions' variances or scale parameters. We show that ComB...

Translational Psychiatry - Individual-level deviations from normative brain morphology in violence, psychosis, and psychopathy

Despite their promise, current neuroimaging biomarkers often fail to capture the full spectrum of inter-individual variability in brain structure and aging effects. This limits their ability to detect...

Individuals with schizophrenia show reduced structural similarity in temporal, cingulate, and insular lobes, especially those with worse cognition and symptoms, affecting late maturing association areas with low metabolism and high neurotransmission.

How to carry out reproductions and replications in the social, cognitive, and behavioral sciences

Conventional and advanced diffusion MRI approaches predict brain age consistently, yet best when combined. Fornix and forceps minor were central regions for these predictions across diffusion approa.....

In this Stage 2 Registered Report, Buchanan et al. show evidence confirming the phenomenon of semantic priming across speakers of 19 diverse languages.

When processing and analyzing empirical data, researchers regularly face choices that may appear arbitrary (e.g., how to define and handle outliers). If one chooses to exclusively focus on a particula...

Background Brain atrophy is a hallmark of multiple sclerosis (MS). For clinical translatability and individual-level predictions, brain atrophy needs to be put into context of the broader population, ...

Molecular Psychiatry - Associations of polygenic risk scores for major depression and depression severity: an investigation of 105 623 individuals with 16 years follow-up

Type 2 diabetes, hypertension, and hyperlipidemia are associated with a high risk of developing all-cause dementia in participants already diagnosed with mild cognitive impairment (MCI). Type 2 diabet...

Alzheimer’s disease (AD) is now defined based on its underlying brain pathology[1][1], with the presence of amyloid (Aβ) plaques at high enough levels sufficient to warrant a diagnosis in the absence of cognitive symptoms. High levels of PET-detectable Aβ are widely thought to be the first imaging marker, with structural brain changes detectable on MRI scans thought to occur later. We combined 4570 longitudinal MRIs and 1684 Aβ PET scans from three cognitively healthy cohorts to test the difference in cortical thickness and its change between those that subsequently converted to be Aβ-positive or stayed Aβ-negative, using MRIs acquired exclusively in the years before conversion. We found those that subsequently developed elevated Aβ levels show both thicker cortex and less cortical thinning, even when the last MRI used to estimate their thickness trajectories was acquired at least seven years before conversion. Many effects remained when accounting for quantitative Aβ levels, suggesting some cortical thickness effects may be partly independent of Aβ. Differences in cortical thickness and its change between converters and Aβ-negative individuals showed moderate alignment with patterns of Aβ deposition, and the timing of thickness changes tracked the temporal progression of Aβ accumulation. Thus, if amyloid is AD[1][1], we show that high levels of PET-detectable amyloid are not the first imaging marker of AD, as cortical thickness changes can be traced years before pathological amyloid. This has implications for understanding the sequence of events leading up to the earliest stages of AD. ### Competing Interest Statement W.J.J. serves on data monitoring committees for Lilly, holds equity in Optoceutics and Molecular Medicine, receives research support from Biogen and grants from ZonMW, Alzheimer Nederland, St. Rinsum-Ponsen. E.H.L. is the CSO and a shareholder in baba.vision. All other authors declare no competing interests. [1]: #ref-1