selected publications

1. A bias-accounting meta-analytic approach refines and expands the cerebellar behavioral topography Magielse N^*, Manoli A, Eickhoff S, Fox P, Saberi A^†, and Valk S^*† Neuroscience & Biobehavioral Reviews 2025 [abstract] [url] [pdf]

   The cerebellum plays important roles in motor, cognitive, and emotional behaviors. Previous cerebellar coordinate-based meta-analyses (CBMAs) have complemented precision-mapping and parcellation approaches by finding generalizable cerebellar activations across the largest possible set of behaviors. However, cerebellar CBMAs face challenges due to inherent methodological limitations, exacerbated by historical cerebellar neglect in neuroimaging studies. Here, we show overrepresentation of superior activations, rendering the null hypothesis of standard activation likelihood estimation (ALE) unsuitable. Our new method, cerebellum-specific ALE (C-SALE), finds behavioral convergence beyond baseline activation rates. It does this by testing experimental activations versus null models sampled from a data-driven probability distribution of finding activations at any cerebellar location. Task-specific mappings in the BrainMap meta-analytic database illustrated improved specificity of the new method. Multiple (sub)domains reached convergence in specific cerebellar subregions, supporting dual motor representations and placing cognition in posterior-lateral regions. We show our method and findings are replicable using the NeuroSynth database. Across both databases, 54/138 task domains or behavioral terms, including sustained attention, somesthesis, inference, anticipation and rhythm, reached convergence in specific cerebellar subgregions. Our meta-analyic maps largely corresponded with cerebellar atlases but also showed many complementary mappings. Repeated subsampling analysis showed that motor behaviors, and to a lesser extent language and working memory, mapped to especially consistent cerebellar subregions. Lastly, we found that cerebellar clusters were parts of brain-wide coactivation networks with cortical and subcortical regions implied in these behaviors. Together, our method further complements and expands understanding of cerebellar involvement in human behavior, highlighting regions for future investigation in both basic and clinical applications.

2. Adolescent maturation of cortical excitation-inhibition ratio based on individualized biophysical network modeling Saberi A, Wischnewski K, Jung K, Lotter L, Schaare H, Banaschewski T, Barker G, Bokde A, Desrivières S, Flor H, Grigis A, Garavan H, Gowland P, Heinz A, Brühl R, Martinot J, Martinot M, Artiges E, Nees F, Papadopoulos Orfanos D, Lemaitre H, Poustka L, Hohmann S, Holz N, Baeuchl C, Smolka M, Vaidya N, Walter H, Whelan R, Schumann G, IMAGEN CONSORTIUM , Paus T, Dukart J, Bernhardt B, Popovych O, Eickhoff S, and Valk S^* Science Advances 2025 [abstract] [url] [pdf]

   The excitation-inhibition ratio is a key functional property of cortical microcircuits which changes throughout an individual’s lifespan. Adolescence is considered a critical period for maturation of excitation-inhibition ratio. This has primarily been observed in animal studies. However, there is limited human in vivo evidence for maturation of excitation-inhibition ratio at the individual level. Here, we developed an individualized in vivo marker of regional excitation-inhibition ratio in human adolescents, estimated using large-scale simulations of biophysical network models fitted to resting-state functional imaging data from both cross-sectional (n = 752) and longitudinal (n = 149) cohorts. In both datasets, we found a widespread decrease in excitation-inhibition ratio in association areas, paralleled by an increase or lack of change in sensorimotor areas. This developmental pattern was aligned with multiscale markers of sensorimotor-association differentiation. Although our main findings were robust across alternative modeling configurations, we observed local variations, highlighting the importance of methodological choices for future studies.

3. Convergent functional effects of antidepressants in major depressive disorder: a neuroimaging meta-analysis Saberi A, Ebneabbasi A, Rahimi S, Sarebannejad S, Sen Z, Graf H, Walter M, Sorg C, Camilleri J, Laird A, Fox P, Valk S, Eickhoff S, and Tahmasian M^* Molecular Psychiatry 2024 [abstract] [url] [pdf]

   Neuroimaging studies have provided valuable insights into the macroscale impacts of antidepressants on brain functions in patients with major depressive disorder. However, the findings of individual studies are inconsistent. Here, we aimed to provide a quantitative synthesis of the literature to identify convergence of the reported findings at both regional and network levels and to examine their associations with neurotransmitter systems.

4. Regional patterns of human cortex development correlate with underlying neurobiology Lotter L, Saberi A, Hansen J, Misic B, Paquola C, Barker G, Bokde A, Desrivières S, Flor H, Grigis A, Garavan H, Gowland P, Heinz A, Brühl R, Martinot J, Paillère M, Artiges E, Papadopoulos Orfanos D, Paus T, Poustka L, Hohmann S, Fröhner J, Smolka M, Vaidya N, Walter H, Whelan R, Schumann G, Nees F, Banaschewski T, Eickhoff S, and Dukart J^* Nature Communications 2024 [abstract] [url] [pdf]

   Human brain morphology undergoes complex changes over the lifespan. Despite recent progress in tracking brain development via normative models, current knowledge of underlying biological mechanisms is highly limited. We demonstrate that human cortical thickness development and aging trajectories unfold along patterns of molecular and cellular brain organization, traceable from population-level to individual developmental trajectories. During childhood and adolescence, cortex-wide spatial distributions of dopaminergic receptors, inhibitory neurons, glial cell populations, and brain-metabolic features explain up to 50% of the variance associated with a lifespan model of regional cortical thickness trajectories. In contrast, modeled cortical thickness change patterns during adulthood are best explained by cholinergic and glutamatergic neurotransmitter receptor and transporter distributions. These relationships are supported by developmental gene expression trajectories and translate to individual longitudinal data from over 8000 adolescents, explaining up to 59% of developmental change at cohort- and 18% at single-subject level. Integrating neurobiological brain atlases with normative modeling and population neuroimaging provides a biologically meaningful path to understand brain development and aging in living humans.

5. The regional variation of laminar thickness in the human isocortex is related to cortical hierarchy and interregional connectivity Saberi A, Paquola C, Wagstyl K, Hettwer M, Bernhardt B, Eickhoff S, and Valk S^* PLOS Biology 2023 [abstract] [url] [pdf]

   The human isocortex consists of tangentially organized layers with unique cytoarchitectural properties. These layers show spatial variations in thickness and cytoarchitecture across the neocortex, which is thought to support function through enabling targeted corticocortical connections. Here, leveraging maps of the 6 cortical layers based on 3D human brain histology, we aimed to quantitatively characterize the systematic covariation of laminar structure in the cortex and its functional consequences. After correcting for the effect of cortical curvature, we identified a spatial pattern of changes in laminar thickness covariance from lateral frontal to posterior occipital regions, which differentiated the dominance of infra- versus supragranular layer thickness. Corresponding to the laminar regularities of cortical connections along cortical hierarchy, the infragranular-dominant pattern of laminar thickness was associated with higher hierarchical positions of regions, mapped based on resting-state effective connectivity in humans and tract-tracing of structural connections in macaques. Moreover, we show that regions with similar laminar thickness patterns have a higher likelihood of structural connections and strength of functional connections. In sum, here, we characterize the organization of laminar thickness in the human isocortex and its association with cortico-cortical connectivity, illustrating how laminar organization may provide a foundational principle of cortical function.