Biology subjects

Manoli, A.

Publications and source records attributed to Manoli, A..

6 recordsLinked to original sources

bioRxiv2026

The cerebellum supports two systems for understanding others in early childhood

The cerebellum has increasingly been implicated in Theory of Mind (ToM), a hallmark of human social cognition. Yet its role in the development of social understanding remains poorly understood, despite evidence linking early cerebellar disruptions to profound social cognitive deficits. Although explicit ToM reasoning emerges only around four years of age, preverbal infants already excel at predicting others actions, raising the question of how the cerebellum supports social cognition early in development. Here, we investigated structural cerebellar correlates of ToM (explicit false belief understanding) and nonverbal action prediction in children aged 3-4 years, a critical developmental period during which explicit ToM emerges. Greater gray matter volume in Crus II, a core node of the adult cerebellar ToM network, was associated with better explicit ToM performance. By contrast, nonverbal action prediction was linked to distinct, non-overlapping clusters in inferior lobule VIIB and the posterior vermis, regions implicated in action observation and salience processing in adults. These cerebellar regions further exhibited dissociable patterns of covariance with cerebral networks, linking Crus II to the canonical ToM network and VIIB/vermal regions to salience-related areas. Our findings reveal neuroanatomically distinct cerebellar substrates supporting two separable components of early social cognition: one anchored to explicit mental-state reasoning and another to an earlier-emerging nonverbal action prediction system potentially grounded in the processing of salient social cues. Together, these findings identify the cerebellum as a key contributor to multiple stages of social cognitive development and suggest that distinct cerebellar systems scaffold the emergence of mature social understanding.

neuroscience↗

bioRxiv2026

Nucleus-level thalamic organization anchors multimodal signatures of thalamocortical maturation

The human thalamus is composed of multiple nuclei that differ in structure and function. From early development onwards, these nuclei form reciprocal, nucleus-specific connections with the cerebral cortex, contributing to sensory and cognitive processing. In childhood and adolescence, a key period of neurocognitive development, these connections undergo widespread refinement, yet how developmental trajectories of thalamocortical connections vary across nuclei remains unknown. Here, we leveraged the Human Connectome Project in Development dataset (HCP-D, N = 604, age range 8-21) and segmented 10 thalamic nuclei using a segmentation approach optimized for intrathalamic contrast. Applying probabilistic tractography, we reconstructed nucleus-specific thalamocortical connections and charted their maturational profiles based on changes in fractional anisotropy (FA) using generalized additive models. We found FA to increase in thalamocortical connections, with nucleus-specific variation in temporal profiles and magnitude of age effects. Connections of core-cell-rich, sensory-projecting nuclei, such as the lateral geniculate nucleus, showed earlier maturational plateaus, whereas matrix-cell-rich, association-projecting nuclei, such as ventral anterior nucleus, showed more sustained maturation. This links maturational heterochronicity to thalamic organization of cell distribution and connectivity embedding. In parallel, functional thalamocortical connectivity decreased with age, with FA and functional connectivity age effects coupled in nucleus-connections showing prolonged maturation. Finally, concordant age effects in connectivity and nucleus volumes suggest that intra-nucleus remodeling may support refinement of structural connections while reducing thalamocortical functional synchrony. Together, our work reveals that thalamocortical maturation is anchored in the developmental and organizational heterogeneity of thalamic nuclei, offering a framework for understanding how diverse thalamic nuclei contribute to neurocognitive development.

neuroscience↗

bioRxiv2025

Cerebellar growth is associated with domain-specific cerebral maturation and socio-linguistic behavioral outcomes

The cerebellums involvement in cognitive functions is increasingly recognized, yet its developmental contribution to cognition remains poorly understood. The cerebellum undergoes rapid development in early life, paralleling major cognitive and behavioral changes. Although clinical studies have linked early cerebellar disruptions to profound developmental deficits, it remains largely unclear how typical cerebellar maturation supports the development of cognitive functions and how it interacts with broader brain development. Here, we apply a normative modeling framework to map cerebellar volumetric growth from infancy to young adulthood (N = 751; ages 1-21 years). Using lobular and functional cerebellar parcellations, we comprehensively characterize typical cerebellar development and examine how it aligns with cerebral development and behavioral outcomes. Across parcellations, posterior higher association areas consistently show steeper growth trajectories than anterior sensorimotor areas. Cerebellar and cerebral areas with similar functional roles demonstrate coordinated maturation, and volumetric growth in the posterior cerebellum relates to individual differences in socio-linguistic behaviors. These findings establish a comprehensive reference for typical cerebellar development, highlight cerebellar co-maturation with the cerebral cortex, and underscore the cerebellums role in supporting emerging higher cognitive functions.

neuroscience↗

bioRxiv2025

Transcranial magnetic stimulation induced pupil dilations can serve as a cortical excitability measure

The application of non-invasive brain stimulation (NIBS) often relies on proxy estimates of cortical excitability (CE), such as the resting motor threshold (rMT), measured through transcranial magnetic stimulation (TMS). However, estimating the rMT is not always possible, as it requires an intact corticospinal pathway for neural signals to travel from the cortex to the periphery. To broaden the application of NIBS there is a need for additional CE measures. In three experiments combining TMS, transcranial direct current stimulation (tDCS), and eye-tracking, we measured TMS-induced pupil dilations as a potential CE proxy. We present Bayesian evidence (Experiment 1: BF > 9; Experiment 2: BF > 46; Experiment 3: BFs > 6) that TMS-induced pupil dilations serve as an objective CE proxy, with larger pupil size reflecting higher CE. We also show that these effects are not due to auditory, muscle, or sensory confounds. The introduction of this novel measure paves the way for a deeper understanding of CE by enabling objective NIBS measures beyond the motor cortex. Moving away from the reliance on the motor cortex would allow NIBS research and therapy to become more inclusive, allowing access to populations that are affected by damage along the corticospinal pathway.

neuroscience↗

bioRxiv2024

Bias-accounting meta-analyses overcome cerebellar neglect to refine the cerebellar behavioral topography

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. 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 were replicable within NeuroSynth. Across both databases, 54/138 task domains or behavioral terms, including sustained attention, somesthesis, inference, anticipation and rhythm, reached convergence in specific cerebellar subgregions. Maps largely corresponded with cerebellar atlases but also showed many complementary mappings. Repeated subsampling 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. Highlights[bullet] Biases in reported cerebellar activations strongly favors superior regions. [bullet]A new method of meta-analysis increases cerebellar mapping specificity and accuracy. [bullet]Large-scale meta-analyses support cerebellar roles in cognitive, affective, and motor behaviors. [bullet]54 task domains/ terms converged, including sustained attention, somesthesis, inference, anticipation and rhythm. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=100 SRC="FIGDIR/small/621398v3_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@716ea0org.highwire.dtl.DTLVardef@11601fforg.highwire.dtl.DTLVardef@1dd1208org.highwire.dtl.DTLVardef@caf535_HPS_FORMAT_FIGEXP M_FIG Graphical abstract C_FIG

neuroscience↗

bioRxiv2024

Functional recruitment and connectivity of the cerebellum supports the emergence of Theory of Mind in early childhood

There is accumulating evidence that the human cerebellum is heavily implicated in adult social cognition. Yet, its involvement in the development of Theory of Mind (ToM), a hallmark of social cognition, remains elusive. In a functional MRI study involving children with emerging ToM abilities (N=41, age range: 3-12 years) and adults (N=78), we showed that children with ToM abilities activated cerebellar Crus I-II in response to ToM events during a movie-watching task, similar to adults. This activation was absent in children lacking ToM abilities. Functional connectivity profiles between cerebellar and cerebral ToM regions differed as a function of childrens ToM abilities. Notably, task-driven connectivity shifted from upstream to downstream connections between cerebellar and cerebral ToM regions from childhood to adulthood. Greater dependence on connections emerging from the cerebellum early in life suggests an important role of the cerebellum in establishing the cognitive processes underlying ToM in childhood and thus for the undisrupted development of social cognition.

neuroscience↗