Biology subjects

van der Zwaag, W.

Publications and source records attributed to van der Zwaag, W..

10 recordsLinked to original sources

bioRxiv2026

Neonatal Muscle Tone Predicts Cerebellar Morphology Later in Development Without Mediating Autistic Traits

Background: Infant muscle tone reflects early central nervous system integrity and has been associated with later motor and cognitive development, including autism traits. The cerebellum regulates both motor control and higher-order socio-cognitive functions and has been repeatedly implicated in autism, but its role in linking infant muscle tone to adolescent autistic traits has not previously been studied in a large, prospective population cohort. Methods: We used data from the prospective Generation R Study. Infant muscle tone (hypotonia and hypertonia) was assessed via Prechtl examination, and third-trimester fetal transcerebellar diameter was measured using ultrasound n=6,842). Cerebellar morphology at ages 6, 10, and 14 years (n=4,861) was measured using structural MRI. Linear mixed-effects models tested associations between infant muscle tone and 35 anatomical and 10 functional cerebellar regions. Causal mediation models tested whether cerebellar volume mediated associations between infant muscle tone and adolescent autistic traits at age 14 (Social Responsiveness Scale). Results: Hypotonia predicted larger vermis IX volumes across childhood (beta=0.037, pFDR =0.043). Hypertonia showed an age-dependent association with left lateral lobule IX (beta=-0.0027, pFDR =0.041), with differences diminishing with age. Third-trimester transcerebellar diameter did not predict postnatal muscle tone. Given its significant main effect, vermis IX volume was tested as a mediator, but did not mediate the pathway to adolescent autistic traits. However, infant hypotonia showed a small direct association with elevated autistic traits at age 14, specific to girls (beta=0.0255, p=0.020). Conclusions: Infant muscle tone is associated with localized differences in cerebellar volumes. These associations are specific to vermal and left hemispheric lobule IX, a region commonly implicated in spinocerebellar postural control, axial stability, and higher-order sensorimotor integration. Furthermore, infant muscle tone was not predicted by prenatal cerebellar diameter, and cerebellar volumes did not mediate the association between infant hypotonia and adolescent autistic traits in our study. Future research should further investigate these findings in clinical populations, integrating longitudinal whole-brain, multi-modal imaging to clarify the association between infant muscle tone, the cerebellar functioning, and autistic traits.

neuroscience↗

bioRxiv2025

Mesoscale imaging of the human cerebellum reveals converging regional specialization of its morphology, vasculature and cytoarchitecture.

The human cerebellar cortex contains the highest density and number of neurons in the human brain, yet this thin and tightly-folded structure has remained largely inaccessible to in-vivo imaging. We introduce an imaging framework to enable high-resolution, comprehensive imaging of the human cerebellar cortex. We validated the in-vivo estimates of cortical morphology against post-mortem measures. Crucially, our findings challenge the commonly held view of the cerebellar cortex as being uniform. Our findings reveal interlobular heterogeneity in both cortical morphology and vascular organization. We demonstrate that this spatial heterogeneity correlates with granular layer cell density. This convergence of morphology, cytoarchitecture and vascularization offers new mechanistic insights and reframes how cerebellar structure and function should be interpreted in health and disease.

neuroscience↗

bioRxiv2023

A 7T interleaved fMRS and fMRI study on visual contrast dependency in the human brain.

IntroductionsFunctional magnetic resonance spectroscopy (fMRS) is a non-invasive technique for measuring dynamic changes in neurometabolites. While previous studies have observed concentration changes in metabolites during neural activation, the relationship between neurometabolite response and stimulus intensity and timing requires further investigation. To address this, we conducted an interleaved fMRS and functional magnetic resonance imaging (fMRI) experiment using a visual stimulus with varying contrast levels. MethodsA total of 20 datasets were acquired on a 7T MRI scanner. The visual task consisted of two STIM blocks (30s/20s ON/OFF, four minutes), with 10% or 100% contrast, interleaved with a four minutes REST block. A dynamic fitting approach was used for fMRS data analysis. For metabolite level changes, the STIM conditions were modeled in two different ways: either considering the full STIM block as active condition (full-block model) or only modeling the ON blocks as active condition (sub-block model). For linewidth changes due to the BOLD effect, STIM conditions were modeled using the sub-block model. ResultsFor both models, we observed significant increases in glutamate levels for both the 10% and 100% visual contrasts, but no significant difference between the contrasts. Decreases in aspartate, and glucose, and increases in total N-acetylaspartate and total creatine were also detected, although less consistently across both 10% and 100% visual contrasts. BOLD-driven linewidth decreases and fMRI-derived BOLD increases within the MRS voxel were observed at both 10% and 100% contrasts, with larger changes at 100% compared to 10% in the fMRI-derived BOLD only. We observed a non-linear relation between visual contrast, the BOLD response, and the glutamate response. ConclusionOur study highlights the potential of fMRS as a complementary technique to BOLD fMRI for investigating the complex interplay between visual contrast, neural activity, and neurometabolism. Future studies should further explore the temporal response profiles of different neurometabolites and refine the statistical models used for fMRS analysis.

neuroscience↗

bioRxiv2021

Depth-resolved intersubject functional correlation of 7T BOLD signals reveals increased stimulus related information sharing across deep layers in premotor and parietal nodes for predictable actions

While the brain regions involved in action observation are relatively well documented in humans and primates, how these regions communicate to help understand and predict actions remains poorly understood. Traditional views emphasized a feed-forward architecture in which visual features are organized into increasingly complex representations that feed onto motor programs in parietal and then premotor cortices where the matching of observed actions upon the observers own motor programs contributes to action understanding. Predictive coding models place less emphasis on feed-forward connections and propose that feed-back connections from premotor regions back to parietal and visual neurons represent predictions about upcoming actions that can supersede visual inputs when actions become predictable, with visual input then merely representing prediction errors. Here we leverage the notion that feed-back connections target specific cortical layers to help adjudicate across these views. Specifically, we test whether observing sequences of hand actions in their natural order, which permits participants to predict upcoming actions, triggers more feed-back input to parietal regions than seeing the same actions in a scrambled sequence that hinders making predictions. Using submillimeter fMRI acquisition at 7T, we find that watching predictable sequences triggers more action-related activity (as measured using intersubject functional correlation) in the parietal cortical area PFt at depths receiving feed-back connections (layers III and V/VI) than watching the exact same actions in scrambled and hence unpredictable sequence. In addition, functional connectivity analysis performed using intersubject functional connectivity confirms that these increased action-related signals in PFt could originate from ventral premotor region BA44. This data showcases the utility of intersubject functional correlation in combination with 7T MRI to explore the architecture of social cognition under more naturalistic conditions, and provides evidence for models that emphasize the importance of feed-back connections in action prediction.

neuroscience↗

bioRxiv2020

Palm-to-finger cortical functional interactions in primary somatosensory cortex: a 7T fMRI study

Many studies focused on the cortical representations of fingers, while the palm is relatively neglected despite its importance for hand function. Here, we investigated palm representation (PR) and its interactions with finger representations (FRs) in primary somatosensory cortex (S1). Few studies in humans suggested that PR is located medially with respect to FRs in S1, yet to date, no study directly quantified the somatotopic organization of PR and the five FRs. Importantly, the relationship between the somatotopic organization and the cortical functional interactions between PR and FRs remains largely unexplored. Using 7T fMRI, we mapped PR and the five FRs at the single subject level. First, we analyzed the cortical distance between PR and FRs to determine their somatotopic organization. Results show that the PR was located medially with respect to D5. Second, we tested whether the observed cortical distances would predict palm-finger functional interactions. Using three complementary measures of functional interactions (co-activations, pattern similarity and resting-state connectivity), we show that palm-finger functional interactions were not determined by their somatotopic organization, that is, there was no gradient moving from D5 to D1, except for resting-state connectivity, which was predicted by the somatotopy. Instead, we show that the representational geometry of palm-finger functional interactions reflected the physical structure of the hand. Collectively, our findings suggest that the spatial proximity between topographically organized neuronal populations do not necessarily predicts their functional interactions, rather the structure of the sensory space (e.g. the hand shape) better predicts the observed functional interactions.

neuroscience↗

bioRxiv2020

Ultra-high resolution fMRI reveals origins of feedforward and feedback activity within laminae of human ocular dominance columns

Ultra-high field MRI can functionally image the cerebral cortex of human subjects at the submillimeter scale of cortical columns and laminae. Here, we investigate both in concert, by, for the first time, imaging ocular dominance columns (ODCs) in primary visual cortex (V1) across different cortical depths. We ensured that putative ODC patterns in V1 (a) are stable across runs, sessions, and scanners located in different continents (b) have a width ([~]1.3 mm) expected from post-mortem and animal work and (c) are absent at the retinotopic location of the blind spot. We then dissociated the effects of bottom-up thalamo-cortical input and attentional feedback processes on activity in V1 across cortical depth. Importantly, the separation of bottom-up information flows into ODCs allowed us to validly compare attentional conditions while keeping the stimulus identical throughout the experiment. We find that, when correcting for draining vein effects and using both model-based and model-free approaches, the effect of monocular stimulation is largest at deep and middle cortical depths. Conversely, spatial attention influences BOLD activity exclusively near the pial surface. Our findings show that simultaneous interrogation of columnar and laminar dimensions of the cortical fold can dissociate thalamocortical inputs from top-down processing, and allow the investigation of their interactions without any stimulus manipulation. Significance StatementThe advent of ultra-high field fMRI allows for the study of the human brain non-invasively at submillimeter resolution, bringing the scale of cortical columns and laminae into focus. De Hollander et al imaged the ocular dominance columns and laminae of V1 in concert, while manipulating top-down attention. This allowed them to separate feedforward from feedback processes in the brain itself, without resorting to the manipulation of incoming information. Their results show how feedforward and feedback processes interact in the primary visual cortex, highlighting the different computational roles separate laminae play.

neuroscience↗

bioRxiv2020

Comparing fMRI responses measured at 3 versus 7 Tesla across human cortex, striatum, and brainstem

Significant progress has been made in ultra-high field functional magnetic resonance imaging (fMRI) at 7 Tesla (T). While fMRI at 7 T promises a general increase in sensitivity compared to lower field strengths, the benefits may be most pronounced for specific applications. The current study aimed to evaluate the relative benefit of 7 T over 3 T fMRI for the assessment of task-evoked fMRI responses in different brain regions. We compared the amplitude of task-evoked responses between 3 T and 7 T measured from the same human participants. Participants performed a challenging random dot motion discrimination task with delayed monetary feedback, which animal physiology has linked to several cortical and subcortical structures including extrastriate (dorsal) visual cortical areas, the striatum, and the brainstem including dopaminergic midbrain nuclei. We quantified the evoked fMRI responses in each of these brain regions during the decision interval and the post-feedback interval of the task, and compared them between brain regions and field strengths. The dependence of response amplitudes on field strength during the decision interval differed between cortical, striatal, and brainstem regions, with a generally bigger 7 T vs. 3 T benefit in subcortical (in particular brainstem) structures. We also found stronger differential responses during easy than hard decisions at 7 T for the dopaminergic nuclei, possibly reflecting reward expectation. Our results demonstrate the potential of 7 T fMRI for illuminating the contribution of small brainstem nuclei to the orchestration of cognitive computations in the human brain. HighlightsO_LIWe compared 7 T to 3 T fMRI during perceptual decision-making under uncertainty. C_LIO_LIDifferences between 7 T and 3 T evoked responses and tSNR varied across the brain. C_LIO_LIEvoked responses in dopaminergic brainstem nuclei were bigger at 7 T than 3 T. C_LIO_LIThe responses of dopaminergic nuclei are consistent with reward expectation. C_LIO_LIResults highlight the potential of 7 T fMRI for imaging small brainstem nuclei. C_LI

neuroscience↗

bioRxiv2019

Denoising High-field Multi-dimensional MRI with Local Complex PCA

Modern high field and ultra high field magnetic resonance imaging (MRI) experiments routinely collect multi-dimensional data with high spatial resolution, whether multi-parametric structural, diffusion or functional MRI. While diffusion and functional imaging have benefited from recent advances in multi-dimensional signal analysis and denoising, structural MRI has remained untouched. In this work, we propose a denoising technique for multi-parametric quantitative MRI, combining a highly popular denoising method from diffusion imaging, over-complete local PCA, with a reconstruction of the complex-valued MR signal in order to define stable estimates of the noise in the decomposition. With this approach, we show signal to noise ratio (SNR) improvements in high resolution MRI without compromising the spatial accuracy or generating spurious perceptual boundaries.

bioinformatics↗

bioRxiv2018

Retinotopic maps of visual space in the human cerebellum

While the cerebellum is instrumental for motor control, it is not traditionally implicated in vision. Here, we report the existence of 5 ipsilateral visual field maps in the human cerebellum. These maps are located within the oculomotor vermis and cerebellar nodes of the dorsal attention and visual networks. These findings imply that the cerebellum is closely involved in visuospatial cognition, and that its contributions are anchored in sensory coordinates.

neuroscience↗

bioRxiv2018

Chronotopic Maps in Human Medial Premotor Cortex

Time is a fundamental dimension of everyday experiences. We can unmistakably sense its passage and adjust our behavior accordingly. Despite its ubiquity, the neuronal mechanisms underlying the capacity to perceive time remains unclear. Here, in two experiments using ultra-high-field 7-Tesla functional magnetic resonance imaging, we show that in the medial premotor cortex of the human brain, neural units tuned to different durations are orderly mapped in contiguous portions of the cortical surface, so as to form chronomaps. The response of each portion in a chronomap is enhanced by preferred and neighboring durations and suppressed by non-preferred durations represented in distant portions of the map. These findings identify duration-sensitive tuning as a neural mechanism underlying the recognition of time and demonstrate for the first time that the representation of an abstract feature such as time can be instantiated by a topographical arrangement of duration-sensitive neural populations.

neuroscience↗