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Derakhshan, S.

Publications and source records attributed to Derakhshan, S..

3 recordsLinked to original sources

Visuomotor coordination on the road: low-dimensional representations reveal adaptive, context-dependent reductions in the dimensionality of natural driving behavior

The brains ability to transform complex, high-dimensional sensory and motor inputs into coordinated, goal-directed behavior remains a central challenge in neuroscience research. Current research suggests that behavior is generated through patterns within a low-dimensional structure. What visuomotor patterns underlie complex, unconstrained behaviors such as driving, and how stereotypical they are, remain poorly understood. Driving involves complex perception-action interactions, which we hypothesize are specific to the drivers role and adapt to task demands. Here, we unfold these dynamics using an immersive virtual drive that recreates ten hazardous on-road events. We collected eye, head, and vehicle movements from participants assigned to either a manual or an autonomous driving condition. From the behavioral movements of 284 drivers, we constructed a common time-resolved behavioral state space based on collective variance, computed via principal component analysis across participants. The obtained low-dimensional manifold thus represents generalized visuomotor coordination strategies. We then characterized the evolving low-dimensional structure with cosine similarity and various entropy-based measures of effective dimensionality. We tested whether early components contained condition-specific information using discriminant analysis. Across the entire drive, a few components accounted for most of the variance in behavior, and effective dimensionality decreased reliably around critical events, indicating tighter coordination between perceptual and motor variables. During periods of low effective dimensionality, the contributions of eye, head, steering, and vehicle heading reorganized toward early dimensions in a task-dependent manner. As a result, behaviors became more distinct across driving conditions, enabling better classification of driving modes using only the first two components. These results show that naturalistic driving is supported by shared low-dimensional visuomotor coordination strategies that are flexibly reshaped by contextual demands, and provide a principled behavioral framework for linking neural manifolds, human driver models, and the design of adaptive autonomous vehicles. Author summaryHuman behavior is complex. Driving, for instance, means constantly turning what we see into the right movements of our head, hands, and feet. Research using constrained repeated actions suggests that these seemingly complex behaviors are highly coordinated and can be described by a relatively small number of variables. We want to know whether these aspects also hold during natural, unconstrained tasks. We asked people to complete a virtual drive comprising ten sudden hazards, such as animals and pedestrians on the road. Some participants drove the car, while others sat in a self-driving car. We recorded where people looked, how they moved their heads, and steered the vehicle. Then, we used statistical methods to reduce the datas dimensionality and looked for patterns that could explain all these signals together. We found that a small number of patterns were enough to describe behavior. These patterns became even simpler and more linked around hazards, differentiating autonomous from manual driving behavior. Our results suggest that even complex driving behavior follows a few basic coordination strategies that become more pronounced around specific situations. These basic dimensions contain important details that are unique to certain groups, ultimately helping us better understand and compare human behavior.

neuroscience↗

An engineered tumor organoid model reveals cellular identity and signaling trajectories underlying translocation RCC.

Translocation renal cell carcinoma (tRCC) is a rare, aggressive type of kidney cancer primarily occurring in children. They are genetically defined by translocations involving MiT/TFE gene family members, TFE3 or, in rare cases, TFEB. The biology underlying tRCC development remains poorly understood, partly due to the lack of representative experimental models. Here, we utilized human kidney organoids, or tubuloids, to engineer a tRCC model by expression of one of the most common MiT/TFE fusions, SFPQ-TFE3. Fusion expressing tubuloids adopt a tRCC-like phenotype and gene expression signature in vitro and grow as clear cell RCC upon xenotransplantation in mice. Genome-wide binding analysis reveals that SFPQ-TFE3 reprograms gene expression signatures by aberrant, gain-of-function genome-wide DNA binding. Combining these analyses with single-cell mRNA readouts reveals an epithelium-to-mesenchymal differentiation trajectory underlying tRCC transformation, potentially caused by deregulated Wnt signaling. Our study demonstrates that SFPQ-TFE3 expression is sufficient to transform kidney epithelial cells into tRCC and defines the trajectories underlying malignant transformation, thereby facilitating the development of new therapeutic interventions.

cancer biology↗

Long-term expanding human airway organoids for disease modelling.

Organoids are self-organizing 3D structures grown from stem cells that recapitulate essential aspects of organ structure and function. Here we describe a method to establish long-term-expanding human airway organoids from broncho-alveolar biopsies or lavage material. The pseudostratified airway organoid epithelium consists of basal cells, functional multi-ciliated cells, mucus-producing goblet cells, and CC10-secreting club cells. Airway organoids derived from cystic fibrosis (CF) patients allow assessment of CFTR function in an organoid swelling assay. Organoid culture conditions also allow gene editing as well as the derivation of various types of lung cancer organoids. Respiratory syncytial virus (RSV) infection recapitulated central disease features and dramatically increases organoid cell motility, found to be driven by the non-structural viral NS2 protein. We conclude that human airway organoids represent versatile models for the in vitro study of hereditary, malignant, and infectious pulmonary disease.

cell biology↗