Molecular docking is a crucial step in the development of new drugs as it guides the positioning of a small molecule (ligand) within the pocket of a target protein. In the literature, a feasibility study explored the potential of D-Wave quantum annealers for purely geometric molecular docking, neglecting physicochemical interactions between the protein and the ligand and focusing solely on their simplified geometries. To achieve this, the ligands were represented as graphs incorporating their geometric properties and then mapped onto a grid that discretized the three-dimensional space of the protein pocket. The quality of the ligand pose on the protein pocket was evaluated through the isomorphism between the ligand graph and the spatial grid. This paper builds on the previous study by introducing physicochemical interactions between the protein-ligand pair into the QUBO problem to improve the accuracy of the docking results. This paper presents a novel QUBO formulation that includes Coulomb and van der Waals forces, together with components representing H-bond and hydrophobic interactions. We integrate these physical interactions as corrective terms to the previous purely geometric QUBO formulation, and provide experimental results using the D-Wave quantum annealers to demonstrate their impact on the accuracy of the docking results.

Bipartition cover probabilities quantify whether a collection of gene trees contains every bipartition of the underlying species tree, a condition that underlies finite-sample guarantees for summary methods such as ASTRAL. We study this problem under the multispecies coalescent (MSC) model and derive topology-free upper bounds on the number of loci required to obtain a bipartition cover with prescribed confidence, improving upon the existing bounds of Uricchio et al. (2016). Practically, our bounds remain below biologically realistic numbers of loci across a substantially broader range of parameter settings, expanding their usefulness for empirical datasets. Theoretically, our analysis sharpens our understanding of coalescence under the MSC model and develops new asymptotics for these bounds and absorption times under Kingman's coalescent in the natural short branch regime. We further compare our new bounds with existing work using simulations under a variety of different species-tree topologies.

The accelerometer has become an almost ubiquitous device, providing enormous opportunities in healthcare monitoring beyond step counting or other average energy estimates in 15-60 second epochs. Objective: To develop an open data set with associated open-source code for processing 50 Hz tri-axial accelerometry-based to classify patient activity levels and natural types of movement. Approach: Data were collected from 23 healthy subjects (16 males and seven females) aged between 23 and 62 years using an ambulatory device, which included a triaxial accelerometer and synchronous lead II equivalent ECG for an average of 26 minutes each. Participants followed a standardized activity routine involving five distinct activities: lying, sitting, standing, walking, and jogging. Two classifiers were constructed: a signal processing technique to distinguish between high and low activity levels and a convolutional neural network (CNN)-based approach to classify each of the five activities. Main results: The binary (high/low) activity classifier exhibited an F1 score of 0.79. The multi-class CNN-based classifier provided an F1 score of 0.83. The code for this analysis has been made available under an open-source license together with the data on which the classifiers were trained and tested. Significance: The classification of behavioral activity, as demonstrated in this study, offers valuable context for interpreting traditional health metrics and may provide contextual information to support the future development of clinical decision-making tools for patient monitoring, predictive analytics, and personalized health interventions.

Identifying dynamically influential nodes in biological networks is a central problem in systems biology, particularly for prioritizing intervention targets in gene regulatory networks. In this paper, we propose a Shapley-value-based framework for assessing the importance of nodes in a Boolean network with respect to a given target node. The framework comprises two complementary measures: the Knock-out and the Knock-in Shapley values. Moreover, we present a propagation-based method that enables their efficient computation. By exploiting the logical structure of the network, the method avoids exhaustive simulations. The approach is exact for acyclic networks and provides good approximations for cyclic networks. Evaluation on benchmark models from the Cell Collective database shows that the propagation method accurately recovers node importance rankings while achieving substantial speed-ups.

Labelling tissue components in histology whole slide images (WSIs) is prohibitively labour-intensive: a single slide may contain tens of thousands of structures--cells, nuclei, and other morphologically distinct objects--each requiring manual boundary delineation and classification. We present a cloudnative, end-to-end pipeline that automates this process through a cluster-first paradigm. Our system tiles WSIs, filters out tiles deemed unlikely to contain valuable information, segments tissue components with Cellpose-SAM (including cells, nuclei, and other morphologically similar structures), extracts neural embeddings via a pretrained ResNet-50, reduces dimensionality with UMAP, and groups morphologically similar objects using DBSCAN clustering. Under this paradigm, a human annotator labels representative clusters rather than individual objects, reducing annotation effort by orders of magnitude. We evaluate the pipeline on 3,696 tissue components across 13 diverse tissue types from three species (human, rat, rabbit), measuring how well unsupervised clusters align with independent human labels via per-tile Hungarian-algorithm matching. Our system achieves a weighted cluster-label alignment accuracy of 96.8%, with 7 of 13 tissue types reaching perfect agreement. The pipeline, a companion labelling web application, and all evaluation code are released as open-source software.

Generative models can now propose thousands of \emph{de novo} antibody sequences, yet translating these designs into viable therapeutics remains constrained by the cost of biophysical characterization. Here we present CrossAbSense, a framework of property-specific neural oracles that combine frozen protein language model encoders with configurable attention decoders, identified through a systematic hyperparameter campaign totaling over 200 runs per property. On the GDPa1 benchmark of 242 therapeutic IgGs, our oracles achieve notable improvements of 12--20\% over established baselines on three of five developability assays and competitive performance on the remaining two. The central finding is that optimal decoder architectures \emph{invert} our initial biological hypotheses: self-attention alone suffices for aggregation-related properties (hydrophobic interaction chromatography, polyreactivity), where the relevant sequence signatures -- such as CDR-H3 hydrophobic patches -- are already fully resolved within single-chain embeddings by the high-capacity 6B encoder. Bidirectional cross-attention, by contrast, is required for expression yield and thermal stability -- properties that inherently depend on the compatibility between heavy and light chains. Learned chain fusion weights independently confirm heavy-chain dominance in aggregation ($w_H = 0.62$) versus balanced contributions for stability ($w_H = 0.51$). We demonstrate practical utility by deploying CrossAbSense on 100 IgLM-generated antibody designs, illustrating a path toward substantial reduction in experimental screening costs.

We consider the Lotka-Volterra system and provide necessary conditions for an equilibrium to be stable. Our results naturally complement earlier fundamental results by N. Adachi, Y. Takeuchi, and H. Tokumaru, who, in a series of papers, give sufficient (and for some cases necessary) conditions for the existence of a stable equilibrium point.

Diffusion magnetic resonance imaging (MRI) has revealed important insights into white matter microstructure, but its application to gray matter remains comparatively less explored. Here, we investigate whether global patterns of gray-matter microstructure can be captured through neurite orientation dispersion and density imaging (NODDI) and whether such patterns are predictive of cognitive performance. Using diffusion MRI and behavioral data from the Human Connectome Project Young Adult study, we derive region averaged NODDI parameters and apply principal component analysis (PCA) to construct general gray-matter microstructure factors. We find that the factor derived from isotropic volume fraction explained substantial inter-individual variability and was significantly correlated with specific cognitive scores collected from the NIH Toolbox. In particular, the isotropic volume fraction factor is linked to reading and vocabulary performance and to cognitive fluidity. Our findings demonstrate that PCA-based global indicators of gray-matter microstructure provide complementary markers of structure-function relationships, extending beyond region-specific analyses. Our results suggest that general microstructure factors may serve as population-level exploratory biomarkers for studying cognition and cortical organization.

Biological and artificial learners are inherently exposed to a stream of data and experience throughout their lifetimes and must constantly adapt to, learn from, or selectively ignore the ongoing input. Recent findings reveal that, even when the performance remains stable, the underlying neural representations can change gradually over time, a phenomenon known as representational drift. Studying the different sources of data and noise that may contribute to drift is essential for understanding lifelong learning in neural systems. However, a systematic study of drift across architectures and learning rules, and the connection to task, are missing. Here, in an online learning setup, we characterize drift as a function of data distribution, and specifically show that the learning noise induced by task-irrelevant stimuli, which the agent learns to ignore in a given context, can create long-term drift in the representation of task-relevant stimuli. Using theory and simulations, we demonstrate this phenomenon both in Hebbian-based learning -- Oja's rule and Similarity Matching -- and in stochastic gradient descent applied to autoencoders and a supervised two-layer network. We consistently observe that the drift rate increases with the variance and the dimension of the data in the task-irrelevant subspace. We further show that this yields different qualitative predictions for the geometry and dimension-dependency of drift than those arising from Gaussian synaptic noise. Overall, our study links the structure of stimuli, task, and learning rule to representational drift and could pave the way for using drift as a signal for uncovering underlying computation in the brain.

Von Economo neurons (VENs) are large bipolar projection neurons found exclusively in the anterior cingulate cortex (ACC) and frontal insula of species with complex social cognition, including humans, great apes, and cetaceans. Their selective depletion in frontotemporal dementia (FTD) and altered development in autism implicate them in rapid social decision-making, yet no computational model of VEN function has previously existed. We introduce the Fast Lane Hypothesis: VENs implement a biological speed-accuracy tradeoff (SAT) by providing a sparse, fast projection pathway that enables rapid social decisions at the cost of deliberate processing accuracy. We model VENs as fast leaky integrate-and-fire (LIF) neurons with membrane time constant 5 ms and sparse dendritic fan-in of eight afferents, compared to 20 ms and eighty afferents for standard pyramidal neurons, within a spiking cortical circuit of 2,000 neurons trained on a social discrimination task. Networks are evaluated under three clinically motivated conditions across 10 independent random seeds: typical (2% VENs), autism-like (0.4% VENs), and FTD-like (post-training VEN ablation). All configurations achieve equivalent asymptotic classification accuracy (99.4%), consistent with the prediction that VENs modulate decision speed rather than representational capacity. Temporal analysis confirms that VENs produce median first-spike latencies 4 ms earlier than pyramidal neurons. At a fixed decision threshold, the typical condition is significantly faster than FTD-like (t=-23.31, p<0.0001), while autism-like is intermediate (mean RT=26.91+/-9.01 ms vs. typical 20.70+/-2.02 ms; p=0.078). A preliminary evolutionary analysis shows qualitative correspondence between model-optimal VEN fraction and the primate phylogenetic gradient. To our knowledge, this is the first computational model that asks what a Von Economo neuron actually computes.

Tokens serve as the basic units of representation in DNA language models (DNALMs), yet their design remains underexplored. Unlike natural language, DNA lacks inherent token boundaries or predefined compositional rules, making tokenization a fundamental modeling decision rather than a naturally specified one. While existing approaches like byte-pair encoding (BPE) excel at capturing token structures that reflect human-generated linguistic regularities, DNA is organized by biological function and evolutionary constraint rather than linguistic convention. We argue that DNA tokenization should prioritize functional sequence patterns like regulatory motifs-short, recurring segments under evolutionary constraint and typically preserved across species. We incorporate evolutionary information directly into the tokenization process through EvoLen, a tokenizer that combines evolutionary stratification with length-aware decoding to better preserve motif-scale functional sequence units. EvoLen uses cross-species evolutionary signals to group DNA sequences, trains separate BPE tokenizers on each group, merges the resulting vocabularies via a rule prioritizing preserved patterns, and applies length-aware decoding with dynamic programming. Through controlled experiments, EvoLen improves the preservation of functional sequence patterns, differentiation across genomic contexts, and alignment with evolutionary constraint, while matching or outperforming standard BPE across diverse DNALM benchmarks. These results demonstrate that tokenization introduces a critical inductive bias and that incorporating evolutionary information yields more biologically meaningful and interpretable sequence representations.

Net primary productivity (NPP) forms the basis of biological carbon pump, but its estimates in high-latitude regions remain highly uncertain despite its disproportional importance for the global carbon sink. Optical satellites are limited by cloud cover, low irradiance, and shallow light penetration, with uncertainties further exacerbated by the lack of in situ validations and regional model tuning for NPP measurements. This study compared two satellite-based models, a global (VGPM) and a regionally tuned (BIO) NPP model, with a time series of in situ NPP. Using a high-frequency, depth-resolved moored profiler in the subpolar Northwest Atlantic (56°N) in 2016, in situ NPP was estimated by daily bio-optical profiles and prior measurement of photosynthesis-irradiance (P-I) parameters. Our findings indicated that satellite-derived estimates of depth-integrated NPP were overestimated by a factor of 2.5 to 4. However, the reasons for the discrepancies varied between the VGPM and BIO model. VGPM used global photosynthetic parameters with a simplified depth assumption, leading to an unrealistic vertical structure for depth-integrated NPP, despite its surface values were lower than in situ estimates. A major phytoplankton bloom in June-July was missed by VGPM, likely due to the use of non-regionally calibrated OCI Chl-a, which led to an underestimation of biomass. In contrast, the BIO model used regionally tuned POLY4 Chl-a products, and the differences in the assignment of P-I parameters accounted for the remaining discrepancies. This study showed the possibility to reach good agreement between satellite and in situ NPPs if the challenge of P-I assignment can be overcome. We recommend further studies to investigate discrepancies of NPP estimates in high-latitude regions, focusing on data sources and model choices, as well as improving regional model calibration to enhance NPP accuracy.

Various effects in human cognition, often considered `non-classical', have been argued to be most naturally modelled by quantum-like models of decision making. We extend this approach to describe models of cognition and decision-making in general probabilistic process theories, which include both classical probabilistic models and quantum instrument models as special cases. We show how many aspects of quantum-like cognition can be described diagrammatically in process theories, before using our approach to assess the arguments for quantum-like models. While standard Bayesian classical models are insufficient, we prove that any sequential decision data can in fact be given a more general form of classical instrument model, and see that even simple deterministic models can exhibit all cognitive effects. Restricting attention to instruments induced by measurements, such as classical Bayesian and quantum POVM models, rules out such a result, but is challenged by the fact that such instruments cannot account for certain effects. Finally, we argue that to strictly rule out classical instrument models one should make use of parallel composition in the modelling of joint decisions, and find real world cognitive data violating Bell inequalities.

Existing deep learning methods for radiology report generation enhance diagnostic efficiency but often overlook physician-informed medical priors. This leads to a suboptimal alignment between the structured explanations and disease manifestations. Eye gaze data provides critical insights into a radiologist's visual attention, enhancing the relevance and interpretability of extracted features while aligning with human decision-making processes. However, despite its promising potential, the integration of eye gaze information into AI-driven medical imaging workflows is impeded by challenges such as the complexity of multimodal data fusion and the high cost of gaze acquisition, particularly its absence during inference, limiting its practical applicability in real-world clinical settings. To address these issues, we introduce Gaze2Report, a framework which leverages a scanpath prediction module and Graph Neural Network (GNN) to generate joint visual-gaze tokens. Combined with instruction and report tokens, these form a multimodal prompt used to fine-tune LoRA layers of large language models (LLMs) for autoregressive report generation. Gaze2Report enhances report quality through eye-gaze-guided visual learning and incorporates on-the-fly scanpath prediction, enabling the model to operate without gaze input during inference.

The widespread adoption of generative artificial intelligence conversational agents (AICAs) among university students constitutes a novel cognitive social environment whose impact on the maturing brain remains elusive. Combining surveys with high resolution structural MRI, we examined patterns of general, functional, and socio emotional AICA use, academic performance, mental health, and brain structural signatures in a comparatively large sample of 222 young individuals. Across computational anatomy, meta analytic network level, and behavioral decoding analyses, we observed use specific associations. Higher general and functional AICA use frequencies were linked to better academic outcomes (GPA), larger dorsolateral prefrontal and calcarine gray matter volume, and enhanced hippocampal network clustering and local efficiency. In contrast, more frequent socio emotional AICA use was associated with poorer mental health (depression, social anxiety) and lower volume of superior temporal and amygdalar regions central to social and affective processing. These findings indicate that the same class of AI tools exerts distinct effects depending on usage patterns and motivations, engaging prefrontal hippocampal systems that support cognition versus socio emotional systems that may track distress linked usage. These heterogeneities are crucial for designing environments that harness the educational benefits of AI while mitigating mental health risks.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) affects 30-40% of US adults and is the most common chronic liver disease. Although often asymptomatic, progression can lead to cirrhosis. The objective of the study was to develop and evaluate an electronic health record (EHR) based prediction model to support early detection of MASLD in primary care settings. Methods: We evaluated LASSO logistic regression, random forest, XGBoost, and a neural network model for MASLD prediction using clinical feature subsets from a large EHR database, including the top 10 ranked features. To reduce disparities in true positive rates across racial and ethnic subgroups, we applied an equal opportunity postprocessing method in a prediction model called MASLD EHR Static Risk Prediction (MASER). Results: This retrospective cohort study included 59,492 participants in the training data, 24,198 in the validating data, and 25,188 in the testing data. The LASSO logistic regression model with the top 10 features was selected for its interpretability and comparable performance. Before fairness adjustment, the model achieved AUROC of 0.84, accuracy of 78%, sensitivity of 72%, specificity of 79%, and F1-score of 0.617. After equal opportunity postprocessing, accuracy modestly increased to 81% and specificity to 94%, while sensitivity decreased to 41% and F1-score to 0.515, reflecting the fairness trade-off. Conclusions: MASER achieved competitive performance for MASLD prediction, comparable to previously reported ensemble and tree-based models, while using a limited and routinely collected feature set and a diverse study population. The model is designed to support early detection and potential integration into primary care workflows. MASER demonstrates EHR-ready MASLD prediction with fairness adjustments, supporting future primary care implementation pending prospective validation.

Aging is a universal consequence of life, yet researchers have identified no universal theme. This manuscript considers aging from the perspective of entropy, wherein things fall apart. We first examine biological information change as a mutational distance, analogous to physical distance. In this model, informational change over time is fitted to an advection-diffusion equation, a normal distribution with a time component. The solution of the advection-diffusion equation provides a means of measuring the entropy of diverse biological systems. The binomial distribution is also sufficient to demonstrate that entropy increases as mutations or epimutations accumulate. As modeled, entropy scales with lifespans across the tree of life. This perspective provides potential mechanistic insights and testable hypotheses as to how evolution has attained enhanced longevity: entropy management. We find entropy is an inclusive rather than exclusive aging theory.

This position and survey paper identifies the emerging convergence of neuroscience, artificial general intelligence (AGI), and neuromorphic computing toward a unified research paradigm. Using a framework grounded in brain physiology, we highlight how synaptic plasticity, sparse spike-based communication, and multimodal association provide design principles for next-generation AGI systems that potentially combine both human and machine intelligences. The review traces this evolution from early connectionist models to state-of-the-art large language models, demonstrating how key innovations like transformer attention, foundation-model pre-training, and multi-agent architectures mirror neurobiological processes like cortical mechanisms, working memory, and episodic consolidation. We then discuss emerging physical substrates capable of breaking the von Neumann bottleneck to achieve brain-scale efficiency in silicon: memristive crossbars, in-memory compute arrays, and emerging quantum and photonic devices. There are four critical challenges at this intersection: 1) integrating spiking dynamics with foundation models, 2) maintaining lifelong plasticity without catastrophic forgetting, 3) unifying language with sensorimotor learning in embodied agents, and 4) enforcing ethical safeguards in advanced neuromorphic autonomous systems. This combined perspective across neuroscience, computation, and hardware offers an integrative agenda for in each of these fields.

While Large Language Models (LLMs) demonstrate strong performance across domains, their long-context capabilities are limited by transient neural activations causing information decay and unstructured feed-forward network (FFN) weights leading to semantic fragmentation. Inspired by the brain's working memory and cortical modularity, we propose PaceLLM, featuring two innovations: (1) a Persistent Activity (PA) Mechanism that mimics prefrontal cortex (PFC) neurons' persistent firing by introducing an activation-level memory bank to dynamically retrieve, reuse, and update critical FFN states, addressing contextual decay; and (2) Cortical Expert (CE) Clustering that emulates task-adaptive neural specialization to reorganize FFN weights into semantic modules, establishing cross-token dependencies and mitigating fragmentation. Extensive evaluations show that PaceLLM achieves 6% improvement on LongBench's Multi-document QA and 12.5-17.5% performance gains on Infinite-Bench tasks, while extending measurable context length to 200K tokens in Needle-In-A-Haystack (NIAH) tests. This work pioneers brain-inspired LLM optimization and is complementary to other works. Besides, it can be generalized to any model and enhance their long-context performance and interpretability without structural overhauls.

Human aging is marked by a steady rise in the risk of dying with age-a process demographers call senescence. Over the past century, life expectancy has risen dramatically, but is this because we are aging slower, or simply starting it later? Vaupel hypothesizes that the pace at which individuals age may be constant, with gains in longevity coming from the delayed onset of senescence rather than its slowing down. We test this idea using a new framework that decomposes the pace of senescence into three components: a biological baseline, a long-term trend, and the cumulative impact of period shocks. Applying this to cohort mortality data above age 80 from 12 countries, we find that once period shocks are accounted for, there is no statistical evidence of a long-term trend, consistent with Vaupel's hypothesis. Analyses using lower starting ages yield the same qualitative conclusion. Rather than indicating a change in the process that drives senescence, these variations are consistent with echoes of shared historical events. These results suggest that while longevity has shifted, the rhythm of human aging may be conserved.

The genome contains genetic information essential for cell's life. The genome's spatial organization inside the cell nucleus is critical for its proper function including gene regulation. The two major genomic compartments -- euchromatin and heterochromatin -- contain largely transcriptionally active and silenced genes, respectively, and exhibit distinct dynamics. In this work, we present a hydrodynamic framework that describes the large-scale behavior of euchromatin and heterochromatin, and accounts for the interplay of mechanical forces, active processes, and nuclear confinement. Our model shows contractile stresses from cross-linking proteins lead to the formation of heterochromatin droplets via mechanically driven phase separation. These droplets grow, coalesce, and in nuclear confinement, wet the boundary. Active processes, such as gene transcription in euchromatin, introduce non-equilibrium fluctuations that drive long-range, coherent motions of chromatin as well as the nucleoplasm, and thus alter the genome's spatial organization. These fluctuations also indirectly deform heterochromatin droplets, by continuously changing their shape. Taken together, our findings reveal how active forces, mechanical stresses and hydrodynamic flows contribute to the genome's organization at large scales and provide a physical framework for understanding chromatin organization and dynamics in live cells.

Eukaryotic cells demonstrate a wide variety of dynamic patterns of filamentous actin (F-actin) and its regulators. Some of these patterns play important roles in cell functions, such as distinct motility modes, which motivate this study. We devise a mass-conserved reaction-diffusion model for active and inactive Rho-GTPase and F-actin in the cell cortex. The mass-conserved Rho-GTPase system promotes F-actin, which feeds back to inactivate the former. We study the model on a 1D periodic domain (edge of thin sheet-like cell) using bifurcation theory in the framework of spatial dynamics, complemented with numerical simulations. Among several discussed bifurcations, the analysis centers on the study of the codimension-2 long wavelength and finite wavenumber Hopf instability, in which we describe a rich structure of steady wave-pinning states (a.k.a. mesas, obeying the Maxwell construction), propagating coherent solutions (fronts and excitable pulses), and travelling and standing waves, all distinguished by mass conservation regimes and classified by domain sizes. Specifically, we highlight the unexpected conditions for bistability between steady wave-pinning and travelling wave states on moderate domain sizes, i.e., unfolding through domain length. These results uncover and exemplify possible mechanisms of coexistence, robustness, and transitions between distinct cellular motility modes, including directed migration, turning, and ruffling. More broadly, the results indicate that non-gradient reaction-diffusion models comprising mass conservation have distinct pattern formation mechanisms that motivate further investigations, such as the unfolding of codimension-3 instabilities and T-points.

The brain can efficiently learn a wide range of tasks, motivating the search for biologically inspired learning rules for improving current artificial intelligence technology. Most biological models are composed of point neurons, and cannot achieve the state-of-the-art performances in machine learning. Recent works have proposed that segregation of dendritic input (neurons receive sensory information and higher-order feedback in segregated compartments) and generation of high-frequency bursts of spikes would support error backpropagation in biological neurons. However, these approaches require propagating errors with a fine spatio-temporal structure to the neurons, which is unlikely to be feasible in a biological network. To relax this assumption, we suggest that bursts and dendritic input segregation provide a natural support for biologically plausible target-based learning, which does not require error propagation. We propose a pyramidal neuron model composed of three separated compartments. A coincidence mechanism between the basal and the apical compartments allows for generating high-frequency bursts of spikes. This architecture allows for a burst-dependent learning rule, based on the comparison between the target bursting activity triggered by the teaching signal and the one caused by the recurrent connections, providing the support for target-based learning. We show that this framework can be used to efficiently solve spatio-temporal tasks, such as the store and recall of 3D trajectories. Finally, we suggest that this neuronal architecture naturally allows for orchestrating ``hierarchical imitation learning'', enabling the decomposition of challenging long-horizon decision-making tasks into simpler subtasks. This can be implemented in a two-level network, where the high-network acts as a ``manager'' and produces the contextual signal for the low-network, the ``worker''.

The brain can learn to solve a wide range of tasks with high temporal and energetic efficiency. However, most biological models are composed of simple single compartment neurons and cannot achieve the state-of-art performances of artificial intelligence. We propose a multi-compartment model of pyramidal neuron, in which bursts and dendritic input segregation give the possibility to plausibly support a biological target-based learning. In target-based learning, the internal solution of a problem (a spatio temporal pattern of bursts in our case) is suggested to the network, bypassing the problems of error backpropagation and credit assignment. Finally, we show that this neuronal architecture naturally support the orchestration of hierarchical imitation learning, enabling the decomposition of challenging long-horizon decision-making tasks into simpler subtasks.

Affinity maturation is crucial for improving the binding affinity of antibodies to antigens. This process is mainly driven by point substitutions caused by somatic hypermutations of the immunoglobulin gene. It also includes deletions and insertions of genomic material known as indels. While the landscape of point substitutions has been extensively studied, a detailed statistical description of indels is still lacking. Here we present a probabilistic inference tool to learn the statistics of indels from repertoire sequencing data, which overcomes the pitfalls and biases of standard annotation methods. The model includes antibody-specific maturation ages to account for variable mutational loads in the repertoire. After validation on synthetic data, we applied our tool to a large dataset of human immunoglobulin heavy chains. The inferred model allows us to identify universal statistical features of indels in heavy chains. We report distinct insertion and deletion hotspots, and show that the distribution of lengths of indels follows a geometric distribution, which puts constraints on future mechanistic models of the hypermutation process.

Thanks to novel, powerful brain activity recording techniques, we can create data-driven models from thousands of recording channels and large portions of the cortex, which can improve our understanding of brain-states neuromodulation and the related richness of traveling waves dynamics. We investigate the inference of data-driven models and the comparison among experiments and simulations, through the characterization of the spatio-temporal features of cortical waves in experimental recordings and simulations. Inference is built in two steps: the inner loop that optimizes by likelihood maximization a mean-field model, and the outer loop that optimizes a periodic neuro-modulation by relying on direct comparison of observables apt for the characterization of cortical slow waves. The model is capable to reproduce most of the features of the non-stationary and non-linear dynamics displayed by the high-resolution recording of the in-vivo mouse brain obtained by wide-field calcium imaging techniques. The proposed approach is of interest for both experimental and computational neuroscientists.