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Abstract Understanding healthy human brain function is crucial to identify and map pathological tissue within it. Whilst previous studies have mapped intracranial EEG (icEEG) from non-epileptogenic brain regions, they often neglect age and sex effects. Further, they are limited by small sample sizes due to the modality’s invasive nature. This study substantially expands the subject pool compared to existing literature, to create a multi-centre, normative map of brain activity which considers the effects of age, sex and recording hospital. Using interictal icEEG recordings from$$n = 502$$subjects across 15 centres, we constructed a normative map of non-pathological brain activity by regressing age and sex on relative band power in five frequency bands. A linear mixed model was implemented to account for the hospital effect. Variable importance was assessed using standard statistical measures, and regression coefficients (and their standard errors) were analysed at both whole-brain and regional scales. Recording hospital significantly impacted normative icEEG maps in all frequency bands, and age was a more influential predictor of band power than sex. The age effect varied by frequency band, but no spatial patterns were observed at the region-specific level. Certainty about regression coefficients was also frequency band specific and moderately impacted by sample size. The concept of a normative map is well-established in neuroscience research and particularly relevant to the icEEG modality, which does not allow healthy control baselines. Our key results regarding the hospital site and age effect guide future work utilising normative maps in icEEG. 

Abstract Low-intensity Transcranial Ultrasound Stimulation is a promising non-invasive technique for brain stimulation and focal neuromodulation. Research with humans and animal models has raised the possibility that TUS can be biased towards enhancing or suppressing neural function. Here, we first collate a set of hypotheses on the directionality of TUS effects and conduct an initial meta-analysis on the available healthy human participant TUS studies reporting stimulation parameters and outcomes (n = 47 studies, 52 experiments). In these initial exploratory analyses, we find that parameters such as the intensity and continuity of stimulation (duty cycle) with univariate tests show only statistical trends towards likely enhancement or suppressed of function with TUS. Multivariate machine learning analyses are currently limited by the small sample size. Given that human TUS sample sizes will continue to increase, predictability on the directionality of TUS effects could improve if this database can continue to grow as TUS studies more systematically explore the TUS stimulation parameter space and report outcomes. Therefore, we establish an inTUS database and resource for the systematic reporting of TUS parameters and outcomes to assist in greater precision in TUS use for brain stimulation and neuromodulation. The paper concludes with a selective review of human clinical TUS studies illustrating how hypotheses on the directionality of TUS effects could be developed for empirical testing in the intended clinical application, not limited to the examples provided. 

A reliable, accurate, and yet simple dynamic model is important to analyzing, designing, and controlling hybrid rigid–continuum robots. Such models should be fast, as simple as possible, and user-friendly to be widely accepted by the ever-growing robotics research community. In this study, we introduce two new modeling methods for continuum manipulators: a general reduced-order model (ROM) and a discretized model with absolute states and Euler–Bernoulli beam segments (EBA). In addition, a new formulation is presented for a recently introduced discretized model based on Euler–Bernoulli beam segments and relative states (EBR). We implement these models in a Matlab software package, named TMTDyn, to develop a modeling tool for hybrid rigid–continuum systems. The package features a new high-level language (HLL) text-based interface, a CAD-file import module, automatic formation of the system equation of motion (EOM) for different modeling and control tasks, implementing Matlab C-mex functionality for improved performance, and modules for static and linear modal analysis of a hybrid system. The underlying theory and software package are validated for modeling experimental results for (i) dynamics of a continuum appendage, and (ii) general deformation of a fabric sleeve worn by a rigid link pendulum. A comparison shows higher simulation accuracy (8–14% normalized error) and numerical robustness of the ROM model for a system with a small number of states, and computational efficiency of the EBA model with near real-time performances that makes it suitable for large systems. The challenges and necessary modules to further automate the design and analysis of hybrid systems with a large number of states are briefly discussed. 

Abstract Direct electrical stimulation (eSTIM) is widely used clinically, from neurosurgical mapping to therapeutic interventions for neurological and neuropsychiatric disorders^1–10. Despite over a century of application, its molecular and cellular underpinnings remain unknown. Here, using state-of-the-art single-nuclei multiomic profiling, we map changes in cell-type-specific gene expression and chromatin accessibilityin vivoin the human cortex following eSTIM of neurosurgery patients. eSTIM impacts a network of cells that extends beyond excitatory neurons to include inhibitory neurons, astrocytes, oligodendrocytes and microglia. We observed an upregulation of canonical immediate-early genes (IEGs:FOS,NPAS4,EGR4) in excitatory and inhibitory neurons and induction of cytokine-related genesCCL3 and CCL4in microglia. The cross-species conservation of this gene signature, together with our examination of a cohort of both epilepsy and cancer patients, underscores the fundamental role of these changes in stimulation-driven plasticity while controlling for disease and environmental confounds. Our study of changes in chromatin accessibility reveals a common code that involves a cell-type specific signature of transcription factor binding motifs for members of the EGR family. By addressing these previously unexplored questions about activity-induced gene expressionin vivoin the human brain, our findings challenge the long-standing neuron-centric view of eSTIM, highlighting the broader role of non-neuronal cells, including microglia, in mediating the impact of brain stimulation.