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01.
medRxiv (Medicine) 2026-06-22

Virtual Responsive Neurostimulation Implantation: From Intracranial Connectivity to Optimized Lead Placement

Authors:
Feys↗Walsh↗K. G↗Nix↗K. C↗Josyula↗Sinha↗Lavelle↗S. B↗Wagenaar↗Michalak↗Morrell↗…

Responsive neurostimulation (RNS) is an implanted device that delivers direct brain stimulation for drug-resistant focal epilepsy. Individual responses are highly variable, and no validated framework exists to predict outcome or guide lead placement before implantation. We hypothesized that this variability is partly explained by lead placement in relation to patterns of functional connectivity in brain networks. Fourty-nine patients with drug-resistant focal epilepsy who underwent pre-implantation intracranial EEG (iEEG) and RNS implantation across three independent epilepsy centers were retrospectively studied. We developed a composite functional connectivity score, based on simple Spearman correlation, combining the standard deviation and kurtosis of interictal iEEG connectivity distributions to predict the response outcome in a training cohort (HUP, n=18) and validated in two independent cohorts (NYU, n=17; UCSF, n=14). We accounted for a spatial mismatch between iEEG and RNS electrodes with a distance-based correction. The score was extended to generate patient-specific 3D maps of predicted RNS efficacy across 200 simulated, or virtual RNS, lead configurations. Accuracy of the score in predicting clinical outcome was 72% at the group level, 61% at the individual patient level, and, after distance-based optimization, 100% in patients with RNS electrodes placed close to location of iEEG electrodes. Applied to the validation cohort, the same score reached 68% accuracy (71% balanced accuracy, 55% sensitivity, 88% specificity). The spatial combination of the scores at different SEEG contacts localization gives a spatial score for each patient. Responders showed significantly higher spatial scores than non-responders, supporting that actual RNS lead placement in responders was located in map-identified favorable regions. Interictal iEEG functional connectivity predicts individual RNS response across independent epilepsy centers, and patient-specific 3D maps derived from this biomarker could prospectively guide lead implantation toward favorable network regions, opening a promising avenue toward network-informed RNS surgical planning.

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02.
medRxiv (Medicine) 2026-06-22

Assessment of adaptive functioning in Angelman syndrome using the Vineland Adaptive Behavior Scales, Third Edition

Authors:
Potter↗S. N↗Zhang↗Friedman↗Gable↗Ali↗Barbieri-Welge↗R. L↗Ben-Tall↗Caravella↗K. E↗DeRamus↗…

Purpose: This study examined longitudinal trajectories of adaptive functioning in 331 individuals with Angelman syndrome (AS) using the Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) and examined differences by molecular subtype. Methods: A total of 331 individuals (156 females, 47%) with genetically confirmed AS (ages 6 months to 52 years) were assessed between 2018 and 2025, including 207 with a deletion subtype, 63 with uniparental disomy or imprinting defect, and 61 with a UBE3A point mutation. Growth scale values were analyzed using linear mixed-effects models with log2-transformed age. Results: Individuals with deletion subtypes demonstrated significantly lower adaptive functioning across domains compared to those with non-deletion subtypes. Adaptive skills across all Vineland-3 subdomains increased nonlinearly with age, showing faster growth early in life that slowed over time, with largely parallel trajectories across subtypes. Conclusion: Individuals with AS demonstrate slow but steady growth in adaptive functioning that continues into adulthood, with progress varying by molecular subtype. These findings provide updated natural history benchmarks and demonstrate the utility of the Vineland-3 for clinical trials.

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03.
arXiv (CS.LG) 2026-06-19

Toward all-optical unsupervised Hebbian learning in deep photonic neuromorphic networks

Authors:
Xi Li↗Disha Biswas↗Peng Zhou↗Wesley H. Brigner↗Anna Capuano↗Joseph S. Friedman↗Qing Gu↗

arXiv:2601.22300v3 Announce Type: replace-cross Abstract: We propose a deep photonic neuromorphic network (PNN) architecture based on phase-change material (PCM) synapses and local optical feedback for online, unsupervised Hebbian learning. The proposed architecture combines optical vector-matrix multiplication, non-volatile PCM synaptic weighting, and local coincidence-driven synaptic adaptation within a multilayer photonic crossbar framework compatible with photonic integrated circuits. Unlike conventional PNNs that rely on externally computed gradients, repeated optical-electrical-optical conversions, or global backpropagation, the proposed framework employs local Hebbian learning governed directly by correlated pre- and post-synaptic optical activity. To investigate the feasibility of the proposed learning mechanism, we implemented the PNN design using fiber-optic components, programmable variable optical attenuators, and real-time software control that incorporates PCM thermal dynamics. Supervised and unsupervised learning behaviors were experimentally evaluated under both offline and online learning conditions using representative image-recognition tasks. The experimental results demonstrate adaptive synaptic evolution, successful optical inference, and autonomous pattern encoding through local Hebbian learning under realistic fiber-optic hardware conditions. These results establish a pathway toward future integrated photonic neuromorphic systems capable of scalable and energy-efficient online Hebbian learning.

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04.
arXiv (CS.CV) 2026-06-16

SiGnature: Explicit Motion Diffusion for Stylized Semantic Gesture

Authors:
Adi Rosenthal↗Tomer Koren↗Nadav Shaked↗Doron Friedman↗Ariel Shamir↗

While recent advances in co-speech gesture generation have achieved impressive rhythmic synchronization, synthesizing gestures that are both semantically meaningful and faithful to a speaker's unique non-verbal style remains an open challenge. Semantic gestures, such as iconic shapes or deictic pointing, are statistically sparse, making them difficult to learn effectively within standard generative models. We present SiGnature, a framework for Stylized and Semantic Gesture generation that reconciles precise semantic control with high-fidelity style preservation. Unlike prevalent methods that rely on entangled latent representations, SiGnature operates in an explicit joint-rotation space. This design enables our core contribution, Joint Motion Integration (JMI), a training-free inference mechanism capable of injecting any external motion sequence, particularly in-the-wild semantic gestures, directly into the diffusion process. JMI automatically identifies the specific ``active joints'' conveying a semantic action and injects them into the generation, while relying on the diffusion backbone to synthesize the remaining body dynamics, including posture and flow, in accordance with the pre-learned style of the target speaker. This allows for the plug-and-play integration of arbitrary motions, including complex semantic gestures, without retraining or introducing the ``Frankenstein'' artifacts typical of cut-and-paste methods. Extensive experiments and perceptual studies demonstrate that SiGnature offers superior semantic motion control while maintaining smooth and natural co-speech gesture generation and preserving the distinct characteristics of the speaker, thereby outperforming state-of-the-art baselines.

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05.
arXiv (CS.CV) 2026-06-11

FOCUS on Contamination: Hydrology-Informed Noise-Aware Learning for Geospatial PFAS Mapping

Authors:
Jowaria Khan↗Alexa Friedman↗Sydney Evans↗Rachel Klein↗Runzi Wang↗Katherine E. Manz↗Kaley Beins↗David Q. Andrews↗Elizabeth Bondi-Kelly↗

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants with significant public health impacts, yet large-scale monitoring remains severely limited due to the high cost and logistical challenges of field sampling. The lack of samples leads to difficulty simulating their spread with physical models and limited scientific understanding of PFAS transport in surface waters. Yet, rich geospatial and satellite-derived data describing land cover, hydrology, and industrial activity are widely available. We introduce FOCUS, a geospatial deep learning framework for PFAS contamination mapping that integrates sparse PFAS observations with large-scale environmental context, including priors derived from hydrological connectivity, land cover, source proximity, and sampling distance. These priors are integrated into a principled, noise-aware loss, yielding a robust training objective under sparse labels. Across extensive ablations, robustness analyses, and real-world validation, FOCUS consistently outperforms baselines including sparse segmentation, Kriging, and pollutant transport simulations, while preserving spatial coherence and scalability over large regions. Our results demonstrate how AI can support environmental science by providing screening-level risk maps that prioritize follow-up sampling and help connect potential sources to surface-water contamination patterns in the absence of complete physical models.

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