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Role of Prefrontal Cortex Circuitry in Maintaining Social Homeostasis

Biological Psychiatry 2025年第10期97卷 953-960页

作者： Lee, SeungHyun Williams, Ziv M. Department of Neurosurgery Massachusetts General Hospital Harvard Medical School Boston Massachusetts United States Harvard-MIT Division of Health Sciences and Technology Boston Massachusetts United States Program in Neuroscience Harvard Medical School Boston Massachusetts United States

Homeostasis is a fundamental concept in biology and ensures the stability of life by maintaining the constancy of physiological processes. Recent years have witnessed a surge in research interest in these physiological processes, with a growing focus on understanding the mechanisms underlying social homeostasis. This shift in focus underscores our increasing understanding of the importance of social interactions and their impact on individual well-being. In this review, we explore the interconnected research across 3 primary categories: understanding the neural mechanisms influencing set points, defining contemporary factors that can disrupt social homeostasis, and identifying the potential contributions of social homeostatic failure in the development of psychiatric diseases. We also delve into the role of the prefrontal cortex and its circuitry in regulating social behavior, decision-making processes, and the manifestation of neuropsychiatric disorders, such as depression and anxiety. Finally, we examine the influence of more recent factors such as growing social media exposure and the COVID-19 pandemic on mental health, highlighting their disruptive effects. We also identify gaps in current literature through the analysis of research trends and propose future research directions to advance our understanding of social homeostasis, with implications for mental health interventions. © 2024 Society of Biological Psychiatry

关键词： COVID Homeostasis Media Neuroscience Prefrontal Social

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Probabilistic genotype-phenotype maps reveal mutational robustness of RNA folding, spin glasses, and quantum circuits

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Physical Review Research 2025年第1期7卷 013118-013118页

作者： Anna Sappington Vaibhav Mohanty Department of Electrical Engineering and Computer Science Massachusetts Institute of Technology Cambridge Massachusetts 02139 USA Harvard-MIT Program in Health Sciences and Technology Harvard Medical School Boston Massachusetts 02115 USA and Massachusetts Institute of Technology Cambridge Massachusetts 02139 USA Harvard/MIT MD-PhD Program Harvard Medical School Boston Massachusetts 02115 USA and Massachusetts Institute of Technology Cambridge Massachusetts 02139 USA Department of Chemistry and Chemical Biology Harvard University Cambridge Massachusetts 02138 USA

Recent studies of genotype-phenotype maps have reported universally enhanced phenotypic robustness to genotype mutations, a feature essential to evolution. Virtually all of these studies make a simplifying assumption that each genotype—represented as a sequence—maps deterministically to a single phenotype, such as a discrete structure. Here we introduce probabilistic genotype-phenotype (PrGP) maps, where each genotype maps to a vector of phenotype probabilities, as a more realistic and universal language for investigating robustness in a variety of physical, biological, and computational systems. We study three model systems to show that PrGP maps offer a generalized framework which can handle uncertainty emerging from various physical sources: (1) thermal fluctuation in RNA folding, (2) external field disorder in the spin-glass ground state search problem, and (3) superposition and entanglement in quantum circuits, which are realized experimentally on IBM quantum computers. In all three cases, we observe a biphasic robustness scaling which is enhanced relative to random expectation for more frequent phenotypes and approaches random expectation for less frequent phenotypes. We derive an analytical theory for the behavior of PrGP robustness, and we demonstrate that the theory is highly predictive of empirical robustness.

关键词： Quantum computers

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Measurement of peripheral nerve magnetostimulation thresholds of a head solenoid coil between 200 Hz and 88.1 kHz

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IEEE Journal of Translational Engineering in health and Medicine 2025年

作者： Barksdale, Alex C. Ferris, Natalie G. Mattingly, Eli Sliwiak, Monika Guerin, Bastien Wald, Lawrence L. Davids, Mathias Klein, Valerie MIT Department of Electrical Engineering and Computer Science CambridgeMA United States Martinos Center for Biomedical Imaging CharlestownMA United States Harvard University Harvard Graduate Program in Biophysics CambridgeMA United States Harvard-MIT Division of Health Sciences and Technology BostonMA United States Harvard Medical School BostonMA United States

Objective: Magnetic fields switching at kilohertz frequencies induce electric fields in the body, which can cause peripheral nerve stimulation (PNS). Although magnetostimulation has been extensively studied below 10 kHz, the behavior of PNS at higher frequencies remains poorly understood. This study aims to investigate PNS thresholds at frequencies up to 88.1 kHz and to explore deviations from the widely accepted hyperbolic strength-duration curve (SDC). Methods and procedures: PNS thresholds were measured in the head of 8 human volunteers using a solenoidal coil at 16 distinct frequencies, ranging from 200 Hz to 88.1 kHz. A hyperbolic SDC was used as a reference to compare the frequency-dependent behavior of PNS thresholds. Results: Contrary to the predictions of the hyperbolic SDC, PNS thresholds did not decrease monotonically with frequency. Instead, thresholds reached a minimum near 25 kHz, after which they increased by an average of 39% from 25 kHz to 88.1 kHz across subjects. This pattern indicates a significant deviation from previously observed behavior at lower frequencies. Conclusion: Our results suggest that PNS thresholds exhibit a non-monotonic frequency dependence at higher frequencies, diverging from the traditional hyperbolic SDC. These findings offer critical data for refining neurodynamic models and provide insights for setting PNS safety limits in applications like MRI gradient coils and magnetic particle imaging (MPI). Further investigation is needed to understand the biological mechanisms driving these deviations beyond 25 kHz. Clinical impact: These findings call for further basic research into biological mechanisms underlying high frequency PNS threshold trends, and supports refinement of safety guidelines for MRI and MPI systems for clinical implementation. © 2013 IEEE.

关键词： Neuroimaging

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Experience influences the refinement of feature selectivity in the mouse primary visual thalamus

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Neuron 2025年第9期113卷 1352-1362.e4页

作者： Sonoda, Takuma Stephany, Céleste-Élise Kelley, Kaleb Kang, Di Wu, Rui Uzgare, Meghna R. Fagiolini, Michela Greenberg, Michael E. Chen, Chinfei Department of Neurology F.M. Kirby Neurobiology Center Boston Children's Hospital Boston 02115 MA United States Department of Neurobiology Harvard Medical School Boston 02115 MA United States Harvard-MIT Health Sciences and Technology Program Harvard Medical School Boston 02115 MA United States

Neurons exhibit selectivity for specific features: a property essential for extracting and encoding relevant information in the environment. This feature selectivity is thought to be modifiable by experience at the level of the cortex. Here, we demonstrate that selective exposure to a feature during development can alter the population representation of that feature in the primary visual thalamus. This thalamic plasticity is not due to changes in corticothalamic inputs and is blocked in mutant mice that exhibit deficits in retinogeniculate refinement, suggesting that plasticity is a direct result of changes in feedforward connectivity. Notably, experience-dependent changes in thalamic feature selectivity also occur in adult animals, although these changes are transient, unlike in juvenile animals, where they are long lasting. These results reveal an unexpected degree of plasticity in the visual thalamus and show that salient environmental features can be encoded in thalamic circuits during a discrete developmental window. © 2025 Elsevier Inc.

关键词： circuit development dLGN experience-dependent plasticity feature selectivity retinogeniculate synaptic plasticity thalamus

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Randomizing the human genome by engineering recombination between repeat elements

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Science (New York, N.Y.) 2025年第6733期387卷 eado3979页

作者： Koeppel, Jonas Ferreira, Raphael Vanderstichele, Thomas Riedmayr, Lisa Maria Peets, Elin Madli Girling, Gareth Weller, Juliane Murat, Pierre Liberante, Fabio Giuseppe Ellis, Tom Church, George McDonald Parts, Leopold Hinxton United Kingdom Harvard Medical School Department of Genetics Boston MA United States Wyss Institute for Biologically Inspired Engineering Harvard University Boston MA United States Broad Institute of Massachusetts Institute of Technology and Harvard University Cambridge MA United States Department of Bioengineering Imperial College London London United Kingdom Harvard-MIT Program in Health Sciences and Technology Cambridge MA United States Harvard Medical School Boston MA United States

We lack tools to edit DNA sequences at scales necessary to study 99% of the human genome that is noncoding. To address this gap, we applied CRISPR prime editing to insert recombination handles into repetitive sequences, up to 1697 per cell line, which enables generating large-scale deletions, inversions, translocations, and circular DNA. Recombinase induction produced more than 100 stochastic megabase-sized rearrangements in each cell. We tracked these rearrangements over time to measure selection pressures, finding a preference for shorter variants that avoided essential genes. We characterized 29 clones with multiple rearrangements, finding an impact of deletions on expression of genes in the variant but not on nearby genes. This genome-scrambling strategy enables large deletions, sequence relocations, and the insertion of regulatory elements to explore genome dispensability and organization.

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Accessing the viscera: Technologies for interoception research

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Current Opinion in Neurobiology 2025年 93卷 103050-103050页

作者： Pang, Karen K.L. Mondal, Rajib Sahasrabudhe, Atharva Anikeeva, Polina Department of Brain and Cognitive Sciences Massachusetts Institute of Technology United States K. Lisa Yang Brain-Body Center Massachusetts Institute of Technology United States McGovern Institute for Brain Research Massachusetts Institute of Technology United States Research Laboratory of Electronics Massachusetts Institute of Technology United States MIT-Harvard Graduate Program in Health Sciences and Technology United States Department of Materials Science and Engineering Massachusetts Institute of Technology United States

Interoception, or the perception and regulation of body signals by the central nervous system, is critical for maintaining homeostasis and coordination of behaviors. Deciphering the mechanisms of interoception requires identifying pathways and decoding of diverse signals across the brain-body axis. These studies are enabled by tools to modulate and record physiological processes in the brain and visceral organs. While numerous advanced neurotechnologies are well-established in the brain, these techniques often offer limited utility for other organs, such as the gastrointestinal tract, heart, liver, or bladder. In this review, we highlight recent advances in technologies for recording and modulation of visceral organ physiology in small animals in vivo, with a focus on implantable bioelectronic organ interfaces that can be deployed in behaving animals. We discuss how such interfaces are made possible through innovations in materials and electronics and outline unmet technological challenges in interoception research. © 2025 Elsevier Ltd

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Molecular-driven Foundation Model for Oncologic Pathology

arXiv

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arXiv 2025年

作者： Vaidya, Anurag Zhang, Andrew Jaume, Guillaume Song, Andrew H. Ding, Tong Wagner, Sophia J. Lu, Ming Y. Doucet, Paul Robertson, Harry Almagro-Pérez, Cristina Chen, Richard J. ElHarouni, Dina Ayoub, Georges Bossi, Connor Ligon, Keith L. Gerber, Georg Le, Long Phi Mahmood, Faisal Department of Pathology Brigham and Women’s Hospital Harvard Medical School BostonMA United States Department of Pathology Massachusetts General Hospital Harvard Medical School BostonMA United States Cancer Program Broad Institute of Harvard and MIT CambridgeMA United States Health Sciences and Technology Harvard-MIT CambridgeMA United States Harvard John A. Paulson School of Engineering and Applied Sciences Harvard University CambridgeMA United States Helmholtz Munich – German Research Center for Environment and Health Munich Germany School of Computation Information and Technology TUM Munich Germany CambridgeMA United States Sydney Precision Data Science Center The University of Sydney CamperdownNSW Australia Department of Oncologic Pathology Dana-Farber Cancer Institute BostonMA02215 United States Department of Pathology Boston Children’s Hospital BostonMA02115 United States Harvard Data Science Initiative Harvard University CambridgeMA United States

Foundation models are reshaping computational pathology by enabling transfer learning, where models pre-trained on vast datasets can be adapted for downstream diagnostic, prognostic, and therapeutic response tasks. Despite these advances, foundation models are still limited in their ability to encode the entire gigapixel whole-slide images without additional training and often lack complementary multimodal data. Here, we introduce THREADS, a slide-level foundation model capable of generating universal representations of whole-slide images of any size. THREADS was pretrained using a multimodal learning approach on a diverse cohort of 47,171 hematoxylin and eosin (H&E)-stained tissue sections, paired with corresponding genomic and transcriptomic profiles—the largest such paired dataset to be used for foundation model development to date. This unique training paradigm enables THREADS to capture the tissue’s underlying molecular composition, yielding powerful representations applicable to a wide array of downstream tasks. In extensive benchmarking across 54 oncology tasks, including clinical subtyping, grading, mutation prediction, immunohistochemistry status determination, treatment response prediction and survival prediction THREADS outperformed all baselines while demonstrating remarkable generalizability and label efficiency. It is particularly well-suited for predicting rare events, further emphasizing its clinical utility. We intend to make the model publicly available for the broader community. © 2025, CC BY-NC-ND.

关键词： Transfer learning

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BPS2025 - Time-resolved high-pressure freezing for dynamic, nanoscale imaging

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Biophysical Journal 2025年第3期124卷 312a-312a页

作者： Ami U. Thakrar Daphne-Eleni Archonta Maxim B. Prigozhin Harvard-MIT Program in Health Sciences and Technology Massachusetts Institute of Technology Cambridge MA USA Department of Molecular and Cellular Biology Harvard University Cambridge MA USA Bioengineering Program Harvard University Cambridge MA USA Applied Physics Program Harvard University Cambridge MA USA

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A new technique utilizing thermistor probes for the measurement of thermal properties of biomaterials

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Cryobiology 1976年第5期13卷 572-580页

作者： Bowman, H.Frederick Balasubramaniam, T.A. Department of Mechanical Engineering Northeastern University Boston MA 02115 United States Concurrently with the Harvard-MIT Program in Health Sciences and Technology MIT Cambridge MA 02139 United States

The thermal limitations inherent with the use of invasive thermistor probes in the measurement of thermal properties of biomaterials have been investigated. An electronic temperature controller has been developed which provides a nearly instantaneous step rise in average probe resistance (temperature). The method of experimentally determining the heat rate required to maintain the average probe temperature constant and incorporation of that heat rate into the general heat diffusion equation provides a solution which allows the determination of both thermal conductivity and diffusivity values with improved accuracy. The method is general to all media which wet the surface of the probe;the need for calibrating media is avoided. The solution also predicts the minimum required sample size. © 1976.

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BPS2025 - VIS-À-VIS: Visualization and vitrification of sub-second cellular dynamics

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Biophysical Journal 2025年第3期124卷 172a-172a页

作者： Daphne-Eleni Archonta Ami U. Thakrar Maxim B. Prigozhin Harvard John A. Paulson School Of Engineering and Applied Sciences Harvard University Cambridge MA USA Harvard-MIT Program in Health Sciences and Technology Massachusetts Institute of Technology Cambridge MA USA Department of Molecular and Cellular Biology Harvard University Cambridge MA USA

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