Tuesday, June 10, 2025

Mice can recognize an artificial limb as their own

Animal model of forelimb embodiment could be used to develop better neuroprostheses

PLOS

Mice can recognize an artificial limb as their own — image:
The rubber-hand illusion was translated to the mouse model. Just like in humans, embodiment in mice can be achieved by brushing the real forelimb of the mouse and the artificial limb (yellow) in synchrony to generate matching visual and touch percepts.
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Credit: Luc Estebanez (CC-BY 4.0, https://creativecommons.org/licenses/by/4.0/)

Mice can develop a sense of embodiment of an artificial limb, similar to humans who participate in the rubber-hand illusion experiment, according to a study published June 5th in the open-access journal PLOS Biology by Luc Estebanez from CNRS: Centre National de la Recherche Scientifique, France, and colleagues.

We perceive our limbs as part of ourselves, and we feel threatened by any menace to them. This sense of embodiment can be disrupted by brain injuries leading to a loss of recognition of body parts, and even to their active rejection from the body representation. In the case of amputated patients, efficient use of a prosthesis can be hampered by a lack of prosthesis embodiment, thereby causing a progressive decrease in daily prosthesis use and finally an abandonment of the prosthetic limb. In contrast, prosthesis embodiment is associated with a reduction in the sensations arising from the phantom of the missing limb, including painful perceptions.

In an experimental setting, it is possible to either build or disrupt the sense of embodiment of an artificial limb by manipulating the temporal coincidence of tactile and visual stimulations. In particular, in the rubber-hand illusion experiment, a rubber limb is placed in a position that makes it visible to the participant, while the real hand is hidden from view. Both the hidden real hand and the visible artificial hand are stroked in synchrony with a brush. A large fraction of the subjects in these experiments report that after this stimulation, the rubber hand they are seeing is their real hand. So far, the physiological bases of sensory-based forelimb embodiment remain unclear, partly due to the lack of an animal model to study embodiment.

To address this challenge, Estebanez and colleagues developed an analog of the rubber-hand illusion embodiment protocol for mice. The researchers presented head-fixed mice with an artificial, 3D-printed static replica of their right forelimb at a plausible physiological location. At the same time, their real forelimb was hidden from sight and held in place below the platform where the artificial limb was located. During a two-minute pairing sequence, the researchers applied mechanically-controlled synchronous or asynchronous brush strokes to the real and the artificial forelimbs. Then the researchers dropped a sharp object toward the artificial forelimb that was within view of the animal.

During this sequence, the gaze of the mice was tracked with high-speed videography. Consistent with the broader literature on the rubber-hand illusion, the mice focused their gaze on the threat for several seconds when brush strokes were synchronous, but not when they were asynchronous. The behavioral response was also stronger when the artificial forelimb looked similar to a limb versus a white cube-shaped object.

According to the authors, this work has practical implications for the study of forelimb embodiment in a model that offers unparalleled experimental venues. For example, mapping out the brain circuits of embodiment using genetic and optogenetic research tools could lead to novel embodiment restoration strategies. Beyond this, the research also supports the idea that rodents can display behavioral correlates of embodiment in settings that are known to trigger embodiment in humans. This adds to a series of recent findings suggesting that rodents, and mice in particular, can display some capabilities that have been associated with higher cognitive functions.

The authors add, “The rubber hand illusion is a staple of the study of body representation in humans, but so far there was no equivalent of this test in the most actionable model: mice. Here we have shown that limb embodiment can be triggered and measured efficiently in mice. This opens up many opportunities to better understand the basic mechanisms of body ownership and apply it for instance to improve prosthetics.”

In your coverage, please use this URL to provide access to the freely available paper in PLOS Biology: https://plos.io/3Ft1HUi

Citation: Hayatou Z, Wang H, Chaillet A, Shulz DE, Ego-Stengel V, Estebanez L (2025) Embodiment of an artificial limb in mice. PLoS Biol 23(6): e3003186. https://doi.org/10.1371/journal.pbio.3003186

Author countries: France, China

Funding: This work was funded by LE PRC Hermin, ANR. https://anr.fr/ to LE, JCJC Mesobrain, ANR. https://anr.fr/ to LE, PRC Expect, ANR. https://anr.fr/ to DES, PRC PerBaCo, ANR. https://anr.fr/ to DES, Fondation 3DS https://www.lafondation3ds.org/fr/ to LE, 80|Prime 2020, CNRS, https://www.cnrs.fr/ to LE and AC, MITI PRIME 2024, CNRS, https://www.cnrs.fr/ to LE and AC, PRC MotorSense, ANR. https://anr.fr/ to VE, RISE iNavigate, 873178, Horizon 2020 Framework Programme. https://cordis.europa.eu/project/id/873178 to DES, OI hCODE, Université Paris-Saclay, https://www.universite-paris-saclay.fr/objets-interdisciplinaires/h-code to LE. The funders played no role in the design of the study, data collection and analysis, preparation of the manuscript, or decision du publish.

Journal

PLOS Biology

DOI

10.1371/journal.pbio.3003186

Method of Research

Observational study

Subject of Research

Animals

Personality disorder pioneer reveals half-century journey transforming psychiatric classification

Former American Psychiatric Assocition (APA) President John Oldham reflects on reshaping personality disorder diagnosis from rigid categories to dimensional understanding

Genomic Press

NEW YORK, New York, USA, 10 June 2025 -- In a comprehensive Genomic Press Interview published today in Brain Medicine, John M. Oldham, MD, MS, one of psychiatry's most influential architects of personality disorder theory, traces his remarkable journey from frontier medicine roots in Oklahoma to revolutionizing how mental health professionals understand and diagnose personality pathology.

Transforming Diagnostic Paradigms

Dr. Oldham's contributions have fundamentally reshaped personality disorder classification, moving the field from rigid diagnostic categories toward a more nuanced dimensional system. As former President of both the American Psychiatric Association and the International Society for the Study of Personality Disorders, he and a team of colleagues spearheaded the development of the Alternative DSM-5 Model for Personality Disorders (AMPD), marking what many consider the most significant epistemological shift in psychiatric diagnosis for these conditions in decades.

"The dimensional approach more accurately reflects the gradations and interplay of personality traits we see in clinical practice," Dr. Oldham explains in the interview. His innovative New Personality Self-Portrait online assessment tool (npsp25.com), based on a book continuously in print for 35 years, has provided both clinicians and the public with accessible ways to understand personality styles and potential pathology.

From Bedside to Policy Leadership

Dr. Oldham's career trajectory exemplifies the integration of clinical expertise with systems-level innovation. After training at Columbia, including psychoanalytic study under Otto Kernberg, he participated in the development of one of the first semi-structured clinical research interviews for DSM-III personality disorders, the Personality Disorders Examination (PDE). This groundbreaking work emerged during his tenure at Cornell, where he served as chief of an inpatient unit specializing in intensive treatment.

"My training took place when the Vietnam War was winding down. I was fortunate to enroll in the Berry Plan, which allowed me to complete my specialty training before assuming active duty," Dr. Oldham reflects. His two years of military service as a Major in the US Air Force, including interviews with returning POWs who had endured solitary confinement for up to 7 years, provided early lessons in resilience and crisis response that would prove invaluable throughout his career.

His leadership extended beyond academic medicine when he accepted the role of Chief Medical Officer for the New York State Office of Mental Health, a position he held from 1988 to 2002. In this capacity, he served as the senior physician in a large public system that, when he first assumed the role, operated approximately 25,000 inpatient beds. He emphasized bridging the gap between the state hospital centers and academic education, fostering formal teaching partnerships between the hospitals and medical school psychiatry departments. . Following the September 11, 2001 (9/11) attacks, Dr. Oldham helped navigate that unprecedented mental health crisis with what colleagues describe as exceptional clarity and resolve.

Advancing Scientific Understanding Through Collaboration

Throughout his career, Dr. Oldham has demonstrated how collaborative research can advance understanding of complex psychiatric conditions. As co-Principal Investigator of the New York site for the Collaborative Longitudinal Personality Disorders Study (CLPS), he contributed to generating crucial findings about personality disorder trajectories over more than a decade. This ambitious NIMH-funded project represented one of the most comprehensive investigations into personality pathology ever undertaken.

Questions remain about how dimensional approaches to personality disorders will be implemented in routine clinical practice. How will training programs need to adapt to teach these new diagnostic frameworks? What implications does this shift have for treatment planning and insurance coverage? These considerations highlight ongoing challenges as the field transitions from traditional categorical thinking.

Editorial Excellence and Mentorship

Currently serving as editor or co-editor for three major journals, Journal of Psychiatric Practice, Journal of Personality Disorders, and Borderline Personality Disorder and Emotion Dysregulation, Dr. Oldham continues to shape scientific discourse in the field. His editorial work emphasizes pragmatic, evidence-informed approaches to complex psychopathology while fostering the next generation of researchers and clinicians. "My family values have always made me conscientious and a good team player. The best leader is the leader who listens," Dr. Oldham shares, reflecting on the leadership principles that have guided his editorial work.

The interview reveals personal insights that illuminate Dr. Oldham's professional philosophy. His early life, in a family culture that emphasized concern and respect for others, profoundly influenced his approach to patient care, particularly his later focus on helping individuals with serious medical illnesses cope with psychological distress. This humanistic perspective permeates his scientific contributions, from developing assessment tools to advocating for improved treatment access.

Legacy and Future Directions

Dr. Oldham's work raises intriguing questions about the future of psychiatric diagnosis. As genetic and neurobiological research advances, how will dimensional models of personality integrate with emerging biomarkers? What role will technology play in implementing these more sophisticated diagnostic approaches in clinical settings? His contributions provide a foundation for addressing these challenges while maintaining focus on improving patient outcomes.

The evolution from categorical to dimensional understanding of personality disorders represents more than a technical advancement, it reflects a fundamental shift in how psychiatry conceptualizes human psychological variation. This transformation promises more personalized treatment approaches but also demands new frameworks for clinical training and practice guidelines.

Dr. John M. Oldham's Genomic Press interview is part of a larger series called Innovators & Ideas that highlights the people behind today's most influential scientific breakthroughs. Each interview in the series offers a blend of cutting-edge research and personal reflections, providing readers with a comprehensive view of the scientists shaping the future. By combining a focus on professional achievements with personal insights, this interview style invites a richer narrative that both engages and educates readers. This format provides an ideal starting point for profiles that explore the scientist's impact on the field, while also touching on broader human themes. More information on the research leaders and rising stars featured in our Innovators & Ideas – Genomic Press Interview series can be found in our publications website: https://genomicpress.kglmeridian.com/.

The Genomic Press Interview in Brain Medicine titled "John M. Oldham: Personality styles and personality disorders, a dimensional framework," is freely available via Open Access on 10 June 2025 in Brain Medicine at the following hyperlink: https://doi.org/10.61373/bm025k.0059.

About Brain Medicine: Brain Medicine (ISSN: 2997-2639, online and 2997-2647, print) is a peer-reviewed medical research journal published by Genomic Press, New York. Brain Medicine is a new home for the cross-disciplinary pathway from innovation in fundamental neuroscience to translational initiatives in brain medicine. The journal's scope includes the underlying science, causes, outcomes, treatments, and societal impact of brain disorders, across all clinical disciplines and their interface.

Visit the Genomic Press Virtual Library: https://issues.genomicpress.com/bookcase/gtvov/

Our full website is at: https://genomicpress.kglmeridian.com/

A few days after 9/11, several New York state officials in hard hats at Ground Zero, which was still smoldering, as a reminder of the staggering challenges that were being faced–John Oldham, then Chief Medical Officer, NY State Office of Mental Health, is on the right, with his jacket over his shoulder.

Credit

John Oldham