Kashay, A. Q. | bioRxiv Science

bioRxiv2025

A Biosynthetic Thumb Prosthesis

In cases of severe damage to the extremities, the function and structure of compromised biological tissues must be replaced. If biological reconstruction using autologous tissue is not feasible, amputation and replacement with a synthetic prosthesis is often the next best option. Currently, the synthetic materials available for prostheses are limited, especially in their ability to restore skin sensation. Here we show a biosynthetic prosthesis that combines the versatility of titanium with the rich sensory capabilities of biological skin, to both increase movement and restore sensation to an amputated thumb. The prosthesis recreates opposition pinch by linking motion of the prosthetic joint to that of the residual biological joint. The device is enclosed in neurotized skin from the patients own body, providing natural sensation. We validated the biosynthetic thumbs ability to reproduce opposition pinch on the benchtop and in a cadaver, and showed in vivo viability of the skin interface in an animal model. These results provide a framework for functional reconstruction of amputated digits using a combination of synthetic materials and biological tissues. One Sentence SummaryA prosthetic thumb made up of a titanium mechanism and living skin can restore opposition pinch and touch sensation following thumb amputation.

bioengineering↗

bioRxiv2022

Neural activity in the anterior cingulate cortex is required for effort-based decision making

Adaptive decision making requires the evaluation of cost-benefit tradeoffs to guide action selection. Effort-based decision making (EBD) involves weighing predicted gains against effort costs and is disrupted in several neuropsychiatric disorders. The anterior cingulate cortex (ACC) is postulated to control effort-based choice via its role in encoding the value of overcoming effort costs in rodent EBD assays. However, temporally precise methods of manipulating neural activity have rarely been applied to EBD. We developed and validated a mouse version of the barrier T-maze EBD task, in which action selection is spatiotemporally segregated from surmounting an effortful obstacle and effort is minimally confounded with time cost. Optogenetic silencing of ACC excitatory neurons during action selection, rapidly and reversibly impaired preference to exert greater effort for a larger reward, when a less effortful alternative was available. Detailed analysis of mouse choice trajectories revealed that silencing ACC disrupts kinematics, especially prior to high effort choices. However, there were no effects on overall mobility or tendency to exert effort in non-choice assays. These findings establish causality between ACC neural activity and effortful action selection during spatial cost-benefit decision making. SIGNIFICANCE STATEMENTDisturbances in evaluating effort-based costs during decision making occur in depression, schizophrenia, addiction and Parkinsons disease. Precisely resolving the function of prefrontal brain regions in mediating these processes will reveal key loci of dysfunction and potential therapeutic intervention in these disorders.

neuroscience↗