Using AI to Write a Review Article Examining the Role of the Nervous System on Skeletal Homeostasis and Fracture Healing.

PURPOSE OF REVIEW: Three review articles have been written that discuss the roles of the central and peripheral nervous systems in fracture healing. While content among the articles is overlapping, there is a key difference between them: the use of artificial intelligence (AI). In one paper, the first draft was written solely by humans. In the second paper, the first draft was written solely by AI using ChatGPT 4.0 (AI-only or AIO). In the third paper, the first draft was written using ChatGPT 4.0 but the literature references were supplied from the human-written paper (AI-assisted or AIA). This project was done to evaluate the capacity of AI to conduct scientific writing. Importantly, all manuscripts were fact checked and extensively edited by all co-authors rendering the final manuscript drafts significantly different from the first drafts. RECENT FINDINGS: Unsurprisingly, the use of AI decreased the time spent to write a review. The two AI-written reviews took less time to write than the human-written paper; however, the changes and editing required in all three manuscripts were extensive. The human-written paper was edited the most. On the other hand, the AI-only paper was the most inaccurate with inappropriate reference usage and the AI-assisted paper had the greatest incidence of plagiarism. These findings show that each style of writing presents its own unique set of challenges and advantages. While AI can theoretically write scientific reviews, from these findings, the extent of editing done subsequently, the inaccuracy of the claims it makes, and the plagiarism by AI are all factors to be considered and a primary reason why it may be several years into the future before AI can present itself as a viable alternative for traditional scientific writing.

Role of the Neurologic System in Fracture Healing: An Extensive Review.

PURPOSE OF REVIEW: Despite advances in orthopedics, there remains a need for therapeutics to hasten fracture healing. However, little focus is given to the role the nervous system plays in regulating fracture healing. This paucity of information has led to an incomplete understanding of fracture healing and has limited the development of fracture therapies that integrate the importance of the nervous system. This review seeks to illuminate the integral roles that the nervous system plays in fracture healing. RECENT FINDINGS: Preclinical studies explored several methodologies for ablating peripheral nerves to demonstrate ablation-induced deficits in fracture healing. Conversely, activation of peripheral nerves via the use of dorsal root ganglion electrical stimulation enhanced fracture healing via calcitonin gene related peptide (CGRP). Investigations into TLR-4, TrkB agonists, and nerve growth factor (NGF) expression provide valuable insights into molecular pathways influencing bone mesenchymal stem cells and fracture repair. Finally, there is continued research into the connections between pain and fracture healing with findings suggesting that anti-NGF may be able to block pain without affecting healing. This review underscores the critical roles of the central nervous system (CNS), peripheral nervous system (PNS), and autonomic nervous system (ANS) in fracture healing, emphasizing their influence on bone cells, neuropeptide release, and endochondral ossification. The use of TBI models contributes to understanding neural regulation, though the complex influence of TBI on fracture healing requires further exploration. The review concludes by addressing the neural connection to fracture pain. This review article is part of a series of multiple manuscripts designed to determine the utility of using artificial intelligence for writing scientific reviews.

Cracking the Code: The Role of Peripheral Nervous System Signaling in Fracture Repair.

PURPOSE OF REVIEW: The traditionally understated role of neural regulation in fracture healing is gaining prominence, as recent findings underscore the peripheral nervous system's critical contribution to bone repair. Indeed, it is becoming more evident that the nervous system modulates every stage of fracture healing, from the onset of inflammation to repair and eventual remodeling. RECENT FINDINGS: Essential to this process are neurotrophins and neuropeptides, such as substance P, calcitonin gene-related peptide, and neuropeptide Y. These molecules fulfill key roles in promoting osteogenesis, influencing inflammation, and mediating pain. The sympathetic nervous system also plays an important role in the healing process: while local sympathectomies may improve fracture healing, systemic sympathetic denervation impairs fracture healing. Furthermore, chronic activation of the sympathetic nervous system, often triggered by stress, is a potential impediment to effective fracture healing, marking an important area for further investigation. The potential to manipulate aspects of the nervous system offers promising therapeutic possibilities for improving outcomes in fracture healing. This review article is part of a series of multiple manuscripts designed to determine the utility of using artificial intelligence for writing scientific reviews.

Do Not Lose Your Nerve, Be Callus: Insights Into Neural Regulation of Fracture Healing.

PURPOSE OF REVIEW: Fractures are a prominent form of traumatic injury and shall continue to be for the foreseeable future. While the inflammatory response and the cells of the bone marrow microenvironment play significant roles in fracture healing, the nervous system is also an important player in regulating bone healing. RECENT FINDINGS: Considerable evidence demonstrates a role for nervous system regulation of fracture healing in a setting of traumatic injury to the brain. Although many of the impacts of the nervous system on fracture healing are positive, pain mediated by the nervous system can have detrimental effects on mobilization and quality of life. Understanding the role the nervous system plays in fracture healing is vital to understanding fracture healing as a whole and improving quality of life post-injury. This review article is part of a series of multiple manuscripts designed to determine the utility of using artificial intelligence for writing scientific reviews.

Angular Head Velocity Cells within Brainstem Nuclei Projecting to the Head Direction Circuit.

The sense of orientation of an animal is derived from the head direction (HD) system found in several limbic structures and depends on an intact vestibular labyrinth. However, how the vestibular system influences the generation and updating of the HD signal remains poorly understood. Anatomical and lesion studies point toward three key brainstem nuclei as key components for generating the HD signal-nucleus prepositus hypoglossi, supragenual nucleus, and dorsal paragigantocellularis reticular nuclei. Collectively, these nuclei are situated between the vestibular nuclei and the dorsal tegmental and lateral mammillary nuclei, which are thought to serve as the origin of the HD signal. To determine the types of information these brain areas convey to the HD network, we recorded neurons from these regions while female rats actively foraged in a cylindrical enclosure or were restrained and rotated passively. During foraging, a large subset of cells in all three nuclei exhibited activity that correlated with the angular head velocity (AHV) of the rat. Two fundamental types of AHV cells were observed; (1) symmetrical AHV cells increased or decreased their firing with increases in AHV regardless of the direction of rotation, and (2) asymmetrical AHV cells responded differentially to clockwise and counterclockwise head rotations. When rats were passively rotated, some AHV cells remained sensitive to AHV, whereas firing was attenuated in other cells. In addition, a large number of AHV cells were modulated by linear head velocity. These results indicate the types of information conveyed from the vestibular nuclei that are responsible for generating the HD signal.SIGNIFICANCE STATEMENT Extracellular recording of brainstem nuclei (nucleus prepositus hypoglossi, supragenual nucleus, and dorsal paragigantocellularis reticular nucleus) that project to the head direction circuit identified different types of AHV cells while rats freely foraged in a cylindrical environment. The firing of many cells was also modulated by linear velocity. When rats were restrained and passively rotated, some cells remained sensitive to AHV, whereas others had attenuated firing. These brainstem nuclei provide critical information about the rotational movement of the head of the rat in the azimuthal plane.

Angular head velocity cells within brainstem nuclei projecting to the head direction circuit.

An animal's perceived sense of orientation depends upon the head direction (HD) system found in several limbic structures and depends upon an intact peripheral vestibular labyrinth. However, how the vestibular system influences the generation, maintenance, and updating of the HD signal remains poorly understood. Anatomical and lesion studies point towards three key brainstem nuclei as being potential critical components in generating the HD signal: nucleus prepositus hypoglossi (NPH), supragenual nucleus (SGN), and dorsal paragigantocellularis reticular nuclei (PGRNd). Collectively, these nuclei are situated between the vestibular nuclei and the dorsal tegmental and lateral mammillary nuclei, which are thought to serve as the origin of the HD signal. To test this hypothesis, extracellular recordings were made in these areas while rats either freely foraged in a cylindrical environment or were restrained and rotated passively. During foraging, a large subset of cells in all three nuclei exhibited activity that correlated with changes in the rat's angular head velocity (AHV). Two fundamental types of AHV cells were observed: 1) symmetrical AHV cells increased or decreased their neural firing with increases in AHV regardless of the direction of rotation; 2) asymmetrical AHV cells responded differentially to clockwise (CW) and counter-clockwise (CCW) head rotations. When rats were passively rotated, some AHV cells remained sensitive to AHV whereas others had attenuated firing. In addition, a large number of AHV cells were modulated by linear head velocity. These results indicate the types of information conveyed in the ascending vestibular pathways that are responsible for generating the HD signal. Significance Statement: Extracellular recording of brainstem nuclei (nucleus prepositus hypoglossi, supragenual nucleus, and dorsal paragigantocellularis reticular nucleus) that project to the head direction circuit identified different types of angular head velocity (AHV) cells while rats freely foraged in a cylindrical environment. The firing of many cells was also modulated by linear velocity. When rats were restrained and passively rotated some cells remained sensitive to AHV, whereas others had attenuated firing. These brainstem nuclei provide critical information about the rotational movement of the rat's head in the azimuthal plane.

Landmark-modulated directional coding in postrhinal cortex.

Visual landmarks can anchor an animal's internal sense of orientation to the external world. The rodent postrhinal cortex (POR) may facilitate this processing. Here, we demonstrate that, in contrast to classic head direction (HD) cells, which have a single preferred orientation, POR HD cells develop a second preferred orientation when an established landmark cue is duplicated along another environmental wall. We therefore refer to these cells as landmark-modulated-HD (LM-HD) cells. LM-HD cells discriminate between landmarks in familiar and novel locations, discriminate between visually disparate landmarks, and continue to respond to the previous location of a familiar landmark following its removal. Rats initially exposed to different stable landmark configurations show LM-HD tuning that may reflect the integration of visual landmark information into an allocentric HD signal. These results provide insight into how visual landmarks are integrated into a framework that supports the neural encoding of landmark-based orientation.