{"title":"The use of animals in physiological science: the past, the presence, and the future.","authors":"Klaus-Dieter Schlüter","doi":"10.1007/s00424-024-03009-9","DOIUrl":"10.1007/s00424-024-03009-9","url":null,"abstract":"<p><p>Physiology is a scientific discipline of how people's and animals' bodies function that requires traditionally suitable experimental models that often rely on animals. However, at the end of the 50th of the last century, researchers themselves addressed concerns about the use of animals for biomedical science and physiology in particular. At that time, the so-called 3R strategy was implicated where the three \"R\" stand for replacement, reduction, and refinement. When addressing these concerns, researchers nevertheless realized that a critical dispute about experimental models in the light of the 3R initiative may require further attention to other points such as robustness, registration, reporting, reproducibility, and rigor of the work. The question that has to be addressed now is first whether the use of animals in physiology changed in the post-3R period, whether it led to a replacement, reduction, or refinement of animal handling, and most importantly, how this affected the scientific progress in (patho)physiology. In order to address open questions concerning the relationship between the use of animals and physiological research, complete volumes of the Pflügers Archiv - European Journal of Physiology were analyzed every 10 years starting in 1950 and ending in 2020 and compared to volumes of the Journal of Physiology. It analyzed how scientists organize their projects published in the journal and what kind of models they used. The results show that physiological science has dramatically changed in the last 70 years. Replacement, reduction, and refinement were achieved to a certain level. However, during the last years, no further achievement could be seen. It seems that a certain level of animal testing is required for biomedical science and physiology in particular. Physiological studies in the present time are dominated by investigation of the physiological function of small rodents mainly mice and rats with only a few exceptions. The analysis also shows that in the future, researchers must have a critical look at further requirements of their research such as data robustness, improvement of reproducibility of data, and generation of rigor data as a prerequisite to improve our physiological view on life.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"1653-1663"},"PeriodicalIF":2.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11481686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142081144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chiara Pappalettera, Francesca Miraglia, Alessia Cacciotti, Lorenzo Nucci, Giulia Tufo, Paolo Maria Rossini, Fabrizio Vecchio
{"title":"The impact of virtual reality and distractors on attentional processes: insights from EEG.","authors":"Chiara Pappalettera, Francesca Miraglia, Alessia Cacciotti, Lorenzo Nucci, Giulia Tufo, Paolo Maria Rossini, Fabrizio Vecchio","doi":"10.1007/s00424-024-03008-w","DOIUrl":"10.1007/s00424-024-03008-w","url":null,"abstract":"<p><p>Virtual reality (VR) allows to create controlled scenarios in which the quantity of stimuli can be modulated, as happen in real-life, where humans are subjected to various multisensory-often overlapping-stimuli. The present research aimed to study changes in attentional processes within an auditory oddball paradigm during a virtual exploration, while varying the amount of distractors. Twenty healthy volunteers underwent electroencephalography (EEG) during three different experimental conditions: an auditory oddball without VR (No-VR condition), an auditory oddball during VR exploration without distractors (VR-Empty condition), and an auditory oddball during VR exploration with a high level of distractors (VR-Full condition). Event-related potentials (ERPs) were computed averaging epochs of EEGs and analyzing peaks at 100 ms (N100) and 300 ms (P300) latencies. Results showed modulation of N100 amplitude in Fz and of P300 amplitude in Pz. Statistically significant differences in latency were observed only for P300 where the latency results delayed from the No-VR to VR-Full. The scalp topography revealed for P100 no significant differences between frequent and rare stimuli in either the No-VR and VR-Empty conditions. However, significant results were found in N100 in VR-Full condition. For P300, results showed differences between frequent and rare stimuli, in every condition. However, this difference is gradually less widespread from No-VR condition to the VR-Full. The emerging integration of VR with EEG may have important implications for studying brain attentional processing.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"1727-1742"},"PeriodicalIF":2.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Neuroprotective actions of norepinephrine in neurological diseases.","authors":"Maedeh Ghasemi, Nasrin Mehranfard","doi":"10.1007/s00424-024-02999-w","DOIUrl":"10.1007/s00424-024-02999-w","url":null,"abstract":"<p><p>Precise control of norepinephrine (NE) levels and NE-receptor interaction is crucial for proper function of the brain. Much evidence for this view comes from experimental studies that indicate an important role for NE in the pathophysiology and treatment of various conditions, including cognitive dysfunction, Alzheimer's disease, Parkinson's disease, multiple sclerosis, and sleep disorders. NE provides neuroprotection against several types of insults in multiple ways. It abrogates oxidative stress, attenuates neuroinflammatory responses in neurons and glial cells, reduces neuronal and glial cell activity, promotes autophagy, and ameliorates apoptotic responses to a variety of insults. It is beneficial for the treatment of neurodegenerative diseases because it improves the generation of neurotrophic factors, promotes neuronal survival, and plays an important role in the regulation of adult neurogenesis. This review aims to present the evidence supporting a principal role for NE in neuroprotection, and molecular mechanisms of neuroprotection.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"1703-1725"},"PeriodicalIF":2.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ayaka Mikami, Hai Huang, Aiko Hyodo, Kengo Horie, Keiko Yasumatsu, Yuzo Ninomiya, Yoshihiro Mitoh, Seiji Iida, Ryusuke Yoshida
{"title":"The role of GABA in modulation of taste signaling within the taste bud.","authors":"Ayaka Mikami, Hai Huang, Aiko Hyodo, Kengo Horie, Keiko Yasumatsu, Yuzo Ninomiya, Yoshihiro Mitoh, Seiji Iida, Ryusuke Yoshida","doi":"10.1007/s00424-024-03007-x","DOIUrl":"10.1007/s00424-024-03007-x","url":null,"abstract":"<p><p>Taste buds contain 2 types of GABA-producing cells: sour-responsive Type III cells and glial-like Type I cells. The physiological role of GABA, released by Type III cells is not fully understood. Here, we investigated the role of GABA released from Type III cells using transgenic mice lacking the expression of GAD67 in taste bud cells (Gad67-cKO mice). Immunohistochemical experiments confirmed the absence of GAD67 in Type III cells of Gad67-cKO mice. Furthermore, no difference was observed in the expression and localization of cell type markers, ectonucleoside triphosphate diphosphohydrolase 2 (ENTPD2), gustducin, and carbonic anhydrase 4 (CA4) in taste buds between wild-type (WT) and Gad67-cKO mice. Short-term lick tests demonstrated that both WT and Gad67-cKO mice exhibited normal licking behaviors to each of the five basic tastants. Gustatory nerve recordings from the chorda tympani nerve demonstrated that both WT and Gad67-cKO mice similarly responded to five basic tastants when they were applied individually. However, gustatory nerve responses to sweet-sour mixtures were significantly smaller than the sum of responses to each tastant in WT mice but not in Gad67-cKO mice. In summary, elimination of GABA signalling by sour-responsive Type III taste cells eliminates the inhibitory cell-cell interactions seen with application of sour-sweet mixtures.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"1761-1775"},"PeriodicalIF":2.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11461785/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142110786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abdoulaye Issotina Zibrila, Jun Zhou, Xiaomin Wang, Ming Zeng, Md Ahasan Ali, Xiaoxu Liu, Asma A Alkuhali, Zhaoshu Zeng, Yuan Meng, Zheng Wang, Xuelan Li, Jinjun Liu
{"title":"Placental ischemia-upregulated angiotensin II type 1 receptor in hypothalamic paraventricular nucleus contributes to hypertension in rat.","authors":"Abdoulaye Issotina Zibrila, Jun Zhou, Xiaomin Wang, Ming Zeng, Md Ahasan Ali, Xiaoxu Liu, Asma A Alkuhali, Zhaoshu Zeng, Yuan Meng, Zheng Wang, Xuelan Li, Jinjun Liu","doi":"10.1007/s00424-024-03010-2","DOIUrl":"10.1007/s00424-024-03010-2","url":null,"abstract":"<p><p>Preeclampsia (PE) is associated with increased angiotensin II sensitivity and poor neurological outcomes marked by temporal loss of neural control of blood pressure. Yet the role of centrally expressed angiotensin II type 1 receptor (AT1R) within the paraventricular nucleus of the hypothalamus (PVN) in the PE model is not understood. In a PE rat model with reduced placental perfusion pressure (RUPP) induced on gestational day 14 (GD14), the PVN expression and cellular localization of AT1R were assessed using immunofluorescence and western blotting. The sensitivity of RUPP to acute angiotensin II infusion was assessed. AT1R was antagonized by losartan (100 µg/kg/day) for 5 days intracerebroventricularly (ICV). Hemodynamic data and samples were collected on GD19 for further analysis. RUPP upregulated (p < 0.05) mRNA and protein of AT1R within the PVN and lowered (p < 0.05) circulating angiotensin II in rats. RUPP increased neural and microglial activation. Cellular localization assessment revealed that AT1R was primarily expressed in neurons and slightly in microglia and astrocytes. Infusion of 100 ng/kg as bolus increased the mean arterial pressure (MAP in mmHg) in both RUPP and Sham. ICV losartan infusion attenuated RUPP-increased MAP (113.6 ± 6.22 in RUPP vs. 92.16 ± 5.30 in RUPP + Los, p = 0.021) and the expression of nuclear transcription factor NF-κB, tyrosine hydroxylase (TH), NADPH oxidase 4 (NOX4) and reactive oxygen species (ROS) in the PVN. Our data suggest that centrally expressed AT1R, within the PVN, contributes to placental ischemia-induced hypertension in RUPP rats highlighting its therapeutic potential in PE.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"1677-1691"},"PeriodicalIF":2.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142110785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alembert Lino-Alvarado, Octavio A C Maia, Maria Aparecida Oliveira, Ana C Takakura, Wothan Tavares-Lima, Henrique T Moriya, Thiago S Moreira
{"title":"Central and peripheral mechanisms underlying respiratory deficits in a mouse model of accelerated senescence.","authors":"Alembert Lino-Alvarado, Octavio A C Maia, Maria Aparecida Oliveira, Ana C Takakura, Wothan Tavares-Lima, Henrique T Moriya, Thiago S Moreira","doi":"10.1007/s00424-024-03006-y","DOIUrl":"10.1007/s00424-024-03006-y","url":null,"abstract":"<p><p>Aging invariably decreases sensory and motor stimuli and affects several neuronal systems and their connectivity to key brain regions, including those involved in breathing. Nevertheless, further investigation is needed to fully comprehend the link between senescence and respiratory function. Here, we investigate whether a mouse model of accelerated senescence could develop central and peripheral respiratory abnormalities. Adult male Senescence Accelerated Mouse Prone 8 (SAMP8) and the control SAMR1 mice (10 months old) were used. Ventilatory parameters were assessed by whole-body plethysmography, and measurements of respiratory input impedance were performed. SAMP8 mice exhibited a reduction in the density of neurokinin-1 receptor immunoreactivity in the entire ventral respiratory column. Physiological experiments showed that SAMP8 mice exhibited a decreased tachypneic response to hypoxia (FiO2 = 0.08; 10 min) or hypercapnia (FiCO2 = 0.07; 10 min). Additionally, the ventilatory response to hypercapnia increased further due to higher tidal volume. Measurements of respiratory mechanics in SAMP8 mice showed decreased static compliance (Cstat), inspiratory capacity (IC), resistance (Rn), and elastance (H) at different ages (3, 6, and 10 months old). SAMP8 mice also have a decrease in contractile response to methacholine compared to SAMR1. In conclusion, our findings indicate that SAMP8 mice display a loss of the NK1-expressing neurons in the respiratory brainstem centers, along with impairments in both central and peripheral respiratory mechanisms. These observations suggest a potential impact on breathing in a senescence animal model.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"1665-1676"},"PeriodicalIF":2.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Immune-mediated impairment of tonic immobility defensive behavior in an experimental model of colonic inflammation.","authors":"Leda Menescal-de-Oliveira, Mariulza Rocha Brentegani, Fernanda Pincelli Teixeira, Humberto Giusti, Rafael Simone Saia","doi":"10.1007/s00424-024-03011-1","DOIUrl":"10.1007/s00424-024-03011-1","url":null,"abstract":"<p><p>Ulcerative colitis has been associated with psychological distress and an aberrant immune response. The immunomodulatory role of systemic cytokines produced during experimental intestinal inflammation in tonic immobility (TI) defensive behavior remains unknown. The present study characterized the TI defensive behavior of guinea pigs subjected to colitis induction at the acute stage and after recovery from intestinal mucosa injury. Moreover, we investigated whether inflammatory mediators (tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-8, IL-10, and prostaglandins) act on the mesencephalic nucleus, periaqueductal gray matter (PAG). Colitis was induced in guinea pigs by intrarectal administration of acetic acid. The TI defensive behavior, histology, cytokine production, and expression of c-FOS, IBA-1, and cyclooxygenase (COX)-2 in PAG were evaluated. Colitis reduced the duration of TI episodes from the first day, persisting throughout the 7-day experimental period. Neuronal c-FOS immunoreactivity was augmented in both columns of the PAG (ventrolateral (vlPAG) and dorsal), but there were no changes in IBA-1 expression. Dexamethasone, infliximab, and parecoxib treatments increased the duration of TI episodes, suggesting a modulatory role of peripheral inflammatory mediators in this behavior. Immunoneutralization of TNF-α, IL-1β, and IL-8 in the vlPAG reversed all effects produced by colitis. In contrast, IL-10 neutralization further reduced the duration of TI episodes. Our results reveal that peripherally produced inflammatory mediators during colitis may modulate neuronal functioning in mesencephalic structures such as vlPAG.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"1743-1760"},"PeriodicalIF":2.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142110784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
H Fehmi Özel, Mustafa Özbek, Merve Temel Özden, H Seda Vatansever
{"title":"Cardioprotective effects of H3 receptor activation could be double-sided: insights from isoproterenol-induced cardiac injury.","authors":"H Fehmi Özel, Mustafa Özbek, Merve Temel Özden, H Seda Vatansever","doi":"10.1007/s00424-024-03039-3","DOIUrl":"10.1007/s00424-024-03039-3","url":null,"abstract":"<p><p>Histamine H3 receptors (H3Rs) are known to modulate neurotransmitter release in the nervous system, but their role in cardiac injury remains unclear. The present study aimed to investigate the cardioprotective role of H3Rs in a mouse model of myocardial injury. Forty BALB/c male mice were divided into four groups: Control (SF), Isoproterenol (ISO), Imetit (IMT), and IMT + ISO. The IMT and IMT + ISO groups were pretreated orally with 10 mg/kg imetit-dihydrobromide(imetit) for 7 days. In the last 2 days, the ISO and IMT + ISO groups received a subcutaneous injection of 85 mg/kg isoproterenol to induce myocardial ischemia. Electrocardiogram (ECG) recordings were obtained, and heart tissues were analyzed histopathologically. The results demonstrated that the administration of imetit resulted in the prolongation of the PR interval in the IMT group. QRS and QT intervals were prolonged in the ISO group. The J-wave area in the ISO group was significantly larger than in the other groups. Histopathological analyses revealed the presence of small vacuoles, inflammatory cell infiltration, and collagen aggregates in cardiomyocytes in the ISO group. No significant cellular changes were observed in the IMT group, in contrast. The IMT + ISO group exhibited fewer ischemic findings than the ISO group. Immunohistochemical analyses revealed positive H3R immunoreactivity in all groups. Imetit pretreatment increased the immunoreactivity of H3Rs in both the IMT and IMT + ISO groups. The findings of this study suggest that H3Rs may be present on the postsynaptic side in cardiac myocytes, in addition to adrenergic presynaptic nerve endings. Furthermore, imetit has been found to significantly reduce the effects of myocardial ischemia by activating H3Rs. The better characterization of the postsynaptic role of H3Rs offers potential for the development of new therapeutic strategies.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Juliana A da Silva, Samuel S P Araújo, Ana Flávia M da Silva, José Guilherme V de Assunção, Pâmela de S Santos, José L Pereira Júnior, Carlos Eduardo S Dos Reis, Liana de M Santana, Regina G Silva, Ariell A de Oliveira, Francisca V S Nunes, Aldeidia P de Oliveira, Damião P de Sousa, Renato Nery Soriano, Luiz G S Branco, Helio C Salgado, João Paulo J Sabino
{"title":"Chronic rose oxide and exercise synergistically modulate cardiovascular and autonomic functions in hypertensive rats.","authors":"Juliana A da Silva, Samuel S P Araújo, Ana Flávia M da Silva, José Guilherme V de Assunção, Pâmela de S Santos, José L Pereira Júnior, Carlos Eduardo S Dos Reis, Liana de M Santana, Regina G Silva, Ariell A de Oliveira, Francisca V S Nunes, Aldeidia P de Oliveira, Damião P de Sousa, Renato Nery Soriano, Luiz G S Branco, Helio C Salgado, João Paulo J Sabino","doi":"10.1007/s00424-024-03035-7","DOIUrl":"https://doi.org/10.1007/s00424-024-03035-7","url":null,"abstract":"<p><p>With the alarming rise in cases of arterial hypertension worldwide, there is an urgent need to develop combined therapies to mitigate this scenario. Rose oxide (RO), a monoterpene with anti-inflammatory and hypotensive properties, emerges as an alternative. The present study is the first to evaluate the effect of RO administered chronically and combined with physical exercise (swimming) since both have been reported to have beneficial impacts on hypertension. Male SHR and Wistar rats (aged 12 weeks) received RO for 34 consecutive days (orally; 100 mg/kg). The progression of systolic arterial pressure (SAP) was monitored through tail-cuff plethysmography. Twenty-four hours before the end of the treatment, the animals were anesthetized, and the femoral artery and vein were cannulated to record the pulsatile arterial pressure and to administer drugs, respectively. Hemodynamic and autonomic parameters and baroreflex sensitivity and intrinsic heart rate (IHR) were evaluated. Treatment with RO, administered alone or combined with exercise, reduced SAP and mean arterial pressure in SHR. The swimming protocol did not prevent increases in BP, but when combined with RO, it improved autonomic control, assessed through heart rate variability and parasympathetic tone. IHR was attenuated in SHR, and none of the treatments reversed this response. Therefore, combining RO with physical exercise may enhance their antihypertensive effects, improving autonomic function, reducing oxidative stress and inflammation, providing synergistic cardiovascular benefits, improving metabolic health, promoting a comprehensive lifestyle intervention, and potentially allowing for reduced medication dosages. This multifaceted approach could offer a more effective and sustainable strategy for managing hypertension.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Causality and scientific explanation of artificial intelligence systems in biomedicine.","authors":"Florian Boge, Axel Mosig","doi":"10.1007/s00424-024-03033-9","DOIUrl":"https://doi.org/10.1007/s00424-024-03033-9","url":null,"abstract":"<p><p>With rapid advances of deep neural networks over the past decade, artificial intelligence (AI) systems are now commonplace in many applications in biomedicine. These systems often achieve high predictive accuracy in clinical studies, and increasingly in clinical practice. Yet, despite their commonly high predictive accuracy, the trustworthiness of AI systems needs to be questioned when it comes to decision-making that affects the well-being of patients or the fairness towards patients or other stakeholders affected by AI-based decisions. To address this, the field of explainable artificial intelligence, or XAI for short, has emerged, seeking to provide means by which AI-based decisions can be explained to experts, users, or other stakeholders. While it is commonly claimed that explanations of artificial intelligence (AI) establish the trustworthiness of AI-based decisions, it remains unclear what traits of explanations cause them to foster trustworthiness. Building on historical cases of scientific explanation in medicine, we here propagate our perspective that, in order to foster trustworthiness, explanations in biomedical AI should meet the criteria of being scientific explanations. To further undermine our approach, we discuss its relation to the concepts of causality and randomized intervention. In our perspective, we combine aspects from the three disciplines of biomedicine, machine learning, and philosophy. From this interdisciplinary angle, we shed light on how the explanation and trustworthiness of artificial intelligence relate to the concepts of causality and robustness. To connect our perspective with AI research practice, we review recent cases of AI-based studies in pathology and, finally, provide guidelines on how to connect AI in biomedicine with scientific explanation.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}