Relevance of primate research


Social value: expected outcomes on human and animal health

Basic neurophysiological research in non-human primates has produced, in the last 20-30 years and considering only the specific contribution of the physiology group of the University of Parma, a scientific literature that has accumulated thousands of citations, appears in most of the manuals of neuroscience and neurophysiology for the education of medical and healthcare personnel[1][2], and guided the formulation of new neurorehabilitation approaches[3] based on action observation[4] for neurological [5] [6] [7], neuropsychiatric[7][8] and orthopedic patients[10], all derived from monkey neurophysiological data and the studies on the mirror system.
Although it is impossible to predict the possible outcomes of basic research projects on human health, the historical facts just mentioned above demonstrate that basic non-human primate research represents the starting point for several development in the clinical and translational field that could not be predicted when the experiments were carried out. The committees in charge of the evaluation of the research proposals specifically pursue the goal of assessing the innovative potential and feasibility of each project, retaining for funding and/or authorizing only the bests in terms of originality, novelty and cost/harm-benefit ratio.
The growing attention towards the study of brain activity in ecological conditions, most similar to those occurring in natural settings, the application of innovative neural and behavioral data analysis techniques, including artificial intelligence approaches potentially capable to predict individual’s behavior based on the recorded neural signal, make it possible to exploit the collected data for developing and refining neuroprosthetics systems[11] more and more flexible and adaptable to the variability of behaviors and conditions in of daily life.
Finally, innovative technologies and methods employed offer clear benefits for health and well-being of non-human primates used in neuroscientific research, which are still unreplaceable in many basic researches on motor and socio-cognitive skills[11][12]. For example, the possibility to remove every constrain on animals’ movement for many types of neurophysiological studies and to perform neurophysiological recording during free behavior, will allow the full exploration of the species-specific behavioral repertoire, with considerable benefits both in terms of ecological validity and generalizability of the experimental findings[14] and in terms of psychophysical well-being and cumulative life-time experience of the animals.


Economic value: expected impact in the economic-industrial sector

The contribution to the development and improvement of recording technologies in terms of multielectrode probes for neuronal recording[15], stimulation[16] and injection of pharmacologically active drugs while monitoring neuronal activity[17], as well as the use of wireless recording systems[18] or remote data-logging systems[19][20] to capture neural activity during unconstrained behavior, can contribute to the development of technologies with translational relevance for the treatment of human neurological or psychiatric diseases[21][11]. The established collaboration with the University of Freiburg (IMTEK, [22][15][23][24]) and the close relationship with AtlasNeuroengineering (Belgium), a spin-off group derived from a previous European project, offer the maximum guarantees of the possibility of refining and distributing technological innovations gradually developed and validated for pre-marketing optimization.


Educational value: expected outcomes in education

The two main areas in which the educational and training value of the ongoing projects can apply are the basic university education of students in biomedical and psychological disciplines and the high post-graduate training of future researchers and professionals in the biomedical and basic research sector.
The studies conducted by the physiology group of the University of Parma have led to a body of knowledge that is now widely used in the most famous physiology and neurosciences handbooks all over the world, and adopted in university courses in Medicine, Psychology and Biology (for example[1][25][2]). The new discoveries generated by the ongoing research projects will help to increase our understanding of the way in which the investigated brain regions work, to the benefit of the basic education of medical doctors, psychologists, biologists and healthcare professionals in general.
Internship of undergraduate and graduate students allows us to offer fundamental practical training for future researchers, specialized technical personnel or professionals of experimental research in the biomedical sector. These opportunities allow them to address some research topics not only from a theoretical point of view but also through a concrete approach to laboratory activity.
Finally, it must be stressed that we employ a number of pioneering refinement methodologies (e.g. computerized self-training of the animal in its home cage, no leashes and collars to move the animals from their home cage to the lab), which are used to date only in a few big primate centers in the world. We are also validating new methodological paradigms for the study of neuronal activity in freely moving animals, overcoming the movement restrictions typically imposed to the animals in classical neuroscientific studies, which we expect can greatly contribute to improve diffusion and communication not only of the research results but also of the methodologies employed to get them. Altogether, these initiatives may lead to develop an ever more “ethically acceptable neurophysiology”: we believe that the responsibility of the researcher in directly communicate to the public not only research findings but also rules and procedures for achieving them (see[26][27]), is crucial to contrast anti-scientific drifts against animal research, which typically does not lead to any advantage neither in terms of knowledge not in terms of health for humans or animal welfare.



[1] E. R. Kandel, J. H. Schwartz, T. M. Jessell, S. A. Siegelbaum, and A. J. Hudspeth, Principles of Neural Science, Fifth Edition, vol. 3. 2014.
[2] F. Conti, Fisiologia medica, no. v. 1. Edi-Ermes, 2010.
[3] E. Sarasso, M. Gemma, F. Agosta, M. Filippi, and R. Gatti, “Action observation training to improve motor function recovery: a systematic review,” Arch. Physiother., vol. 5, no. 1, p. 14, 2015.
[4] G. Buccino, “Action observation treatment: a novel tool in neurorehabilitation,” Philos. Trans. R. Soc. B Biol. Sci., vol. 369, no. 1644, Jun. 2014.
[5] D. Ertelt et al., “Action observation has a positive impact on rehabilitation of motor deficits after stroke,” Neuroimage, vol. 36, pp. T164–T173, 2007.
[6] G. Abbruzzese, L. Avanzino, R. Marchese, and E. Pelosin, “Action Observation and Motor Imagery: Innovative Cognitive Tools in the Rehabilitation of Parkinson’s Disease,” Parkinson’s Disease, vol. 2015. 2015.
[7] W. Chen, C. H. Liu, H. Li, K. Tong, N. Ren, and X. Fu, “Facial expression at retrieval affects recognition of facial identity,” Front. Psychol., vol. 6, p. 780, Jun. 2015.
[8] G. Sgandurra et al., “Upper limb children action-observation training (UP-CAT): a randomised controlled trial in Hemiplegic Cerebral Palsy,” BMC Neurol., vol. 11, no. 1, p. 80, 2011.
[9] A. P. Basu, J. Pearse, S. Kelly, V. Wisher, and J. Kisler, “Early intervention to improve hand function in hemiplegic cerebral palsy,” Frontiers in Neurology, vol. 5. 2015.
[10] G. Bellelli, G. Buccino, B. Bernardini, A. Padovani, and M. Trabucchi, “Action observation treatment improves recovery of postsurgical orthopedic patients: Evidence for a top-down effect?,” Arch. Phys. Med. Rehabil., vol. 91, no. 10, pp. 1489–1494, 2010.
[11] M. Capogrosso et al., “A brain–spine interface alleviating gait deficits after spinal cord injury in primates,” Nature, vol. 539, p. 284, Nov. 2016.
[12] P. R. Roelfsema and S. Treue, “Basic neuroscience research with nonhuman primates: A small but indispensable component of biomedical research,” Neuron, vol. 82, no. 6. pp. 1200–1204, 2014.
[13] L. Friedli et al., “Pronounced species divergence in corticospinal tract reorganization and functional recovery after lateralized spinal cord injury favors primates,” Sci. Transl. Med., vol. 7, no. 302, p. 302ra134-302ra134, Aug. 2015.
[14] H. Würbel, “More than 3Rs: the importance of scientific validity for harm-benefit analysis of animal research,” Lab Anim. (NY)., vol. 46, p. 164, Mar. 2017.
[15] F. P. and L. B. and M. L. and A. L. and L. F. and G. A. O. and O. P. and P. Ruther, “Chronic neural probe for simultaneous recording of single-unit, multi-unit, and local field potential activity from multiple brain sites,” J. Neural Eng., vol. 13, no. 4, p. 46006, 2016.
[16] C. G. Ferroni, M. Maranesi, A. Livi, M. Lanzilotto, and L. Bonini, “Comparative performance of linear multielectrode probes and single-tip electrodes for intracortical microstimulation and single-neuron recording in macaque monkey,” Front. Syst. Neurosci., vol. 11, 2017.
[17] S. Spieth et al., “Approaches for drug delivery with intracortical probes,” Biomed. Tech., vol. 59, no. 4, pp. 291–303, 2014.
[18] M. Yin et al., “Wireless neurosensor for full-spectrum electrophysiology recordings during free behavior,” Neuron, vol. 84, no. 6, pp. 1170–1182, 2014.
[19] A. Sarel, A. Finkelstein, L. Las, and N. Ulanovsky, “Vectorial representation of spatial goals in the hippocampus of bats,” Science (80-. )., vol. 355, no. 6321, p. 176 LP-180, Jan. 2017.
[20] D. B. Omer, S. R. Maimon, L. Las, and N. Ulanovsky, “Social place-cells in the bat hippocampus,” Science (80-. )., vol. 359, no. 6372, p. 218 LP-224, Jan. 2018.
[21] C. Dejean et al., “Neuronal Circuits for Fear Expression and Recovery: Recent Advances and Potential Therapeutic Strategies,” Biol. Psychiatry, vol. 78, no. 5, pp. 298–306, 2015.
[22] F. Pothof et al., “Fabrication and characterization of a high-resolution neural probe for stereoelectroencephalography and single neuron recording,” in 2014 36th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, 2014, pp. 5244–5247.
[23] M. Lanzilotto et al., “Extending the Cortical Grasping Network: Pre-supplementary Motor Neuron Activity During Vision and Grasping of Objects,” Cereb. Cortex, vol. 26, no. 12, pp. 4435–4449, Dec. 2016.
[24] F. Barz et al., “Versatile, modular 3D microelectrode arrays for neuronal ensemble recordings: From design to fabrication, assembly, and functional validation in non-human primates,” J. Neural Eng., vol. 14, no. 3, 2017.
[25] M. J. Zigmond, Neuroscienze cognitive e comportamentali. Edises, 2003.
[26] M. M. Metzger, “Knowledge of the Animal Welfare Act and Animal Welfare Regulations Influences Attitudes toward Animal Research,” J. Am. Assoc. Lab. Anim. Sci., vol. 54, no. 1, pp. 70–75, 2015.
[27] A. J. Bennett and D. L. Ringach, “Animal Research in Neuroscience: A Duty to Engage,” Neuron, vol. 92, no. 3. pp. 653–657, 2016.