Techniques for chronic monitoring of brain activity in freely moving sheep using wireless EEG recording

BACKGROUND Large mammals with complex central nervous systems offer new possibilities for translational research into basic brain function. Techniques for monitoring brain activity in large mammals, however, are not as well developed as they are in rodents. NEW METHOD We have developed a method for chronic monitoring of electroencephalographic (EEG) activity in unrestrained sheep. We describe the methods for behavioural training prior to implantation, surgical procedures for implantation, a protocol for reliable anaesthesia and recovery, methods for EEG data collection, as well as data pertaining to suitability and longevity of different types of electrodes. RESULTS Sheep tolerated all procedures well, and surgical complications were minimal. Electrode types used included epidural and subdural screws, intracortical needles and subdural disk electrodes, with the latter producing the best and most reliable results. The implants yielded longitudinal EEG data of consistent quality for periods of at least a year, and in some cases up to 2 years. COMPARISON WITH EXISTING METHODS This is the first detailed methodology to be described for chronic brain function monitoring in freely moving unrestrained sheep. CONCLUSIONS The developed method will be particularly useful in chronic investigations of brain activity during normal behaviour that can include sleep, learning and memory. As well, within the context of disease, the method can be used to monitor brain pathology or the progress of therapeutic trials in transgenic or natural disease models in sheep.

[1]  A. Morton,et al.  Translational neurophysiology in sheep: measuring sleep and neurological dysfunction in CLN5 Batten disease affected sheep , 2015, Brain : a journal of neurology.

[2]  Robert Oostenveld,et al.  An improved index of phase-synchronization for electrophysiological data in the presence of volume-conduction, noise and sample-size bias , 2011, NeuroImage.

[3]  A. Gunn,et al.  Outcome after ischemia in the developing sheep brain: An electroencephalographic and histological study , 1992, Annals of neurology.

[4]  Partha P. Mitra,et al.  Chronux: A platform for analyzing neural signals , 2010, Journal of Neuroscience Methods.

[5]  D. Whitteridge,et al.  The cortical visual areas of the sheep. , 1976, The Journal of physiology.

[6]  David P Wolfer,et al.  Miniature neurologgers for flying pigeons: multichannel EEG and action and field potentials in combination with GPS recording. , 2006, Journal of neurophysiology.

[7]  A. Morton,et al.  Large genetic animal models of Huntington's Disease. , 2013, Journal of Huntington's disease.

[8]  P. Taylor,et al.  Anaesthesia in sheep , 2000, In Practice.

[9]  S. Teitelbaum THE PURSE‐STRING SUTURE , 1998, Plastic and reconstructive surgery.

[10]  B. Rabin,et al.  Exposure to physical and psychological stressors elevates plasma interleukin 6: relationship to the activation of hypothalamic-pituitary-adrenal axis. , 1993, Endocrinology.

[11]  C. Ayoub,et al.  Attenuation of the Preoperative Stress Response with Midazolam: Effects on Postoperative Outcomes , 2000, Anesthesiology.

[12]  A. Boissy,et al.  Stress during pregnancy alters dendritic spine density and gene expression in the brain of new-born lambs , 2015, Behavioural Brain Research.

[13]  Benjamin R. Arenkiel,et al.  In Vivo Light-Induced Activation of Neural Circuitry in Transgenic Mice Expressing Channelrhodopsin-2 , 2007, Neuron.

[14]  T. Whittem,et al.  Plasma pharmacokinetics of alfaxalone in dogs after an intravenous bolus of Alfaxan-CD RTU. , 2006, Veterinary anaesthesia and analgesia.

[15]  X. Moll,et al.  Maternal and Foetal Cardiovascular Effects of the Anaesthetic Alfaxalone in 2-Hydroxypropyl-β-cyclodextrin in the Pregnant Ewe , 2013, TheScientificWorldJournal.

[16]  J. Praud,et al.  A radiotelemetry system for polysomnographic recordings in lambs. , 2003, Methods.

[17]  Scott R. Stanslaski,et al.  Brain Stimulation for Epilepsy – Local and Remote Modulation of Network Excitability , 2014, Brain Stimulation.

[18]  R. Craen,et al.  Does Hyperventilation Improve Operating Condition During Supratentorial Craniotomy? A Multicenter Randomized Crossover Trial , 2008, Anesthesia and analgesia.

[19]  L. Fell,et al.  Salivary cortisol and behavioural indicators of stress in sheep. , 1988 .

[20]  A. Morton,et al.  Automated detection and characterisation of rumination in sheep using in vivo electrophysiology , 2016, Physiology & Behavior.

[21]  S. Smith EEG in the diagnosis, classification, and management of patients with epilepsy , 2005, Journal of Neurology, Neurosurgery & Psychiatry.

[22]  B. Pierscionek,et al.  The kinetics of hyaluronan in normal and acutely inflamed synovial joints: observations with experimental arthritis in sheep. , 1993, Seminars in arthritis and rheumatism.

[23]  Kevin Murphy,et al.  Neural correlates of the LSD experience revealed by multimodal neuroimaging , 2016, Proceedings of the National Academy of Sciences.

[24]  G. Holmes,et al.  Prognostic value of background patterns in the neonatal EEG. , 1993, Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society.

[25]  Jonathan W Peirce,et al.  Functional asymmetry in sheep temporal cortex , 2002, Neuroreport.

[26]  Arnaud Delorme,et al.  EEGLAB: an open source toolbox for analysis of single-trial EEG dynamics including independent component analysis , 2004, Journal of Neuroscience Methods.

[27]  J. Illera,et al.  Heart and respiratory rates and adrenal response to propofol or alfaxalone in rabbits , 2012, Veterinary Record.

[28]  P. Flecknell,et al.  Chapter 17 – Anesthesia and Analgesia in Nonhuman Primates , 2012 .

[29]  M E Raichle,et al.  Hyperventilation and Cerebral Blood Flow , 1972, Stroke.

[30]  M. Palmarini,et al.  Jaagsiekte Sheep Retrovirus Is Necessary and Sufficient To Induce a Contagious Lung Cancer in Sheep , 1999, Journal of Virology.

[31]  S. Ley,et al.  The effect of chronic clinical pain on thermal and mechanical thresholds in sheep , 1989, Pain.

[32]  V. Molony,et al.  Assessment of acute pain in farm animals using behavioral and physiological measurements. , 1997, Journal of animal science.

[33]  W. Russell,et al.  Ethical and Scientific Considerations Regarding Animal Testing and Research , 2011, PloS one.

[34]  G. Tononi,et al.  Breakdown of Cortical Effective Connectivity During Sleep , 2005, Science.

[35]  Robert Oostenveld,et al.  FieldTrip: Open Source Software for Advanced Analysis of MEG, EEG, and Invasive Electrophysiological Data , 2010, Comput. Intell. Neurosci..

[36]  L. Visai,et al.  Pain assessment in animal models: do we need further studies? , 2014, Journal of pain research.

[37]  J. Shneerson,et al.  Sleep Medicine: A Guide to Sleep and its Disorders , 2005 .

[38]  S. Sawiak,et al.  An EEG Investigation of Sleep Homeostasis in Healthy and CLN5 Batten Disease Affected Sheep , 2016, The Journal of Neuroscience.

[39]  T. J. Zuber The mattress sutures: vertical, horizontal, and corner stitch. , 2002, American family physician.