Event-related functional MRI of awake behaving pigeons at 7T

Animal-fMRI is a powerful method to understand neural mechanisms of cognition, but it remains a major challenge to scan actively participating small animals under low-stress conditions. Here, we present an event-related functional MRI platform in awake pigeons using single-shot RARE fMRI to investigate the neural fundaments for visually-guided decision making. We established a head-fixated Go/NoGo paradigm, which the animals quickly learned under low-stress conditions. The animals were motivated by water reward and behavior was assessed by logging mandibulations during the fMRI experiment with close to zero motion artifacts over hundreds of repeats. To achieve optimal results, we characterized the species-specific hemodynamic response function. As a proof-of-principle, we run a color discrimination task and discovered differential neural networks for Go-, NoGo-, and response execution-phases. Our findings open the door to visualize the neural fundaments of perceptual and cognitive functions in birds—a vertebrate class of which some clades are cognitively on par with primates.

[1]  Michael Brady,et al.  Improved Optimization for the Robust and Accurate Linear Registration and Motion Correction of Brain Images , 2002, NeuroImage.

[2]  Mark W. Woolrich,et al.  Advances in functional and structural MR image analysis and implementation as FSL , 2004, NeuroImage.

[3]  O. Güntürkün,et al.  A comparative analysis of the dopaminergic innervation of the executive caudal nidopallium in pigeon, chicken, zebra finch, and carrion crow , 2020, The Journal of comparative neurology.

[4]  J. Fuster,et al.  Visuo-tactile cross-modal associations in cortical somatosensory cells. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[5]  Stephen M. Smith,et al.  Improved Optimization for the Robust and Accurate Linear Registration and Motion Correction of Brain Images , 2002, NeuroImage.

[6]  N. Logothetis,et al.  Functional imaging of the monkey brain , 1999, Nature Neuroscience.

[7]  R. Turner,et al.  Event-Related fMRI: Characterizing Differential Responses , 1998, NeuroImage.

[8]  N. Logothetis,et al.  Neurophysiological investigation of the basis of the fMRI signal , 2001, Nature.

[9]  A. Shackman,et al.  Contributions of the Central Extended Amygdala to Fear and Anxiety , 2016, The Journal of Neuroscience.

[10]  J. Wild,et al.  Afferent and efferent projections of the mesopallium in the pigeon (Columba livia) , 2012, The Journal of comparative neurology.

[11]  O. Güntürkün,et al.  Functional MRI and functional connectivity of the visual system of awake pigeons , 2013, Behavioural Brain Research.

[12]  E. Dumont Bone density and the lightweight skeletons of birds , 2010, Proceedings of the Royal Society B: Biological Sciences.

[13]  J. Cockrem,et al.  Variation within and between birds in corticosterone responses of great tits (Parus major). , 2002, General and comparative endocrinology.

[14]  Wenjing Chen,et al.  Awake and behaving mouse fMRI during Go/No-Go task , 2019, NeuroImage.

[15]  Lars Schwabe,et al.  Stress and multiple memory systems: from ‘thinking’ to ‘doing’ , 2013, Trends in Cognitive Sciences.

[16]  Onur Güntürkün,et al.  In vivo measurement of T1 and T2 relaxation times in awake pigeon and rat brains at 7T , 2018, Magnetic resonance in medicine.

[17]  J. Balthazart,et al.  Seasonal changes in some plasma hormones in pigeons: diurnal variation under natural photoperiods with constant or seasonally changing ambient temperature. , 1986, Comparative biochemistry and physiology. A, Comparative physiology.

[18]  L. Medina,et al.  Subdivisions and derivatives of the chicken subpallium based on expression of LIM and other regulatory genes and markers of neuron subpopulations during development , 2009, The Journal of comparative neurology.

[19]  O. Güntürkün,et al.  Asymmetrical Commissural Control of the Subdominant Hemisphere in Pigeons. , 2018, Cell reports.

[20]  O. Güntürkün,et al.  Functional Connectivity Pattern of the Internal Hippocampal Network in Awake Pigeons: A Resting-State fMRI Study , 2017, Brain, Behavior and Evolution.

[21]  Kevin Whittingstall,et al.  Functional magnetic resonance imaging of awake behaving macaques. , 2010, Methods.

[22]  J. Wild,et al.  Efferent and afferent connections of the olfactory bulb and prepiriform cortex in the pigeon (Columba livia) , 2014, The Journal of comparative neurology.

[23]  A. Wyrwicz,et al.  Effects of Anesthesia on BOLD Signal and Neuronal Activity in the Somatosensory Cortex , 2015, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[24]  Jonathan Winawer,et al.  GLMdenoise: a fast, automated technique for denoising task-based fMRI data , 2013, Front. Neurosci..

[25]  S. Panzeri,et al.  Infraslow State Fluctuations Govern Spontaneous fMRI Network Dynamics , 2019, Current Biology.

[26]  M. Verhoye,et al.  Light stimulus frequency dependence of activity in the rat visual system as studied with high-resolution BOLD fMRI. , 2006, Journal of neurophysiology.

[27]  Yi Zhang,et al.  High-resolution fMRI mapping of ocular dominance layers in cat lateral geniculate nucleus , 2010, NeuroImage.

[28]  Karsten Mueller,et al.  Commentary: Cluster failure: Why fMRI inferences for spatial extent have inflated false-positive rates , 2017, Front. Hum. Neurosci..

[29]  Hanna Damasio,et al.  Predicting visual stimuli on the basis of activity in auditory cortices , 2010, Nature Neuroscience.

[30]  L. Hess Corticosteroid synthesis and metabolism in birds , 2002 .

[31]  H. Karten,et al.  A stereotaxic atlas of the brain of the pigeon (Columba livia) , 1967 .

[32]  M. Verhoye,et al.  Auditory evoked BOLD responses in awake compared to lightly anaesthetized zebra finches , 2017, Scientific Reports.

[33]  Olli Gröhn,et al.  Awake Rat Brain Functional Magnetic Resonance Imaging Using Standard Radio Frequency Coils and a 3D Printed Restraint Kit , 2018, Front. Neurosci..

[34]  O. Güntürkün,et al.  Functional subdivisions of the ascending visual pathways in the pigeon , 1999, Behavioural Brain Research.

[35]  Toru Shimizu,et al.  Calcium‐binding protein distributions and fiber connections of the nucleus accumbens in the pigeon (columba livia) , 2011, The Journal of comparative neurology.

[36]  M. Verhoye,et al.  Implementation of spin‐echo blood oxygen level‐dependent (BOLD) functional MRI in birds , 2010, NMR in biomedicine.

[37]  Jan Sijbers,et al.  Spatiotemporal properties of the BOLD response in the songbirds' auditory circuit during a variety of listening tasks , 2005, NeuroImage.

[38]  Michael Czisch,et al.  The brain’s hemodynamic response function rapidly changes under acute psychosocial stress in association with genetic and endocrine stress response markers , 2018, Proceedings of the National Academy of Sciences.

[39]  D. Norris,et al.  An Experimental Test of the Capture-Restraint Protocol for Estimating the Acute Stress Response , 2013, Physiological and Biochemical Zoology.

[40]  O. Güntürkün,et al.  Afferent and efferent connections of the caudolateral neostriatum in the pigeon (Columba livia): A retro‐ and anterograde pathway tracing study , 1999, The Journal of comparative neurology.

[41]  J. Wild,et al.  The avian somatosensory system: connections of regions of body representation in the forebrain of the pigeon , 1987, Brain Research.

[42]  W Hodos,et al.  Neural connections of the “visual wulst” of the avian telencephalon. Experimental studies in the pigeon (Columba livia) and owl (Speotyto cunicularia) , 1973, The Journal of comparative neurology.

[43]  J. Wild,et al.  Telencephalic connections of the trigeminal system in the pigeon (Columba livia): A trigeminal sensorimotor circuit , 1985, The Journal of comparative neurology.

[44]  J. Currey The many adaptations of bone. , 2003, Journal of biomechanics.

[45]  W. E. van den Brom,et al.  Action of ACTH1-24 upon plasma corticosterone concentrations in racing pigeons (Columba livia domestica). , 1987, Avian pathology : journal of the W.V.P.A.

[46]  O. Güntürkün,et al.  Retinal afferents to the tectum opticum and the nucleus opticus principalis thalami in the pigeon , 1991, The Journal of comparative neurology.

[47]  R. Bogacz,et al.  Action Initiation Shapes Mesolimbic Dopamine Encoding of Future Rewards , 2015, Nature Neuroscience.

[48]  Karl Zilles,et al.  The receptor architecture of the pigeons’ nidopallium caudolaterale: an avian analogue to the mammalian prefrontal cortex , 2011, Brain Structure and Function.

[49]  O. Güntürkün,et al.  Plasticity in D1-Like Receptor Expression Is Associated with Different Components of Cognitive Processes , 2012, PloS one.

[50]  O. Güntürkün,et al.  Dopaminergic innervation of the telencephalon of the pigeon (Columba livia): A study with antibodies against tyrosine hydroxylase and dopamine , 1995, The Journal of comparative neurology.

[51]  J. Reed,et al.  Repeatability of baseline corticosterone concentrations. , 2008, General and comparative endocrinology.

[52]  O. Güntürkün,et al.  Electrophysiological and morphological properties of cell types in the chick neostriatum caudolaterale , 2002, Neuroscience.

[53]  T. Bugnyar,et al.  Cognition without Cortex , 2016, Trends in Cognitive Sciences.

[54]  B. Gineste,et al.  Breeding status affects the hormonal and metabolic response to acute stress in a long-lived seabird, the king penguin. , 2016, General and comparative endocrinology.

[55]  David A. Leopold,et al.  fMRI in the awake marmoset: Somatosensory-evoked responses, functional connectivity, and comparison with propofol anesthesia , 2013, NeuroImage.

[56]  O. Güntürkün,et al.  The Neural Basis of Long-Distance Navigation in Birds. , 2016, Annual review of physiology.

[57]  J. Vandeweerd,et al.  Cardiorespiratory parameters in the awake pigeon and during anaesthesia with isoflurane. , 2016, Veterinary anaesthesia and analgesia.

[58]  O. Güntürkün,et al.  Functional MRI in the Nile crocodile: a new avenue for evolutionary neurobiology , 2018, Proceedings of the Royal Society B: Biological Sciences.

[59]  Á. Miklósi,et al.  Voice-Sensitive Regions in the Dog and Human Brain Are Revealed by Comparative fMRI , 2014, Current Biology.

[60]  R. Malinow,et al.  Stress transforms lateral habenula reward responses into punishment signals , 2019, Proceedings of the National Academy of Sciences.

[61]  O. Hikosaka The habenula: from stress evasion to value-based decision-making , 2010, Nature Reviews Neuroscience.

[62]  Maik C. Stüttgen,et al.  Stimulus-Response-Outcome Coding in the Pigeon Nidopallium Caudolaterale , 2013, PloS one.

[63]  S. Bottjer,et al.  Response properties of single neurons in higher level auditory cortex of adult songbirds. , 2019, Journal of neurophysiology.

[64]  M. Colombo,et al.  Apes, feathered apes, and pigeons: differences and similarities , 2017, Current Opinion in Behavioral Sciences.

[65]  O. Güntürkün,et al.  Functional organization of telencephalic visual association fields in pigeons , 2016, Behavioural Brain Research.

[66]  Amir Shmuel,et al.  Robust controlled functional MRI in alert monkeys at high magnetic field: Effects of jaw and body movements , 2007, NeuroImage.

[67]  O. Güntürkün,et al.  Telencephalic organization of the olfactory system in homing pigeons (Columba livia) , 2011, Neuroscience.

[68]  Hans Knutsson,et al.  Cluster failure: Why fMRI inferences for spatial extent have inflated false-positive rates , 2016, Proceedings of the National Academy of Sciences.

[69]  Alessandro Gozzi,et al.  Functional connectivity hubs of the mouse brain , 2015, NeuroImage.

[70]  O. Güntürkün,et al.  A 3-dimensional digital atlas of the ascending sensory and the descending motor systems in the pigeon brain , 2012, Brain Structure and Function.

[71]  Adrian T. Lee,et al.  fMRI of human visual cortex , 1994, Nature.

[72]  Nan-kuei Chen,et al.  fMRI of the Conscious Rabbit during Unilateral Classical Eyeblink Conditioning Reveals Bilateral Cerebellar Activation , 2003, The Journal of Neuroscience.

[73]  Alice M Stamatakis,et al.  Activation of lateral habenula inputs to the ventral midbrain promotes behavioral avoidance , 2012, Nature Neuroscience.