Ultra-High Field MRI Post Mortem Structural Connectivity of the Human Subthalamic Nucleus, Substantia Nigra, and Globus Pallidus

Introduction: The subthalamic nucleus, substantia nigra, and globus pallidus, three nuclei of the human basal ganglia, play an important role in motor, associative, and limbic processing. The network of the basal ganglia is generally characterized by a direct, indirect, and hyperdirect pathway. This study aims to investigate the mesoscopic nature of these connections between the subthalamic nucleus, substantia nigra, and globus pallidus and their surrounding structures. Methods: A human post mortem brain specimen including the substantia nigra, subthalamic nucleus, and globus pallidus was scanned on a 7 T MRI scanner. High resolution diffusion weighted images were used to reconstruct the fibers intersecting the substantia nigra, subthalamic nucleus, and globus pallidus. The course and density of these tracks was analyzed. Results: Most of the commonly established projections of the subthalamic nucleus, substantia nigra, and globus pallidus were successfully reconstructed. However, some of the reconstructed fiber tracks such as the connections of the substantia nigra pars compacta to the other included nuclei and the connections with the anterior commissure have not been shown previously. In addition, the quantitative tractography approach showed a typical degree of connectivity previously not documented. An example is the relatively larger projections of the subthalamic nucleus to the substantia nigra pars reticulata when compared to the projections to the globus pallidus internus. Discussion: This study shows that ultra-high field post mortem tractography allows for detailed 3D reconstruction of the projections of deep brain structures in humans. Although the results should be interpreted carefully, the newly identified connections contribute to our understanding of the basal ganglia.

[1]  A. Nambu,et al.  Functional significance of the cortico–subthalamo–pallidal ‘hyperdirect’ pathway , 2002, Neuroscience Research.

[2]  M B Carpenter,et al.  Nigrostriatal and nigrothalamic fibers in the rhesus monkey , 1972, The Journal of comparative neurology.

[3]  Alan Connelly,et al.  MRtrix: Diffusion tractography in crossing fiber regions , 2012, Int. J. Imaging Syst. Technol..

[4]  S. Haber,et al.  The Organization of Prefrontal-Subthalamic Inputs in Primates Provides an Anatomical Substrate for Both Functional Specificity and Integration: Implications for Basal Ganglia Models and Deep Brain Stimulation , 2013, The Journal of Neuroscience.

[5]  H. Kita,et al.  Excitatory cortical inputs to pallidal neurons via the subthalamic nucleus , 1998, Neuroscience Research.

[6]  Thomas Wichmann,et al.  Circuits and circuit disorders of the basal ganglia. , 2007, Archives of neurology.

[7]  Tipu Z. Aziz,et al.  Topography of cortical and subcortical connections of the human pedunculopontine and subthalamic nuclei , 2007, NeuroImage.

[8]  Geoffrey J. M. Parker,et al.  Probabilistic fibre tracking: Differentiation of connections from chance events , 2008, NeuroImage.

[9]  Alexander Hammers,et al.  Volumes, spatial extents and a probabilistic atlas of the human basal ganglia and thalamus , 2007, NeuroImage.

[10]  A. Roebroeck,et al.  Ultra-high field magnetic resonance imaging of the basal ganglia and related structures , 2014, Front. Hum. Neurosci..

[11]  Cyril Poupon,et al.  7 tesla magnetic resonance imaging: A closer look at substantia nigra anatomy in Parkinson's disease , 2014, Movement disorders : official journal of the Movement Disorder Society.

[12]  Kailash P Bhatia,et al.  The expanding universe of disorders of the basal ganglia , 2014, The Lancet.

[13]  A. Nambu Somatotopic Organization of the Primate Basal Ganglia , 2011, Front. Neuroanat..

[14]  A. Nambu,et al.  The distribution of the globus pallidus neurons with input from various cortical areas in the monkeys , 1993, Brain Research.

[15]  G. Sapiro,et al.  Comprehensive in vivo Mapping of the Human Basal Ganglia and Thalamic Connectome in Individuals Using 7T MRI , 2012, PloS one.

[16]  M. Jahanshahi,et al.  Bilateral globus pallidus stimulation for severe Tourette's syndrome: a double-blind, randomised crossover trial , 2015, The Lancet Neurology.

[17]  E. Hirsch,et al.  Dopaminergic innervation of the subthalamic nucleus in the normal state, in MPTP‐treated monkeys, and in Parkinson's disease patients , 2000, The Journal of comparative neurology.

[18]  K. Scheffler,et al.  Three-dimensional strain fields in human brain resulting from formalin fixation , 2011, Journal of Neuroscience Methods.

[19]  Jiangyang Zhang,et al.  Feasibility of creating a high-resolution 3D diffusion tensor imaging based atlas of the human brainstem: A case study at 11.7T , 2013, NeuroImage.

[20]  P. Strick,et al.  Basal ganglia and cerebellar loops: motor and cognitive circuits , 2000, Brain Research Reviews.

[21]  H. Steinbusch,et al.  The functional role of the subthalamic nucleus in cognitive and limbic circuits , 2005, Progress in Neurobiology.

[22]  Shailendra Kapoor,et al.  Subthalamic nucleus stimulation in severe obsessive-compulsive disorder. , 2009, The New England journal of medicine.

[23]  A. Parent,et al.  Axonal branching pattern of neurons of the subthalamic nucleus in primates , 2000, The Journal of comparative neurology.

[24]  M. Jenkinson Non-linear registration aka Spatial normalisation , 2007 .

[25]  Guido Gerig,et al.  User-guided 3D active contour segmentation of anatomical structures: Significantly improved efficiency and reliability , 2006, NeuroImage.

[26]  G. E. Alexander,et al.  Parallel organization of functionally segregated circuits linking basal ganglia and cortex. , 1986, Annual review of neuroscience.

[27]  L. Tremblay,et al.  Motor control in basal ganglia circuits using fMRI and brain atlas approaches. , 2006, Cerebral cortex.

[28]  G. Deuschl,et al.  Neurostimulation for Parkinson's disease with early motor complications. , 2013, The New England journal of medicine.

[29]  W. Nauta,et al.  Projections of the lentiform nucleus in the monkey. , 1966, Brain research.

[30]  B. Biswal,et al.  Functional connectivity of human striatum: a resting state FMRI study. , 2008, Cerebral cortex.

[31]  H. Kita,et al.  Excitatory Cortical Inputs to Pallidal Neurons Via the Subthalamic Nucleus in the Monkey , 2000 .

[32]  Paul M. Matthews,et al.  Connectivity-based segmentation of the substantia nigra in human and its implications in Parkinson's disease , 2010, NeuroImage.

[33]  H. Kita,et al.  Balance of Monosynaptic Excitatory and Disynaptic Inhibitory Responses of the Globus Pallidus Induced after Stimulation of the Subthalamic Nucleus in the Monkey , 2005, The Journal of Neuroscience.

[34]  P. Strick,et al.  Multiple output channels in the basal ganglia. , 1993, Science.

[35]  H. Bergman,et al.  The primate subthalamic nucleus. I. Functional properties in intact animals. , 1994, Journal of neurophysiology.

[36]  A. Parent,et al.  Anatomical aspects of information processing in primate basal ganglia , 1993, Trends in Neurosciences.

[37]  C. Gerfen The neostriatal mosaic. I. compartmental organization of projections from the striatum to the substantia nigra in the rat , 1985, The Journal of comparative neurology.

[38]  Richard S. Frackowiak,et al.  Confirmation of functional zones within the human subthalamic nucleus: Patterns of connectivity and sub-parcellation using diffusion weighted imaging , 2012, NeuroImage.

[39]  M. Dettling,et al.  Subthalamic nucleus stimulation in severe obsessive-compulsive disorder. , 2009, The New England journal of medicine.

[40]  Martin Lévesque,et al.  Extrastriatal dopaminergic innervation of human basal ganglia , 1999, Neuroscience Research.

[41]  R. Quester,et al.  The shrinkage of the human brain stem during formalin fixation and embedding in paraffin , 1997, Journal of Neuroscience Methods.

[42]  Patrick T. Hickey,et al.  Postmortem diffusion MRI of the human brainstem and thalamus for deep brain stimulator electrode localization , 2015, Human brain mapping.

[43]  B. M. ter Haar Romeny,et al.  Structural and Resting State Functional Connectivity of the Subthalamic Nucleus: Identification of Motor STN Parts and the Hyperdirect Pathway , 2012, PloS one.

[44]  A. Hopf,et al.  Substance P in the human brain , 1986, Neuroscience.

[45]  Mark W. Woolrich,et al.  FSL , 2012, NeuroImage.