Do we need to revise the tripartite subdivision hypothesis of the human subthalamic nucleus (STN)?

The exciting development of ultra-high resolution 7Tesla (T) magnetic resonance imaging (MRI) has made it possible to clearly visualize and delineate the subthalamic nucleus (STN). Ultra-high resolution MRI provides a first step in the ongoing improvement of imaging techniques rendering it likely that in the near future specific subareas of small brain nuclei such as the STN can be visualized. These developments can contribute to improve clinical imaging, allowing even more accurate targeting of the STN. This is interesting in view of putative limbic, associative, and sensomotoric subdivisions within the STN. The concept of anatomically distinct subdivisions is attractive, both from an anatomical as well as a clinical perspective. However, we argue that the current leading hypothesis of three STN subdivisions is based on low numbers of clinical observations and primate tracing studies. 7T imaging provides us with markers that could potentially help us to distinguish subdivisions, but our preliminary findings do not indicate the existence of subdivisions. In our opinion additional research is needed. As a consequence the tripartite hypothesis should therefore still be a topic of debate. In view of the possible clinical implications, we would like to raise the question whether anatomical evidence on the topological organization within the STN points towards delineated subdivisions, or an organization without strict anatomical boundaries or septa. The latter would require a revision of the current tripartite hypothesis of the human STN.

[1]  Ferdinand Schweser,et al.  Quantitative imaging of intrinsic magnetic tissue properties using MRI signal phase: An approach to in vivo brain iron metabolism? , 2011, NeuroImage.

[2]  Robert Turner,et al.  Toward in vivo histology: A comparison of quantitative susceptibility mapping (QSM) with magnitude-, phase-, and R2 ⁎-imaging at ultra-high magnetic field strength , 2013, NeuroImage.

[3]  Hagai Bergman,et al.  Subthalamic span of beta oscillations predicts deep brain stimulation efficacy for patients with Parkinson's disease. , 2010, Brain : a journal of neurology.

[4]  André Parent,et al.  GABAergic interneurons in human subthalamic nucleus , 2005, Movement disorders : official journal of the Movement Disorder Society.

[5]  L. Hazrati,et al.  Functional anatomy of the basal ganglia , 1995 .

[6]  Erwan Bezard,et al.  Enhanced Preproenkephalin-B–Derived Opioid Transmission in Striatum and Subthalamic Nucleus Converges Upon Globus Pallidus Internalis in L-3,4-dihydroxyphenylalanine–Induced Dyskinesia , 2007, Biological Psychiatry.

[7]  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.

[8]  M. Okun,et al.  Management of referred deep brain stimulation failures: a retrospective analysis from 2 movement disorders centers. , 2005, Archives of neurology.

[9]  A. Charara,et al.  Pre- and postsynaptic localization of GABAB receptors in the basal ganglia in monkeys , 1999, Neuroscience.

[10]  Y. Agid,et al.  Stimulation of subterritories of the subthalamic nucleus reveals its role in the integration of the emotional and motor aspects of behavior , 2007, Proceedings of the National Academy of Sciences.

[11]  A. Parent,et al.  Serotonin innervation of basal ganglia in monkeys and humans , 2011, Journal of Chemical Neuroanatomy.

[12]  J. Rafols,et al.  The neurons in the primate subthalamic nucleus: A Golgi and electron microscopic study , 1976, The Journal of comparative neurology.

[13]  A. Parent,et al.  Functional anatomy of the basal ganglia. I. The cortico-basal ganglia-thalamo-cortical loop , 1995, Brain Research Reviews.

[14]  A. Parent,et al.  Calcium-binding proteins in primate basal ganglia , 1996, Neuroscience Research.

[15]  A. Lozano,et al.  Acute complications of movement disorders surgery: Effects of age and comorbidities , 2013, Movement disorders : official journal of the Movement Disorder Society.

[16]  J. Penney,et al.  Localization of dopaminergic markers in the human subthalamic nucleus , 2000, The Journal of comparative neurology.

[17]  A. Benazzouz,et al.  High-Frequency Stimulation of the Subthalamic Nucleus and l-3,4-Dihydroxyphenylalanine Inhibit In Vivo Serotonin Release in the Prefrontal Cortex and Hippocampus in a Rat Model of Parkinson's Disease , 2010, The Journal of Neuroscience.

[18]  Scott D. Brown,et al.  Cortico-striatal connections predict control over speed and accuracy in perceptual decision making , 2010, Proceedings of the National Academy of Sciences.

[19]  Ferdinand Schweser,et al.  Quantitative susceptibility mapping (QSM) as a means to measure brain iron? A post mortem validation study , 2012, NeuroImage.

[20]  S Afsharpour,et al.  Topographical projections of the cerebral cortex to the subthalamic nucleus , 1985, The Journal of comparative neurology.

[21]  T. Dawson,et al.  Animal models of Parkinson's disease: vertebrate genetics. , 2012, Cold Spring Harbor perspectives in medicine.

[22]  Y. Sano,et al.  Immunohistochemical demonstration of serotonin nerve fibers in the subthalamic nucleus of the rat, cat and monkey , 1985, Neuroscience Letters.

[23]  D. Joel,et al.  The connections of the primate subthalamic nucleus: indirect pathways and the open-interconnected scheme of basal ganglia-thalamocortical circuitry , 1997, Brain Research Reviews.

[24]  G. E. Alexander,et al.  Functional architecture of basal ganglia circuits: neural substrates of parallel processing , 1990, Trends in Neurosciences.

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

[26]  A. Lozano,et al.  Direct visualization of deep brain stimulation targets in Parkinson disease with the use of 7-tesla magnetic resonance imaging. , 2010, Journal of neurosurgery.

[27]  A. Parent Extrinsic connections of the basal ganglia , 1990, Trends in Neurosciences.

[28]  K. Kultas‐Ilinsky,et al.  Expression of 10 GABA(A) receptor subunit messenger RNAs in the motor-related thalamic nuclei and basal ganglia of Macaca mulatta studied with in situ hybridization histochemistry. , 1998, Neuroscience.

[29]  John S. Thornton,et al.  High resolution MR anatomy of the subthalamic nucleus: Imaging at 9.4T with histological validation , 2012, NeuroImage.

[30]  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.

[31]  B. Forstmann,et al.  Ultra-High 7T MRI of Structural Age-Related Changes of the Subthalamic Nucleus , 2012, The Journal of Neuroscience.

[32]  S. Afsharpour,et al.  Light microscopic analysis of golgi‐impregnated rat subthalamic neurons , 1985, The Journal of comparative neurology.

[33]  A. Aron,et al.  Stimulation at dorsal and ventral electrode contacts targeted at the subthalamic nucleus has different effects on motor and emotion functions in Parkinson's disease , 2011, Neuropsychologia.

[34]  Murtaza Z Mogri,et al.  Optical Deconstruction of Parkinsonian Neural Circuitry , 2009, Science.

[35]  Y. Ben-Shlomo,et al.  Stimulation of the caudal zona incerta is superior to stimulation of the subthalamic nucleus in improving contralateral parkinsonism. , 2006, Brain : a journal of neurology.

[36]  F. Mundinger Stereotaxic interventions on the zona incerta area for treatment of extrapyramidal motor disturbances and their results. , 1965, Confinia neurologica.

[37]  A. Parent,et al.  Efferent projections of the subthalamic nucleus in the squirrel monkey as studied by the PHA‐L anterograde tracing method , 1990, The Journal of comparative neurology.

[38]  B. Forstmann,et al.  A gradual increase of iron toward the medial‐inferior tip of the subthalamic nucleus , 2014, Human brain mapping.

[39]  Y. Hurd,et al.  D1 and D2 dopamine receptor mRNA expression in whole hemisphere sections of the human brain , 2001, Journal of Chemical Neuroanatomy.

[40]  J. Hedreen Tyrosine hydroxylase‐immunoreactive elements in the human globus pallidus and subthalamic nucleus , 1999, The Journal of comparative neurology.

[41]  S. Augood,et al.  Localization of calcium-binding proteins and GABA transporter (GAT-1) messenger RNA in the human subthalamic nucleus , 1999, Neuroscience.

[42]  B. Forstmann,et al.  Are there three subdivisions in the primate subthalamic nucleus? , 2012, Front. Neuroanat..

[43]  P. Whiting,et al.  Expression of 10 GABAA receptor subunit messenger RNAs in the motor-related thalamic nuclei and basal ganglia of Macaca mulatta studied with in situ hybridization histochemistry , 1998, Neuroscience.

[44]  Pierre-Louis Bazin,et al.  Cortico-subthalamic white matter tract strength predicts interindividual efficacy in stopping a motor response , 2012, NeuroImage.

[45]  Y. Smith,et al.  Subcellular and subsynaptic localization of group I metabotropic glutamate receptors in the monkey subthalamic nucleus , 2004, The Journal of comparative neurology.

[46]  H. Steinbusch,et al.  Inhibition of 5-HT neuron activity and induction of depressive-like behavior by high-frequency stimulation of the subthalamic nucleus , 2007, Proceedings of the National Academy of Sciences.