Functional imaging of the brainstem during visually-guided motor control reveals visuomotor regions in the pons and midbrain

Integrating visual information for motor output is an essential process of visually-guided motor control. The brainstem is known to be a major center involved in the integration of sensory information for motor output, however, limitations of functional imaging in humans have impaired our knowledge about the individual roles of sub-nuclei within the brainstem. Thus, the bulk of our knowledge surrounding the function of the brainstem is based on anatomical and behavioral studies in non-human primates, cats, and rodents, despite studies demonstrating differences in the organization of visuomotor processing between mammals. fMRI studies in humans have examined activity related to visually-guided motor tasks, however, few have done so while controlling for both force without visual feedback activity and visual stimuli without force activity. Of the studies that have controlled for both conditions, none have reported brainstem activity. Here, we employed a novel fMRI paradigm focused on the brainstem and cerebellum to systematically investigate the hypothesis that the pons and midbrain are critical for the integration of visual information for motor control. Visuomotor activity during visually-guided pinch-grip force was measured while controlling for force without visual feedback activity and visual stimuli without force activity in healthy adults. Using physiological noise correction and multiple task repetitions, we demonstrated that visuomotor activity occurs in the inferior portion of the basilar pons and the midbrain. These findings provide direct evidence in humans that the pons and midbrain support the integration of visual information for motor control.  We also determined the effect of physiological noise and task repetitions on the visuomotor signal that will be useful in future studies of neurodegenerative diseases affecting the brainstem.

[1]  M. Jüptner,et al.  A review of differences between basal ganglia and cerebellar control of movements as revealed by functional imaging studies. , 1998, Brain : a journal of neurology.

[2]  R. Pearson,et al.  The Human Nervous System. Basic Elements of Structure and Function , 1967, The Yale Journal of Biology and Medicine.

[3]  J. Stein,et al.  Connectivity of the human pedunculopontine nucleus region and diffusion tensor imaging in surgical targeting. , 2007, Journal of neurosurgery.

[4]  S. Kollias,et al.  Duvernoy's Atlas of the Human Brain Stem and Cerebellum , 2009 .

[5]  S. Mori,et al.  Controlled locomotion in the mesencephalic cat: distribution of facilitatory and inhibitory regions within pontine tegmentum. , 1978, Journal of neurophysiology.

[6]  D. Coon The Human Nervous System 2nd ed , 1975 .

[7]  Jörn Diedrichsen,et al.  A probabilistic MR atlas of the human cerebellum , 2009, NeuroImage.

[8]  Hiroshi Imamizu,et al.  Activation of the cerebellum in co-ordinated eye and hand tracking movements: an fMRI study , 2000, Experimental Brain Research.

[9]  M. Hariz,et al.  Stereotactic localization of the human pedunculopontine nucleus: atlas-based coordinates and validation of a magnetic resonance imaging protocol for direct localization. , 2008, Brain : a journal of neurology.

[10]  W Fries,et al.  The distribution of pontine projection cells in visual and association cortex of the cat: An experimental study with horseradish peroxidase , 1981, The Journal of comparative neurology.

[11]  M. L. Shik,et al.  [Control of walking and running by means of electric stimulation of the midbrain]. , 1966, Biofizika.

[12]  P. Winn,et al.  Is the cuneiform nucleus a critical component of the mesencephalic locomotor region? An examination of the effects of excitotoxic lesions of the cuneiform nucleus on spontaneous and nucleus accumbens induced locomotion , 1996, Brain Research Bulletin.

[13]  Mark S. Cohen,et al.  Parametric Analysis of fMRI Data Using Linear Systems Methods , 1997, NeuroImage.

[14]  U Klose,et al.  Detection of a relation between respiration and CSF pulsation with an echoplanar technique , 2000, Journal of magnetic resonance imaging : JMRI.

[15]  F. Beissner,et al.  Functional MRI of the Brainstem: Common Problems and their Solutions , 2015, Clinical Neuroradiology.

[16]  X Hu,et al.  Retrospective estimation and correction of physiological fluctuation in functional MRI , 1995, Magnetic resonance in medicine.

[17]  Mesbah Alam,et al.  The pedunculopontine nucleus area: critical evaluation of interspecies differences relevant for its use as a target for deep brain stimulation. , 2011, Brain : a journal of neurology.

[18]  M. Glickstein,et al.  Corticopontine projection in the macaque: The distribution of labelled cortical cells after large injections of horseradish peroxidase in the pontine nuclei , 1985, The Journal of comparative neurology.

[19]  M. Alexander,et al.  Principles of Neural Science , 1981 .

[20]  Hartwig R. Siebner,et al.  Brain activity is similar during precision and power gripping with light force: An fMRI study , 2008, NeuroImage.

[21]  Aki Vehtari,et al.  Dynamic retrospective filtering of physiological noise in BOLD fMRI: DRIFTER , 2012, NeuroImage.

[22]  Catie Chang,et al.  Influence of heart rate on the BOLD signal: The cardiac response function , 2009, NeuroImage.

[23]  R W Cox,et al.  AFNI: software for analysis and visualization of functional magnetic resonance neuroimages. , 1996, Computers and biomedical research, an international journal.

[24]  Karl J. Friston,et al.  Analysis of fMRI Time-Series Revisited , 1995, NeuroImage.

[25]  G. Paxinos,et al.  THE HUMAN NERVOUS SYSTEM , 1975 .

[26]  S. Luck,et al.  The effects of electrode impedance on data quality and statistical significance in ERP recordings. , 2010, Psychophysiology.

[27]  G. Leichnetz,et al.  Cortical projections to the paramedian tegmental and basilar pons in the monkey , 1984, The Journal of comparative neurology.

[28]  Leslie G. Ungerleider,et al.  Object vision and spatial vision: two cortical pathways , 1983, Trends in Neurosciences.

[29]  M. Goulding,et al.  Locomotion Control: Brainstem Circuits Satisfy the Need for Speed , 2018, Current Biology.

[30]  Stephen D. Mayhew,et al.  fMRI characterisation of widespread brain networks relevant for behavioural variability in fine hand motor control with and without visual feedback , 2017, NeuroImage.

[31]  M. Behbehani,et al.  Nucleus cuneiformis and pain modulation: anatomy and behavioral pharmacology , 1988, Brain Research.

[32]  P. Strick,et al.  Preferential activity of dentate neurons during limb movements guided by vision. , 1993, Journal of neurophysiology.

[33]  Hong Yu,et al.  Role of individual basal ganglia nuclei in force amplitude generation. , 2007, Journal of neurophysiology.

[34]  D. Ryczko,et al.  The multifunctional mesencephalic locomotor region. , 2013, Current pharmaceutical design.

[35]  Stephan P. Swinnen,et al.  Specific cerebellar regions are related to force amplitude and rate of force development , 2012, NeuroImage.

[36]  Ralf Deichmann,et al.  fMRI of the brainstem using dual-echo EPI , 2011, NeuroImage.

[37]  Fernando Calamante,et al.  Contralateral cortico-ponto-cerebellar pathways reconstruction in humans in vivo: implications for reciprocal cerebro-cerebellar structural connectivity in motor and non-motor areas , 2017, Scientific Reports.

[38]  Olivia K. Faull,et al.  Physiological Noise in Brainstem fMRI , 2013, Front. Hum. Neurosci..

[39]  K. Muthusamy,et al.  A Review of the Pedunculopontine Nucleus in Parkinson's Disease , 2018, Front. Aging Neurosci..

[40]  M. Stryker,et al.  Identification of a Brainstem Circuit Regulating Visual Cortical State in Parallel with Locomotion , 2014, Neuron.

[41]  J. Voges,et al.  Deep Brain Stimulation of the Pedunculopontine Tegmental Nucleus (PPN) Influences Visual Contrast Sensitivity in Human Observers , 2016, PloS one.

[42]  Joseph Tomasch The numerical capacity of the human cortico-pontocerebellar system. , 1969, Brain research.

[43]  Mitchell Glickstein How are visual areas of the brain connected to motor areas for the sensory guidance of movement? , 2000, Trends in Neurosciences.

[44]  Armin Blickenstorfer,et al.  Differential representation of dynamic and static power grip force in the sensorimotor network , 2010, The European journal of neuroscience.

[45]  Shik Ml,et al.  Control of walking and running by means of electric stimulation of the midbrain , 1966 .

[46]  O Kiehn,et al.  Midbrain circuits that set locomotor speed and gait selection , 2017, Nature.

[47]  F. Tomasello,et al.  In vivo atlas of deep brain structures : with 3D reconstructions , 2002 .

[48]  R. Depoortère,et al.  Aversion induced by electrical stimulation of the mesencephalic locomotor region in the intact and freely moving rat , 1990, Physiology & Behavior.

[49]  M. Rushworth,et al.  Cortical and subcortical connections within the pedunculopontine nucleus of the primate Macaca mulatta determined using probabilistic diffusion tractography , 2009, Journal of Clinical Neuroscience.

[50]  Stephano J. Chang,et al.  Dissecting Brainstem Locomotor Circuits: Converging Evidence for Cuneiform Nucleus Stimulation , 2020, Frontiers in Systems Neuroscience.

[51]  D. Pandya,et al.  Anatomic Organization of the Basilar Pontine Projections from Prefrontal Cortices in Rhesus Monkey , 1997, The Journal of Neuroscience.

[52]  Jörn Diedrichsen,et al.  A spatially unbiased atlas template of the human cerebellum , 2006, NeuroImage.

[53]  G H Glover,et al.  Image‐based method for retrospective correction of physiological motion effects in fMRI: RETROICOR , 2000, Magnetic resonance in medicine.

[54]  J. de Olmos,et al.  Autoradiographic studies of the projections of the midbrain reticular formation: Ascending projections of nucleus cuneiformis , 1976, The Journal of comparative neurology.

[55]  A. Lang,et al.  Long‐term double‐blinded unilateral pedunculopontine area stimulation in Parkinson's disease , 2016, Movement disorders : official journal of the Movement Disorder Society.

[56]  M. Glickstein,et al.  Visual pontocerebellar projections in the macaque , 1994, The Journal of comparative neurology.

[57]  M. Inase,et al.  Neuronal activity in the primate premotor, supplementary, and precentral motor cortex during visually guided and internally determined sequential movements. , 1991, Journal of neurophysiology.

[58]  J. Ashburner,et al.  Nonlinear spatial normalization using basis functions , 1999, Human brain mapping.

[59]  K. Saitoh,et al.  Basal ganglia efferents to the brainstem centers controlling postural muscle tone and locomotion: a new concept for understanding motor disorders in basal ganglia dysfunction , 2003, Neuroscience.

[60]  P. Brodal The corticopontine projection from the visual cortex in the cat. II. The projection from areas 18 and 19. , 1972, Brain research.

[61]  Francisco J. Valero-Cuevas,et al.  Dissociation of brain areas associated with force production and stabilization during manipulation of unstable objects , 2011, Experimental Brain Research.

[62]  Jing Z. Liu,et al.  Relationship between muscle output and functional MRI-measured brain activation , 2001, Experimental Brain Research.

[63]  D. Vaillancourt,et al.  Neural Basis for the Processes That Underlie Visually-guided and Internally-guided Force Control in Humans , 2003 .

[64]  W. Heide,et al.  The cerebellum in the cerebro-cerebellar network for the control of eye and hand movements--an fMRI study. , 2005, Progress in brain research.

[65]  S. Edwards Autoradiographic studies of the projections of the midbrain reticular formation: Descending projections of nucleus cuneiformis , 1975, The Journal of comparative neurology.

[66]  Stephen D. Mayhew,et al.  Brainstem functional magnetic resonance imaging: Disentangling signal from physiological noise , 2008, Journal of magnetic resonance imaging : JMRI.

[67]  K Ugurbil,et al.  Activation of visuomotor systems during visually guided movements: a functional MRI study. , 1998, Journal of magnetic resonance.

[68]  A. Lozano,et al.  Involvement of the human pedunculopontine nucleus region in voluntary movements , 2010, Neurology.

[69]  P. Dean,et al.  The projection from superior colliculus to cuneiform area in the rat , 2004, Experimental Brain Research.