Information

Related Research Units

Fetal Neonatal Neuroimaging and Developmental Science Center Research
Newborn Medicine Research

Research Overview

Web Site:  Fetal-Neonatal Neuroimaging and Developmental Science Center

Dr. Okada is currently engaged in several areas of research: 

Human brain development - Dr. Okada is the Director of the Magnetoencephalography (MEG) Program at Children's Hospital Boston. This program is part of the Fetal-Neonatal Neuroimaging and Developmental Science (FNNDSC) of the Newborn Medicine Research Center and the Division of Epilepsy of Department of Neurology at Children’s. It is dedicated to furthering our understanding of mechanisms of human brain development,  electrophysiological bases of information processing in the human brain and physiological bases of functional abnormality in children with various neurological and psychiatric disorders. Dr. Okada hopes that this MEG program will provide unique opportunities for scientists at Harvard University to discover the fundamental issues concerning human brain functions and development in health and disease.

Neural current MRI – Dr. Okada and his colleague, Dr. Padma Sundaram, Instructor of Radiology at Children’s recently succeeded in showing that Magnetic Resonance Imaging (MRI) can be used to directly measure neuronal currents from the brain of animals, specifically in an intact brain structure called cerebellum in turtle. Dr. Okada believes that this ncMRI can be developed to image neuronal activity directly with MRI in humans.

Electrophysiology of cortical neuronal networks and brain plasticity – Dr. Okada has designed a novel neuroimaging instrument to stimulate one or more focal regions of the cerebral cortex with magnetic pulses and measure functional coupling within various neural networks of interest.  He believes that this new instrument can be used to provide novel understanding of functional roles of various neuronal networks in human brain. He also believes the new technology can be used to help with rehabilitation of children and adults who suffer from various types of brain injury by accelerating reorganization of the brain to optimize the functions of surviving neurons.

Research Background

Dr. Okada received his PhD from the Rockefeller University in New York City in the field of psychology and neuroscience. He is the pioneer in the study of the physiological basis of magnetoencephalography (MEG) and electroencephalography (EEG). He has established through his research carried out over a period of 25 years that these two noninvasive techniques provide direct measurements of the electrophysiological activity of synchronously active neurons.

Dr. Okada has made contributions to the development of novel biomagnetic instruments that have opened new ways to study the electrophysiology of the brain and is an inventor of new instruments that are in the process of development. These instruments include a pediatric MEG system called “babySQUID”, the first of its kind optimized for studying the electrophysiological development of human brain, a second-generation pediatric MEG system called “babyMEG”, which is based on the babySQUID, but provides a whole-head coverage with sensitivities and spatial resolution that are higher than any existing MEG instruments, an inverted SQUID (superconducting quantum interference device ) microscope capable of simultaneously measuring biomagnetic fields, electrical potentials and optical images from biological preparations and a whole-head cryogenically cooled Transcranial Magnetic Stimulation (TMS) system that will provide unique novel methods for studying functional networks of the human brain.

Dr. Okada is a founder of a center called “Biomedical Research and Integrative Neuroimaging Center” or BRaIN Imaging Center at the University of New Mexico prior to joining Harvard Medical School. This BRaIN Imaging Center is a state-of-the-art multimodal neuroimaging facility with many types of neuroimaging methods created to provide a research environment for neuroscientists at the University for carrying out competitive research and to provide a training and education environment for developing the careers of the junior faculty members of the University.

Publications

  1. How conductivity boundaries influence the electric field induced by transcranial magnetic stimulation in in vitro experiments. Brain Stimul. 2024 Sep-Oct; 17(5):1034-1044. View Abstract
  2. Delays in latencies of median-nerve evoked magnetic fields in patients with succinic semialdehyde dehydrogenase deficiency. Clin Neurophysiol. 2024 May; 161:52-58. View Abstract
  3. Ultrasound-Induced Membrane Hyperpolarization in Motor Axons and Muscle Fibers of the Crayfish Neuromuscular Junction. Ultrasound Med Biol. 2023 12; 49(12):2527-2536. View Abstract
  4. Effects of Osmolarity on Ultrasound-Induced Membrane Depolarization in Isolated Crayfish Motor Axon. Ultrasound Med Biol. 2022 Oct; 48(10):2040-2051. View Abstract
  5. Alkaline brain pH shift in rodent lithium-pilocarpine model of epilepsy with chronic seizures. Brain Res. 2021 05 01; 1758:147345. View Abstract
  6. Influence of unfused cranial bones on magnetoencephalography signals in human infants. Clin Neurophysiol. 2021 03; 132(3):708-719. View Abstract
  7. Boundary Element Fast Multipole Method for Enhanced Modeling of Neurophysiological Recordings. IEEE Trans Biomed Eng. 2021 01; 68(1):308-318. View Abstract
  8. A 3-axis coil design for multichannel TMS arrays. Neuroimage. 2021 01 01; 224:117355. View Abstract
  9. Direct Activation of Cortical Neurons in the Primary Somatosensory Cortex of the Rat in Vivo Using Focused Ultrasound. Ultrasound Med Biol. 2020 09; 46(9):2349-2360. View Abstract
  10. Epileptic Activity Intrinsically Generated in the Human Cerebellum. Ann Neurol. 2020 08; 88(2):418-422. View Abstract
  11. Vibrotactile piezoelectric stimulation system with precise and versatile timing control for somatosensory research. J Neurosci Methods. 2019 04 01; 317:29-36. View Abstract
  12. Focused ultrasound transiently increases membrane conductance in isolated crayfish axon. J Neurophysiol. 2019 02 01; 121(2):480-489. View Abstract
  13. Noise cancellation for a whole-head magnetometer-based MEG system in hospital environment. Biomed Phys Eng Express. 2018 Sep; 4(5). View Abstract
  14. MNE Scan: Software for real-time processing of electrophysiological data. J Neurosci Methods. 2018 06 01; 303:55-67. View Abstract
  15. Reply to "Prospective advances in fetal biomagnetometry - Challenges remain". Clin Neurophysiol. 2018 02; 129(2):505-506. View Abstract
  16. Development of Auditory Evoked Responses in Normally Developing Preschool Children and Children with Autism Spectrum Disorder. Dev Neurosci. 2017; 39(5):430-441. View Abstract
  17. The role of plasmin in the pathogenesis of murine multiple myeloma. Biochem Biophys Res Commun. 2017 06 24; 488(2):387-392. View Abstract
  18. Versatile synchronized real-time MEG hardware controller for large-scale fast data acquisition. Rev Sci Instrum. 2017 May; 88(5):055110. View Abstract
  19. BabyMEG: A whole-head pediatric magnetoencephalography system for human brain development research. Rev Sci Instrum. 2016 Sep; 87(9):094301. View Abstract
  20. Direct neural current imaging in an intact cerebellum with magnetic resonance imaging. Neuroimage. 2016 05 15; 132:477-490. View Abstract
  21. Editorial on emerging neuroimaging tools for studying normal and abnormal human brain development. Front Hum Neurosci. 2015; 9:127. View Abstract
  22. Invariance in current dipole moment density across brain structures and species: physiological constraint for neuroimaging. Neuroimage. 2015 May 01; 111:49-58. View Abstract
  23. Inhibition of plasmin protects against colitis in mice by suppressing matrix metalloproteinase 9-mediated cytokine release from myeloid cells. Gastroenterology. 2015 Mar; 148(3):565-578.e4. View Abstract
  24. Cortical somatosensory reorganization in children with spastic cerebral palsy: a multimodal neuroimaging study. Front Hum Neurosci. 2014; 8:725. View Abstract
  25. Localization of the epileptogenic foci in tuberous sclerosis complex: a pediatric case report. Front Hum Neurosci. 2014; 8:175. View Abstract
  26. Effective connectivity maps in the swine somatosensory cortex estimated from electrocorticography and validated with intracortical local field potential measurements. Brain Connect. 2014 Mar; 4(2):100-11. View Abstract
  27. Targeting of white matter tracts with transcranial magnetic stimulation. Brain Stimul. 2014 Jan-Feb; 7(1):80-4. View Abstract
  28. Comparison of spherical and realistically shaped boundary element head models for transcranial magnetic stimulation navigation. Clin Neurophysiol. 2013 Oct; 124(10):1995-2007. View Abstract
  29. Effects of sutures and fontanels on MEG and EEG source analysis in a realistic infant head model. Neuroimage. 2013 Aug 01; 76:282-93. View Abstract
  30. Evoked magnetic fields from primary and secondary somatosensory cortices: a reliable tool for assessment of cortical processing in the neonatal period. Clin Neurophysiol. 2012 Dec; 123(12):2377-83. View Abstract
  31. Maturation of somatosensory cortical processing from birth to adulthood revealed by magnetoencephalography. Clin Neurophysiol. 2009 Aug; 120(8):1552-61. View Abstract
  32. Somatosensory evoked magnetic fields from the primary and secondary somatosensory cortices in healthy newborns. Neuroimage. 2008 Apr 01; 40(2):738-745. View Abstract
  33. Somatosensory and spinal evoked potentials in patients with upper cervical neurinoma. J Clin Neurophysiol. 2007 Aug; 24(4):352-7. View Abstract
  34. Bifunctional [2',6'-dimethyl-L-tyrosine1]endomorphin-2 analogues substituted at position 3 with alkylated phenylalanine derivatives yield potent mixed mu-agonist/delta-antagonist and dual mu-agonist/delta-agonist opioid ligands. J Med Chem. 2007 Jun 14; 50(12):2753-66. View Abstract
  35. Modeling and detecting deep brain activity with MEG & EEG. Annu Int Conf IEEE Eng Med Biol Soc. 2007; 2007:4937-40. View Abstract
  36. Transformation of mu-opioid receptor agonists into biologically potent mu-opioid receptor antagonists. Bioorg Med Chem. 2007 Feb 01; 15(3):1237-51. View Abstract
  37. Immaturity of somatosensory cortical processing in human newborns. Neuroimage. 2006 Oct 15; 33(1):195-203. View Abstract
  38. Contributions of principal neocortical neurons to magnetoencephalography and electroencephalography signals. J Physiol. 2006 Sep 15; 575(Pt 3):925-36. View Abstract
  39. Recursive artifact windowed-single tone extraction method (RAW-STEM) as periodic noise filter for electrophysiological signals with interfering transients. J Neurosci Methods. 2006 Sep 15; 155(2):308-18. View Abstract
  40. Transhemispheric depolarizations persist in the intracerebral hemorrhage swine brain following corpus callosal transection. Brain Res. 2006 Feb 16; 1073-1074:481-90. View Abstract
  41. Potent Dmt-Tic pharmacophoric delta- and mu-opioid receptor antagonists. J Med Chem. 2005 Dec 15; 48(25):8035-44. View Abstract
  42. Effects of temporary bilateral ligation of the internal carotid arteries on the low- and high-frequency somatic evoked potentials in the swine. Clin Neurophysiol. 2005 Oct; 116(10):2420-8. View Abstract
  43. Evaluation of the distortion of EEG signals caused by a hole in the skull mimicking the fontanel in the skull of human neonates. Clin Neurophysiol. 2005 May; 116(5):1141-52. View Abstract
  44. Development of potent mu-opioid receptor ligands using unique tyrosine analogues of endomorphin-2. J Med Chem. 2005 Jan 27; 48(2):586-92. View Abstract
  45. Origins of the somatic N20 and high-frequency oscillations evoked by trigeminal stimulation in the piglets. Clin Neurophysiol. 2005 Apr; 116(4):827-41. View Abstract
  46. Acute changes in cortical excitability in the cortex contralateral to focal intracerebral hemorrhage in the swine. Brain Res. 2004 Nov 12; 1026(2):218-26. View Abstract
  47. Depressed cortical excitability and elevated matrix metalloproteinases in remote brain regions following intracerebral hemorrhage. Brain Res. 2004 Nov 12; 1026(2):227-34. View Abstract
  48. Somatosensory evoked potentials and magnetic fields elicited by tactile stimulation of the hand during active and quiet sleep in newborns. Clin Neurophysiol. 2004 Feb; 115(2):448-55. View Abstract
  49. Contribution of ionic currents to magnetoencephalography (MEG) and electroencephalography (EEG) signals generated by guinea-pig CA3 slices. J Physiol. 2003 Dec 15; 553(Pt 3):975-85. View Abstract
  50. Unique high-affinity synthetic mu-opioid receptor agonists with central- and systemic-mediated analgesia. J Med Chem. 2003 Jul 17; 46(15):3201-9. View Abstract
  51. Identification and functional characterization of the trigeminal ventral cervical reflex pathway in the swine. Clin Neurophysiol. 2003 Feb; 114(2):263-71. View Abstract
  52. Stable synchronized high-frequency signals from the main sensory and spinal nuclei of the pig activated by Abeta fibers of the maxillary nerve innervating the snout. Brain Res. 2003 Jan 03; 959(1):1-10. View Abstract
  53. Physiological origins of evoked magnetic fields and extracellular field potentials produced by guinea-pig CA3 hippocampal slices. J Physiol. 2002 Oct 01; 544(Pt 1):237-51. View Abstract
  54. Synchronized spikes of thalamocortical axonal terminals and cortical neurons are detectable outside the pig brain with MEG. J Neurophysiol. 2002 Jan; 87(1):626-30. View Abstract

Contact Yoshio Okada

Phone: 781-216-1128
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