Transcranial Magnetic Stimulation to Improve Speech

Summary

Principal Investigator: MARGARET NAESER
Abstract: This is a resubmission for the competing continuation renewal of our research on the therapeutic utility of repetitive transcranial magnetic stimulation (rTMS) to improve speech in chronic, nonfluent and severe aphasia. Functional MRI studies in these patients have shown "over-activation" in right (R) perisylvian language homologues;possibly representing a maladaptive plasticity. Our hypothesis is that suppression of this over-activation with IMS may improve speech. Significant improvement in picture naming was observed immediately following rTMS for 10 min. to suppress R pars triangularis (R BA 45), with decreased reaction time (RT). rTMS to 3 other R ROIs produced no improvement. In a later phase, we applied 1-HzrTMS to R BA 45 for 20 min.daily, 10 days. Significant improvement in picture naming was observed at 2 Mo. post- TMS;and at 8 Mo.post-TMS, despite no individualized speech therapy. Pilot studies with sham rTMS have shown no effect. We propose a blinded, sham-controlled, incomplete crossover design, over a 5-Yr. period (20 mild-moderate nonfluent;20 severe nonfluent patients) with fMRI to study mechanisms of action of TMS. To insure recruitment of an adequate number of patients, we have added a second site, the Univ. of PA, where half of the patients will be studied. We have developed an overt naming fMRI BOLD paradigm for use with nonfluent patients. Pilot data indicate that pre-rTMS, there is over-activation in R frontal areas (including R inferior frontal gyrus, R BA 45;and motor cortex-mouth), with little activation in temporal lobe and poor naming performance. Post-rTMS where 1-Hz rTMS was applied to R BA 45 for 20 min.daily, 10days, improved naming was associated with less over-activation in R BA 45 and M1-mouth, with new temporal lobe activation. Overt naming fMRI will be obtained pre-real/sham rTMS, and at 2 Mo. post-real/sham rTMS. Those receiving sham rTMS are then crossed-over to real-rTMS. We hypothesize that patients who receive real rTMS will have significant improvement in picture naming at 2 Mo. post-real rTMS, versus those who receive sham rTMS. Only the real rTMS group will show suppression of R BA 45 on fMRI. Relevance to public health: The U.S.population is increasing in age;thus, an increase in stroke and need for sophisticated treatment. The number of people with aphasia in the U.S. today is estimated to be 1 million;80,000 new cases each year. This research has direct clinical relevance for aphasia patients.
Funding Period: ----------------2002 - ---------------2011-
more information: NIH RePORT

Top Publications

  1. pmc Processing nouns and verbs in the left frontal cortex: a transcranial magnetic stimulation study
    Marinella Cappelletti
    Beth Israel Deaconess Medical Center and Harvard Medical School
    J Cogn Neurosci 20:707-20. 2008
  2. pmc Left lateralizing transcranial direct current stimulation improves reading efficiency
    Peter E Turkeltaub
    Laboratory for Cognition and Neural Stimulation, Department of Neurology, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA
    Brain Stimul 5:201-7. 2012
  3. pmc The right hemisphere is not unitary in its role in aphasia recovery
    Peter E Turkeltaub
    Laboratory for Cognition and Neural Stimulation, Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA
    Cortex 48:1179-86. 2012
  4. pmc Transcranial magnetic stimulation and brain atrophy: a computer-based human brain model study
    Tim Wagner
    Division of Health Sciences and Technology, Harvard Medical School Massachusetts Institute of Technology, Boston, MA, USA
    Exp Brain Res 186:539-50. 2008
  5. ncbi Safety of rTMS to non-motor cortical areas in healthy participants and patients
    Katsuyuki Machii
    Center for Noninvasive Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, KS 452, Boston, MA 02215, USA
    Clin Neurophysiol 117:455-71. 2006
  6. ncbi Diminishing risk-taking behavior by modulating activity in the prefrontal cortex: a direct current stimulation study
    Shirley Fecteau
    Berenson Allen Center for Noninvasive Brain Stimulation, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Neurosci 27:12500-5. 2007
  7. ncbi Brain stimulation in poststroke rehabilitation
    Miguel Alonso-Alonso
    Berenson Allen Center for Noninvasive Brain Stimulation, Behavioral Neurology Unit, Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Mass, USA
    Cerebrovasc Dis 24:157-66. 2007
  8. ncbi Technology insight: noninvasive brain stimulation in neurology-perspectives on the therapeutic potential of rTMS and tDCS
    Felipe Fregni
    Harvard Medical School and the Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    Nat Clin Pract Neurol 3:383-93. 2007
  9. ncbi Noninvasive human brain stimulation
    Timothy Wagner
    Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Department of Neurology, Harvard Medical School, Boston, Massachusetts 02215, USA
    Annu Rev Biomed Eng 9:527-65. 2007
  10. ncbi Transcranial magnetic stimulation and stroke: a computer-based human model study
    Tim Wagner
    Center for Non Invasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
    Neuroimage 30:857-70. 2006

Scientific Experts

  • MARGARET NAESER
  • Roy H Hamilton
  • Alvaro Pascual-Leone
  • Felipe Fregni
  • Tim Wagner
  • Paula I Martin
  • Peter E Turkeltaub
  • Shirley Fecteau
  • Marinella Cappelletti
  • Paulo S Boggio
  • Elina Kaplan
  • Michael Ho
  • Ciro Ramos-Estebanez
  • Sergio P Rigonatti
  • H Branch Coslett
  • Jennifer Benson
  • Yunyan Wang
  • Masahito Kobayashi
  • Errol H Baker
  • Hugo Theoret
  • Antoni Valero-Cabre
  • Alan Grodzinsky
  • Uri Eden
  • Markus Zahn
  • Miguel Alonso-Alonso
  • Timothy Wagner
  • Merari J L Ferreira
  • Marcelo Riberto
  • F Fregni
  • Steven D Freedman
  • James R Carey
  • Katsuyuki Machii
  • Michael A Nitsche
  • Marom Bikson
  • Olufunsho Faseyitan
  • Amy L Thomas
  • Catherine Norise
  • Abhishek Datta
  • Errol Baker
  • Jacquie Kurland
  • Miguel Alonso
  • Marjorie Nicholas
  • Ethan Treglia
  • Jerome Kaplan
  • Karl W Doron
  • Valerie Pronio-Stelluto
  • Alfonso Caramazza
  • Kevin Shapiro
  • Paola Liguori
  • Elizabeth S Spelke
  • Paulo Boggio
  • Hilary Barth
  • David H Zald
  • Daria Knoch
  • Natasha Sultani
  • A Pascual-Leone
  • M A Nitsche
  • Daniel Cohen
  • S P Rigonatti
  • T G Sanchez
  • Daniel R Souza
  • M A Marcolin
  • Julia Duarte
  • Anita W Castro
  • Angela C Valle
  • Renata R Rocha
  • P S Boggio
  • R Marcondes
  • Moises C Lima

Detail Information

Publications29

  1. pmc Processing nouns and verbs in the left frontal cortex: a transcranial magnetic stimulation study
    Marinella Cappelletti
    Beth Israel Deaconess Medical Center and Harvard Medical School
    J Cogn Neurosci 20:707-20. 2008
    ..Moreover, none of the regions stimulated was preferentially engaged in the production of regular or irregular inflection, raising questions about the role of the frontal lobes in processing inflectional morphology...
  2. pmc Left lateralizing transcranial direct current stimulation improves reading efficiency
    Peter E Turkeltaub
    Laboratory for Cognition and Neural Stimulation, Department of Neurology, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA
    Brain Stimul 5:201-7. 2012
    ..Previous research has demonstrated a relationship between left posterior temporal cortex (pTC) function and reading ability, regardless of dyslexia status...
  3. pmc The right hemisphere is not unitary in its role in aphasia recovery
    Peter E Turkeltaub
    Laboratory for Cognition and Neural Stimulation, Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA
    Cortex 48:1179-86. 2012
    ..No support is found for interhemispheric inhibition, the theoretical framework on which most therapeutic brain stimulation protocols for aphasia are based...
  4. pmc Transcranial magnetic stimulation and brain atrophy: a computer-based human brain model study
    Tim Wagner
    Division of Health Sciences and Technology, Harvard Medical School Massachusetts Institute of Technology, Boston, MA, USA
    Exp Brain Res 186:539-50. 2008
    ..Clinical applications of TMS should be carefully considered in light of these findings...
  5. ncbi Safety of rTMS to non-motor cortical areas in healthy participants and patients
    Katsuyuki Machii
    Center for Noninvasive Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, KS 452, Boston, MA 02215, USA
    Clin Neurophysiol 117:455-71. 2006
    ..We reviewed the literature and our own data to assess the safety of rTMS to non-motor areas...
  6. ncbi Diminishing risk-taking behavior by modulating activity in the prefrontal cortex: a direct current stimulation study
    Shirley Fecteau
    Berenson Allen Center for Noninvasive Brain Stimulation, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Neurosci 27:12500-5. 2007
    ....
  7. ncbi Brain stimulation in poststroke rehabilitation
    Miguel Alonso-Alonso
    Berenson Allen Center for Noninvasive Brain Stimulation, Behavioral Neurology Unit, Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Mass, USA
    Cerebrovasc Dis 24:157-66. 2007
    ..In this review, we provide readers with a basic introduction to the field, summarize preliminary studies and discuss future directions...
  8. ncbi Technology insight: noninvasive brain stimulation in neurology-perspectives on the therapeutic potential of rTMS and tDCS
    Felipe Fregni
    Harvard Medical School and the Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    Nat Clin Pract Neurol 3:383-93. 2007
    ..We review randomized controlled studies, in focal epilepsy, Parkinson's disease, recovery from stroke, and chronic pain, to illustrate these principles, and we present evidence for the clinical effects of these two techniques...
  9. ncbi Noninvasive human brain stimulation
    Timothy Wagner
    Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Department of Neurology, Harvard Medical School, Boston, Massachusetts 02215, USA
    Annu Rev Biomed Eng 9:527-65. 2007
    ..Finally, we discuss potential biomedical and electrical engineering developments that could lead to more effective stimulation devices, better suited for the specific applications...
  10. ncbi Transcranial magnetic stimulation and stroke: a computer-based human model study
    Tim Wagner
    Center for Non Invasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
    Neuroimage 30:857-70. 2006
    ....
  11. ncbi A sham-controlled, phase II trial of transcranial direct current stimulation for the treatment of central pain in traumatic spinal cord injury
    Felipe Fregni
    Harvard Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
    Pain 122:197-209. 2006
    ..We discuss potential mechanisms for pain amelioration after tDCS, such as a secondary modulation of thalamic nuclei activity...
  12. ncbi A sham-controlled trial of a 5-day course of repetitive transcranial magnetic stimulation of the unaffected hemisphere in stroke patients
    Felipe Fregni
    Harvard Center for Non Invasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, KS 452, Boston, Massachusetts 02215, USA
    Stroke 37:2115-22. 2006
    ..We therefore conducted a randomized, sham-controlled, phase II trial to evaluate whether five sessions of low-frequency rTMS can increase the magnitude and duration of these effects and whether this approach is safe...
  13. ncbi Cognitive effects of repeated sessions of transcranial direct current stimulation in patients with depression
    Felipe Fregni
    Depress Anxiety 23:482-4. 2006
  14. ncbi rTMS combined with motor learning training in healthy subjects
    James R Carey
    Program in Physical Therapy, University of Minnesota, Minneapolis, MN 55455, USA
    Restor Neurol Neurosci 24:191-9. 2006
    ..This study explored the effects of motor learning training combined with repetitive transcranial magnetic stimulation (rTMS) on motor performance in healthy subjects...
  15. ncbi Transient tinnitus suppression induced by repetitive transcranial magnetic stimulation and transcranial direct current stimulation
    F Fregni
    Harvard Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
    Eur J Neurol 13:996-1001. 2006
    ..These effects were short lasting. These results replicate the findings of the previous study and, in addition, show preliminary evidence that anodal tDCS of LTA induces a similar transient tinnitus reduction as high-frequency rTMS...
  16. ncbi Disrupting the brain to guide plasticity and improve behavior
    Alvaro Pascual-Leone
    Department of Neurology, Center for Non Invasive Brain Stimulation, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    Prog Brain Res 157:315-329. 2006
    ..Such interventions to guide behavior or treat pathological symptomatology might be more immediate in their behavioral repercussion and thus more effective than approaches intent on addressing underlying genetic predispositions...
  17. pmc rTMS over the intraparietal sulcus disrupts numerosity processing
    Marinella Cappelletti
    Center for Non Invasive Brain Stimulation, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA
    Exp Brain Res 179:631-42. 2007
    ....
  18. ncbi Activation of prefrontal cortex by transcranial direct current stimulation reduces appetite for risk during ambiguous decision making
    Shirley Fecteau
    Berenson Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
    J Neurosci 27:6212-8. 2007
    ..The ability to modify risk-taking behavior may be translated into therapeutic interventions for disorders such as drug abuse, overeating, or pathological gambling...
  19. pmc Suppression of ipsilateral motor cortex facilitates motor skill learning
    Masahito Kobayashi
    Behavioral Neurology Unit, Department of Neurology, Berenson Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
    Eur J Neurosci 29:833-6. 2009
    ..This supports the notion of inter-hemispheric competition and provides novel insights that may be applicable to neurorehabilitation...
  20. pmc Overt naming fMRI pre- and post-TMS: Two nonfluent aphasia patients, with and without improved naming post-TMS
    Paula I Martin
    Harold Goodglass Boston University Aphasia Research Center, Department of Neurology, Boston University School of Medicine and the Veterans Affairs Boston Healthcare System, Boston, MA 02130, USA
    Brain Lang 111:20-35. 2009
    ..The fMRI data of our patient who had good response following TMS support the notion that restoration of the LH language network is linked in part, to better recovery of naming and phrase length in nonfluent aphasia...
  21. pmc Research with transcranial magnetic stimulation in the treatment of aphasia
    Paula I Martin
    Aphasia Research Center 12 A, VA Boston Healthcare System, Boston, MA 02130, USA
    Curr Neurol Neurosci Rep 9:451-8. 2009
    ..The potential role of mirror neurons in the right pars opercularis and ventral premotor cortex in aphasia recovery is discussed...
  22. pmc Stimulating conversation: enhancement of elicited propositional speech in a patient with chronic non-fluent aphasia following transcranial magnetic stimulation
    Roy H Hamilton
    Laboratory for Cognition and Neural Stimulation, Department of Neurology, University of Pennsylvania, Philadelphia, PA 19104, USA
    Brain Lang 113:45-50. 2010
    ..These findings suggest that manipulation of the intact contralesional cortex in patients with non-fluent aphasia may result in language benefits that generalize beyond naming to include other aspects of language production...
  23. pmc Improved language in a chronic nonfluent aphasia patient after treatment with CPAP and TMS
    Margaret A Naeser
    Department of Neurology, Harold Goodglass Boston University Aphasia Research Center, Boston University School of Medicine and the Veterans Affairs Boston Healthcare System, Boston, MA 02130, USA
    Cogn Behav Neurol 23:29-38. 2010
    ....
  24. pmc Horizontal portion of arcuate fasciculus fibers track to pars opercularis, not pars triangularis, in right and left hemispheres: a DTI study
    Elina Kaplan
    Veterans Affairs Boston Healthcare System and the Harold Goodglass Boston University Aphasia Research Center, Department of Neurology, Boston University School of Medicine, USA
    Neuroimage 52:436-44. 2010
    ..These results replicate previous studies for the LH, but are new, for the RH. They could contribute to better understanding of recovery in aphasia...
  25. pmc Research with rTMS in the treatment of aphasia
    Margaret A Naeser
    Veterans Affairs Boston Healthcare System and the Harold Goodglass Boston University Aphasia Research Center, Department of Neurology, Boston University School of Medicine, Boston, MA 02130, USA
    Restor Neurol Neurosci 28:511-29. 2010
    ..Part 4 also addresses some of the possible mechanisms involved with improved naming and speech, following rTMS with nonfluent aphasia patients...
  26. pmc TMS suppression of right pars triangularis, but not pars opercularis, improves naming in aphasia
    Margaret A Naeser
    V A Boston Healthcare System, Harold Goodglass Boston University Aphasia Research Center, Boston University School of Medicine, USA
    Brain Lang 119:206-13. 2011
    ..Differential effects following suppression of right PTr versus right POp suggest different functional roles for these regions...
  27. pmc Transcranial magnetic stimulation and aphasia rehabilitation
    Margaret A Naeser
    Veterans Affairs Boston Healthcare System and Harold Goodglass Boston University Aphasia Research Center, Department of Neurology, Boston University School of Medicine, Boston, MA, USA
    Arch Phys Med Rehabil 93:S26-34. 2012
    ..In part 3, some possible mechanisms associated with improvement after a series of TMS treatments in stroke patients with aphasia are discussed...