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Alvaro Pascual-Leone, M.D., Ph.D.

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Overview
At the Berenson-Allen Center for Noninvasive Brain Stimulation that I direct we have three distinct missions: (1) Research explores brain-behavior relations, brain plasticity and its modulation, employing different noninvasive brain stimulation techniques combined with careful task design, electroencephalography, and functional brain imaging. (2) Educational efforts feature an intensive course in noninvasive brain stimulation offered three times per year as part of Harvard’s Continuing Medical Education program. (3) Clinical work includes diagnostic studies therapeutic applications of noninvasive brain stimulation for treatment of neuropsychiatric disorders.
My work has been fundamental in establishing transcranial magnetic stimulation (TMS) as a tool capable of revealing causal brain-behavior relations and the timing of information flow and dynamic adaptation in neural networks. My laboratory has contributed to increasing the knowledge about the mechanisms of action and improving the methodology of TMS and its combination with other neurophysiologic and brain imaging methods. For example we developed a method to interface TMS with EEG to allow the study of the effects of brain stimulation on ongoing brain activity and ultimately enable the use of EEG activity as a means of controlling the stimulation applied, and a novel methodology to introduce TMS into the MRI scanner in order to be able to study the neural activity evoked by TMS and thus correlate behavioral with underlying neurophysiologic effects.
I was the first to show that trains of repetitive TMS can be reliably and safely disrupt the activity of a given brain region transiently and thus provide insights about the causality of brain activity in behavior. I demonstrated the rapid plasticity of motor cortical outputs during motor learning, the requirement of visual cortex input for tactile Braille reading in the blind, the causal role of primary visual cortex and the dynamics of interhemipheric compensatory processes during mental imagery, and the need for fast back-projections in visual awareness tasks. Moreover, coupling TMS with physiologic and imaging techniques, I showed that repetitive TMS can induce lasting changes in regional brain excitability and exert trans-synaptic modulatory effects on neural network activity in animal and human studies. This allows for the investigation of the rapid neuroplastic changes that compensate for brain injury or dysfunction, and permits the model-driven, individually-tailored modulation of disrupted networks for treating common neuropsychiatric conditions. We showed that TMS can aide in the recovery of hand function and aphasia after stroke, the adaptation to blindness, the rehabilitation of neglect, the control of addictive behavior, and the acquisition of language and imitation behavior in autism. My laboratory carried out the first double blind study of rTMS in major depression, and the first proof-of-principle studies suggesting therapeutic possibilities of TMS in epilepsy, Parkinson's disease, visceral pain and dystonia. This work provides support to the notion that modulation of activity along a distributed neural network can induce long-lasting plastic changes, even in the adult brain, and have behavioral consequences, which in certain conditions may be therapeutic.

Mentoring
EEG microstates and repetitive TMS: Changes in EEG microstate dynamics following continuous theta burst stimulation to the dorsolateral prefrontal cortex
Summer, 06/17/13 - 08/09/13
Lateralized Motor Evoked Potentials via Transcranial Magnetic Stimulation
Summer, 06/01/08 - 09/01/08
Cortical Plasticity Associated with Blindness
Full Time, 07/03/00 - 01/28/01
Time Course of Activation of Visual Cortex in Braille Reading by Blind Patients: A Transcranial magnetic Stimulation Study
Part Time, 03/01/00 - 03/31/00
Decision-making in people with narcolepsy and healthy age-matched controls
Full Time/Year Long, 11/01/06 - 06/29/07
Time Course of Activation of visual Cortex in Braille Reading y blind Patients: A Transcranial Magnetic Stimulation Study
Summer, 06/12/00 - 08/25/00
Modulation of the dorsolateral prefrontal cortex with repetitive transcranial magnetic stimulation in obesity.
Summer, 06/18/07 - 08/10/07

Research
The research activities and funding listed below are automatically derived from NIH ExPORTER and other sources, which might result in incorrect or missing items. Faculty can login to make corrections and additions.
  1. R01AG076708 (PASCUAL-LEONE, ALVARO) Sep 30, 2022 - Aug 31, 2027
    NIH
    Multifocal transcranial current stimulation for cognitive and motor dysfunction in dementia
    Role: Principal Investigator
  2. R01MH117063 (PRESS, DANIEL Z.) Aug 23, 2018 - May 31, 2022
    NIH
    The Development and Human Translation of Temporal Interference Brain Stimulation
    Role: Principal Investigator
  3. R01MH115949 (SHAFI, MOUHSIN) Jun 1, 2018 - Feb 28, 2023
    NIH/NIMH
    Reliability of Repetitive TMS-induced Modulation of Cortical Excitability
    Role: Principal Investigator
  4. R21AG051846 (PASCUAL-LEONE, ALVARO) Jun 1, 2016 - Dec 24, 2018
    NIH
    Brain Plasticity Measures in MCI
    Role: Principal Investigator
  5. R01MH100186 (ROTENBERG, ALEXANDER) Aug 15, 2014 - Apr 30, 2020
    NIH
    Cortical Plasticity in Autism Spectrum Disorders
    Role: Principal Investigator

Bibliographic
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Funded by the NIH National Center for Advancing Translational Sciences through its Clinical and Translational Science Awards Program, grant number UL1TR002541.