Precision Neuroscience & Neuromodulation Program


The Precision Neuroscience & Neuromodulation (PNN) program aims at the identification of novel biomarkers and therapeutic approaches for patients with neurological and psychiatric conditions, including the development of cognitive enhancement solutions to optimize brain function and behavior, and promote brain health across the lifespan.   

The Approach

The Precision Neuroscience & Neuromodulation (PNN) program, directed by Dr. Emiliano Santarnecchi, leverages the combination of multimodal neuroimaging techniques (e.g., fMRI, DTI and PET), electrophysiology (EEG), cognitive neuroscience, computational modeling, and noninvasive brain stimulation methods for the investigation of brain circuitry and its relationship to cognitive abilities. The program is centered around the concepts of brain connectomics, network neuroscience and brain plasticity, offering a transversal view of healthy and pathological brain functioning from micro to meso and macro scale.  

Areas of Interest

Areas of Interest

Cognitive Neuroscience, Biological and Artificial Intelligence

Understanding the link between human cognition and brain structural and functional architecture is a key building block of the program. We are looking at the neural correlates of global phenomenon like general and fluid intelligence in humans, as well as at the interplay between different brain networks necessary to generate fine cognitive skills such as memory, attention, mental flexibility. In particular, we focus on dynamic brain states analysis, looking at how brain activity evolves over time by extracting spatio-temporal patterns able to inform closed-loop feedback applications. The study of intelligence, creativity and memory is also revealing essential in informing models of artificial intelligence (A.I.) aimed at mimicking human cognition and decision making, including learning models and theories of consciousness.

Tadayon et al. 2019
Madeo et al. 2020

Brain Health, Longevity, and Pathological Aging

Brain health is becoming a key aspect of modern-day life, and a successful predictor of healthy aging. We are interested in both cognitive and neural aspect of brain health, spanning from the idea of brain resilience to external perturbation to the role of brain efficiency and brain plasticity, also looking at how these factors interact in the context of cognitive reserve.  We are particularly interested on how changes in connectomics and brain oscillatory activity (e.g., gamma and theta activity) might lead to cognitive decline and impairment of quality of life. We are currently running clinical trials investigating experimental therapeutic opportunities for the treatment of conditions such as Alzheimer’s disease and Frontotemporal dementia, including studies involving the application of noninvasive brain stimulation techniques.

Santarnecchi et al. 2018
Menardi et al. 2021

Noninvasive Brain Stimulation and Connectome Rewiring

The program addressed the need for personalized, image-guided solutions to modulate brain “activity” and manipulate the human brain connectome, for both cognitive enhancement and clinical applications. Brain imaging and electrophysiology techniques such as fMRI, EEG, MEG, are combined with noninvasive brain stimulation methods such as Transcranial Magnetic Stimulation (TMS) and transcranial electrical stimulation (tES) to create a “Perturbation-based” causal connectome, as well as to identify optimal targets to induce brain state-to-state and trait-to-trait change. Approaches including network control theory and evolutionary game theory models of brain functioning are used to identify personalized stimulation targets and maximize brain control, while techniques like cortico-cortical paired associative stimulation (ccPAS) TMS and transcranial alternating current stimulation (tACS) are leveraged to induce synchronization of brain networks. Recent efforts have been pointed in the direction of modulation of the brain cancer connectome (Sprugnoli et al.).

Ozdemir et al. 2020
Santarnecchi et al. 2018

Brain Plasticity, Learning and Cognitive Enhancement

The impact of external perturbation on brain and cognitive dynamics is evaluated via various approaches, with the goal of understanding how the brain adapt to novel stimuli in the context of brain plasticity processes, including the role of sleep and memory consolidation. Given the unique insight offered by the response to different interventions, our studies focus on a variety of interventions, ranging from psychotherapy to meditation, motor learning, dietary supplements, cognitive training and videogames. Given its impact on performance, our work is expanding on clinical and non-clinical areas, including research on space physiology and the development of potential countermeasures to maintain optimal brain performance in extreme environments such as during space flight.

Santarnecchi et al. 2013 Current Biology Abstract Reasoning

Spugnoli et al. 2020 Creativity

Clinical Biomarkers Discovery and Therapeutic Applications

We use multimodal neuroimaging and electrophysiology to identify novel biomarkers of neurological and psychiatric conditions, using techniques such as combined TMS-EEG, tACS-EEG, fMRI, DTI and PET. When potential biomarkers have been identified, we promote experimental therapeutic solutions including those based on noninvasive brain stimulation. Recent work by our group has focused on neurodegenerative disorders such as Alzheimer’s disease and related dementias, brain tumors, depression and disorders of consciousness.

Sprugnoli et al. 2019
Dhaynaut et al. 2022


Emiliano Santarnecchi

Emiliano Santarnecchi, PhD

Program Director Associate Professor of Radiology

Lorella Battelli, PhD

Assistant Professor of Neurology

Alberto Benelli

PhD Student

Alessandra Cinti

PhD Student

Nainika Groover

Research Coordinator

Francesco Lomi

Graduate Student

Arianna Menardi, PhD

Visiting Postdoctoral Fellow

Stacey Monsell

Clinical Research Assistant

Francesco Neri

PhD Student

Siddhartha Pandit

Siddhartha Pandit

Postdoctoral Fellow

Thomas Pandolfi

Research Student

Julianne Reilly

Clinical Research Coordinator

Sara Romanella

Sara Romanella

Postdoctoral Research Fellow

Deborah Scherrer

PhD Student

Carmelo Smeralda

Carmelo Luca Smeralda

Research Scholar

Filippo Tonietto, BCS

Computer Science
Unity Developer

Giulia Sprugnoli, MD

PhD Student, Neuroradiologist

Sonia Turrini

Sonia Turrini

PhD Student

Past Members
  • Sonika Agarwal, Research Assistant
  • Martina Assogna, MD, Visiting Physician Scientist
  • Ahsan Ayaz, MD, Visiting Physician Scientist
  • Pierre Boucher, Graduate Student, Research Assistant
  • Matthew Burke, MD, Research Fellow
  • Davide Cappon, Postdoctoral Fellow
  • Abigail Goldberg, Coop Student 
  • Kelly A. Karakhanyan, Research Assistant
  • Fae Kayarian, Graduate Student
  • Joanna Macone, Research Nurse Coordinator
  • Lucia Mencarelli, PhD, PhD student
  • Davide Momi, Visiting Student, Research Assistant
  • Beatrice Moret, PhD, PhD student
  • Christian S. Musaeus, MD, Visiting Physician Scientist
  • Recep Ozdemir, PhD, Postdoctoral Fellow
  • Rachel Pacioreck, Research Coordinator 
  • Kelly Riddle, Coop student
  • Ehsan Tadayon, Postdoctoral Fellow
  • Alexandra Tautan, Eng., Fulbright scholar

Obinna Ama, Biom.Eng.

Biomedical Engineer

Simone Rossi, MD

Professor of Physiology, University of Siena

Carmen Sergiou, PhD

Visiting Postdoctoral Fellow

Elisa Tatti, PhD

Postdoctoral Fellow

Relevant Literature

Relevant Literature
  • Sprugnoli G,Monti L, Lippa L, Neri F,Mencarelli L, Ruffini G, Salvador R, Oliveri G, Batani B, Momi D,Cerase A, Pascual-Leone A,Rossi A, Rossi S, Santarnecchi E.  Reduction of intratumoral brain perfusion by noninvasive transcranial electrical stimulation. Science Advances August 2019; DOI: 10.1126/sciadv.aau9309
  • Ozdemir RA, Tadayon E, Boucher P, Momi D, Karakhanyan K. K., Fox MD, Halko, MA, Pascual-Leone A., Shafi MM, Santarnecchi E. Individualized Perturbation of the Human Connectome Reveals Reproducible Biomarkers of Network Dynamics Relevant to Cognition. PNAS 2020, Mar 19. pii: 201911240. DOI: 10.1073/pnas.1911240117
  • Sprugnoli G, Cagle Y, Santarnecchi E. Impact of Microgravity and Cosmic Radiations during Space Exploration as a window into Neurodegeneration on Earth. JAMA Neurology 2019; Nov 25. DOI: 10.1001/jamaneurol.2019.4003
  • DhaynautM, SprugnoliG, Cappon D, MaconeJ, SanchezJS, NormandinA, Nicolas Guehl, Koch G, PaciorekR, ConnorA, Press D, JohnsonK, Pascual-LeoneA, Georges El-Fakhri G, Santarnecchi E. Impact of 40Hz tACS on cerebral Tau burden in patients with Alzheimer’s disease: A Case Series. J Alzheimers Dis. 2021 DOI: 10.3233/JAD-215072
  • Santarnecchi E, Polizzotto NR, Godone M, Giovannelli F, Feurra M, Matzen L, Rossi A, Rossi S. Frequency-dependent enhancement of fluid intelligence induced by transcranial oscillatory potentials. Current Biology 2013 Aug 5;23(15):1449-53.
  • Burke MJ*, Romanella SM*, Mencarelli L, Greben R, Fox MD, Kaptchuk TJ, Pascual-Leone A, Santarnecchi E. Placebo effects and neuromodulation for depression: A meta-analysis and evaluation of shared mechanisms. Molecular Psychiatry 2021 (accepted). DOI: 10.1038/s41380-021-01397
  • Menardi A., Rossi S., Koch G., Hampel H., Vergallo A., Nitsche MA, Stern Y, Borroni B, Cappa SF, Cotelli M, Ruffini G, El-Fakhri G, Rossini PM, Dickerson B, Antal A., Babiloni C, Lefaucheur JP, Dubois B, Deco G, Ziemann U, Pascual-Leone A, Santarnecchi E. Toward noninvasive brain stimulation 2.0 in Alzheimer’s disease. Ageing Research Reviews 75, 3 2022, 101555. DOI: 10.1016/j.arr.2021.101555
  • Sprugnoli G, Rossi S, Rotenberg A, Pascual-Leone A, El-Fakhri G, Golby AJ, Santarnecchi E. Personalized, Image-Guided, Noninvasive Brain Stimulation in Gliomas: Rationale, Challenges and Opportunities. Lancet EBiomedicine 2021 Volume 70, 103514, August 01. DOI: 10.1016/j.ebiom.2021.103514

Ongoing Projects

Ongoing Projects



Julianne Reilly 

Clinical Research Coordinator  

Massachusetts General Hospital | Gordon Center for Medical Imaging 

Precision Neuroscience & Neuromodulation Program 


Tel: 617-726-9353