title: The heart side of brain neuromodulation.
abstract: Neuromodulation refers to invasive, minimally invasive or non-invasive techniques to stimulate discrete cortical or subcortical brain regions with therapeutic purposes in otherwise intractable patients: for example, thousands of advanced Parkinsonian patients, as well as patients with tremor or dystonia, benefited by deep brain stimulation (DBS) procedures (neural targets: basal ganglia nuclei). A new era for DBS is currently opening for patients with drug-resistant depression, obsessive-compulsive disorders, severe epilepsy, migraine and chronic pain (neural targets: basal ganglia and other subcortical nuclei or associative fibres). Vagal nerve stimulation (VNS) has shown clinical benefits in patients with pharmacoresistant epilepsy and depression. Non-invasive brain stimulation neuromodulatory techniques such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are also being increasingly investigated for their therapeutic potential in several neurological and psychiatric disorders. In this review, we first address the most common neural targets of each of the mentioned brain stimulation techniques, and the known mechanisms of their neuromodulatory action on stimulated brain networks. Then, we discuss how DBS, VNS, rTMS and tDCS could impact on the function of brainstem centres controlling vital functions, critically reviewing their acute and long-term effects on brain sympathetic outflow controlling heart function and blood pressure. Finally, as there is clear experimental evidence in animals that brain stimulation can affect autonomic and heart functions, we will try to give a critical perspective on how it may enhance our understanding of the cortical/subcortical mechanisms of autonomic cardiovascular regulation, and also if it might find a place among therapeutic opportunities in patients with otherwise intractable autonomic dysfunctions.
authors.affiliation: Gaetano Valenza, Monica Ulivelli Department of Medicine, Surgery and Neuroscience, Unit of Neurology and Clinical Neurophysiology, Brain Investigation and Neuromodulation Lab. (Si-BIN Lab.), Azienda Ospedaliera Universitaria Senese, University of Siena, 53100 Siena, Italy rossisimo@unisi.it.
authors.forename: Simone
authors.identifier: http://orcid.org/0000-0001-6697-9459
authors.initials: S
authors.lastname: Rossi
authors.affiliation: Gaetano Valenza, Monica Ulivelli Department of Medicine, Surgery and Neuroscience, Unit of Neurology and Clinical Neurophysiology, Brain Investigation and Neuromodulation Lab. (Si-BIN Lab.), Azienda Ospedaliera Universitaria Senese, University of Siena, 53100 Siena, Italy Berenson-Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Emiliano
authors.initials: E
authors.lastname: Santarnecchi
authors.affiliation: Department of Information Engineering, and Research Center E. Piaggio, University of Pisa, 56122 Pisa, Italy Neuroscience Statistics Research Lab, Harvard Medical School, Massachusetts General Hospital, Boston, MA 02115, USA Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Valenza
authors.affiliation: Gaetano Valenza, Monica Ulivelli Department of Medicine, Surgery and Neuroscience, Unit of Neurology and Clinical Neurophysiology, Brain Investigation and Neuromodulation Lab. (Si-BIN Lab.), Azienda Ospedaliera Universitaria Senese, University of Siena, 53100 Siena, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Ulivelli
mesh_terms: D018377:Neurotransmitter Agents
chemical_list: D018377:Neurotransmitter Agents
keywords: autonomic function; deep brain stimulation; heart rate variability; repetitive transcranial magnetic stimulation; transcranial direct current stimulation; vagal nerve stimulation