Brain and Heart Dynamics

Stefano Govoni • Pierluigi PolitiEmilio VanoliEditors

Brain and HeartDynamics

With 73 Figures and 48 Tables

EditorsStefano GovoniDepartment of Drug SciencesSection of PharmacologyUniversity of PaviaPavia, Italy

Pierluigi PolitiDepartment of Brain andBehavioral SciencesUniversity of PaviaPavia, Italy

Emilio VanoliDepartment of Molecular MedicineUniversity of PaviaPavia, Italy

ISBN 978-3-030-28007-9 ISBN 978-3-030-28008-6 (eBook)ISBN 978-3-030-28009-3 (print and electronic bundle)https://doi.org/10.1007/978-3-030-28008-6

© Springer Nature Switzerland AG 2020This work is subject to copyright. All rights are reserved by the Publisher, whether the whole orpart of the material is concerned, specifically the rights of translation, reprinting, reuse ofillustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way,and transmission or information storage and retrieval, electronic adaptation, computer software, orby similar or dissimilar methodology now known or hereafter developed.The use of general descriptive names, registered names, trademarks, service marks, etc. in thispublication does not imply, even in the absence of a specific statement, that such names are exemptfrom the relevant protective laws and regulations and therefore free for general use.The publisher, the authors, and the editors are safe to assume that the advice and information in thisbook are believed to be true and accurate at the date of publication. Neither the publisher nor theauthors or the editors give a warranty, expressed or implied, with respect to the material containedherein or for any errors or omissions that may have been made. The publisher remains neutral withregard to jurisdictional claims in published maps and institutional affiliations.

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To Ottavia, Davide, Luca, Camilla, Wang Li, and Olivia: our nextgenerations. They are love and drive to live for

Preface

Donatella said: “I’d like you all to write about how brain and heart talk to eachother.” Pierluigi replayed by saying: “OK, I can collect a group of experts ableto describe many, if not all, aspects of psyche and heart and how the first candrive the second.” Stefano added: “I can collect a group of experts describingall aspects of brain activity, pharmacology and the cardiovascular conse-quences of central neural disorders.” Being the cardiologist of the trio, Emiliofelt like he was bound to be the target of the cross neural firing coming fromabove but he thought of the many years of great learning in neuro-cardiology.Emilio’s looping up was then: “Well guys, I’ll tell you how the heart is drivingyou both! The heart as a ‘sensing organ’ this is what I had learned from mygreat mentors who still guide me with their restless scientific life .” And this ishow our great venture started.

The underlying understanding was that, in this arena, nothing is still and wewere about to deal with “Brain Heart Dynamics” and the title was there! Byjoining our day-to-day scientific life, we had been sharing knowledge, goingfrom the invisible orchestra to face autism to pharmacology of neural diseasesto autonomic bidirectional drive of the heart. This is the deep soul of thisreference book. We hope we fulfilled the goal that we pursued over 2 years ofintensive work.

Moving along the index of the opera the reader will find, step by step, thedescription of the many ways by which the heart is sending its messages to thebrain. This occurs within fractions of seconds so that neuromodulation ofcardiovascular control can take place in a fraction of a second. Think abouthowmany events the brain has to manage in a fraction of a second: we stand upin fraction of a second, maintaining cerebral perfusion against gravity thatwould take all blood to our feet. Emotions, as any other higher cerebralfunction. Need cardiovascular responses in a fraction of a second. Manyaspects of our life run along this high-speed rail: at the time of any minor or,more so, severe perturbation of our mental process, anytime we take a pill orengage in exercise, when awake or sleeping. Of note, sleep is a time whenmostof our functions are under our autonomic nervous system’s control, but ourmind process is reloading, and millions of data are reprocessed.

The entire life fluctuates in fractions of seconds, and this is the dynamicworld still far from being understood that we aimed at describing in the61 chapters that you’ll find available hereafter. We believe there is no needfor a redundant recall of the importance of the continuing research on the

vii

brain–heart interactions, but we would like to recall that this is the central driveof a whole, where any piece plays a role from the tip of the toe to the guts, thekidney, and edge of our hairs. One for all is the case of the novel use ofelectrical stimulation of the cervical vagus to effectively treat resistant epilepsyand depression. Eighty percent of the fibers travelling into the cervical vaguscarries afferent information from all viscera to the CNS. This implies that thecomposite afferent information originating from the body can profoundlymodulate the electrical and biochemical functions of the brain.

The take-home message we hope that the reader will save after workingthrough the chapters of this reference book is, indeed, that our body operates inloops where the chief commander operates the driving and, in turn, is driven bythe whole body. This is so because the heart and the rest of the body aredesigning its route. It seems sometimes as if somebody has indeed designedthis beautiful functional architecture in the human body. Will the human beingever able to duplicate such architecture in her/his world? Meanwhile we hopeyou’ll enjoy travelling along this book.

July 2020 Stefano GovoniPierluigi PolitiEmilio Vanoli

viii Preface

Acknowledgments

First, we would like to thank all contributors and section editors for makingthis book a reality!

An enormous thank to two great women who gave “brain and heart” to theconception of this opera: Donatella Rizza (see preface), who triggered thethought and drove the project to its approval, and Cristina Marelli, whosupervised the project design and progression with her wonderful personalityand bright mind. This work made it to its successful end because of the never-ending guidance by Shruti Datt: thank you so much. We want to express ourprofound gratitude to other fundamental contributors: Sandra Fabiani (Refer-ence Publisher) for her continuous contribution over the entire period ofmanuscripts acquisition and management. We would also like to thank theProduction PMs, Mr. Ragavan Rajasekaran and Ms. Madhivathani MadhiMaran, for their support in copyediting and typesetting.

Two years of wonderful work and learning! GRAZIE from the heart andbrain!

ix

Contents

Part I Functional Anatomy and Molecular Basis of theCardiac-Brain Axis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

1 Brain-Heart Afferent-Efferent Traffic . . . . . . . . . . . . . . . . . . 3Veronica Dusi and Jeffrey L. Ardell

2 Brain-Heart Communication . . . . . . . . . . . . . . . . . . . . . . . . . 25Alessia Pascale and Stefano Govoni

3 The Cardiorenal Cross Talk . . . . . . . . . . . . . . . . . . . . . . . . . . 43Edoardo Gronda and Emilio Vanoli

4 Genetic Determinants Affecting the Relationship Betweenthe Autonomic Nervous System and Sudden Death . . . . . . . 55Rachel M. A. ter Bekke and Paul G. A. Volders

5 Cognitive Decline in Elderly Patients with HypertensiveHeart Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79Ilaria Liguori, Francesco Curcio, Pasquale Abete, andGianluca Testa

Part II Inflammatory Processes Perturbing Brain-HeartDialogue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95

6 Immune System and Mind-Body Medicine:An Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97Laura Calvillo and Gianfranco Parati

7 Nociception, Sympathetic Nervous System, andInflammation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117Veronica Dusi

8 The Role of Emotions, Stress, and Mental State inInflammatory Processes Perturbing Brain-Heart Dialogue . . . 147Pietro Cipresso, Javier Fernández Alvarez, Giuseppe Riva, andLaura Calvillo

xi

Part III Emotional Processes and How They May InfluenceCardiovascular Activity, Disease Onset, Outcomes, andQuality of Life . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165

9 Biofeedback . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167Fredric Shaffer and Donald Moss

10 Distinguishing Cardiac from Psychological SomaticSymptoms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181Alessandro Rodolico and Ludovico Mineo

11 Consequences of Altered Cardiac Activity onBrain Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 197Enrico Baldi and Simone Savastano

12 Emotional Processing and Heart Activity . . . . . . . . . . . . . . . 213Umberto Provenzani

13 The Relationship Between Psychological Distress andBio-behavioral Processes in Cardiovascular Disease . . . . . . . 229Stefania Balzarotti, Barbara Colombo, andAmanda Christensen

Part IV Bidirectional Influences of Common PsychiatricConditions and Cardiovascular Activity . . . . . . . . . . . . . . . . . . . . . . 241

14 Anxiety, Anger, Personality, and Heart Disease . . . . . . . . . . . 243Laura Fusar-Poli and Davide Arillotta

15 Cardiovascular Manifestations of Panic and Anxiety . . . . . . 261Phillip J. Tully, Suzanne Cosh, and Susanne Pedersen

16 Depression and Cardiovascular Diseases . . . . . . . . . . . . . . . . 281Isabella Masci, Sergio Merlino, and Grazia Rutigliano

17 Bipolar Disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 297Camilla Gesi, Barbara Carpita, Filippo M. Barberi,Annalisa Cordone, and Liliana Dell’Osso

18 Borderline Personality Disorder and the Heart . . . . . . . . . . . 315Annalisa Boldrini

19 Cardiovascular Manifestations in Schizophrenia . . . . . . . . . 335Federica Calorio, Cristina Grazia Catania, andMatteo Rocchetti

20 PTSD and Cardiovascular Disease . . . . . . . . . . . . . . . . . . . . . 355Claudia Carmassi, Annalisa Cordone, Virginia Pedrinelli, andLiliana Dell’Osso

21 Psychiatric Aspects of Sudden Cardiac Arrest andImplantable Cardioverter-Defibrillators . . . . . . . . . . . . . . . . 377Simone Savastano, Enrico Baldi, and Natascia Brondino

xii Contents

22 Major Psychiatric Complications of Cardiac Surgery . . . . . 387Benedetta Vanini, Claudio Placenti, and Andrea M. D’Armini

23 Cardiac Transplantation and Psychopathology . . . . . . . . . . . 399Pierluigi Politi and Valentina Martinelli

24 Psychotherapy and Psychological Support for SevereHeart Conditions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 411Marinella Sommaruga and Antonia Pierobon

Part V Neurological Diseases and How They May InfluenceCardiovascular Activity, Disease Onset, Outcomes, andQuality of Life . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 427

25 Heart Activity and Cognition . . . . . . . . . . . . . . . . . . . . . . . . . 429Marco Vercesi

26 Dementia and Cerebrovascular Disease . . . . . . . . . . . . . . . . . 445Giulia Perini, Matteo Cotta Ramusino, Sara Bernini, andAlfredo Costa

27 Autonomic Dysfunction in Acute Stroke . . . . . . . . . . . . . . . . 465Giuseppe Micieli and Isabella Canavero

28 Heart and Embolic Stroke of Undetermined Source . . . . . . . 481Anna Cavallini, Serena Magno, Alessandra Persico, andAndrea Morotti

29 The Heart-Brain Connection in Patients with Disorders ofConsciousness . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 497Francesca Pistoia, Simona Sacco, Marco Sarà, and AntonioCarolei

30 Epilepsy and Cardiovascular Function . . . . . . . . . . . . . . . . . 507Raffaele Manni, Gianpaolo Toscano, and Michele Terzaghi

31 Headache and the Heart . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 517Cristina Tassorelli, Roberto De Icco, Daniele Martinelli, andMichele Viana

32 Multiple Sclerosis and the Heart . . . . . . . . . . . . . . . . . . . . . . . 529Camilla Rocchi, Giorgia Mataluni, and Doriana Landi

33 The Heart-Brain Connection in Patients with DuchenneMuscular Dystrophy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 541Claudia Bearzi and Roberto Rizzi

Part VI Sleep and Heart . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 559

34 Physiological Sleep and Cardiovascular Disease . . . . . . . . . . 561Edgar Toschi-Dias, Eleonora Tobaldini, Nicola Montano, andLuigi Ferini-Strambi

Contents xiii

35 Sleep Disorders and Cardiovascular Disease . . . . . . . . . . . . . 575Michele Terzaghi, Gianpaolo Toscano, and Raffaele Manni

36 Night, Darkness, Sleep, and Cardiovascular Activity . . . . . . 585Alessandro Silvani

Part VII Pain and Heart . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 603

37 When the Heart Hurts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 605Elena G. Bignami and Alberto Castella

38 Neuromodulation for Chronic Refractory Angina . . . . . . . . 615Philippe Mavrocordatos, Gustavo Rodrigues Costa Lages, andLucian Mihai Macrea

39 Analgesic Control During Acute Pain to Protect HeartFunction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 633Dario Bugada, Valentina Bellini, Elena G. Bignami, andLuca F. Lorini

40 Analgesic Drugs and Cardiac Safety . . . . . . . . . . . . . . . . . . . 649Giustino Varrassi, Joseph Pergolizzi, John F. Peppin, andAntonella Paladini

41 Does Chronic Pain Affect Heart Function? . . . . . . . . . . . . . . 671Giovanna Goldaniga and Massimo Allegri

42 Osteopathic Pain Management and CardiovascularDiseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 681Liria Papa

Part VIII Drugs Used in Psychiatry and Neurology AffectingCardiovascular Activity and Cardiovascular Drugs ProducingNeuropsychiatric Alterations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 705

43 Cardiovascular Adverse Effects of Psychotropic Drugs . . . . 707Anna Maria Pugliese, Elisabetta Coppi, Federica Cherchi, andGiancarlo Pepeu

44 Antipsychotics and Cardiac Side Effects . . . . . . . . . . . . . . . . 721Annamaria Mascolo, Cristina Scavone, Concetta Rafaniello,and A. Capuano

45 Psychiatric and Neurological Effects of CardiovascularDrugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 731Stefano Govoni

46 Adrenoceptor Blockers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 745Donato Cappetta, Konrad Urbanek, Liberato Berrino, andAntonella De Angelis

xiv Contents

47 Therapeutic Drug Monitoring in NeuropsychiatricDisorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 753Shivakumar Kolachalam, Stefano Aringhieri, andMarco Scarselli

48 Cardiovascular and Central Nervous System Toxicity byAnticancer Drugs in Breast Cancer Patients . . . . . . . . . . . . . 765Gianfranco Natale and Guido Bocci

Part IX Drugs of Abuse and Cardiovascular Function . . . . . . . . 791

49 Alcohol and Cardiovascular Function . . . . . . . . . . . . . . . . . . 793Maria Margherita Rando, Luisa Sestito, Antonio Mirijello, andGiovanni Addolorato

50 Nicotine and Cardiovascular Function . . . . . . . . . . . . . . . . . . 803Cristiano Ialongo, Diletta Sabatini, and Maria Caterina Grassi

51 The Impact of Morphine or Methadone Administrationon the Heart and Cardiovascular System . . . . . . . . . . . . . . . 817Flavio Moroni

52 Psychostimulants and Cardiovascular Function . . . . . . . . . . 829Emanuela Masini, Silvia Sgambellone, and Cecilia Lanzi

53 New Drugs of Abuse and Cardiovascular Function . . . . . . . 843Carlo Alessandro Locatelli, Davide Lonati, andValeria Margherita Petrolini

Part X Life Style and Activities Influencing Cardiovascularand Cerebral Function . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 869

54 Physical Activity and Cardiovascular Health . . . . . . . . . . . . 871Cosme Franklim Buzzachera, Luca Correale, andGiulia Liberali

55 Nutrition and Cardiovascular Disease . . . . . . . . . . . . . . . . . . 881Andrea Gomes Bernardes, Anna Tagliabue, andCinzia Ferraris

56 Cardiovascular and Emotional Effects of Music . . . . . . . . . . 891Laura Fusar-Poli and Cecilia Guiot

57 Psychological and Cardiovascular Effects of Meditationand Yoga . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 913Marcelo Bigliassi

Part XI Gender and Age Differences Affecting Brain andHeart Connection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 921

58 Pediatric Age and the Ontogeny of the Brain and HeartConnection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 923Lorenzo Mangone, Renzo Guerrini, and Michele Emdin

Contents xv

59 Gender Differences in Brain-Heart Connection . . . . . . . . . . 937Caterina Trevisan, Giuseppe Sergi, and Stefania Maggi

60 Vascular Risk Factors and Cognitive Function . . . . . . . . . . . 953Enrico Mossello and Niccolò Marchionni

61 Neural Effects on Cardiac Electrophysiology . . . . . . . . . . . . 973Elisabetta Cerbai, Raffaele Coppini, Laura Sartiani, andAlessandro Mugelli

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 987

xvi Contents

About the Editors

Stefano Govoni born in Milano, Italy, in 1950, isFull Professor of Pharmacology in the Depart-ment of Drug Sciences at the University ofPavia. He has worked in various Italian Universi-ties (Bari, Brescia, Milano, Pavia) and back in1979–81 at NIMH, St. Elizabeths hospital,Washington, D.C.

At the University of Pavia he has been directorof the Department of Experimental and AppliedPharmacology, President of the Evaluation Office,Chancellor’s Deputy for teaching activities, andVice-Chancellor. Stefano Govoni has been Con-sultant for Biological Research Programs,Alzheimer Unit, FBF Hospital, Brescia; memberof various ethical committees; and director of theBioethical Committee of the San Matteo Hospitalin Pavia, Italy.

Stefano Govoni has worked on brain aging andon Alzheimer’s disease (AD) contributing to thedefinition of the neurobiology and physiology ofbeta amyloid and to the characterization of theantidementia drugs. In 2010, together with EmilioVanoli, he started a search on the role of NGF inheart disease and is co-founder of a spin-off“Neuheart” working within this field. Recentlyhe started a search on the therapeutic appropriate-ness of drugs used in nursing homes and in theelderly. In the period 2000–2011 he has been thenational coordinator of a group of six laboratoriesbelonging to various Italian universities (Pavia,Genoa, Catania, Florence, Foggia, Palermo)working on AD.

Stefano Govoni is author of more than330 papers listed in Medline and some 20 books.

xvii

Pierluigi Politi is Full Professor of Psychiatry atthe University of Pavia, Italy, and Head of MentalHealth and Dependencies Department of ASSTPavia, the Regional Health Trust in Italy, andHead of the Specialization School in Psychiatry.He is also member of tEACH, the didactic subunitof International Association for Communicationin Healthcare, and Full Member of the Interna-tional Psychoanalytical Association.

His interest in heart and brain dynamics datesback to his Ph.D. years, when he supported theheart transplantation team at Pavia, PoliclinicoSan Matteo Foundation; he provided evaluationof the candidates and follow-up of more than onethousand recipients. More recently, he focused hisresearch and clinical work on autism spectrumdisorders, through an intense cooperation withCascina Rossago, the first Italian farm-community tailored for low-functioning peoplewith autism. He thus developed bench to bedsideresearch, besides new strategies of intervention,becoming a point of reference for the specialtalents in autism spectrum disorders. He also pro-moted some innovative job opportunities and abetter quality of life in people belonging to thiscondition.

He authored/coauthored/edited 14 books,many books chapters, and some 140 papers onpeer-reviewed journals. Being also an amateurjazz musician, he founded the OrchestraInvisibile (https://en.wikipedia.org/wiki/Orchestra_Invisibile) in 2005, a large jazz band, whereone half of musicians belong to the autism spec-trum condition.

Emilio Vanoli Graduated in Medicine with laudeand specialization in Cardiology at the Universityof Milano. He has been involved in basic scienceand clinical research on autonomic nervous sys-tem cardiac control since his 4th year med school.Emilio was trained at the Centro FisiologiaClinica and Ipertensione at the University ofMilano, and he developed his research at theDepartment of Physiology at the University ofOklahoma HSC where he reached the position ofadjunct Associate Professor of physiology andcardiology.

xviii About the Editors

His major achievement here was the firstexperimental evidence of feasibility and efficacyof chronic implantable vagal stimulation in ische-mic heart disease. Emilio is author and/orcoauthor of 96 full-length papers and editor of3 books. He is currently teaching at the Interna-tional Harvey School of Medicine at the Univer-sity of Pavia as Associate Professor of Cardiologyin the Department of Molecular Medicine. He issharing with Prof. Govoni the scientific directionof the academic spin-off named “Neu-Heart”whose first mission is active research on theNerve Growth Factor (NGF). Clinically wise, hepracticed as family doctor for 13 years in theItalian public healthcare system. Emilio wasmember of the intensive Coronary Care Unitstaff at the IRCCS San Matteo Hospital in Pavia.He established his role in the area of autonomictreatment of heart failure as member of CIBIS IIand III trials event committee.

Emilio is currently director of the outpatientsHeart Failure Clinic at the IRCCSMultiMedica inSesto San Giovanni (reference CardiovascularClinical Research Center for the Italian Ministryof Health Care) supported by extensive publicfunding to implement remote home monitoringof fragile patients.

About the Editors xix

About the Section Ediotrs

Roberto BergamaschiMultiple Sclerosis CenterIstituto Neurologico Nazionale ‘C. Mondino’Pavia, Italy

Laura CalvilloCardiology Research LaboratoryDepartment of CardiovascularNeural and Metabolic SciencesSan Luca HospitalIstituto Auxologico ItalianoIRCCS, Milan, Italy

Emilia d’EliaCardiovascular DepartmentCardiology 1 UnitAzienda Ospedaliera Papa Giovanni XXIIIBergamo, Italy

xxi

Luigi Ferini-StrambiSleep Disorders Center, Division of NeuroscienceSan Raffaele Scientific InstituteUniversità Vita-Salute San RaffaeleMilan, Italy

Laura Fusar-PoliDepartment of Clinical and ExperimentalMedicine, Section of PsychiatryUniversity of CataniaCatania, Italy

Alessia PascaleDepartment of Drug SciencesSection of PharmacologyUniversity of PaviaPavia, Italy

Matteo RocchettiDepartment of Brain and Behavioral SciencesUniversity of PaviaPavia, Italy

xxii About the Section Ediotrs

Massimo AllegriItalian Pain Group, Milan, ItalyPain Therapy ServicePoliclinico Monza HospitalMonza, Italy

Raffaele CoppiniDepartment of Neurosciences,Psychology, Drug Research and Child HealthUniversity of FlorenceFlorence, Italy

Guido MannaioniDepartment of Neuroscience, PsychologyDrug Research and Child Health(NEUROFARBA)Università degli Studi di FirenzeFirenze, Italy

Natascia BrondinoDepartment of Brain and Behavioral SciencesUniversity of PaviaPavia, Italy

About the Section Ediotrs xxiii

Niccolò MarchionniResearch Unit of Medicine of AgeingDepartment of Experimental and ClinicalMedicineUniversity of FlorenceFlorence, Italy

Enrico MosselloResearch Unit of Medicine of AgeingDepartment of Experimental and Clinical MedicineUniversity of FlorenceFlorence, Italy

xxiv About the Section Ediotrs

Contributors

Pasquale Abete Department of Translational Medical Sciences, Universityof Naples “Federico II”, Naples, Italy

Giovanni Addolorato Department of Internal Medicine and Gastroenterol-ogy, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy

Catholic University of Rome, Milan, Italy

Massimo Allegri Italian Pain Group, Milan, Italy

Pain Therapy Service, Policlinico Monza Hospital, Monza, Italy

Jeffrey L. Ardell Neurocardiology Research Center of Excellence, Univer-sity of California, Los Angeles, CA, USA

Cardiac Arrhythmia Center, University of California, Los Angeles, CA, USA

Davide Arillotta Department of Clinical and Experimental Medicine, Sec-tion of Psychiatry, University of Catania, Catania, Italy

Stefano Aringhieri Department of Translational Research and New Tech-nologies in Medicine and Surgery, University of Pisa, Pisa, Italy

Enrico Baldi Department of Molecular Medicine, Section of Cardiology,University of Pavia, Pavia, Italy

Cardiac Intensive Care Unit, Arrhythmia and Electrophysiology and Experi-mental Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

Division of Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia,Italy

Stefania Balzarotti Department of Psychology, Catholic University of theSacred Heart, Milan, Italy

Filippo M. Barberi Department of Clinical and Experimental Medicine,University of Pisa, Pisa, Italy

Claudia Bearzi Institute for Genetic and Biomedical Research (IRGB),National Research Council of Italy (CNR), Milan, Italy

Fondazione Giovanni Paolo II, Campobasso, Italy

Valentina Bellini Department of Anesthesia, ICU and Pain Therapy, Univer-sity Hospital of Parma, Parma, Italy

xxv

Andrea Gomes Bernardes Department of Physical Education, State Univer-sity of Londrina, Londrina, Brazil

Sara Bernini Center of Cognitive and Behavioral Disorders, National Insti-tute of Neurology IRCCS Mondino Foundation, Pavia, Italy

Liberato Berrino Department of Experimental Medicine, Section of Phar-macology, University of Campania “Luigi Vanvitelli”, Naples, Italy

Marcelo Bigliassi School of Physical Education and Sport, University of SãoPaulo, São Paulo, Brazil

Elena G. Bignami Department of Medicine and Surgery, University ofParma, Parma, Italy

Guido Bocci Dipartimento di Medicina Clinica e Sperimentale, Università diPisa, Pisa, Italy

Annalisa Boldrini Department of Brain and Behavioral Sciences, Universityof Pavia, Pavia, Italy

Natascia Brondino Department of Brain and Behavioral Sciences, Univer-sity of Pavia, Pavia, Italy

Dario Bugada Emergency and Intensive Care Department, ASST PapaGiovanni XXIII, Bergamo, Italy

Cosme Franklim Buzzachera Department of Public Health, ExperimentalMedicine and Forensic Science, University of Pavia, Pavia, Italy

Federica Calorio Department of Brain and Behavioural Sciences, Universityof Pavia, Pavia, Italy

Laura Calvillo Cardiology Research Laboratory, Department of Cardiovas-cular, Neural and Metabolic Sciences, San Luca Hospital, Istituto AuxologicoItaliano, IRCCS, Milan, Italy

Isabella Canavero Dipartimento di Neurologia d’Urgenza, IRCCSFondazione Mondino, Pavia, Italy

Donato Cappetta Department of Experimental Medicine, Section of Phar-macology, University of Campania “Luigi Vanvitelli”, Naples, Italy

A. Capuano Department of Experimental Medicine, Section of Pharmacol-ogy L. Donatelli, University of Campania “Luigi Vanvitelli”, Naples, Italy

Claudia Carmassi Department of Clinical and Experimental Medicine,University of Pisa, Pisa, Italy

Antonio Carolei Neurological Institute, Department of Biotechnological andApplied Clinical Sciences, University of L’Aquila, L’Aquila, Italy

Barbara Carpita Department of Clinical and Experimental Medicine,University of Pisa, Pisa, Italy

xxvi Contributors

Alberto Castella U.O. Anestesia e Rianimazione, IRCCS Ospedale SanRaffaele, Milan, Italy

Cristina Grazia Catania Department of Brain and Behavioural Sciences,University of Pavia, Pavia, Italy

Anna Cavallini Cerebrovascular Department, IRCCS Mondino Foundation,Pavia, Italy

Elisabetta Cerbai Department of Neurosciences, Psychology, DrugResearch and Child Health, University of Florence, Florence, Italy

Federica Cherchi Department of Neuroscience, Psychology, Drug Researchand Child Health (NEUROFARBA), University of Florence, Florence, Italy

Amanda Christensen Neuroscience Lab, Champlain College, Burlington,VT, USA

Pietro Cipresso Applied Technology for Neuro-Psychology Laboratory,Istituto Auxologico Italiano, IRCCS, Milan, Italy

Department of Psychology, Università Cattolica del Sacro Cuore, Milan, Italy

Barbara Colombo Neuroscience Lab, Champlain College, Burlington, VT,USA

Elisabetta Coppi Department of Neuroscience, Psychology, Drug Researchand Child Health (NEUROFARBA), University of Florence, Florence, Italy

Raffaele Coppini Department of Neurosciences, Psychology, Drug Researchand Child Health, University of Florence, Florence, Italy

Annalisa Cordone Department of Clinical and Experimental Medicine, Uni-versity of Pisa, Pisa, Italy

Luca Correale Department of Public Health, Experimental Medicine andForensic Science, University of Pavia, Pavia, Italy

Suzanne Cosh School of Psychology and Behavioural Science, University ofNew England, Armidale, NSW, Australia

Alfredo Costa Center of Cognitive and Behavioral Disorders, National Insti-tute of Neurology IRCCS Mondino Foundation, Pavia, Italy

Department of Brain and Behavior, University of Pavia, Pavia, Italy

Francesco Curcio Department of Translational Medical Sciences, Universityof Naples “Federico II”, Naples, Italy

Andrea M. D’Armini Division of Cardiac Surgery, Fondazione I.R.C.C.S.San Matteo Hospital, Pavia, Italy

Antonella De Angelis Department of Experimental Medicine, Section ofPharmacology, University of Campania “Luigi Vanvitelli”, Naples, Italy

Contributors xxvii

Roberto De Icco Headache Science Centre, IRCCS Mondino Foundation,Pavia, Italy

Department of Brain and Behavioral Sciences, University of Pavia, Pavia,Italy

Liliana Dell’Osso Department of Clinical and Experimental Medicine, Uni-versity of Pisa, Pisa, Italy

Veronica Dusi Department of Molecular Medicine, Section of Cardiology,University of Pavia, Pavia, Italy

Cardiac Intensive Care Unit, Arrhythmia and Electrophysiology and Experi-mental Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

Michele Emdin Institute of Life Science, Scuola Superiore Sant’Anna, Pisa,Italy

Division of Cardiology and Cardiovascular Medicine, Fondazione ToscanaGabriele Monasterio, Pisa, Italy

Luigi Ferini-Strambi Sleep Disorders Center, Division of Neuroscience,San Raffaele Scientific Institute, Università Vita-Salute San Raffaele, Milan,Italy

Javier Fernández Alvarez Department of Psychology, Università Cattolicadel Sacro Cuore, Milan, Italy

Cinzia Ferraris Human Nutrition and Eating Disorder Research Center,Department of Public Health Experimental and Forensic Medicine, Universityof Pavia, Pavia, Italy

Laura Fusar-Poli Department of Clinical and Experimental Medicine, Sec-tion of Psychiatry, University of Catania, Catania, Italy

Camilla Gesi Department of Clinical and Experimental Medicine, Universityof Pisa, Pisa, Italy

Department of Psychiatry, ASST Fatebenefratelli-Sacco, Milan, Italy

Giovanna Goldaniga Department of Anesthesia, Intensive Care and PainTherapy, “Federico II” University of Naples, Naples, Italy

Stefano Govoni Department of Drug Sciences, Section of Pharmacology,University of Pavia, Pavia, Italy

Maria Caterina Grassi Department of Physiology and Pharmacology“V. Erspamer”, “Sapienza” University of Rome, Rome, Italy

Edoardo Gronda Dept Medicina e Specialità Mediche – Nephrology Sec-tion, IRCCS Cà Granda Policlinico di Milano, Milan, Italy

Renzo Guerrini Neuroscience Department, Children’s Hospital AnnaMeyer – University of Florence, Florence, Italy

Cecilia Guiot Department of Brain and Behavioral Sciences, University ofPavia, Pavia, Italy

xxviii Contributors

Cristiano Ialongo Department of Physiology and Pharmacology“V. Erspamer”, “Sapienza” University of Rome, Rome, Italy

Shivakumar Kolachalam Department of Translational Research and NewTechnologies in Medicine and Surgery, University of Pisa, Pisa, Italy

Gustavo Rodrigues Costa Lages Interdisciplinary Pain Center, Swiss PainInstitute, Lausanne, Switzerland

Doriana Landi Multiple Sclerosis Unit, Department of Systems Medicine,University of Rome “Tor Vergata”, Rome, Italy

Cecilia Lanzi AOUC Hospital, Medical Toxicology Unit, Florence, Italy

Giulia Liberali Department of Public Health, Experimental Medicine andForensic Science, University of Pavia, Pavia, Italy

Ilaria Liguori Department of Translational Medical Sciences, University ofNaples “Federico II”, Naples, Italy

Carlo Alessandro Locatelli Toxicology Unit, Pavia Poison Centre andNational Toxicology Information Centre, Laboratory of Clinical and Experi-mental Toxicology, Pavia Hospital, Istituti Clinici Scientifici Maugeri IRCCS,Pavia, Italy

Davide Lonati Toxicology Unit, Pavia Poison Centre and National Toxicol-ogy Information Centre, Laboratory of Clinical and Experimental Toxicology,Pavia Hospital, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy

Luca F. Lorini Emergency and Intensive Care Department, ASST PapaGiovanni XXIII, Bergamo, Italy

Lucian Mihai Macrea Interdisciplinary Pain Center, Swiss Pain Institute,Lausanne, Switzerland

Stefania Maggi National Research Council, Neuroscience Institute, Padova,Italy

Serena Magno Cerebrovascular Department, IRCCS Mondino Foundation,Pavia, Italy

Lorenzo Mangone Scuola Superiore Sant’Anna, Pisa, Italy

Raffaele Manni Sleep Medicine and Epilepsy Unit, IRCCS Mondino Foun-dation, Pavia, Italy

Niccolò Marchionni Research Unit of Medicine of Ageing, Department ofExperimental and Clinical Medicine, University of Florence, Florence, Italy

Valentina Martinelli Department of Brain and Behavioral Sciences, Univer-sity of Pavia, Pavia, Italy

Daniele Martinelli Headache Science Centre, IRCCS Mondino Foundation,Pavia, Italy

Department of Brain and Behavioral Sciences, University of Pavia, Pavia,Italy

Contributors xxix

Isabella Masci Department of Clinical and Experimental Medicine, Univer-sity of Pisa, Pisa, Italy

Annamaria Mascolo Department of Experimental Medicine, Section ofPharmacology L. Donatelli, University of Campania “Luigi Vanvitelli”,Naples, Italy

Emanuela Masini Department of Neurosciences, Psychology, DrugResearch and Child Health (NEUROFARBA), University of Florence, Flor-ence, Italy

AOUC Hospital, Medical Toxicology Unit, Florence, Italy

Giorgia Mataluni Multiple Sclerosis Unit, Department of Systems Medi-cine, University of Rome “Tor Vergata”, Rome, Italy

Philippe Mavrocordatos Interdisciplinary Pain Center, Swiss Pain Institute,Lausanne, Switzerland

Sergio Merlino Department of Clinical and Experimental Medicine, Univer-sity of Pisa, Pisa, Italy

Giuseppe Micieli Dipartimento di Neurologia d’Urgenza, IRCCSFondazione Mondino, Pavia, Italy

Ludovico Mineo Department of Clinical and Experimental Medicine, Psy-chiatry Unit, University of Catania, Catania, Italy

Antonio Mirijello Department of Medical Sciences, IRCCS Casa Sollievodella Sofferenza Hospital, San Giovanni Rotondo, Italy

Nicola Montano Department of Internal Medicine, Fondazione IRCCS Ca’Granda, Ospedale Maggiore Policlinico, Milan, Italy

Department of Clinical Sciences and Community Health, University of Milan,Milan, Italy

Flavio Moroni Department of Neurofarba, University of Florence, Firenze,Italy

Andrea Morotti Cerebrovascular Department, IRCCS Mondino Founda-tion, Pavia, Italy

Donald Moss College of Integrative Medicine and Health Sciences,Saybrook University, Pasadena, CA, USA

Enrico Mossello Research Unit of Medicine of Ageing, Department ofExperimental and Clinical Medicine, University of Florence, Florence, Italy

Alessandro Mugelli Department of Neurosciences, Psychology, DrugResearch and Child Health, University of Florence, Florence, Italy

Gianfranco Natale Dipartimento di Ricerca Traslazionale e delle NuoveTecnologie in Medicina e Chirurgia, and Museo di Anatomia Umana “FilippoCivinini”, Università di Pisa, Pisa, Italy

xxx Contributors

Antonella Paladini Dipartimento di Medicina clinica, Sanità Pubblica,Scienze della Vita e dell’Ambiente, Università degli Studi dell’Aquila,L’Aquila, Italy

Liria Papa International College of Osteopathic Medicine (ICOM Educa-tional), Cinisello Balsamo (Mi), Italy

European Research Center for Osteopathic Medicine (ERCOM), CiniselloBalsamo, Italy

Gianfranco Parati Department of Medicine and Surgery, University ofMilano-Bicocca, and Istituto Auxologico Italiano IRCCS, S.Luca Hospital;Cardiology Unit and Dept of Cardiovascular, Neural and Metabolic Sciences,Milan, Italy

Alessia Pascale Department of Drug Sciences, Section of Pharmacology,University of Pavia, Pavia, Italy

Susanne Pedersen Department of Psychology, University of Southern Den-mark, Odense, Denmark

Department of Cardiology, Odense University Hospital, Odense, Denmark

Virginia Pedrinelli Department of Clinical and Experimental Medicine,University of Pisa, Pisa, Italy

Giancarlo Pepeu Department of Neuroscience, Psychology, Drug Researchand Child Health (NEUROFARBA), University of Florence, Florence, Italy

John F. Peppin Marian University College of Osteopathic Medicine, India-napolis, IN, USA

Joseph Pergolizzi NEMA Research Inc., Naples, FL, USA

Giulia Perini Center of Cognitive and Behavioral Disorders, National Insti-tute of Neurology IRCCS Mondino Foundation, Pavia, Italy

Department of Brain and Behavior, University of Pavia, Pavia, Italy

Alessandra Persico Cerebrovascular Department, IRCCSMondino Founda-tion, Pavia, Italy

Valeria Margherita Petrolini Toxicology Unit, Pavia Poison Centre andNational Toxicology Information Centre, Laboratory of Clinical and Experi-mental Toxicology, Pavia Hospital, Istituti Clinici Scientifici Maugeri IRCCS,Pavia, Italy

Antonia Pierobon Unità di Psicologia Clinica e Supporto Sociale, IstitutiClinici Scientifici Maugeri, IRCCS, Milan, Italy

Servizio di Psicologia, Istituti Clinici Scientifici Maugeri, IRCCS,Montescano, Italy

Francesca Pistoia Neurological Institute, Department of Biotechnologicaland Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy

Contributors xxxi

Claudio Placenti Department of Brain and Behavioral Sciences, Universityof Pavia, Pavia, Italy

Pierluigi Politi Department of Brain and Behavioral Sciences, University ofPavia, Pavia, Italy

Umberto Provenzani Department of Brain and Behavioral Sciences, Uni-versity of Pavia, Pavia, Italy

Anna Maria Pugliese Department of Neuroscience, Psychology, DrugResearch and Child Health (NEUROFARBA), University of Florence, Flor-ence, Italy

Concetta Rafaniello Department of Experimental Medicine, Section ofPharmacology L. Donatelli, University of Campania “Luigi Vanvitelli”,Naples, Italy

Matteo Cotta Ramusino Center of Cognitive and Behavioral Disorders,National Institute of Neurology IRCCS Mondino Foundation, Pavia, Italy

Department of Brain and Behavior, University of Pavia, Pavia, Italy

Maria Margherita Rando Department of Internal Medicine and Gastroen-terology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome,Italy

Catholic University of Rome, Milan, Italy

Giuseppe Riva Applied Technology for Neuro-Psychology Laboratory,Istituto Auxologico Italiano, IRCCS, Milan, Italy

Department of Psychology, Università Cattolica del Sacro Cuore, Milan, Italy

Roberto Rizzi Institute of Cell Biology and Neurobiology (IBCN), NationalResearch Council of Italy (CNR), Rome, Italy

Fondazione Istituto Nazionale di Genetica Molecolare (INGM) “Romeo edEnrica Invernizzi”, Milan, Italy

Matteo Rocchetti Department of Brain and Behavioural Sciences, Univer-sity of Pavia, Pavia, Italy

Camilla Rocchi Neurology Unit, Department of Systems Medicine, Univer-sity of Rome “Tor Vergata”, Rome, Italy

Alessandro Rodolico Department of Clinical and Experimental Medicine,Psychiatry Unit, University of Catania, Catania, Italy

Grazia Rutigliano Institute of Life Sciences, Scuola Superiore Sant’Anna,Pisa, Italy

Institute of Clinical Physiology, National Research Council, Pisa, Italy

Diletta Sabatini Department of Physiology and Pharmacology “V.Erspamer”, “Sapienza” University of Rome, Rome, Italy

Simona Sacco Neurological Institute, Department of Biotechnological andApplied Clinical Sciences, University of L’Aquila, L’Aquila, Italy

xxxii Contributors

Marco Sarà Post-Coma Rehabilitative Unit, San Raffaele Hospital, Cassino,Italy

IRCCS San Raffaele Pisana, Rome, Italy

Laura Sartiani Department of Neurosciences, Psychology, Drug Researchand Child Health, University of Florence, Florence, Italy

Simone Savastano Cardiac Intensive Care Unit, Arrhythmia and Electro-physiology and Experimental Cardiology, Fondazione IRCCS Policlinico SanMatteo, Pavia, Italy

Division of Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia,Italy

Marco Scarselli Department of Translational Research and New Technolo-gies in Medicine and Surgery, University of Pisa, Pisa, Italy

Cristina Scavone Department of Experimental Medicine, Section of Pharma-cology L. Donatelli, University of Campania “Luigi Vanvitelli”, Naples, Italy

Giuseppe Sergi Department of Medicine (DIMED), Geriatrics Division,University of Padova, Padova, Italy

Luisa Sestito Department of Internal Medicine and Gastroenterology,Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy

Catholic University of Rome, Milan, Italy

Silvia Sgambellone Department of Neurosciences, Psychology, DrugResearch and Child Health (NEUROFARBA), University of Florence, Flor-ence, Italy

Fredric Shaffer Department of Psychology, Center for Applied Psychophys-iology, Truman State University, Kirksville, MO, USA

Alessandro Silvani Department of Biomedical and Neuromotor Sciences,University of Bologna, Bologna, Italy

Marinella Sommaruga Unità di Psicologia Clinica e Supporto Sociale,Istituti Clinici Scientifici Maugeri, IRCCS, Milan, Italy

Servizio di Psicologia, Istituti Clinici Scientifici Maugeri, IRCCS,Montescano, Italy

Anna Tagliabue Human Nutrition and Eating Disorder Research Center,Department of Public Health Experimental and Forensic Medicine, Universityof Pavia, Pavia, Italy

Cristina Tassorelli Headache Science Centre, IRCCS Mondino Foundation,Pavia, Italy

Department of Brain and Behavioral Sciences, University of Pavia, Pavia,Italy

Rachel M. A. ter Bekke Department of Cardiology, CardiovascularResearch Institute Maastricht (CARIM), Maastricht University Medical Cen-ter, Maastricht, The Netherlands

Contributors xxxiii

Michele Terzaghi Sleep Medicine and Epilepsy Unit, IRCCS MondinoFoundation, Pavia, Italy

Department of Brain and Behavioural Sciences, University of Pavia, Pavia,Italy

Gianluca Testa Department of Translational Medical Sciences, University ofNaples “Federico II”, Naples, Italy

Department of Medicine and Health Sciences, University of Molise,Campobasso, Italy

Eleonora Tobaldini Department of Internal Medicine, Fondazione IRCCSCa’ Granda, Ospedale Maggiore Policlinico, Milan, Italy

Department of Clinical Sciences and Community Health, University of Milan,Milan, Italy

Gianpaolo Toscano Sleep Medicine and Epilepsy Unit, IRCCS MondinoFoundation, Pavia, Italy

Department of Brain and Behavioural Sciences, University of Pavia, Pavia,Italy

Edgar Toschi-Dias Department of Internal Medicine, Fondazione IRCCSCa’ Granda, Ospedale Maggiore Policlinico, Milan, Italy

Department of Clinical Sciences and Community Health, University of Milan,Milan, Italy

Heart Institute (InCor), University of Sao Paulo Medical School, São Paulo,Brazil

Caterina Trevisan Department of Medicine (DIMED), Geriatrics Division,University of Padova, Padova, Italy

Phillip J. Tully Centre for Men’s Health, University of Adelaide, NorthTerrace, SA, Australia

School of Medicine, The University of Adelaide, Adelaide, SA, Australia

Konrad Urbanek Department of Experimental Medicine, Section ofPharmacology, University of Campania “Luigi Vanvitelli”, Naples, Italy

Benedetta Vanini Division of Cardiac Surgery, Fondazione I.R.C.C.S. SanMatteo Hospital, Pavia, Italy

Emilio Vanoli Department of Molecular Medicine, University of Pavia,Pavia, Italy

Cardiovascular Department IRCCS MultiMedica, Sesto San Giovanni, Italy

Giustino Varrassi Paolo Procacci Foundation (FPP), Rome, Italy

Marco Vercesi Dipartimento di Scienze del Sistema Nervoso e delComportamento, Università degli Studi di Pavia, Pavia, Italy

xxxiv Contributors

Michele Viana Headache Science Centre, IRCCS Mondino Foundation,Pavia, Italy

Paul G. A. Volders Department of Cardiology, Cardiovascular ResearchInstitute Maastricht (CARIM), Maastricht University Medical Center, Maas-tricht, The Netherlands

Contributors xxxv