NICOLETTA MANZO

Dottoressa di ricerca

ciclo: XXXIV


supervisore: Prof. Alfredo Berardelli
relatore: Prof. Alfredo Berardelli
co-supervisore: Prof. Antonella Conte

Titolo della tesi: Investigating the pathophysiology of idiopathic focal dystonia: evidence of motor and somatosensory cortex abnormalities from a TMS and an EEG study

The first part of the present thesis provides an introduction to focal idiopathic dystonia. Evidence available from neurophysiological studies are briefly reviewed, with particular focus on sensorimotor cortex abnormalities. The occurrence of somatosensory symptoms, as well as neurophysiological alteration in the somatosensory system, are also highlighted. In the final part of the introduction, previous pathophysiological hypotheses, and relative limitations due to unclear and controversial features of the evidenced abnormalities, are detailed. The second part of this thesis is composed of some of the experimental studies that I conducted during my Ph.D at the Department of Human Neuroscience at Sapienza University of Rome, Italy. The research questions were 1) to provide evidence of defective inhibitory activity and sensory motor integration abnormalities in different forms of focal dystonia, focusing on their possible topographical specificity 2) to investigate mechanisms of sensory trick (ST), a manoeuvre used by a large amount of patients with dystonia to transiently alleviate motor symptoms, by evaluating changes in cortical oscillations in the sensorimotor cortex induced by ST. Study 1 aimed to seek cortical abnormalities in a rare form of focal idiopathic dystonia, namely oromandibular dystonia (OMD). Only a few studies investigated cortical abnormalities in OMD, and only one neurophysiological study performed with transcranial magnetic stimulation (TMS) investigated face M1 and recorded from facial muscles. Whether OMD share cortical abnormalities with other forms of dystonia, and whether cortical abnormalities are present a topographical specificity is unknown. The presence of a direct relationship between the possible alterations at cortical level and dystonic motor symptoms may also shed light on a role of these abnormalities in determining clinical manifestations. To answer these questions we used TMS to investigate both face and hand M1 in a sample of patients with OMD, compared to healthy controls. Results showed that both abnormal intracortical inhibition, and sensory-motor integration are altered in OMD, only in the affected cortical area and muscle. The present finding suggests a topographic specificity of cortical abnormalities in OMD and offers possible speculations on mechanism underlain, as well as on their role. Study 2 aimed to investigate mechanisms underlying effects of ST in dystonia. Several hypotheses have been proposed, but the contribution of sensory and motor systems and their role in determining the effects of ST are unknown. In this study, we investigated whether ST modulates cortical oscillations. Possible changes in sensorimotor cortex oscillations during the execution of an effective ST have been sought in different experimental conditions, each designed to investigate the role of a specific components of sensory and motor systems on its effect. The presence of possible cortical changes related to the execution of an effective ST, and their occurrence in specific experimental conditions, may offer new information on whether and how sensorimotor cortex oscillations relate to the clinical effect of ST. Moreover this information would allow the role of different components of sensory and motor system in the effect of ST to be discussed. To this aim we used electroencephalogram (EEG) to record possible ST related modulation of cortical oscillations in the sensorimotor cortex before, during, and after ST execution in patients with cervical dystonia (CD) with effective ST, compared to patients without ST. Results showed an event related desynchronization (ERD) in the mu (8-13) band in sensorimotor cortical regions in patients performing an effective ST, that was present during its execution and that temporarily related to reduced electromyography (EMG) activity in the dystonic muscles. Moreover, we found that the ERD in the mu band occurs when ST is actively prepared and performed by the patients, but also, though to a lesser extent, when ST is passively executed, and even when this is performed without touching the skin. Overall, our findings suggest that oscillatory activity changes in the mu band over the sensorimotor cortex are involved in the pathophysiology of ST, and also that proprioceptive changes related to ST execution play a crucial role in determining the observed EEG changes in the sensory motor cortex. In the general discussion of this thesis, we formulated possible interpretation of results obtained, discussed in the light of previous evidence and hypotheses. We proposed a crucial role of proprioceptive information, as well as its abnormal processing, in determining cortical abnormalities in different forms of idiopathic focal dystonia. Moreover, we discussed the possible role of proprioceptive alterations in determining motor symptoms and peculiar features of different forms of idiopathic focal dystonia.

Produzione scientifica

11573/1703310 - 2023 - A Novel Paired Somatosensory-Cerebellar Stimulation Induces Plasticity on Cerebellar-Brain Connectivity
Ginatempo, F; Manzo, N; Spampinato, D; Loi, N Burgio F; Rothwell, Jc; Deriu, F - 01a Articolo in rivista
rivista: THE CEREBELLUM (New York: Springer London: Martin Dunitz Ltd, 2002-) pp. - - issn: 1473-4230 - wos: WOS:001088862900001 (0) - scopus: 2-s2.0-85174940350 (0)

11573/1683398 - 2023 - Abnormalities in the face primary motor cortex in oromandibular dystonia
Ginatempo, Francesca; Manzo, Nicoletta; Loi, Nicola; Belvisi, Daniele; Cutrona, Carolina; Conte, Antonella; Berardelli, Alfredo; Deriu, Franca - 01a Articolo in rivista
rivista: CLINICAL NEUROPHYSIOLOGY ([S.l.] : Elsevier Science) pp. 151-160 - issn: 1872-8952 - wos: WOS:001019737800001 (3) - scopus: 2-s2.0-85157982301 (2)

11573/1692234 - 2023 - Changes in cerebellar output abnormally modulates cortical myoclonus sensorimotor hyperexcitability
Latorre, Anna; Rocchi, Lorenzo; Paparella, Giulia; Manzo, Nicoletta; Bhatia, Kailash P; Rothwell, John C - 01a Articolo in rivista
rivista: BRAIN (-Oxford: Oxford University Press -Oxford: Clarendon Press -London: Macmillan -London: Butterworths Scientific Publications, 1878-) pp. - - issn: 0006-8950 - wos: WOS:001163259100001 (0) - scopus: (0)

11573/1683373 - 2023 - Investigating the Effects of a Focal Muscle Vibration Protocol on Sensorimotor Integration in Healthy Subjects
Manzo, Nicoletta; Ginatempo, Francesca; Belvisi, Daniele; Arcara, Giorgio; Parrotta, Ilaria; Leodori, Giorgio; Deriu, Franca; Celletti, Claudia; Camerota, Filippo; Conte, Antonella - 01a Articolo in rivista
rivista: BRAIN SCIENCES (Basel: Molecular Diversity Preservation International) pp. 664- - issn: 2076-3425 - wos: WOS:000979232100001 (0) - scopus: 2-s2.0-85156187534 (0)

11573/1683330 - 2023 - Cortical mechanisms of sensory trick in cervical dystonia
Manzo, Nicoletta; Leodori, Giorgio; Ruocco, Giulia; Belvisi, Daniele; Merchant, Shabbir Hussain I; Fabbrini, Giovanni; Berardelli, Alfredo; Conte, Antonella - 01a Articolo in rivista
rivista: NEUROIMAGE. CLINICAL (Amsterdam : Elsevier) pp. 103348- - issn: 2213-1582 - wos: WOS:000976369500001 (4) - scopus: 2-s2.0-85147925419 (4)

11573/1705665 - 2023 - White and gray matter alterations in de novo PD patients: which matter most?
Pietracupa, Sara; Belvisi, Daniele; Piervincenzi, Claudia; Tommasin, Silvia; Pasqua, Gabriele; Petsas, Nikolaos; De Bartolo, Maria Ilenia; Fabbrini, Andrea; Costanzo, Matteo; Manzo, Nicoletta; Berardelli, Alfredo; Pantano, Patrizia - 01a Articolo in rivista
rivista: JOURNAL OF NEUROLOGY (Heidelberg: Springer Verlag Heidelberg: Steinkopff) pp. - - issn: 1432-1459 - wos: WOS:000932870700002 (3) - scopus: 2-s2.0-85147744127 (4)

11573/1660141 - 2022 - A combined panel of salivary biomarkers in de novo Parkinson's Disease
De Bartolo, Maria Ilenia; Vivacqua, Giorgio; Belvisi, Daniele; Mancinelli, Romina; Fabbrini, Andrea; Manzo, Nicoletta; Costanzo, Matteo; Leodori, Giorgio; Conte, Antonella; Fabbrini, Giovanni; Morini, Sergio; Berardelli, Alfredo; Md, - 01a Articolo in rivista
rivista: ANNALS OF NEUROLOGY ([Boston] : American Neurological Association, c1977-) pp. - - issn: 1531-8249 - wos: WOS:000906409600001 (15) - scopus: 2-s2.0-85145367515 (18)

11573/1631592 - 2022 - Transcranial alternating current stimulation modulates cortical processing of somatosensory information in a frequency- and time-specific manner
Fabbrini, A.; Guerra, A.; Giangrosso, M.; Manzo, N.; Leodori, G.; Pasqualetti, P.; Conte, A.; Di Lazzaro, V.; Berardelli, A. - 01a Articolo in rivista
rivista: NEUROIMAGE (Academic Press Incorporated:6277 Sea Harbor Drive:Orlando, FL 32887:(800)543-9534, (407)345-4100, EMAIL: ap@acad.com, INTERNET: http://www.idealibrary.com, Fax: (407)352-3445) pp. 119119- - issn: 1053-8119 - wos: WOS:000806921500006 (8) - scopus: 2-s2.0-85127472722 (8)

11573/1617750 - 2022 - Pathophysiological mechanisms of oromandibular dystonia
Manzo, N.; Ginatempo, F.; Belvisi, D.; Defazio, G.; Conte, A.; Deriu, F.; Berardelli, A. - 01d Recensione
rivista: CLINICAL NEUROPHYSIOLOGY (Elsevier Science Ireland Limited:PO Box 85, Limerick Ireland:011 353 61 709600, 011 353 61 61944, EMAIL: usinfo-f@elsevier.com, INTERNET: http://www.elsevier.com, Fax: 011 353 61 709114) pp. 73-80 - issn: 1388-2457 - wos: WOS:000791948200008 (7) - scopus: 2-s2.0-85121981271 (7)

11573/1508124 - 2021 - Brainstem Reflexes in Idiopathic Cervical Dystonia: Does Medullary Dysfunction Play a Role?
Manzo, N.; Tocco, P.; Ginatempo, F.; Bertolasi, L.; Rocchi, L. - 01a Articolo in rivista
rivista: MOVEMENT DISORDERS CLINICAL PRACTICE (Hoboken, NJ : John Wiley & Sons, 2014-) pp. - - issn: 2330-1619 - wos: WOS:000617353700001 (0) - scopus: 2-s2.0-85100837912 (1)

11573/1449313 - 2020 - The Pathophysiological Correlates of Parkinson's Disease Clinical Subtypes
Belvisi, D.; Fabbrini, A.; De Bartolo, M. I.; Costanzo, M.; Manzo, N.; Fabbrini, G.; Defazio, G.; Conte, A.; Berardelli, A. - 01a Articolo in rivista
rivista: MOVEMENT DISORDERS (-WILEY-LISS, DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, USA, NJ, 07030 -Lippincott, Williams & Wilkins:530 Walnut Street:Philadelphia, PA 19106:(800)638-3030, (301)223-2300, EMAIL: orders@lww.com, INTERNET: http://www.lww.com, Fax: (301)223-2320, (301)223-2320) pp. - - issn: 0885-3185 - wos: WOS:000578436500001 (19) - scopus: 2-s2.0-85092267171 (26)

11573/1405597 - 2020 - Botulinum toxin effects on sensorimotor integration in focal dystonias
De Bartolo, M. I.; Manzo, N.; Ferrazzano, G.; Baione, V.; Belvisi, D.; Fabbrini, G.; Berardelli, A.; Conte, A. - 01a Articolo in rivista
rivista: TOXINS (Basel : Molecular Diversity Preservation International MDPI) pp. 277- - issn: 2072-6651 - wos: WOS:000541799400062 (6) - scopus: 2-s2.0-85084169588 (6)

11573/1473162 - 2020 - Happy faces selectively increase the excitability of cortical neurons innervating frowning muscles of the mouth
Ginatempo, Francesca; Manzo, Nicoletta; Ibanez-Pereda, Jaime; Rocchi, Lorenzo; Rothwell &Amp;, John C.; Deriu, Franca - 01a Articolo in rivista
rivista: EXPERIMENTAL BRAIN RESEARCH (Germany: Springer Verlag) pp. 1043-1049 - issn: 0014-4819 - wos: WOS:000528209400023 (2) - scopus: 2-s2.0-85082123601 (3)

11573/1447074 - 2020 - Investigating the effects of transcranial alternating current stimulation on primary somatosensory cortex
Manzo, N.; Guerra, A.; Giangrosso, M.; Belvisi, D.; Leodori, G.; Berardelli, A.; Conte, A. - 01a Articolo in rivista
rivista: SCIENTIFIC REPORTS (London: Springer Nature London: Nature Publishing Group) pp. 17129- - issn: 2045-2322 - wos: WOS:000582693200002 (6) - scopus: 2-s2.0-85092517663 (7)

11573/1350074 - 2019 - Exploring the connectivity between the cerebellum and facial motor cortex
Ginatempo, F.; Spampinato, D. A.; Manzo, N.; Rothwell, J. C.; Deriu, F. - 01f Lettera, Nota
rivista: BRAIN STIMULATION (Amsterdam, Oxford : Elsevier, 2008-) pp. 1586-1587 - issn: 1935-861X - wos: WOS:000496276700029 (7) - scopus: 2-s2.0-85073719455 (7)

11573/1350072 - 2019 - Lack of evidence for interhemispheric inhibition in the lower face primary motor cortex
Ginatempo, Francesca; Manzo, Nicoletta; Rothwell, John C; Deriu, Franca - 01a Articolo in rivista
rivista: CLINICAL NEUROPHYSIOLOGY ([S.l.] : Elsevier Science) pp. 1917-1925 - issn: 1872-8952 - wos: WOS:000485832400019 (9) - scopus: 2-s2.0-85070753654 (10)

11573/1225229 - 2018 - Voluntary movement takes shape. the link between movement focusing and sensory input gating
Belvisi, Daniele; Conte, Antonella; Cortese, Francesca Natalia; Tartaglia, Matteo; Manzo, Nicoletta; Li Voti, Pietro; Suppa, Antonio; Berardelli, Alfredo - 01a Articolo in rivista
rivista: FRONTIERS IN HUMAN NEUROSCIENCE (Lausanne : Frontiers Research Foundation) pp. 1-7 - issn: 1662-5161 - wos: WOS:000441977200001 (4) - scopus: 2-s2.0-85054816146 (3)

11573/1225118 - 2018 - Abnormal sensory gating in patients with different types of focal dystonias
Conte, Antonella; Belvisi, Daniele; De Bartolo, Maria Ilenia; Manzo, Nicoletta; Cortese, Francesca Natalia; Tartaglia, Matteo; Ferrazzano, Gina; Fabbrini, Giovanni; Berardelli, Alfredo - 01a Articolo in rivista
rivista: MOVEMENT DISORDERS (-WILEY-LISS, DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, USA, NJ, 07030 -Lippincott, Williams & Wilkins:530 Walnut Street:Philadelphia, PA 19106:(800)638-3030, (301)223-2300, EMAIL: orders@lww.com, INTERNET: http://www.lww.com, Fax: (301)223-2320, (301)223-2320) pp. 1910-1917 - issn: 0885-3185 - wos: WOS:000454126400012 (20) - scopus: 2-s2.0-85056158693 (22)

11573/1137723 - 2018 - Somatosensory temporal discrimination in Parkinson's disease, dystonia and essential tremor: Pathophysiological and clinical implications
Conte, Antonella; Ferrazzano, Gina; Belvisi, Daniele; Manzo, Nicoletta; Battista, Emanuele; Li Voti, Pietro; Nardella, Andrea; Fabbrini, Giovanni; Berardelli, Alfredo - 01a Articolo in rivista
rivista: CLINICAL NEUROPHYSIOLOGY (Elsevier Science Ireland Limited:PO Box 85, Limerick Ireland:011 353 61 709600, 011 353 61 61944, EMAIL: usinfo-f@elsevier.com, INTERNET: http://www.elsevier.com, Fax: 011 353 61 709114) pp. 1849-1853 - issn: 1388-2457 - wos: WOS:000440658200008 (21) - scopus: 2-s2.0-85049421268 (22)

11573/1081137 - 2017 - Does the somatosensory temporal discrimination threshold change over time in focal dystonia?
Conte, Antonella; Ferrazzano, Gina; Belvisi, Daniele; Manzo, Nicoletta; Suppa, Antonio; Fabbrini, Giovanni; Berardelli, Alfredo - 01a Articolo in rivista
rivista: NEURAL PLASTICITY (Cairo : Hindawi Publishing Corporation) pp. 1-6 - issn: 2090-5904 - wos: WOS:000411644400001 (11) - scopus: 2-s2.0-85030651840 (11)

11573/907765 - 2016 - Understanding the link between somatosensory temporal discrimination and movement execution in healthy subjects
Conte, Antonella; Belvisi, Daniele; Manzo, Nicoletta; Bologna, Matteo; Barone, Francesca; Tartaglia, Matteo; Upadhyay, Neeraj; Berardelli, Alfredo - 01a Articolo in rivista
rivista: PHYSIOLOGICAL REPORTS () pp. - - issn: 2051-817X - wos: WOS:000387443500002 (20) - scopus: 2-s2.0-84992206994 (19)

11573/884749 - 2016 - Somatosensory temporal discrimination threshold in Parkinson's disease parallels disease severity and duration
Conte, Antonella; Leodori, Giorgio; Ferrazzano, Gina; De Bartolo, Maria Ilenia; Manzo, Nicoletta; Fabbrini, Giovanni; Berardelli, Alfredo - 01a Articolo in rivista
rivista: CLINICAL NEUROPHYSIOLOGY (Elsevier Science Ireland Limited:PO Box 85, Limerick Ireland:011 353 61 709600, 011 353 61 61944, EMAIL: usinfo-f@elsevier.com, INTERNET: http://www.elsevier.com, Fax: 011 353 61 709114) pp. 2985-2989 - issn: 1388-2457 - wos: WOS:000381080400004 (27) - scopus: 2-s2.0-84989916314 (29)

11573/779986 - 2015 - Somatosensory temporal discrimination in essential tremor and isolated head and voice tremors
Conte, Antonella; Ferrazzano, Gina; Manzo, Nicoletta; Leodori, Giorgio; Fabbrini, Giovanni; Fasano, Alfonso; Tinazzi, Michele; Berardelli, Alfredo - 01a Articolo in rivista
rivista: MOVEMENT DISORDERS (-WILEY-LISS, DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, USA, NJ, 07030 -Lippincott, Williams & Wilkins:530 Walnut Street:Philadelphia, PA 19106:(800)638-3030, (301)223-2300, EMAIL: orders@lww.com, INTERNET: http://www.lww.com, Fax: (301)223-2320, (301)223-2320) pp. 822-827 - issn: 0885-3185 - wos: WOS:000354731500013 (30) - scopus: 2-s2.0-84929654379 (28)

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