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Associations between neuromelanin depletion and cortical rhythmic activity in Parkinson's disease

2024; Oxford University Press; Linguagem: Inglês

10.1093/brain/awae295

1460-2156

Alex I. Wiesman, Victoria Madge, Edward A. Fon, Alain Dagher, D. Louis Collins, Sylvain Baillet, Sylvia Villeneuve, Judes Poirier, John C.S. Breitner, Mohamed Badawy, Sylvain Baillet, Andrée‐Ann Baril, Pierre Bellec, Véronique D. Bohbot, Danilo Bzdok, M. Mallar Chakravarty, D. Louis Collins, Mahsa Dadar, Simon Ducharme, Alan C. Evans, Claudine Gauthier, Maiya R. Geddes, Rick Hoge, Yasser Ituria-Medina, Maxime Montembeault, Gerhard Multhaup, Lisa Marie Munter, Natasha Rajah, Pedro Rosa‐Neto, Taylor W. Schmitz, Jean-Paul R. Soucy, R. Nathan Spreng, Christine L. Tardif, Étienne Vachon‐Presseau, Mohammadali Javanray, Meishan Ai, Philippe Amouyel, Jiarui Ao, Nicholas J. Ashton, Gabriel Aumont‐Rodrigue, Julie Bailly, Guilia Baracchini, Charles Beauchesne, Kaj Blennow, Christian Bocti, Lianne Boisvert, Ann Brinkmalm Westman, Nolan-Patrick Cunningham, Alain Dagher, Xing Dai, Thien Thanh Dang‐Vu, Samir Das, Marina Dauar-Tedeschi, Louis De Beaumont, Christine Déry, Maxime Descoteaux, Alfonso Fajardo Valdez, Vladimir Fonov, David Morgan, Jonathan Gallago, Aurelie Garrone, Louise Hudon, Adam Hull, Gabriel Jean, Anne Labonté, Robert Laforce, Marc Lalancette, Jean‐Charles Lambert, Jeannie‐Marie Leoutsakos, Laurence Maligne Bruneau, Julien Menes, Bratislav Misic, Béry Mohammediyan, Eugenia Nita Capota, Alix Noly‐Gandon, Adrian Eduardo Noriega de la Colina, Pierre Orban, Valentin Ourry, Cynthia Picard, Alexa Pichet Binette, Nathalie Prenevost, Ting Qiu, Marc James Quesnel, Charles Ramassamy, J.-P. Raoult, Jordana Remz, Erica Rothman, Isabel Sarty, Elisabeth Sylvain, Andràs Tikàsz, Stefanie A Tremblay, Jennifer Tremblay‐Mercier, Stéphanie Tullo, Jacob Turcotte, Irem Ulku, Paolo Vitali, Alfie Wearn, Kayla Williams, Yara Yakoub, Robert J. Zatorre, Henrik Zetterberg, Pierre Étienne, Serge Gauthier, Vasavan Nair, Jens C. Pruessner, Paul Aisen, Elena Anthal, Melissa Appleby, Nathalie Arbour, Daniel Auld, Gülebru Ayrancı, Alan Barkun, Thomas Beaudry, Christophe Bedetti, Marie‐Lise Béland, Fatiha Benbouhoud, Sophie Boutin, Jason Brandt, Leopoldina Carmo, Charles Edouard Carrier, Marianne Chapleau, Laksanun Cheewakriengkrai, Yalin Chen, Tima Chokr, Blandine Courcot, Doris Couture, Suzanne Craft, A. Claudio Cuello, Christian Dansereau, Leslie-Ann Daoust, Doris Dea, Clément Debacker, René Désautels, Sylvie Dubuc, Guerda Duclair, Marianne Dufour, Alana Dunlop, Mark J. Eisenberg, Rana El-Khoury, M Elie, Sarah Farzin, Anne-Marie Faubert, Fabiola Ferdinand, David Fontaine, Josée Frappier, Joanne Frenette, Guylaine Gagné, Valérie Gervais, Renuka Giles, Julie Gonneaud, Renee Gordon, Claudia Greco, Brittany Intzandt, Clifford R. Jack, Benoı̂t Jutras, Justin Kat, Christina Kazazian, Zaven S. Khachaturian, David S. Knopman, Theresa Köbe, Penelope Kostopoulos, Marie‐Élyse Lafaille‐Magnan, Felix Lapalme, Corina Lazarenco, Gloria Leblond-Baccichet, Tanya Lee, Marilou Lefebvre, David Lemay, Claude Lepage, Illana Leppert, Li Cai, Cécile Madjar, Laura Mahar, David Maillet, Jean-Robert Maltais, Axel Mathieu, Sulantha Mathotaarachchi, Ginette Mayrand, Melissa McSweeney, Pierre‐François Meyer, Diane Michaud, Justin Miron, Thomas J. Montine, John C. Morris, Jamie Near, Holly Newbold-Fox, Nathalie Nilsson, Hazal Ozlen, Véronique Pagé, Tharick A. Pascoal, Sandra Peillieux, Mirela Petkova, Morteza Pishnamazi, Galina Pogossova, Alexandre Poirier, Jean-Baptiste Poline, Sheida Rabipour, Marie-Josée Richer, Pierre Rioux, Mark A. Sager, Eunice Farah Saint-Fort, Alyssa Salaciak, Mélissa Savard, Matthew Settimi, Reisa A. Sperling, Frédéric St‐Onge, Cherie Strikwerda‐Brown, Sivaniya Subramaniapillai, Shirin Tabrizi, Angela Tam, Pierre N. Tariot, Eduard Teigner, Louise Théroux, Ronald G. Thomas, Paule‐Joanne Toussaint, Christina Tremblay, Miranda Tuwaig, Isabelle Vallée, Vinod Venugopalan, Sander C.J. Verfaillie, Jacob W. Vogel, Karen Wan, Seqian Wang, Elsa Yu, Isabelle Beaulieu‐Boire, Pierre Blanchet, Sarah Bogard, Manon Bouchard, Sylvain Chouinard, Francesca Cicchetti, Martin Cloutier, Alain Dagher, Samir Das, Clotilde Degroot, Alex Désautels, Marie Dion, Janelle Drouin‐Ouellet, Anne‐Marie Dufresne, Nicolas Dupré, Antoine Duquette, Thomas M. Durcan, Lesley K. Fellows, Edward A. Fon, Jean‐François Gagnon, Ziv Gan-Or, Angela Genge, Nicolas Jodoin, Jason Karamchandani, Anne‐Louise Lafontaine, Mélanie Langlois, Etienne Léveillé, Martin Lévesque, Calvin Melmed, Oury Monchi, Jacques Montplaisir, Michel Panisset, Martin Parent, Minh-Thy Pham-An, Jean-Baptiste Poline, Ronald B. Postuma, Emmanuelle Pourcher, Trisha Rao, J. Rivest, Guy A. Rouleau, Madeleine Sharp, Valérie Soland, Michael Sidel, Sonia Lai Wing Sun, Alexander Thiel, Paolo Vitali,

Parkinson's Disease Mechanisms and Treatments

Abstract Parkinson’s disease (PD) is marked by the death of neuromelanin-rich dopaminergic and noradrenergic cells in the substantia nigra (SN) and the locus coeruleus (LC), respectively, resulting in motor and cognitive impairments. While SN dopamine dysfunction has clear neurophysiological effects, the association of reduced LC norepinephrine signaling with brain activity in PD remains to be established. We used neuromelanin-sensitive T1-weighted MRI (NPD = 58; NHC = 27) and task-free magnetoencephalography (NPD = 58; NHC = 65) to identify neuropathophysiological factors related to the degeneration of the LC and SN in patients with PD. We found pathological increases in rhythmic alpha (8–12 Hz) activity in patients with decreased LC neuromelanin, with a stronger association in patients with worse attentional impairments. This negative alpha–LC neuromelanin relationship is strongest in fronto-motor cortices, where alpha activity is inversely related to attention scores. Using neurochemical colocalization analyses with normative atlases of neurotransmitter transporters, we also show that this effect is more pronounced in regions with high densities of norepinephrine transporters. These observations support a noradrenergic association between LC integrity and alpha band activity. Our data also show that rhythmic beta (15–29 Hz) activity in the left somato-motor cortex decreases with lower levels of SN neuromelanin; the same regions where beta activity reflects axial motor symptoms. Together, our findings clarify the association of well-documented alterations of rhythmic neurophysiology in PD with cortical and subcortical neurochemical systems. Specifically, attention-related alpha activity is related to dysfunction of the noradrenergic system, and beta activity with relevance to motor impairments reflects dopaminergic dysfunction.