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

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. Although SN dopamine dysfunction has clear neurophysiological effects, the association of reduced LC norepinephrine signalling with brain activity in PD remains to be established. We used neuromelanin-sensitive T1-weighted MRI (PD, n = 58; healthy control, n = 27) and task-free magnetoencephalography (PD, n = 58; healthy control, n = 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-band (8-12 Hz) activity in patients with decreased LC neuromelanin, which were more strongly associated in patients with worse attentional impairments. This negative alpha-band-LC neuromelanin relationship is strongest in fronto-motor cortices, where alpha-band activity is inversely related to attention scores. Using neurochemical co-localization 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-band (15-29 Hz) activity in the left somatomotor 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-band activity is related to dysfunction of the noradrenergic system, and beta activity with relevance to motor impairments reflects dopaminergic dysfunction.

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Journal
Brain
Published
2024-09-13
DOI
https://doi.org/10.1093/brain/awae295
Citations
13
Primary Topic
Parkinson's Disease Mechanisms and Treatments
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article
Field-Weighted Citation Impact
4.80

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article

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

Marie‐Élyse Lafaille‐Magnan, Christina Tremblay, Christian Bocti, Jennifer Tremblay‐Mercier et al.
13 citations
Brain
Parkinson's Disease Mechanisms and Treatments
4.80
article

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

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

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. Although SN dopamine dysfunction has clear neurophysiological effects, the association of reduced LC norepinephrine signalling with brain activity in PD remains to be established. We used neuromelanin-sensitive T1-weighted MRI (PD, n = 58; healthy control, n = 27) and task-free magnetoencephalography (PD, n = 58; healthy control, n = 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-band (8-12 Hz) activity in patients with decreased LC neuromelanin, which were more strongly associated in patients with worse attentional impairments. This negative alpha-band-LC neuromelanin relationship is strongest in fronto-motor cortices, where alpha-band activity is inversely related to attention scores. Using neurochemical co-localization 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-band (15-29 Hz) activity in the left somatomotor 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-band activity is related to dysfunction of the noradrenergic system, and beta activity with relevance to motor impairments reflects dopaminergic dysfunction.

BrainVol. 148(3)
Montreal Neurological Institute and Hospital (CA), Simon Fraser University (CA), McGill University (CA)
Pfizer, McGill University, Government of Canada, Canada First Research Excellence Fund, National Institutes of Health, Pfizer Canada, Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, Fonds de Recherche du Québec - Santé
Good health and well-being
Openalex Percentile: Top 4%
Parkinson's Disease Mechanisms and Treatments
4.80
DOIOpen Access PDFOpenAlex
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