Associations between neuromelanin depletion and cortical rhythmic activity in Parkinson’s disease
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 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, Jean‐Michel 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
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.