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1. The neurophysiological brain-fingerprint of Parkinson’s diseaseResearch in context

Author

Jason da Silva Castanheira, Alex I. Wiesman, Justine Y. Hansen, Bratislav Misic, Sylvain Baillet, John Breitner, Judes Poirier, Pierre Bellec, Véronique Bohbot, Mallar Chakravarty, Louis Collins, Pierre Etienne, Alan Evans, Serge Gauthier, Rick Hoge, Yasser Ituria-Medina, Gerhard Multhaup, Lisa-Marie Münter, Natasha Rajah, Pedro Rosa-Neto, Jean-Paul Soucy, Etienne Vachon-Presseau, Sylvia Villeneuve, Philippe Amouyel, Melissa Appleby, Nicholas Ashton, Daniel Auld, Gülebru Ayranci, Christophe Bedetti, Marie-Lise Beland, Kaj Blennow, Ann Brinkmalm Westman, Claudio Cuello, Mahsa Dadar, Leslie-Ann Daoust, Samir Das, Marina Dauar-Tedeschi, Louis De Beaumont, Doris Dea, Maxime Descoteaux, Marianne Dufour, Sarah Farzin, Fabiola Ferdinand, Vladimir Fonov, Julie Gonneaud, Justin Kat, Christina Kazazian, Anne Labonté, Marie-Elyse Lafaille-Magnan, Marc Lalancette, Jean-Charles Lambert, Jeannie-Marie Leoutsakos, Laura Mahar, Axel Mathieu, Melissa McSweeney, Pierre-François Meyer, Justin Miron, Jamie Near, Holly NewboldFox, Nathalie Nilsson, Pierre Orban, Cynthia Picard, Alexa Pichet Binette, Jean-Baptiste Poline, Sheida Rabipour, Alyssa Salaciak, Matthew Settimi, Sivaniya Subramaniapillai, Angela Tam, Christine Tardif, Louise Théroux, Jennifer Tremblay-Mercier, Stephanie Tullo, Irem Ulku, Isabelle Vallée, Henrik Zetterberg, Vasavan Nair, Jens Pruessner, Paul Aisen, Elena Anthal, Alan Barkun, Thomas Beaudry, Fatiha Benbouhoud, Jason Brandt, Leopoldina Carmo, Charles Edouard Carrier, Laksanun Cheewakriengkrai, Blandine Courcot, Doris Couture, Suzanne Craft, Christian Dansereau, Clément Debacker, René Desautels, Sylvie Dubuc, Guerda Duclair, Mark Eisenberg, Rana El-Khoury, Anne-Marie Faubert, David Fontaine, Josée Frappier, Joanne Frenette, Guylaine Gagné, Valérie Gervais, Renuka Giles, Renee Gordon, Clifford Jack, Benoit Jutras, Zaven Khachaturian, David Knopman, Penelope Kostopoulos, Félix Lapalme, Tanya Lee, Claude Lepage, Illana Leppert, Cécile Madjar, David Maillet, Jean-Robert Maltais, Sulantha Mathotaarachchi, Ginette Mayrand, Diane Michaud, Thomas Montine, John Morris, Véronique Pagé, Tharick Pascoal, Sandra Peillieux, Mirela Petkova, Galina Pogossova, Pierre Rioux, Mark Sager, Eunice Farah Saint-Fort, Mélissa Savard, Reisa Sperling, Shirin Tabrizi, Pierre Tariot, Eduard Teigner, Ronald Thomas, Paule-Joanne Toussaint, Miranda Tuwaig, Vinod Venugopalan, Sander Verfaillie, Jacob Vogel, Karen Wan, Seqian Wang, Elsa Yu, Isabelle Beaulieu-Boire, Pierre Blanchet, Sarah Bogard, Manon Bouchard, Sylvain Chouinard, Francesca Cicchetti, Martin Cloutier, Alain Dagher, Clotilde Degroot, Alex Desautels, Marie Hélène Dion, Janelle Drouin-Ouellet, Anne-Marie Dufresne, Nicolas Dupré, Antoine Duquette, Thomas Durcan, Lesley K. Fellows, Edward Fon, Jean-François Gagnon, Ziv Gan-Or, Angela Genge, Nicolas Jodoin, Jason Karamchandani, Anne-Louise Lafontaine, Mélanie Langlois, Etienne Leveille, Martin Lévesque, Calvin Melmed, Oury Monchi, Jacques Montplaisir, Michel Panisset, Martin Parent, Minh-Thy Pham-An, Ronald Postuma, Emmanuelle Pourcher, Trisha Rao, Jean Rivest, Guy Rouleau, Madeleine Sharp, Valérie Soland, Michael Sidel, Sonia Lai Wing Sun, Alexander Thiel, and Paolo Vitali

Subjects
Movement disorders, Parkinson’s disease, Neural dynamics, Oscillations, Arrhythmic brain activity, Magnetoencephalography, Medicine, Medicine (General), R5-920
Abstract

Summary: Background: Research in healthy young adults shows that characteristic patterns of brain activity define individual “brain-fingerprints” that are unique to each person. However, variability in these brain-fingerprints increases in individuals with neurological conditions, challenging the clinical relevance and potential impact of the approach. Our study shows that brain-fingerprints derived from neurophysiological brain activity are associated with pathophysiological and clinical traits of individual patients with Parkinson’s disease (PD). Methods: We created brain-fingerprints from task-free brain activity recorded through magnetoencephalography in 79 PD patients and compared them with those from two independent samples of age-matched healthy controls (N = 424 total). We decomposed brain activity into arrhythmic and rhythmic components, defining distinct brain-fingerprints for each type from recording durations of up to 4 min and as short as 30 s. Findings: The arrhythmic spectral components of cortical activity in patients with Parkinson’s disease are more variable over short periods, challenging the definition of a reliable brain-fingerprint. However, by isolating the rhythmic components of cortical activity, we derived brain-fingerprints that distinguished between patients and healthy controls with about 90% accuracy. The most prominent cortical features of the resulting Parkinson’s brain-fingerprint are mapped to polyrhythmic activity in unimodal sensorimotor regions. Leveraging these features, we also demonstrate that Parkinson’s symptom laterality can be decoded directly from cortical neurophysiological activity. Furthermore, our study reveals that the cortical topography of the Parkinson’s brain-fingerprint aligns with that of neurotransmitter systems affected by the disease’s pathophysiology. Interpretation: The increased moment-to-moment variability of arrhythmic brain-fingerprints challenges patient differentiation and explains previously published results. We outline patient-specific rhythmic brain signaling features that provide insights into both the neurophysiological signature and symptom laterality of Parkinson’s disease. Thus, the proposed definition of a rhythmic brain-fingerprint of Parkinson’s disease may contribute to novel, refined approaches to patient stratification. Symmetrically, we discuss how rhythmic brain-fingerprints may contribute to the improved identification and testing of therapeutic neurostimulation targets. Funding: Data collection and sharing for this project was provided by the Quebec Parkinson Network (QPN), the Pre-symptomatic Evaluation of Novel or Experimental Treatments for Alzheimer’s Disease (PREVENT-AD; release 6.0) program, the Cambridge Centre for Aging Neuroscience (Cam-CAN), and the Open MEG Archives (OMEGA). The QPN is funded by a grant from Fonds de Recherche du Québec - Santé (FRQS). PREVENT-AD was launched in 2011 as a $13.5 million, 7-year public-private partnership using funds provided by McGill University, the FRQS, an unrestricted research grant from Pfizer Canada, the Levesque Foundation, the Douglas Hospital Research Centre and Foundation, the Government of Canada, and the Canada Fund for Innovation. The Brainstorm project is supported by funding to SB from the NIH (R01-EB026299-05). Further funding to SB for this study included a Discovery grant from the Natural Sciences and Engineering Research Council of Canada of Canada (436355-13), and the CIHR Canada research Chair in Neural Dynamics of Brain Systems (CRC-2017-00311).

Published
2024
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2. Amyloid and Tau Pathology Associations With Personality Traits, Neuropsychiatric Symptoms, and Cognitive Lifestyle in the Preclinical Phases of Sporadic and Autosomal Dominant Alzheimer’s Disease

Author

Alexa Pichet Binette, Étienne Vachon-Presseau, John Morris, Randall Bateman, Tammie Benzinger, D. Louis Collins, Judes Poirier, John C.S. Breitner, Sylvia Villeneuve, Ricardo Allegri, Fatima Amtashar, Randy Bateman, Sarah Berman, Courtney Bodge, Susan Brandon, William (Bill) Brooks, Jill Buck, Virginia Buckles, Sochenda Chea, Jasmeer Chhatwal, Patricio Chrem, Helena Chui, Jake Cinco, Jack Clifford, Carlos Cruchaga, Mirelle D‘Mello, Tamara Donahue, Jane Douglas, Noelia Edigo, Nilufer Erekin-Taner, Anne Fagan, Marty Farlow, Angela Farrar, Howard Feldman, Gigi Flynn, Nick Fox, Erin Franklin, Hisako Fujii, Cortaiga Gant, Samantha Gardener, Bernardino Ghetti, Alison Goate, Jill Goldman, Brian Gordon, Neill Graff-Radford, Julia Gray, Jenny Gurney, Jason Hassenstab, Mie Hirohara, David Holtzman, Russ Hornbeck, Siri Houeland DiBari, Takeshi Ikeuchi, Snezana Ikonomovic, Gina Jerome, Mathias Jucker, Celeste Karch, Kensaku Kasuga, Takeshi Kawarabayashi, William (Bill) Klunk, Robert Koeppe, Elke Kuder-Buletta, Christoph Laske, Jae-Hong Lee, Johannes Levin, Daniel Marcus, Ralph Martins, Neal Scott Mason, Colin Masters, Denise Maue-Dreyfus, Eric McDade, Lucy Montoya, Hiroshi Mori, Akem Nagamatsu, Katie Neimeyer, James Noble, Joanne Norton, Richard Perrin, Marc Raichle, John Ringman, Jee Hoon Roh, Stephen Salloway, Peter Schofield, Hiroyuki Shimada, Tomoyo Shiroto, Mikio Shoji, Wendy Sigurdson, Hamid Sohrabi, Paige Sparks, Kazushi Suzuki, Laura Swisher, Kevin Taddei, Jen Wang, Peter Wang, Mike Weiner, Mary Wolfsberger, Chengjie Xiong, Xiong Xu, Angela Tam, Anne Labonté, Anne-Marie Faubert, Axel Mathieu, Cécile Madjar, Charles Edouard Carrier, Christian Dansereau, Christina Kazazian, Claude Lepage, Cynthia Picard, David Maillet, Diane Michaud, Doris Couture, Doris Dea, Claudio Cuello, Alan Barkun, Alan Evans, Blandine Courcot, Christine Tardif, Clément Debacker, Clifford R. Jack, David Fontaine, David S. Knopman, Gerhard Maultaup, Jamie Near, Jeannie-Marie Leoutsakos, Jean-Robert Maltais, Jason Brandt, Jens Pruessner, John C. Morris, Laksanun Cheewakriengkrai, Lisa-Marie Münter, Louis Collins, Mallar Chakravarty, Mark A. Sager, Marina Dauar-Tedeschi, Mark Eisenberg, Natasha Rajah, Paul Aisen, Joanne Toussaint, Pedro Rosa-Neto, Pierre Bellec, Penelope Kostopoulos, Pierre Etienne, Pierre N. Tariot, Pierre Orban, Reisa A. Sperling, Rick Hoge, Ronald G. Thomas, Serge Gauthier, Suzanne Craft, Thomas J. Montine, Vasavan Nair, Véronique Bohbot, Vinod Venugopalan, Vladimir Fonov, Yasser Ituria-Medina, Zaven S. Khachaturian, Eduard Teigner, Elena Anthal, Elsa Yu, Fabiola Ferdinand, Galina Pogossova, Ginette Mayrand, Guerda Duclair, Guylaine Gagné, Holly Newbold-Fox, Illana Leppert, Isabelle Vallée, Jacob W. Vogel, Jennifer Tremblay-Mercier, Joanne Frenette, Josée Frappier, Justin Kat, Justin Miron, Karen Wan, Laura Mahar, Leopoldina Carmo, Louise Théroux, Mahsa Dadar, Marianne Dufour, Marie-Elyse Lafaille-Magnan, Melissa Appleby, Mélissa Savard, Miranda Tuwaig, Mirela Petkova, Pierre Rioux, Pierre-François Meyer, Rana El-Khoury, Renee Gordon, Renuka Giles, Samir Das, Seqian Wang, Shirin Tabrizi, Sulantha Mathotaarachchi, Sylvie Dubuc, Tanya Lee, Thomas Beaudry, Valérie Gervais, Véronique Pagé, Julie Gonneaud, Gülebru Ayranci, Tharick A. Pascoal, René Desautels, Fatiha Benbouhoud, Eunice Farah Saint-Fort, Sander C.J. Verfaillie, Sarah Farzin, Alyssa Salaciak, Stephanie Tullo, Etienne Vachon-Presseau, Leslie-Ann Daoust, Theresa Köbe, Nathan Spreng, Melissa McSweeney, Nathalie Nilsson, Morteza Pishnamazi, and Christophe Bedetti

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, tau Proteins, Disease, Article, 03 medical and health sciences, Cognition, 0302 clinical medicine, Alzheimer Disease, Internal medicine, mental disorders, medicine, Humans, Dementia, Big Five personality traits, Family history, Life Style, Biological Psychiatry, Aged, Amyloid beta-Peptides, Extraversion and introversion, business.industry, medicine.disease, Neuroticism, 3. Good health, 030104 developmental biology, Positron-Emission Tomography, Cohort, Alzheimer's disease, business, 030217 neurology & neurosurgery
Abstract

Background Major prevention trials for Alzheimer’s disease (AD) are now focusing on multidomain lifestyle interventions. However, the exact combination of behavioral factors related to AD pathology remains unclear. In 2 cohorts of cognitively unimpaired individuals at risk of AD, we examined which combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle (years of education or lifetime cognitive activity) related to the pathological hallmarks of AD, amyloid-β, and tau deposits. Methods A total of 115 older adults with a parental or multiple-sibling family history of sporadic AD (PREVENT-AD [PRe-symptomatic EValuation of Experimental or Novel Treatments for AD] cohort) underwent amyloid and tau positron emission tomography and answered several questionnaires related to behavioral attributes. Separately, we studied 117 mutation carriers from the DIAN (Dominant Inherited Alzheimer Network) study group cohort with amyloid positron emission tomography and behavioral data. Using partial least squares analysis, we identified latent variables relating amyloid or tau pathology with combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle. Results In PREVENT-AD, lower neuroticism, neuropsychiatric burden, and higher education were associated with less amyloid deposition (p = .014). Lower neuroticism and neuropsychiatric features, along with higher measures of openness and extraversion, were related to less tau deposition (p = .006). In DIAN, lower neuropsychiatric burden and higher education were also associated with less amyloid (p = .005). The combination of these factors accounted for up to 14% of AD pathology. Conclusions In the preclinical phase of both sporadic and autosomal dominant AD, multiple behavioral features were associated with AD pathology. These results may suggest potential pathways by which multidomain interventions might help delay AD onset or progression.

Published
2021

3. Sentence-Level Movements in Parkinson's Disease: Loud, Clear, and Slow Speech

Author

Elaine Kearney, Petros Faloutsos, Melanie Baljko, Brandon Haworth, Yana Yunusova, and Renuka Giles

Subjects
Male, Linguistics and Language, medicine.medical_specialty, Parkinson's disease, Movement, Audiology, Pronunciation, Speech Acoustics, Language and Linguistics, Loudness, 030507 speech-language pathology & audiology, 03 medical and health sciences, Speech and Hearing, Dysarthria, 0302 clinical medicine, Speech Production Measurement, Tongue, medicine, Humans, Aged, Speech Intelligibility, Parkinson Disease, medicine.disease, Biomechanical Phenomena, Comprehension, Case-Control Studies, Female, medicine.symptom, 0305 other medical science, Psychology, 030217 neurology & neurosurgery, Sentence
Abstract

Purpose To further understand the effect of Parkinson's disease (PD) on articulatory movements in speech and to expand our knowledge of therapeutic treatment strategies, this study examined movements of the jaw, tongue blade, and tongue dorsum during sentence production with respect to speech intelligibility and compared the effect of varying speaking styles on these articulatory movements. Method Twenty-one speakers with PD and 20 healthy controls produced 3 sentences under normal, loud, clear, and slow speaking conditions. Speech intelligibility was rated for each speaker. A 3-dimensional electromagnetic articulograph tracked movements of the articulators. Measures included articulatory working spaces, ranges along the first principal component, average speeds, and sentence durations. Results Speakers with PD demonstrated significantly smaller jaw movements as well as shorter than normal sentence durations. Between-speaker variation in movement size of the jaw, tongue blade, and tongue dorsum was associated with speech intelligibility. Analysis of speaking conditions revealed similar patterns of change in movement measures across groups and articulators: larger than normal movement sizes and faster speeds for loud speech, increased movement sizes for clear speech, and larger than normal movement sizes and slower speeds for slow speech. Conclusions Sentence-level measures of articulatory movements are sensitive to both disease-related changes in PD and speaking-style manipulations.

Published
2017

4. Subjective Cognitive Decline Is Associated With Altered Default Mode Network Connectivity in Individuals With a Family History of Alzheimer's Disease

Author

Sander C.J. Verfaillie, Alexa Pichet Binette, Etienne Vachon-Presseau, Shirin Tabrizi, Mélissa Savard, Pierre Bellec, Rik Ossenkoppele, Philip Scheltens, Wiesje M. van der Flier, John C.S. Breitner, Sylvia Villeneuve, Paul Aisen, Elena Anthal, Melissa Appleby, Gülebru Ayranci, Alan Barkun, Thomas Beaudry, Fatiha Benbouhoud, Veronique Bohbot, Jason Brandt, John Breitner, Leopoldina Carmo, Edouard Carrier Charles, Mallar Chakravarty, Laksanun Cheewakriengkrai, Louis Collins, Blandine Courcot, Doris Couture, Suzanne Craft, Claudio Cuello, Mahsa Dadar, Christian Dansereau, null DasSamir, Dauar-Tedeschi Marina, Doris Dea, Clement Debacker, Rene Desautels, Sylvie Dubuc, Guerda Duclair, Marianne Dufour, Mark Eisenberg, Rana El-Khoury, Pierre Etienne, Alan Evans, Anne-Marie Faubert, Fabiola Ferdinand, Vladimir Fonov, David Fontaine, Josée Frappier, Frenette Joanne, Guylaine Gagne, Serge Gauthier, Valérie Gervais, Renuka Giles, Julie Gonneaud, Renee Gordon, Rick Hoge, Bradley Hyman, Yasser Ituria-Medina, Clifford Jack, Justin Kat, Christina Kazazian, Zaven Khachaturian, David Knopman, Penelope Kostopoulos, Anne Labonte, Marie-Elyse Lafaille-Magnan, Tanya Lee, Jeannie-Marie Leoutsakos, Claude Lepage, Illana Leppert, Cécile Madjar, Laura Mahar, David Maillet, Jean-Robert Maltais, Axel Mathieu, Sulantha Mathotaarachchi, Gerhard Maultaup, Ginette Mayrand, Pierre-François Meyer, Diane Michaud, Justin Miron, Thomas Montine, John Morris, Lisa-Marie Münter, Vasavan Nair, Jamie Near, Holly Newbold-Fox, Pierre Orban, Véronique Page, Tharick Pascoal, Mirela Petkova, Cynthia Picard, Galina Pogossova, Judes Poirier, Jens Pruessner, Natasha Rajah, Pierre Rioux, Pedro Rosa-Neto, Mark Sager, Eunice Farah Saint-Fort, Reisa Sperling, Angela Tam, Christine Tardif, Pierre Tariot, Eduard Teigner, Louise Theroux, Ronald Thomas, Paule-Joanne Toussaint, Jennifer Tremblay-Mercier, Miranda Tuwaig, Isabelle Vallee, Vinod Venugopalan, Sander Verfaillie, Jacob Vogel, Karen Wan, Seqian Wang, Elsa Yu, Radiology and nuclear medicine, Amsterdam Neuroscience - Neurodegeneration, Neurology, APH - Personalized Medicine, and APH - Methodology

Subjects
0301 basic medicine, Male, medicine.medical_specialty, Cognitive Neuroscience, Audiology, Neuropsychological Tests, Asymptomatic, 03 medical and health sciences, 0302 clinical medicine, Cognition, Alzheimer Disease, Neural Pathways, Medicine, Dementia, Humans, Radiology, Nuclear Medicine and imaging, Cognitive Dysfunction, Effects of sleep deprivation on cognitive performance, Neuropsychological assessment, Cognitive decline, Family history, Biological Psychiatry, Default mode network, Aged, Brain Mapping, medicine.diagnostic_test, business.industry, Middle Aged, medicine.disease, Magnetic Resonance Imaging, 030104 developmental biology, Disease Progression, Female, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery
Abstract

Background: Both subjective cognitive decline (SCD) and a family history of Alzheimer's disease (AD) portend risk of brain abnormalities and progression to dementia. Posterior default mode network (pDMN) connectivity is altered early in the course of AD. It is unclear whether SCD predicts similar outcomes in cognitively normal individuals with a family history of AD. Methods: We studied 124 asymptomatic individuals with a family history of AD (age 64 ± 5 years). Participants were categorized as having SCD if they reported that their memory was becoming worse (SCD+). We used extensive neuropsychological assessment to investigate five different cognitive domain performances at baseline (n = 124) and 1 year later (n = 59). We assessed interconnectivity among three a priori defined ROIs: pDMN, anterior ventral DMN, medial temporal memory system (MTMS), and the connectivity of each with the rest of brain. Results: Sixty-eight (55%) participants reported SCD. Baseline cognitive performance was comparable between groups (all false discovery rate-adjusted p values >.05). At follow-up, immediate and delayed memory improved across groups, but the improvement in immediate memory was reduced in SCD+ compared with SCD− (all false discovery rate–adjusted p values −, SCD+ subjects showed increased pDMN–MTMS connectivity (false discovery rate–adjusted p

Published
2018

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