Browsing by Author "Miller, Bruce L."
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Publication Network anatomy in logopenic variant of primary progressive aphasia(2023) Mandelli, Maria Luisa; Lorca-Puls, Diego L.; Lukic, Sladjana; Montembeault, Maxime; Gajardo-Vidal, Andrea; Licata, Abigail; Scheffler, Aaron; Battistella, Giovanni; Grasso, Stephanie M.; Bogley, Rian; Ratnasiri, Buddhika M.; La Joie, Renaud; Mundada, Nidhi S.; Europa, Eduardo; Rabinovici, Gil; Miller, Bruce L.; Leon, Jessica De; Henry, Maya L.; Miller, Zachary; Gorno-Tempini, Maria LuisaThe logopenic variant of primary progressive aphasia (lvPPA) is a neurodegenerative syndrome characterized linguistically by gradual loss of repetition and naming skills resulting from left posterior temporal and inferior parietal atrophy. Here, we sought to identify which specific cortical loci are initially targeted by the disease (epicenters) and investigate whether atrophy spreads through predetermined networks. First, we used cross-sectional structural MRI data from individuals with lvPPA to define putative disease epicenters using a surface-based approach paired with an anatomically fine-grained parcellation of the cortical surface (i.e., HCP-MMP1.0 atlas). Second, we combined cross-sectional functional MRI data from healthy controls and longitudinal structural MRI data from individuals with lvPPA to derive the epicenter-seeded resting-state networks most relevant to lvPPA symptomatology and ascertain whether functional connectivity in these networks predicts longitudinal atrophy spread in lvPPA. Our results show that two partially distinct brain networks anchored to the left anterior angular and posterior superior temporal gyri epicenters were preferentially associated with sentence repetition and naming skills in lvPPA. Critically, the strength of connectivity within these two networks in the neurologically-intact brain significantly predicted longitudinal atrophy progression in lvPPA. Taken together, our findings indicate that atrophy progression in lvPPA, starting from inferior parietal and temporoparietal junction regions, predominantly follows at least two partially nonoverlapping pathways, which may influence the heterogeneity in clinical presentation and prognosis.Publication Neural basis of speech and grammar symptoms in non-fluent variant primary progressive aphasia spectrum(2024) Lorca-Puls, Diego L.; Gajardo-Vidal, Andrea; Mandelli, Maria Luisa; Illán-Gala, Ignacio; Ezzes, Zoe; Wauters, Lisa D.; Battistella, Giovanni; Bogley, Rian; Ratnasiri, Buddhika; Licata, Abigail E.; Battista, Petronilla; García, Adolfo M.; Lead Tee, Boon; Lukic, Sladjana; Boxer, Adam L.; Rosen, Howard J.; Seeley, William W.; Grinberg, Lea T.; Spina, Salvatore; Miller, Bruce L.; Henry, Maya L.; Dronkers, Nina F.; Gorno-Tempini, Maria LuisaThe nonfluent/agrammatic variant of primary progressive aphasia (nfvPPA) is a neurodegenerative syndrome primarily defined by the presence of apraxia of speech (AoS) and/or expressive agrammatism. In addition, many patients exhibit dysarthria and/or receptive agrammatism. This leads to substantial phenotypic variation within the speech-language domain across individuals and time, in terms of both the specific combination of symptoms as well as their severity. How to resolve such phenotypic heterogeneity in nfvPPA is a matter of debate. “Splitting” views propose separate clinical entities: “primary progressive apraxia of speech” (PPAOS) when AoS occurs in the absence of expressive agrammatism, “progressive agrammatic aphasia” (PAA) in the opposite case, and “AOS + PAA” when mixed motor speech and language symptoms are clearly present. While therapeutic interventions typically vary depending on the predominant symptom (e.g., AoS vs expressive agrammatism), the existence of behavioral, anatomical, and pathological overlap across these phenotypes argues against drawing such clear-cut boundaries. In the current study, we contribute to this debate by mapping behavior to brain in a large, prospective cohort of well characterized patients with nfvPPA (n = 104). We sought to advance scientific understanding of nfvPPA and the neural basis of speech-language by uncovering where in the brain the degree of MRI-based atrophy is associated with inter-patient variability in the presence and severity of AoS, dysarthria, expressive agrammatism, or receptive agrammatism. Our cross-sectional examination of brain-behavior relationships revealed three main observations. First, we found that the neural correlates of AoS and expressive agrammatism in nfvPPA lie side by side in the left posterior inferior frontal lobe, explaining their behavioral dissociation/association in previous reports. Second, we identified a “left-right” and “ventral-dorsal” neuroanatomical distinction between AoS versus dysarthria, highlighting (i) that dysarthria, but not AoS, is significantly influenced by tissue loss in right-hemisphere motor-speech regions and (ii) that, within the left hemisphere, dysarthria and AoS map onto dorsally versus ventrally located motor-speech regions, respectively. Third, we confirmed that, within the large-scale grammar network, left frontal tissue loss is preferentially involved in expressive agrammatism and left temporal tissue loss in receptive agrammatism. Our findings thus contribute to define the function and location of the epicenters within the large-scale neural networks vulnerable to neurodegenerative changes in nfvPPA. We propose that nfvPPA be redefined as an umbrella term subsuming a spectrum of speech and/or language phenotypes that are closely linked by the underlying neuroanatomy and neuropathology.Item The Multi-Partner Consortium to Expand Dementia Research in Latin America (ReDLat): Driving Multicentric Research and Implementation Science(2021) Ibáñez, Agustín; Yokoyama, Jennifer S.; Possin, Katherine L.; Matallana, Diana; Lopera, Francisco; Nitrini, Ricardo; Takada, Leonel T.; Custodio, Nilton; Sosa Ortiz, Ana Luisa; Avila-Funes, José Alberto; Behrens, María Isabel; Slachevsky, Andrea; Myers, Richard M.; Cochran, J. Nicholas; Brusco, Luis Ignacio; Bruno, Martin A.; Brucki, Sonia M. D.; Pina-Escudero, Stefanie Danielle; Oliveira, Maira Okada de; Donnelly Kehoe, Patricio; Santamaria-Garcia, Hernando; Moguilner, Sebastián; Tagliazucchi, Enzo; Maito, Marcelo; Longoria Ibarrola, Erika Mariana; Pintado-Caipa, Maritza; Godoy, Maria Eugenia; Bakman, Vera; Javandel, Shireen; Kosik, Kenneth S.; Valcour, Victor; Miller, Bruce L.; The Latin America the Caribbean Consortium on Dementia (LAC-CD)Dementia is becoming increasingly prevalent in Latin America, contrasting with stable or declining rates in North America and Europe. This scenario places unprecedented clinical, social, and economic burden upon patients, families, and health systems. The challenges prove particularly pressing for conditions with highly specific diagnostic and management demands, such as frontotemporal dementia. Here we introduce a research and networking initiative designed to tackle these ensuing hurdles, the Multi-partner consortium to expand dementia research in Latin America (ReDLat). First, we present ReDLat’s regional research framework, aimed at identifying the unique genetic, social, and economic factors driving the presentation of frontotemporal dementia and Alzheimer’s disease in Latin America relative to the US. We describe ongoing ReDLat studies in various fields and ongoing research extensions. Then, we introduce actions coordinated by ReDLat and the Latin America and Caribbean Consortium on Dementia (LAC-CD) to develop culturally appropriate diagnostic tools, regional visibility and capacity building, diplomatic coordination in local priority areas, and a knowledge-to-action framework toward a regional action plan. Together, these research and networking initiatives will help to establish strong cross-national bonds, support the implementation of regional dementia plans, enhance health systems’ infrastructure, and increase translational research collaborations across the continent.Item The power of knowledge about dementia in Latin America across health professionals working on aging(2020) Ibanez, Agustin; Flichtentrei, Daniel; Hesse, Eugenia; Dottori, Martin; Tomio, Ailin; Slachevsky, Andrea; Serrano, Cecilia M; Gonzalez-Billaut, Christian; Custodio, Nilton; Miranda, Claudia; Bustin, Julian; Cetckovitch, Marcelo; Torrente, Fernando; Olavarria, Loreto; Leon, Tomas; Costa Beber, Barbara; Bruki, Sonia; Suemoto, Claudia K.; Nitrini, Ricardo; Miller, Bruce L.; Yokoyama, Jennifer S.Methods: We investigated opinions among health professionals working on aging in LACs (N =3365) with regression models including expertise-related information (public policies, BI), individual differences (work, age, academic degree), and location. Results: Experts specified low public policy knowledge (X2 = 41.27, P < .001), high levels of stigma (X2 = 2636.37, P < .001), almost absent BI knowledge (X2 = 56.58, P < .001), and needs for regional diagnostic manuals (X2 = 2893.63, df = 3, P < .001) and data-sharing platforms (X2 = 1267.5, df = 3, P < .001). Lack of dementia knowledge was modulated by different factors. An implemented BI-based treatment for a proposed prevention program improved perception across experts. Discussion: Our findings help to prioritize future potential actions of governmental agencies and non-governmental organizations (NGOs) to improve LACs’ dementia knowledge.