Person: Gajardo-Vidal, Andrea
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Gajardo-Vidal
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Andrea
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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 Network anatomy in logopenic variant of primary progressive aphasia(2022) 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.; Joie, Renaud La; 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 The effect of right temporal lobe gliomas on left and right hemisphere neural processing during speech perception and production tasks(2022) Yamamoto, Adam Kenji; Gajardo-Vidal, Andrea; Sanjuán, Ana; Pope, Rebecca; Parker Jones, Oiwi; Hope, Thomas M. H.; Prejawa, Susan; Oberhuber, Marion; Mancini, Laura; Ekert, Justyna O.; Creasey, Megan; Yousry , Tarek A.; Green, David W.; Price, Cathy J.Using fMRI, we investigated how right temporal lobe gliomas affecting the posterior superior temporal sulcus alter neural processing observed during speech perception and production tasks. Behavioural language testing showed that three pre-operative neurosurgical patients with grade 2, grade 3 or grade 4 tumours had the same pattern of mild language impairment in the domains of object naming and written word comprehension. When matching heard words for semantic relatedness (a speech perception task), these patients showed under-activation in the tumour infiltrated right superior temporal lobe compared to 61 neurotypical participants and 16 patients with tumours that preserved the right postero-superior temporal lobe, with enhanced activation within the (tumour-free) contralateral left superior temporal lobe. In contrast, when correctly naming objects (a speech production task), the patients with right postero-superior temporal lobe tumours showed higher activation than both control groups in the same right postero-superior temporal lobe region that was under-activated during auditory semantic matching. The task dependent pattern of under-activation during the auditory speech task and over-activation during object naming was also observed in eight stroke patients with right hemisphere infarcts that affected the right postero-superior temporal lobe compared to eight stroke patients with right hemisphere infarcts that spared it. These task-specific and site-specific cross-pathology effects highlight the importance of the right temporal lobe for language processing and motivate further study of how right temporal lobe tumours affect language performance and neural reorganisation. These findings may have important implications for surgical management of these patients, as knowledge of the regions showing functional reorganisation may help to avoid their inadvertent damage during neurosurgery.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.