Publications by authors named "Mandelli M"

Based on historic observations that children with reading disabilities were disproportionately both male and non-right-handed, and that early life insults of the left hemisphere were more frequent in boys and non-right-handed children, it was proposed that early focal neuronal injury disrupts typical patterns of motor hand and language dominance and in the process produces developmental dyslexia. To date, these theories remain controversial. We revisited these earliest theories in a contemporary manner, investigating demographics associated with reading disability, and in a subgroup with and without reading disability, compared structural imaging as well as patterns of activity during tasks of verb generation and non-word repetition using magnetoencephalography source imaging.

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  • Semantic dementia (SD) patients, particularly those with semantic variant primary progressive aphasia (svPPA) and semantic behavioral variant frontotemporal dementia (sbvFTD), exhibit challenges in identifying faces due to atrophy in the anterior temporal lobe (ATL).
  • The study involved 74 SD patients and 36 healthy controls, who underwent various face recognition and semantic processing tests, alongside structural MRI scans to assess neural correlates.
  • Findings indicated that while both patient groups struggled with semantic face tasks, they performed similarly on perceptual face tests, suggesting that perceptual deficits may not arise until later stages of the disease with more extensive ATL atrophy.
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Developmental dyslexia is typically associated with difficulties in basic auditory processing and in manipulating speech sounds. However, the neuroanatomical correlates of auditory difficulties in developmental dyslexia (DD) and their contribution to individual clinical phenotypes are still unknown. Recent intracranial electrocorticography findings associated processing of sound amplitude rises and speech sounds with posterior and middle superior temporal gyrus (STG), respectively.

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  • * Researchers used automated speech analysis on audio-recorded picture descriptions from 40 FTD patients and 22 healthy controls to identify linguistic features that could help distinguish between the two types of atrophy associated with each variant.
  • * The analysis revealed key speech features that could differentiate between FTD patients and healthy controls as well as between the two variants of FTD, suggesting potential for a non-invasive diagnostic tool that correlates with specific brain areas involved in language and
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Introduction: Frontotemporal lobar degeneration (FTLD) is associated with FTLD due to tau (FTLD-tau) or TDP (FTLD-TDP) inclusions found at autopsy. Arterial Spin Labeling (ASL) MRI is often acquired in the same session as a structural T1-weighted image (T1w), enabling detection of regional changes in cerebral blood flow (CBF). We hypothesize that ASL-T1w registration with more degrees of freedom using boundary-based registration (BBR) will better align ASL and T1w images and show increased sensitivity to regional hypoperfusion differences compared to manual registration in patient participants.

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  • Semantic dementia (SD) patients, including those with semantic variant primary progressive aphasia (svPPA) and semantic behavioral variant frontotemporal dementia (sbvFTD), struggle with identifying faces and known individuals due to right anterior temporal lobe (ATL) atrophy, but the presence of perceptual deficits in face recognition is still uncertain.
  • A study involving 74 SD patients and 36 cognitively healthy controls used a series of face processing tests and MRI scans to investigate the relationship between face recognition performance and brain structure.
  • Results showed that both svPPA and sbvFTD patients had significant impairments in semantic face processing tasks, but they performed well on perceptual face recognition tests, indicating that perceptual abilities
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  • Itching is common in older adults and may indicate neurodegenerative diseases like frontotemporal lobar degeneration (FTLD-SD) and Alzheimer's disease (AD), as certain brain areas associated with itch sensations could be affected by these conditions.
  • A study compared the incidence of itching in patients with FTLD-SD and AD, using brain MRIs and medical records from a research project at UCSF over a period of nearly 20 years.
  • Results showed that itching was more prevalent in FTLD-SD patients (38%) compared to those with AD (18%), suggesting a possible link between unexplained itching and neurodegenerative processes, particularly in those with behavioral variant frontotemporal dementia.
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Models of speech perception are centered around a hierarchy in which auditory representations in the thalamus propagate to primary auditory cortex, then to the lateral temporal cortex, and finally through dorsal and ventral pathways to sites in the frontal lobe. However, evidence for short latency speech responses and low-level spectrotemporal representations in frontal cortex raises the question of whether speech-evoked activity in frontal cortex strictly reflects downstream processing from lateral temporal cortex or whether there are direct parallel pathways from the thalamus or primary auditory cortex to the frontal lobe that supplement the traditional hierarchical architecture. Here, we used high-density direct cortical recordings, high-resolution diffusion tractography, and hemodynamic functional connectivity to evaluate for evidence of direct parallel inputs to frontal cortex from low-level areas.

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Morphosyntactic assessments are important for characterizing individuals with nonfluent/agrammatic variant primary progressive aphasia (nfvPPA). Yet, standard tests are subject to examiner bias and often fail to differentiate between nfvPPA and logopenic variant PPA (lvPPA). Moreover, relevant neural signatures remain underexplored.

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  • The study explores the impact of Primary Progressive Aphasia (PPA) variants—nonfluent/agrammatic (nfvPPA), logopenic (lvPPA), and semantic (svPPA)—on non-verbal cognitive abilities, specifically processing speed, using a non-verbal task called Match.
  • Results show that lvPPA and nfvPPA patients performed worse on the task compared to healthy controls and svPPA patients.
  • Neuroimaging revealed that poorer task performance correlated with reduced gray and white matter volumes in key brain regions associated with processing speed and executive control.
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  • The study investigates whether primary progressive apraxia of speech (PPAOS) and progressive agrammatic aphasia (PAA) are distinct conditions or part of a larger non-fluent aphasia spectrum.
  • Using a group of 98 patients, the research examined speech and language characteristics, alongside disease severity, to identify meaningful clinical subgroups and potential shared pathologies.
  • Findings indicated that most participants fit known clinical categories, but the overall data showed low clustering tendencies, suggesting that these speech disorders may not form clear, distinct syndromic entities.
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Study Objective: We aimed to characterize intra-operative mechanical ventilation with low or high positive end-expiratory pressure (PEEP) and recruitment manoeuvres (RM) regarding intra-tidal recruitment/derecruitment and overdistension using non-linear respiratory mechanics, and mechanical power in obese surgical patients enrolled in the PROBESE trial.

Design: Prospective, two-centre substudy of the international, multicentre, two-arm, randomized-controlled PROBESE trial.

Setting: Operating rooms of two European University Hospitals.

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Article Synopsis
  • - The non-fluent/agrammatic variant of primary progressive aphasia (nfvPPA) is characterized by symptoms like apraxia of speech and expressive agrammatism, leading to varying speech-language difficulties among patients over time.
  • - There is ongoing debate about whether to classify subtypes of nfvPPA based on symptom presence, including 'primary progressive apraxia of speech' and 'progressive agrammatic aphasia', but overlapping features challenge clear distinctions.
  • - In a study involving 104 patients, researchers linked specific brain atrophy to varying speech-language symptoms, identifying that the neural correlates for both apraxia of speech and expressive agrammatism are located in the left posterior inferior frontal
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Overlapping clinical presentations in primary progressive aphasia (PPA) variants present challenges for diagnosis and understanding pathophysiology, particularly in the early stages of the disease when behavioral (speech) symptoms are not clearly evident. Divergent atrophy patterns (temporoparietal degeneration in logopenic variant lvPPA, frontal degeneration in nonfluent variant nfvPPA) can partially account for differential speech production errors in the two groups in the later stages of the disease. While the existing dogma states that neurodegeneration is the root cause of compromised behavior and cortical activity in PPA, the extent to which neurophysiological signatures of speech dysfunction manifest independent of their divergent atrophy patterns remain unknown.

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Objective: Microtubule-associated protein tau (MAPT) mutations cause frontotemporal lobar degeneration, and novel biomarkers are urgently needed for early disease detection. We used task-free functional magnetic resonance imaging (fMRI) mapping, a promising biomarker, to analyze network connectivity in symptomatic and presymptomatic MAPT mutation carriers.

Methods: We compared cross-sectional fMRI data between 17 symptomatic and 39 presymptomatic carriers and 81 controls with (1) seed-based analyses to examine connectivity within networks associated with the 4 most common MAPT-associated clinical syndromes (ie, salience, corticobasal syndrome, progressive supranuclear palsy syndrome, and default mode networks) and (2) whole-brain connectivity analyses.

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Background And Objectives: Progressive focal anterior temporal lobe (ATL) neurodegeneration has been historically called semantic dementia. More recently, semantic variant primary progressive aphasia (svPPA) and semantic behavioral variant frontotemporal dementia (sbvFTD) have been linked with predominant left and right ATL neurodegeneration, respectively. Nonetheless, clinical tools for an accurate diagnosis of sbvFTD are still lacking.

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  • * Researchers identified key brain regions where the disease begins and examined how atrophy spreads by analyzing MRI data from individuals with lvPPA and healthy controls.
  • * Findings revealed two separate brain networks linked to language skills that predict how atrophy advances in lvPPA, highlighting potential differences in patient symptoms and outcomes.
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The 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 pre-determined 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.

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Developmental dyslexia is typically associated with difficulties in basic auditory processing and in manipulating speech sounds. However, the neuroanatomical correlates of auditory difficulties in developmental dyslexia (DD) and their contribution to individual clinical phenotypes are still unknown. Recent intracranial electrocorticography findings associated processing of sound amplitude rises and speech sounds with posterior and middle superior temporal gyrus (STG), respectively.

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Semantic variant primary progressive aphasia is a clinical syndrome characterized by marked semantic deficits, anterior temporal lobe atrophy and reduced connectivity within a distributed set of regions belonging to the functional network associated with semantic processing. However, to fully depict the clinical signature of semantic variant primary progressive aphasia, it is necessary to also characterize preserved neural networks and linguistic abilities, such as those subserving speech production. In this case-control observational study, we employed whole-brain seed-based connectivity on task-free MRI data of 32 semantic variant primary progressive aphasia patients and 46 healthy controls to investigate the functional connectivity of the speech production network and its relationship with the underlying grey matter.

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Semantic variant primary progressive aphasia (svPPA) is a neurodegenerative disorder characterized by a loss of semantic knowledge in the context of anterior temporal lobe atrophy (left > right). Core features of svPPA include anomia and single-word comprehension impairment. Despite growing evidence supporting treatment for anomia in svPPA, there is a paucity of research investigating neural mechanisms supporting treatment-induced gains and generalization to untrained items.

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Diagnostic criteria for dyslexia describe specific reading difficulties, and single-deficit models, including the phonological deficit theory, have prevailed. Children seeking diagnosis, however, do not always show phonological deficits, and may present with strengths and challenges beyond reading. Through extensive neurological, neuropsychological, and academic evaluation, we describe four children with visuospatial, socio-emotional, and attention impairments and spared phonology, alongside long-standing reading difficulties.

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Background And Objectives: Motor speech function, including speech timing, is a key domain for diagnosing nonfluent/agrammatic variant primary progressive aphasia (nfvPPA). Yet, standard assessments use subjective, specialist-dependent evaluations, undermining reliability and scalability. Moreover, few studies have examined relevant anatomo-clinical alterations in patients with pathologically confirmed diagnoses.

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Task-based functional MRI (tb-fMRI) represents an extremely valuable approach for the identification of language eloquent regions for presurgical mapping in patients with brain tumors. However, its routinely application is limited by patient-related factors, such as cognitive disability and difficulty in coping with long-time acquisitions, and by technical factors, such as lack of equipment availability for stimuli delivery. Resting-state fMRI (rs-fMRI) instead, allows the identification of distinct language networks in a 10-min acquisition without the need of performing active tasks and using specific equipment.

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