“Looks familiar, but I do not know who she is”:The role of the anterior right temporal lobe in famous face recognition

Processing a famous face involves a cascade of steps including detecting the presence of a face, recognizing it as familiar, accessing semantic/biographical information about the person, and finally, if required, production of the proper name. Decades of neuropsychological and neuroimaging studies have identified a network of occipital and temporal brain regions ostensibly comprising the 'core' system for face processing. Recent research has also begun to elucidate upon an 'extended' network, including anterior temporal and frontal regions. However, there is disagreement about which brain areas are involved in each step, as many aspects of face processing occur automatically in healthy individuals and rarely dissociate in patients. Moreover, some common phenomena are not easily induced in an experimental setting, such as having a sense of familiarity without being able to recall who the person is. Patients with the semantic variant of Primary Progressive Aphasia (svPPA) often recognize a famous face as familiar, even when they cannot specifically recall the proper name or biographical details. In this study, we analyzed data from a large sample of 105 patients with neurodegenerative disorders, including 43 svPPA, to identify the neuroanatomical substrates of three different steps of famous face processing. Using voxel-based morphometry, we correlated whole-brain grey matter volumes with scores on three experimental tasks that targeted familiarity judgment, semantic/biographical information retrieval, and naming. Performance in naming and semantic association significantly correlates with grey matter volume in the left anterior temporal lobe, whereas familiarity judgment with integrity of the right anterior middle temporal gyrus. These findings shed light on the neuroanatomical substrates of key components of overt face processing, addressing issues of functional lateralization, and deepening our understanding of neural substrates of semantic knowledge

Neurocognitive Basis of Repetition Deficits in Primary Progressive Aphasia

Previous studies indicate that repetition is affected in primary progressive aphasia (PPA), particularly in the logopenic variant, due to limited auditory-verbal short-term memory (avSTM). We tested repetition of phrases varied by length (short, long) and meaning (meaningful, non-meaningful) in 58 participants (22 logopenic, 19 nonfluent, and 17 semantic variants) and 21 healthy controls using a modified Bayles repetition test. We evaluated the relation between cortical thickness and repetition performance and whether sub-scores could discriminate PPA variants. Logopenic participants showed impaired repetition across all phrases, specifically in repeating long phrases and any phrases that were non-meaningful. Nonfluent, semantic, and healthy control participants only had difficulty repeating long, non-meaningful phrases. Poor repetition of long phrases was associated with cortical thinning in left temporo-parietal areas across all variants, highlighting the importance of these areas in avSTM. Finally, Bayles repetition phrases can assist classification in PPA, discriminating logopenic from nonfluent/semantic participants with 89% accuracy

Outcome of Agenesis of the Corpus Callosum Diagnosed by Fetal MRI

BACKGROUND: Fetal magnetic resonance imaging (MRI) is increasingly utilized for prenatal diagnosis of agenesis of the corpus callosum (ACC). This study aimed to (1) describe cases of ACC diagnosed by fetal MRI, (2) determine the frequency of postnatal confirmation by MRI, and (3) understand postnatal outcomes of infants with ACC. METHODS: Maternal records from Children\u27s National Hospital between January 2012 and June 2019 with a prenatal neurological consultation, fetal MRI, and ACC on imaging were included. Maternal, prenatal, and postnatal infant data were collected. Each case was categorized as complete or partial ACC and isolated or complex ACC by fetal MRI and group comparisons of outcomes were analyzed. RESULTS: A total of 127 maternal-fetal dyads with ACC were categorized into 45 isolated-complete, 17 isolated-partial, 46 complex-complete, and 19 complex-partial ACC. Of 75 live births, 72 had postnatal evaluations. In 43 of 59 (73%) cases with postnatal neuroimaging, prenatal ACC subcategory was confirmed. Children with isolated or complex and with partial or complete ACC had similar rates of developmental delays and epilepsy. Complex ACC cases had worse outcomes than isolated ACC, with complex ACC having more postnatal dysmorphisms and abnormal feeding and vision compared with isolated ACC. Similar neurodevelopmental outcomes were seen for partial and complete ACC. CONCLUSIONS: Children with isolated or complex ACC and with partial or complete ACC have a range of neurodevelopmental outcomes. Fetal and postnatal brain MRI is a valuable tool to understand differences of the corpus callosum that can guide genetic testing, prenatal counseling, and postnatal care

Effects of bilingualism on age at onset in two clinical Alzheimer's disease variants

IntroductionThe effect of bilingualism on age at onset has yet to be examined within different clinical variants of Alzheimer's disease.MethodsWe reviewed the research charts of 287 well-characterized participants with either amnestic Alzheimer's dementia or logopenic variant primary progressive aphasia (lvPPA) and identified bilingual speakers based on regular use of two or more languages and/or ability to communicate with native speakers in two or more languages. We evaluated whether bilingual speakers demonstrated a delay in age of symptom onset relative to monolingual speakers while controlling for other variables known to influence cognitive reserve.ResultsA 5-year delay in age at symptom onset was observed for bilingual relative to monolingual speakers with lvPPA. This delay in onset was not observed in the amnestic Alzheimer's dementia cohort.DiscussionBilingualism may serve as a unique cognitive reserve variable in lvPPA, but not in amnestic Alzheimer's dementia

“Looks familiar, but I do not know who she is”: The role of the anterior right temporal lobe in famous face recognition

Processing a famous face involves a cascade of steps including detecting the presence of a face, recognizing it as familiar, accessing semantic/biographical information about the person, and finally, if required, production of the proper name. Decades of neuropsychological and neuroimaging studies have identified a network of occipital and temporal brain regions ostensibly comprising the 'core' system for face processing. Recent research has also begun to elucidate upon an 'extended' network, including anterior temporal and frontal regions. However, there is disagreement about which brain areas are involved in each step, as many aspects of face processing occur automatically in healthy individuals and rarely dissociate in patients. Moreover, some common phenomena are not easily induced in an experimental setting, such as having a sense of familiarity without being able to recall who the person is. Patients with the semantic variant of Primary Progressive Aphasia (svPPA) often recognize a famous face as familiar, even when they cannot specifically recall the proper name or biographical details. In this study, we analyzed data from a large sample of 105 patients with neurodegenerative disorders, including 43 svPPA, to identify the neuroanatomical substrates of three different steps of famous face processing. Using voxel-based morphometry, we correlated whole-brain grey matter volumes with scores on three experimental tasks that targeted familiarity judgment, semantic/biographical information retrieval, and naming. Performance in naming and semantic association significantly correlates with grey matter volume in the left anterior temporal lobe, whereas familiarity judgment with integrity of the right anterior middle temporal gyrus. These findings shed light on the neuroanatomical substrates of key components of overt face processing, addressing issues of functional lateralization, and deepening our understanding of neural substrates of semantic knowledge

Distinct neurophysiology during nonword repetition in logopenic and non-fluent variants of primary progressive aphasia.

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. We test the hypothesis that nonword deficits in lvPPA and nfvPPA arise from distinct patterns of neural oscillations that are unrelated to atrophy. We use a novel structure-function imaging approach integrating magnetoencephalographic imaging of neural oscillations during a non-word repetition task with voxel-based morphometry-derived measures of gray matter volume to isolate neural oscillation abnormalities independent of atrophy. We find reduced beta band neural activity in left temporal regions associated with the late stages of auditory encoding unique to patients with lvPPA and reduced high-gamma neural activity over left frontal regions associated with the early stages of motor preparation in patients with nfvPPA. Neither of these patterns of reduced cortical oscillations was explained by cortical atrophy in our statistical model. These findings highlight the importance of structure-function imaging in revealing neurophysiological sequelae in early stages of dementia when neither structural atrophy nor behavioral deficits are clinically distinct

Neurocognitive basis of repetition deficits in primary progressive aphasia

Previous studies indicate that repetition is affected in primary progressive aphasia (PPA), particularly in the logopenic variant, due to limited auditory-verbal short-term memory (avSTM). We tested repetition of phrases varied by length (short, long) and meaning (meaningful, non-meaningful) in 58 participants (22 logopenic, 19 nonfluent, and 17 semantic variants) and 21 healthy controls using a modified Bayles repetition test. We evaluated the relation between cortical thickness and repetition performance and whether sub-scores could discriminate PPA variants. Logopenic participants showed impaired repetition across all phrases, specifically in repeating long phrases and any phrases that were non-meaningful. Nonfluent, semantic, and healthy control participants only had difficulty repeating long, non-meaningful phrases. Poor repetition of long phrases was associated with cortical thinning in left temporo-parietal areas across all variants, highlighting the importance of these areas in avSTM. Finally, Bayles repetition phrases can assist classification in PPA, discriminating logopenic from nonfluent/semantic participants with 89% accuracy

Task-Free Functional Language Networks: Reproducibility and Clinical Application

Intrinsic connectivity networks (ICNs) identified through task-free fMRI (tf-fMRI) offer the opportunity to investigate human brain circuits involved in language processes without requiring participants to perform challenging cognitive tasks. In this study, we assessed the ability of tf-fMRI to isolate reproducible networks critical for specific language functions and often damaged in primary progressive aphasia (PPA). First, we performed whole-brain seed-based correlation analyses on tf-fMRI data to identify ICNs anchored in regions known for articulatory, phonological, and semantic processes in healthy male and female controls (HCs). We then evaluated the reproducibility of these ICNs in an independent cohort of HCs, and recapitulated their functional relevance with a post hoc meta-analysis on task-based fMRI. Last, we investigated whether atrophy in these ICNs could inform the differential diagnosis of nonfluent/agrammatic, semantic, and logopenic PPA variants. The identified ICNs included a dorsal articulatory-phonological network involving inferior frontal and supramarginal regions; a ventral semantic network involving anterior middle temporal and angular gyri; a speech perception network involving superior temporal and sensorimotor regions; and a network between posterior inferior temporal and intraparietal regions likely linking visual, phonological, and attentional processes for written language. These ICNs were highly reproducible across independent groups and revealed areas consistent with those emerging from task-based meta-analysis. By comparing ICNs' spatial distribution in HCs with patients' atrophy patterns, we identified ICNs associated with each PPA variant. Our findings demonstrate the potential use of tf-fMRI to investigate the functional status of language networks in patients for whom activation studies can be methodologically challenging.SIGNIFICANCE STATEMENT We showed that a single, short, task-free fMRI acquisition is able to identify four reproducible and relatively segregated intrinsic left-dominant networks associated with articulatory, phonological, semantic, and multimodal orthography-to-phonology processes, in HCs. We also showed that these intrinsic networks relate to syndrome-specific atrophy patterns in primary progressive aphasia. Collectively, our results support the application of task-free fMRI in future research to study functionality of language circuits in patients for whom tasked-based activation studies might be methodologically challenging