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Background Discourse analysis has recently received much attention in the aphasia literature. Even if post-stroke language recovery occurs throughout the longitudinal continuum of recovery, very few studies have documented discourse changes from the hyperacute to the chronic phases of recovery. Aims To document a multilevel analysis of discourse changes from the hyperacute phase to the chronic phase of post-stroke recovery using a series of single cases study designs. Methods & Procedures Four people with mild to moderate post-stroke aphasia underwent four assessments (hyperacute: 0–24 h; acute: 24–72 h; subacute: 7–14 days; and chronic: 6–12 months post-onset). Three discourse tasks were performed at each time point: a picture description, a personal narrative and a story retelling. Multilevel changes in terms of macro- and microstructural aspects were analysed. The results of each discourse task were combined for each time point. Individual effect sizes were computed to evaluate the relative strength of changes in an early and a late recovery time frame. Outcomes & Results Macrostructural results revealed improvements throughout the recovery continuum in terms of coherence and thematic efficiency. Also, the microstructural results demonstrated linguistic output improvement for three out of four participants. Namely, lexical diversity and the number of correct information units/min showed a greater gain in the early compared with the late recovery phase. Conclusions & Implications This study highlights the importance of investigating all discourse processing levels as the longitudinal changes in discourse operate differently at each phase of recovery. Overall results support future longitudinal discourse investigation in people with post-stroke aphasia.

The aim of this study was to explore whether rotational three-dimensional (3D) visualization of optical coherence tomography angiography (OCTA) volume data may yield valuable information regarding diabetic retinal microaneurysm (MA) characteristics. In this retrospective, observational study, we collected data from 20 patients (20 eyes) with diabetic retinopathy. Subjects were imaged with the SS-OCTA system (PLEX Elite 9000, Carl Zeiss Meditec Inc., Dublin, CA, USA). The OCTA volume data were processed with a volume projection removal algorithm and then exported to imageJ in order to obtain a 3D visualization of the analyzed MAs. The rotational three-dimensional OCTA images were qualitatively and quantitatively investigated. A total of 52 MAs were included in the analysis. On rotational 3D OCTA images, the number of vessels associated with each MA varied between 1 and 4, and most MAs (59.6%) were associated with 2 vessels. Moreover, in 20 MAs (38.4%) these vessels seem to originate from the SCP, while 26 MAs (50.0%) had associated vessels originating from the DVC, and 6 MAs had associated vessels arising from both the SCP and DVC (11.6%). Most MAs (31/52) had a ‘saccular’ shape. The number of retinal layers occupied by each MA ranged between 1 and 3 and the inner nuclear layer was the retinal layer most frequently occupied by MAs. In conclusion, this study used an algorithm to obtain rotational three-dimensional visualization of retinal MAs. The MAs’ architecture is complex and 3D visualization may clarify the true vascular origin of these lesions, which is often mistaken using en face OCTA images.

Introduction: Stargardt disease (STGD) is heterogeneous in terms of severity and rate of progression. New advancements in genetic testing and retinal imaging have improved prognostication in the disease. Areas covered: A PubMed-based search was carried out using the terms ‘Stargardt dystrophy’, ‘Stargardt disease’, ‘Fundus flavimaculatus’, and ‘ABCA4’. All studies published in English up to August 2020 were reviewed. Data from international multicenter trials were also considered in the discussion. Expert opinion: Genotype-phenotype correlations represent a challenge in STGD, as other epigenetic and environment modifiers participate in defining the clinical outcome and the long-term prognosis. Earlier age of onset and deleterious ABCA4 variants are the main determinants of severe progression. Quantitative imaging approaches are potentially useful for following-up STGD patients. Non-invasive biomarkers are needed to predict the natural history of the disease or drug effectiveness in future therapeutic trials.

Systemic hypertension is related to a variety of retinal manifestations. Reported herein is a case of malignant hypertension associated with bilateral foveal neurosensory detachment in a middle age woman with stenosis of the left renal artery. The present case outlines the importance of recognizing ocular manifestations as a possible consequence of life-threatening systemic disease.

Background: Previous findings have demonstrated the importance of discourse analysis in post-stroke aphasia, as it allows for in-depth examination of language impairment and represents key components of functional communication. However, little is known about the recovery of discourse over time. Aims: The main aim of this study is to measure the longitudinal changes in descriptive discourse production from the acute to chronic stages of post-stroke aphasia recovery. The secondary aim is to explore the association between discourse measures and overall language impairment severity measures at different testing points. Methods & Procedure: Seventeen French Canadian speakers with various types and severities of aphasia following a first left middle cerebral artery stroke participated in this study. They underwent three language assessments (acute: 0 to 72 hours; subacute: 7 to 14 days; chronic: 6 to 12 months post-onset). The picture description from the Western Aphasia Battery was analyzed at three time points. Changes in terms of thematic informativeness and microstructural variables were analyzed. Outcomes & Results: Regarding the micro-structural variables, the mean length of utterances (MLU) and the number of words per minute showed significant positive changes between the acute and chronic phases. For the thematic informativeness measures, the number of thematic units (TUs), the number of thematic units per minute (TUs/min) and the number of thematic units per utterance (TUs/utt) 4 increased significantly between the acute and chronic phases. Positive correlations between TUs and MLU in the acute phase and a general language impairment severity measure in the acute and chronic phases suggest a relationship between these measures and global language performance suggesting the potential predictive value of these variables in the acute phase. Conclusions & Implications: These findings support the use of thematic units in descriptive discourse analysis during an acute clinical examination of language as they require minimal additional time to score and track changes in post-stroke aphasia recovery. They capture long-term changes in discourse abilities and appear related to overall language measures in both the acute and chronic stages of recovery. The interpretation of the changes in MLU and the number of words per minute is less straightforward, as improvements in these measures carry different interpretations depending on the type of aphasia. Nonetheless, further studies are required to investigate test-retest reliability and the effect of therapy on the changes observed over time when using thematic units to document change in discourse.

The aim of this study was to measure macular perfusion in patients with type 1 diabetes and no signs of diabetic retinopathy (DR) using volume rendered three-dimensional (3D) optical coherence tomography angiography (OCTA). We collected data from 35 patients with diabetes and no DR who had OCTA obtained. An additional control group of 35 eyes from 35 healthy subjects was included for comparison. OCTA volume data were processed with a previously presented algorithm in order to obtain the 3D vascular volume and 3D perfusion density. In order to weigh the contribution of different plexuses’ impairment to volume rendered vascular perfusion, OCTA en face images were binarized in order to obtain two-dimensional (2D) perfusion density metrics. Mean ± SD age was 27.2 ± 10.2 years [range 19–64 years] in the diabetic group and 31.0 ± 11.4 years [range 19–61 years] in the control group (p = 0.145). The 3D vascular volume was 0.27 ± 0.05 mm3 in the diabetic group and 0.29 ± 0.04 mm3 in the control group (p = 0.020). The 3D perfusion density was 9.3 ± 1.6% and 10.3 ± 1.6% in diabetic patients and controls, respectively (p = 0.005). Using a 2D visualization, the perfusion density was lower in diabetic patients, but only at the deep vascular complex (DVC) level (38.9 ± 3.7% in diabetes and 41.0 ± 3.1% in controls, p = 0.001), while no differences were detected at the superficial capillary plexus (SCP) level (34.4 ± 3.1% and 34.3 ± 3.8% in the diabetic and healthy subjects, respectively, p = 0.899). In conclusion, eyes without signs of DR of patients with diabetes have a reduced volume rendered macular perfusion compared to control healthy eyes.

Objective The present study aims to assess the relationship between quantitative measures of connected speech production and performance in confrontation naming in early post-stroke aphasia (8-14 days post-stroke). Method: We collected connected speech samples elicited by a picture description task and administered a confrontation naming task to 20 individuals with early post-stroke aphasia and 20 healthy controls. Transcriptions were made in compliance with the CHAT format guidelines. Several micro- (i.e. duration, total number of words, words per minute, mean length of utterances, ratio of open- to closed-class words and noun-to-verb ratio, VOC-D, repetitions, self-corrections, and phonological and semantic errors) and macrolinguistic (i.e. informativeness and efficiency) measures were extracted. Results: We provide evidence for the presence of impairments in an array of micro- and macrolinguistic measures of speech in individuals with early post-stroke aphasia. We show that in the patient group, confrontation naming abilities most strongly relate to informativeness in a picture description task. Conclusion: Our findings contribute to a better understanding of the relationship between performance in confrontation naming and in connected speech production in the first days after stroke onset and also suggest that discourse analysis may provide unique, possibly more complex information.

The aim of this study was to report normal measurements of green-emitting fluorophores in the macula of healthy young individuals and to assess the repeatability of these quantitative metrics. To do so, healthy young volunteers were imaged twice (7 &plusmn, 3 days apart) using a confocal blue-light fundus autofluorescence (FAF) device with a shorter excitation wavelength (peak at 450 nm) and the capability for separately detecting the red and green components of the emission spectrum. The main outcome measure was the percentage of area occupied by green-emitting fluorophores in the macula. In addition, this measure was performed in separate regions providing a topographical assessment in the foveal, parafoveal and perifoveal regions. Furthermore, the level of agreement between repeated measurements was evaluated. Thirty eyes from 30 healthy volunteers were included in this analysis. Mean age was 26.2 &plusmn, 2.8 years (median: 25.0 years, range: 23.0&ndash, 32.0 years). Median (interquartile range&mdash, IQR) area occupied by green-emitting fluorophores was 3.6% (1.9&ndash, 4.7%) in the macular region. In the topographical analysis, this percentage was higher in the foveal area (median = 33.3%, IQR = 21.9&ndash, 41.2%), as compared with both the parafoveal (median = 5.3%, IQR = 2.4&ndash, 8.1%, p &lt, 0.0001) and perifoveal (median = 0.5%, IQR = 0.2&ndash, 0.8%, 0.0001) regions. The coefficient of variation (CV, ranging from 1.1% to 1.7% in the analyzed regions) and the intraclass correlation coefficient (ICC, ranging from 0.93 to 0.97) indicated high levels of repeatability. In conclusion, the assessment of green-emitting fluorophores is repeatable. The distribution of these fluorophores is highest in the foveal region. Assuming that flavin adenine dinucleotide (FAD) emits in the green autofluorescence spectrum, this variability could be secondary to an increased quantity of mitochondria in the foveal region.

Highlights • Both svPPA and AD manifest hippocampal atrophy. • svPPA and AD have similar pattern of hippocampal shape deformation as detected by deformation-based shape analysis. • Both diseases are characterized by a lateral displacement of the central part (body) of the hippocampus. • Morphological hippocampal changes are part of the early anatomical profile of patients with svPPA., Background Increasing evidence shows that the semantic variant of primary progressive aphasia (svPPA) is characterized by hippocampal atrophy. However, less is known about disease-related morphological hippocampal changes. The goal of the present study is to conduct a detailed characterization of the impact of svPPA on global hippocampus volume and morphology compared with control subjects and patients with Alzheimer’s disease (AD). Methods We measured hippocampal volume and deformation-based shape differences in 22 patients with svPPA compared with 99 patients with AD and 92 controls. Multiple Automatically Generated Templates Brain Segmentation Algorithm (MAGeT-Brain) was used on MRI images obtained at the diagnostic visit. Results Comparable left and right hippocampal atrophy were observed in svPPA and AD. Deformation-based shape analysis showed a common pattern of morphological deformation in svPPA and AD compared with controls. More specifically, both svPPA and AD showed inward deformations in the dorsal surface of the hippocampus, from head to tail on the left side, and more limited to the anterior portion of the body in the right hemisphere. These results also pointed out that both diseases are characterized by a lateral displacement of the central part (body) of the hippocampus. Discussion Our study provides critical new evidence of hippocampal morphological changes in svPPA, similar to those found in AD. These findings highlight the importance of considering morphological hippocampal changes as part of the anatomical profile of patients with svPPA.

Purpose: To evaluate demographic, clinical, imaging, and genetic factors associated with retinal pigment epithelium enlargement in Stargardt disease (STGD1) and to measure the agreement between short-wavelength fundus autofluorescence (SW-FAF) and near-infrared fundus autofluorescence (NIR-FAF). Methods: Retrospective cohort study of patients with STGD1 with >2 gradable SW- FAF images. RPE-atrophy areas were measured on SW-FAF and NIR-FAF at each visit and regressed against time to obtain the rate of RPE-atrophy enlargement. Agreement between SW-FAF and NIR-FAF with regards to baseline atrophic areas and rates of enlargement was evaluated. Baseline factors predictive of faster SW-FAF RPE-atrophy enlargement were investigated with linear mixed models. Results: Fifty-four eyes of 28 patients (median age: 45 years; 13 males) were included. SW-FAF and NIR-FAF agreed well for slow rates of RPE-atrophy progression, but agreement decreased as the rate increased. Median (interquartile range [IQR]) rate of RPE-atrophy expansion was 0.18 (0.10-0.85) mm2/year on SW-FAF and 0.24 (0.08-0.33) mm2/year on NIR-FAF. Larger baseline RPE-atrophy area (estimate: 0.057 mm'/year, P < 0.001), worse visual acuity (0.305 mm'/year, P = 0.005), multifocal disease (0.401 mm"7year, P = 0.02), and SW-FAF pattern (0.534 mnWyear, P =0.03) were associated with a faster rate of progression (predictive R?: 0.65).Conclusions: SW-FAF and NIR-FAF are not interchangeable in the evaluation of RPEatrophy enlargement, and both imaging modalities may be required for optimal detection of disease progression. A multivariable model based on baseline clinical and imaging information may identify patients at higher risk of fast disease progression. Translational Relevance: The knowledge of the agreement of different FAF modalities, the estimated rates of RPE-atrophy enlargement, and factors predictive of faster anatomic decay in STGD1 may allow tailored clinical management and better clinical trials design.

Objective The concepts of mild cognitive impairment (MCI) and subjective cognitive decline (SCD) have been proposed to identify individuals in the early stages of Alzheimer’s disease (AD), or other neurodegenerative diseases. One approach to validate these concepts is to investigate the relationship between pathological brain markers and cognition in those individuals. Method We included 126 participants from the Consortium for the Early Identification of Alzheimer’s disease-Quebec (CIMA-Q) cohort (67 SCD, 29 MCI, and 30 cognitively healthy controls [CH]). All participants underwent a complete cognitive assessment and structural magnetic resonance imaging. Group comparisons were done using cognitive data, and then correlated with hippocampal volumes and white matter hyperintensities (WMHs). Results Significant differences were found between participants with MCI and CH on episodic and executive tasks, but no differences were found when comparing SCD and CH. Scores on episodic memory tests correlated with hippocampal volumes in both MCI and SCD, whereas performance on executive tests correlated with WMH in all of our groups. Discussion As expected, the SCD group was shown to be cognitively healthy on tasks where MCI participants showed impairment. However, SCD’s hippocampal volume related to episodic memory performances, and WMH to executive functions. Thus, SCD represents a valid research concept and should be used, alongside MCI, to better understand the preclinical/prodromal phase of AD.

In the last decade, research has shown that word processing is influenced by the lexical and semantic features of words. However, norms for a crucial semantic variable—that is, conceptual familiarity—have not been available for a sizeable French database. We thus developed French Canadian conceptual familiarity norms for 3,596 nouns. This enriches Desrochers and Thompson’s (2009) database, in which subjective frequency and imageability values are already available for the same words. We collected online data from 313 Canadian French speakers. The full database of conceptual familiarity ratings is freely available at http://lingualab.ca/fr/projets/normes-de-familiarite-conceptuelle . We then demonstrated the utility of these new conceptual familiarity norms by assessing their contribution to lexical decision times. We conducted a stepwise regression model with conceptual familiarity in the last step. This allowed us to assess the independent contribution of conceptual familiarity beyond the contributions of other well-known psycholinguistic variables, such as frequency, imageability, and age of acquisition. The results showed that conceptual familiarity facilitated lexical decision latencies. In sum, these ratings will help researchers select French stimuli for experiments in which conceptual familiarity must be taken into account.

International audience; Posterior cortical atrophy (PCA) is a neurodegenerative disease affecting the posterior region of the brain. Little is known about both the impact of PCA on functioning and how to support patients on a daily basis. The purpose of this study was to describe the functional profile of DD, a woman diagnosed with PCA, as well as to explore a pilot cognitive rehabilitation program designed to optimize functioning in daily living. The ADL Profile was used to assess the daily tasks that DD chose to undertake. Four operations, i.e. formulate a goal, plan, carry out and verify goal attainment, were scored for each task. Difficulties were observed during the execution of all tasks, as she struggled to find items or showed unsafe behaviors. Impairments were also seen in formulating a goal and planning, especially for less routine tasks. DD identified two tasks to be addressed in rehabilitation: setting the table and dealing cards. Learning was optimized using errorless learning and compensatory aids when setting the table, while dealing cards received no intervention. Only setting the table improved significantly with time. Further studies should be conducted to portray a wider functional profile of people living with PCA and develop effective rehabilitation programs.

It is poorly understood whether and how normal aging affects different aspects of connected speech production, such as fluency, informativity, efficiency, and vocabulary use. The present study crosssectionally investigates the effects of age on a broad variety of language production measures, using connected speech samples elicited by the two most frequently used picture description tasks. Twenty-six young (20-25 y.o.) and twenty-two older participants (55-90 y.o.) were included in this study. Speech samples were transcribed using the CLAN program and eight measures were extracted. Our results indicate that, in a picture description task, older adults produce more disruptions to fluency, but that lexical diversity, informativity, and efficiency of speech remain unaffected by age. The use of less frequent words by older adults might reflect a larger vocabulary size. These findings have implications for future studies assessing changes in connected speech production, in both healthy and clinical populations., Le vieillissement normal module certaines habiletés cognitives, mais on ne sait pas si, et de quelle manière, différents aspects de la production du discours continu, tels que la fluence, l’informativité, l’efficacité et l’utilisation du vocabulaire, sont affectés. La présente étude transversale examine les effets de l’âge sur plusieurs mesures langagières à partir d’échantillons de discours continu suscités par les deux tâches de description d’image les plus utilisées. Vingt-six jeunes (20-25 ans) et vingt-deux participants âgés (55-90 ans) ont été recrutés. Les échantillons ont été transcrits via le programme CLAN et huit mesures ont été extraites. Nos résultats indiquent que les adultes plus âgés produisent plus de bris de fluidité verbale, mais que la diversité lexicale, l’informativité et l’efficacité du langage ne sont pas affectées par l’âge. L’usage de mots moins fréquents par les adultes plus âgés pourrait refléter un vocabulaire plus étendu. Ces résultats ont des implications pour les études futures portant sur les changements dans la production de discours continu chez les populations saines et cliniques.

Introduction In vivo clinical, anatomical and metabolic differences between posterior cortical atrophy (PCA) patients presenting with different Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers profiles are still unknown. Methods Twenty-seven PCA patients underwent CSF examination and were classified as 1) PCA with a typical CSF AD profile (PCA-tAD; abnormal amyloid and T-tau/P-tau biomarkers, n = 13); 2) PCA with an atypical AD CSF profile (PCA-aAD; abnormal amyloid biomarker only, n = 9); and 3) PCA not associated with AD (PCA-nonAD; normal biomarkers, n = 5). All patients underwent clinical and cognitive assessment, structural MRI, and a subset of them underwent brain 18F-FDG PET. Results All patients' groups showed a common pattern of posterior GM atrophy and hypometabolism typical of PCA, as well as equivalent demographics and clinical/cognitive profiles. PCA-tAD patients showed a group-specific pattern of hypometabolism in the left fusiform gyrus and inferior temporal gyrus. PCA-aAD did not present a group-specific atrophy pattern. Finally, group-specific gray matter atrophy in the right dorsolateral prefrontal cortex, left caudate nucleus and right medial temporal regions and hypometabolism in the right supplementary motor area and paracentral lobule were observed in PCA-nonAD patients. Conclusion Our findings suggest that both PCA-tAD and PCA-aAD patients are on the AD continuum, in agreement with the recently suggested A/T/N model. Furthermore, in PCA, the underlying pathology has an impact at least on the anatomo-functional presentation. Brain damage observed in PCA-tAD and PCA-aAD was mostly consistent with the well-described presentation of the disease, although it was more widespread in PCA-tAD group, especially in the left temporal lobe. Additional fronto-temporal (especially dorsolateral prefrontal) damage seems to be a clue to underlying non-AD pathology in PCA, which warrants the need for longitudinal follow-ups to investigate frontal symptoms in these patients., Highlights • In our sample, approximately 80% PCA patients presented with an AD CSF profile. • In 20% PCA cases, CSF investigations suggested a non-AD pathology. • PCA-AD and PCA-nonAD patients were not clinically different on general measures. • All PCA patients presented the neurodegeneration profile commonly reported in PCA. • PCA-nonAD patients presented additional group-specific neurodegeneration in more anterior fronto-temporal regions.

The present study investigated the pattern of longitudinal changes in cognition and anatomy in three variants of primary progressive aphasia (PPA). Eight patients with the non-fluent variant of PPA (nfvPPA), 13 patients with the semantic variant (svPPA), seven patients with the logopenic variant (lvPPA), and 29 age-matched, neurologically healthy controls were included in the study. All participants underwent longitudinal MRI, neuropsychological and language testing at baseline and at a 1-year follow-up. Tenser-based morphometry (TBM) was applied to T1-weighted MRI images in order to map the progression of gray and white matter atrophy over a 1-year period. Results showed that each patient group was characterized by a specific pattern of cognitive and anatomical changes. Specifically, nfvPPA patients showed gray matter atrophy progression in the left frontal and subcortical areas as well as a decline in motor speech and executive functions; svPPA patients presented atrophy progression in the medial and lateral temporal lobe and decline in semantic memory abilities; and lvPPA patients showed atrophy progression in lateral/posterior temporal and medial parietal regions with a decline in memory, sentence repetition and calculations. In addition, in all three variants, the white matter fibers underlying the abovementioned cortical areas underwent significant volume contraction over a 1-year period. Overall, these results indicate that the three PPA variants present distinct patterns of neuroanatomical contraction, which reflect their clinical and cognitive progression., Highlights • PPA variants present distinct patterns of neuroanatomical contraction. • Non-fluent variant of PPA shows GM contraction in left frontal and subcortical areas. • Semantic variant of PPA shows GM contraction in medial and lateral temporal lobe. • Logopenic variant of PPA shows GM contraction in lateral/posterior temporal and medial parietal regions.

The ability to recognize a famous person occurs through semantic memory. Previous neuroimaging studies have shown that the anterior temporal lobes (ATLs) are involved in the recognition of famous people. However, it is still a matter of debate whether the semantic processing of names or pictures of famous people has an impact on the activation of ATLs. The aim of this study was to explore the pattern of activation associated with a semantic processing of famous people based on face and written name stimuli. Fifteen healthy young individuals participated in our fMRI study, in which they were asked to perform a semantic categorization judgement task, based on profession, of visually presented pictures and names of famous people. Neuroimaging findings showed a common pattern of activation for faces and names mainly involving the inferior frontal regions, the posterior temporal lobe, the visual cortex and the anterior temporal lobes. We found that the comparison names vs. pictures lead to significant activation in the anterior superior temporal gyrus. On the other hand, faces vs. names seemed associated with increased activation in the medial ATL. Moreover, our results demonstrated that the functional connectivity network anchored to the medial ATL, compared to the anterior STG, is more connected to the bilateral occipital lobe and fusiform gyrus that are regions implicated in the visual system and visual processing of faces. This study provides critical evidence of the differential involvement of ATL regions in semantics of famous people.

Background/objectives: Alzheimer's disease (AD) and semantic dementia (SD) have distinct episodic memory profiles despite the hippocampal atrophy that characterizes both diseases. The aim of this study was to delineate the pattern of gray matter (GM) atrophy associated with AD and SD as well as any differences in these patterns by pooling together the results of previous voxel-based morphometry (VBM) studies.Methods/Overview: We conducted a meta-analysis of VBM studies that investigated GM atrophy in AD patients versus controls (CTRLs) and in SD patients versus CTRLs using the activation likelihood estimation (ALE) approach. Our systematic review allowed us to identify 63 VBM studies. Results: The results confirmed that in addition to the classical cortical pattern of atrophy involving posterior medial and lateral regions in AD and the anterior lateral temporal lobes in SD, both AD and SD patients are characterized by bilateral atrophy of the hippocampus. Furthermore, in SD, the hippocampal atrophy was limited to the anterior portion of the hippocampus, while in AD, both the anterior and posterior parts of the hippocampus exhibited atrophy. When we compared the foci identified in the studies that compared AD patients versus CTRLs with those identified in the studies that compared SD patients versus CTRLs, we observed that the atrophy in the posterior hippocampus and precuneus was more severe in AD. Conclusion: These results support theories that propose that the deficits observed in AD result from damage to the episodic memory network, which involves the posterior hippocampus and posterior medial brain regions. However, sparing of the posterior hippocampus in SD could explain the absence of episodic memory deficits in this population.

OBJECTIVE Alzheimer's disease (AD) is a progressive neurodegenerative disorder that affects the corpus callosum (CC), which plays a key role in interhemispheric coupling in high-demand conditions. Using 3D callosal measurements and a letter-matching paradigm, this 2-part study investigated the neural substrate of interhemispheric coupling in individuals with AD or amnestic mild cognitive impairment (a-MCI) and age-matched healthy individuals (HC). METHOD Thirty-three right-handed participants were MRI scanned to measure the volume of the CC in 5 sections. In Study 1, AD, a-MCI, and HC individuals performed a low-demand perceptual letter shape-matching task (e.g., A-A); in Study 2, a-MCI and HC individuals performed a "case-sensitive" letter-matching task (Study 2A) and a "load-sensitive" letter-matching task (Study 2B). RESULTS The results showed a positive correlation between Response Times and the midbody of the CC at the lowest cognitive demand level (Study 1) in participants with AD, and the total CC, midbody, caudal body, and isthmus of the CC at high cognitive demand levels (Study 2A) in normal aging. The volume of the anterior part of the CC was significantly negatively correlated with the interhemispheric behavioral indices for the a-MCI group (Study 1 and Study 2B). CONCLUSION This study provides evidence that interhemispheric coupling may constitute a flexible mechanism that can improve the brain's ability to meet processing demands for low cognitive demand in AD and for high cognitive demand in normal aging.

Though neuroimaging, pathology and pathophysiology suggest a subcortical and deep cortical involvement in Frontotemporal Lobar Degeneration (FTLD), no studies have comprehensively assessed the associated gray matter (GM) volume changes. We measured caudate, putamen, thalamus, and amygdala GM volume using probabilistic a-priori regions of interest (ROIs) in 53 early FTLD patients (38 behavioral variant FTD [bvFTD], 9 Semantic Dementia [SD], 6 Progressive Non-Fluent Aphasia [PNFA]), and 25 age-matched healthy controls (HC). ANOVA showed significant (P < 0.001) main effect of diagnosis, and significant interactions for diagnosis and region, and diagnosis and hemisphere. Post-hoc comparisons with HC showed bilateral GM atrophy in the caudate, putamen and thalamus, in bvFTD; a left-confined GM reduction in the amygdala in SD; and bilateral GM atrophy in the caudate and thalamus, and left-sided GM reduction in the putamen and amygdala in PNFA. Correlation analyses suggested an association between GM volumes and language, psychomotor speed and behavioral disturbances. This study showed a widespread involvement of subcortical and deep cortical GM in early FTLD with patterns specific for clinical entity.

International audience; Semantic deficits in Alzheimer's disease have been widely documented, but little is known about the integrity of semantic memory in the prodromal stage of the illness. The aims of the present study were to: (i) investigate naming abilities and semantic memory in amnestic mild cognitive impairment (aMCI), early Alzheimer's disease (AD) compared to healthy older subjects; (ii) investigate the association between naming and semantic knowledge in aMCI and AD; (iii) examine if the semantic impairment was present in different modalities; and (iv) study the relationship between semantic performance and grey matter volume using voxel-based morphometry. Results indicate that both naming and semantic knowledge of objects and famous people were impaired in aMCI and early AD groups, when compared to healthy age- and education-matched controls. Item-by-item analyses showed that anomia in aMCI and early AD was significantly associated with underlying semantic knowledge of famous people but not with semantic knowledge of objects. Moreover, semantic knowledge of the same concepts was impaired in both the visual and the verbal modalities. Finally, voxel-based morphometry analyses revealed that semantic impairment in aMCI and AD was associated with cortical atrophy in the anterior temporal lobe (ATL) region as well as in the inferior prefrontal cortex (IPC), some of the key regions of the semantic cognition network. These findings suggest that the semantic impairment in aMCI may result from a breakdown of semantic knowledge of famous people and objects, combined with difficulties in the selection, manipulation and retrieval of this knowledge.

Good cognitive performance requires adherence to rules specific to the task at hand. Patients with neurological disease often make rule violation (RV) errors, but the anatomical basis for RV during cognitive testing remains debated. The present study examined the neuroanatomical correlates of RV errors made on tests of executive functioning in 166 subjects diagnosed with neurodegenerative disease or as neurologically healthy. Specifically, RV errors were voxel-wisely correlated with gray matter volume derived from high-definition magnetic resonance images using voxel-based morphometry implemented in SPM2. Latent variable analysis showed that RV errors tapped a unitary construct separate from repetition errors. This analysis was used to generate factor scores to represent what is common among RV errors across tests. The extracted RV factor scores correlated with tissue loss in the lateral middle and inferior frontal gyri and the caudate nucleus bilaterally. When a more stringent control for global cognitive functioning was applied using Mini Mental State Exam scores, only the correlations with the right lateral prefrontal cortex (PFC) remained significant. These data underscore the importance of right lateral PFC in behavioral monitoring and highlight the potential of RV error assessment for identifying patients with damage to this region. (JINS, 2009,15, 354–364.)

Objective—To investigate the neural correlates of verbal and non-verbal semantic processing in neurodegenerative disease. Background—Semantic memory is often impaired in neurodegenerative disease. Neuropsychological and functional neuroimaging studies suggest that the semantic processing of verbal and non-verbal stimuli may depend on partially distinct brain networks. Methods—We examined this possibility using voxel-based morphometry to correlate performance on verbal and non-verbal versions of a semantic association task with regional gray matter atrophy in 144 individuals with a variety of neurodegenerative diseases. Results—Results showed that, regardless of stimulus type, semantic processing correlated with atrophy in both temporal lobes. In addition, material-specific correlations were found in left temporal regions for verbal stimuli and the right fusiform gyrus for non-verbal stimuli. Conclusions—These results provide evidence for a differential role of the left and right hemispheres in the extraction of semantic information from verbal and pictorial representations. Areas in the right inferior temporal lobe may be necessary to access structural descriptions of visually presented objects

Background: Data on white matter changes in corticobasal degeneration syndrome (CBDS) are not yet available, whereas cortical gray matter loss is a feature of this condition. The structural abnormalities related to a key feature of CBDS (limb apraxia) are unknown. Objectives: To measure selective structural changes in early CBDS using diffusion tensor imaging and voxel-based morphometry and to evaluate the structural correlates of limb apraxia. Design: Patient and control group comparison. Setting: Referral center for dementia and movement disorders. Participants: Twenty patients with CBDS and 21 matched control subjects. Interventions: Clinical and standardized neuropsychological evaluations, including assessment of limb apraxia. Main Outcome Measures: Gray and white matter changes in early CBDS. Results: Diffusion tensor imaging revealed decreases in fractional anisotropy in the long frontoparietal connecting tracts, the intraparietal associative fibers, and the corpus callosum. Fractional anisotropy was also reduced in the sensorimotor projections of the cortical hand areas. Voxel-based morphometry showed a prevalent gray matter reduction in the left hemisphere (in the inferior frontal and premotor cortices, parietal operculum, superotemporal gyrus, and hippocampus). The pulvinar, bilaterally, and the right cerebellar cortex also showed atrophy. Limb apraxia correlated with parietal atrophy and with fractional anisotropy reductions in the parietofrontal associative fibers (P

Frontotemporal dementia (FTD) is a neurodegenerative disease characterized by progressive behavioural abnormalities and frontotemporal atrophy. Here we used tensor based morphometry (TBM) to identify regions of longitudinal progression of gray matter atrophy in FTD compared to controls. T1-weighted MRI images were acquired at presentation and 1-year follow-up from 12 patients with mild to moderate FTD and 12 healthy controls. Using TBM as implemented in SPM2, a voxel-wise estimation of regional tissue volume change was derived from the deformation field required to warp a subject's late to early anatomical images. A whole brain analysis was performed, in which a level of significance of p < 0.05 corrected for multiple comparisons (family wise error-FWF) was accepted. Based on prior studies, a region of interest (1101) analysis was also performed, including in the search area bilateral medial and orbital frontal regions, anterior cingulate gyrus, insula, amygdala and hippocampus. Within this ROI a level of significance of p < 0.001 uncorrected was accepted. In the whole brain analysis, the anterior cingulate/paracingulate gyri were the only regions that showed significant atrophy change over 1 year. In the ROI analysis, the left ventro-medial frontal cortex, right medial superior frontal gyrus, anterior insulae and left amygdala/hippocampus showed significant longitudinal changes. In conclusion, limbic and paralimbic regions showed detectable gray matter contraction over 1 year in FTD, confirming the susceptibility of these regions to the disease and the consistency with their putative role in causing typical presenting behaviours. These results suggest that TBM might be useful in tracking progression of regional atrophy in FTD. (C) 2007 Elsevier Inc. All rights reserved.

Background: Two major clinical variants of frontotemporal dementia (FTD) have been described: frontal variant (fvFTD) and temporal variant (tvFTD). Objective: To analyze white matter (WM) and gray matter (GM) tissue organization in patients with fvFTD and tvFTD by means of diffusion tensor imaging and voxel-based morphometry, and the correlations with neuropsychological and behavioral variables. Design and Setting: Frontotemporal dementia clinic-based cohort and structural magnetic resonance imaging acquisition for voxel-based morphometry and diffusion tensor imaging measurements. Abnormalities were detected by a comparison with healthy control subjects. These variables were also correlated with clinical scores. Patients: Thirty-six patients (28 with fvFTD and 8 with tvFTD) in early disease stage and 23 healthy controls who underwent standardized clinical and neuropsychological evaluation and magnetic resonance imaging. Interventions: Diffusion tensor imaging and voxel-based morphometry. Main Outcome Measures: Neuroimaging analyses resulted in localized GM atrophy and reductions of white matter densities; the latter correlated with behavioral scores. Results: Voxel-based morphometry analysis showed separate patterns of GM atrophy in the 2 groups. Diffusion tensor imaging showed different WM reduction patterns in patients with fvFTD and tvFTD. The fvFTD group showed a selective WM reduction in the superior longitudinal fasciculus, interconnecting the frontal and occipital and the temporal and parietal regions. Conversely, patients with tvFTD were characterized by WM reductions in the inferior longitudinal fasciculus, which affected the connections between anterior temporal and frontal regions. The WM reductions in fvFTD paralleled both behavioral disturbances measured by Frontal Behavioral Inventory and neuropsychological deficits affecting frontal functions. Conclusions: The fvFTD and tvFTD variants are associated not only with selective local GM reductions but also with significant WM damage in early disease phase. The different WM patterns contribute to the different clinical syndromes in FTD and could be responsible for the further progression of atrophy in the later disease stages. ©2007 American Medical Association. All rights reserved.

Background: A comprehensive characterisation of grey and white matter changes in progressive supranuclear palsy (PSP), the second most common extrapyramidal syndrome after Parkinson disease, is still not available. Objective: To evaluate grey and white matter changes in mild PSP patients by voxel based morphometry (VBM) and diffusion tensor imaging (DTI), respectively. Methods: 14 mild PSP patients and 14 healthy controls entered the study and underwent a clinical and neuropsychological evaluation according with a standardised assessment. Each subject had a structural magnetic resonance imaging (MRI) study. Processing analysis of MRI data was carried out according to optimised VBM and fractional anisotropy was determined. Results: Compared with the controls, in PSP patients VBM analysis showed a significant clusters of reduced grey matter in premotor cortex, frontal operculum, anterior insula, hippocampus, and parahippocampal gyrus, bilaterally. With regard to subcortical brain regions, the pulvinar, dorsomedial and anterior nuclei of the thalamus, and superior and inferior culliculum were affected bilaterally. A bilateral decrease in fractional anisotropy in superior longitudinal fasciculus, anterior part of corpus callosum, arcuate fascicolus, posterior thalamic radiations, and internal capsule, probably involving the cortico-bulbar tracts, was present in PSP patients. Conclusions: These data provide evidence for both grey and white matter degeneration in PSP from the early disease stage. These structural changes suggest that atrophy of cortical and subcortical structures and neurodegeneration of specific fibre tracts contribute to neurological deficits in PSP.