scholarly journals The Frontal-Anatomic Specificity of Design Fluency Repetitions and Their Diagnostic Relevance for Behavioral Variant Frontotemporal Dementia

2012 ◽  
Vol 18 (5) ◽  
pp. 834-844 ◽  
Author(s):  
Katherine L. Possin ◽  
Serana K. Chester ◽  
Victor Laluz ◽  
Alan Bostrom ◽  
Howard J. Rosen ◽  
...  
Keyword(s):  
Frontotemporal Dementia ◽  
Inferior Frontal Gyrus ◽  
Temporal Cortex ◽  
Group Differences ◽  
Regression Analyses ◽  
Behavioral Variant Frontotemporal Dementia ◽  
Dementia Patients ◽  
Design Fluency ◽  
The Right ◽  
Correct Design

AbstractOn tests of design fluency, an examinee draws as many different designs as possible in a specified time limit while avoiding repetition. The neuroanatomical substrates and diagnostic group differences of design fluency repetition errors and total correct scores were examined in 110 individuals diagnosed with dementia, 53 with mild cognitive impairment (MCI), and 37 neurologically healthy controls. The errors correlated significantly with volumes in the right and left orbitofrontal cortex (OFC), the right and left superior frontal gyrus, the right inferior frontal gyrus, and the right striatum, but did not correlate with volumes in any parietal or temporal lobe regions. Regression analyses indicated that the lateral OFC may be particularly crucial for preventing these errors, even after excluding patients with behavioral variant frontotemporal dementia (bvFTD) from the analysis. Total correct correlated more diffusely with volumes in the right and left frontal and parietal cortex, the right temporal cortex, and the right striatum and thalamus. Patients diagnosed with bvFTD made significantly more repetition errors than patients diagnosed with MCI, Alzheimer's disease, semantic dementia, progressive supranuclear palsy, or corticobasal syndrome. In contrast, total correct design scores did not differentiate the dementia patients. These results highlight the frontal-anatomic specificity of design fluency repetitions. In addition, the results indicate that the propensity to make these errors supports the diagnosis of bvFTD. (JINS, 2012, 18, 1–11)

scholarly journals Apathy and functional disability in behavioral variant frontotemporal dementia

2018 ◽  
Vol 8 (2) ◽  
pp. 120-128 ◽  
Author(s):  
Mônica S. Yassuda ◽  
Thais B. Lima da Silva ◽  
Claire M. O'Connor ◽  
Shailaja Mekala ◽  
Suvarna Alladi ◽  
...  
Keyword(s):  
Activities Of Daily Living ◽  
Frontotemporal Dementia ◽  
Functional Impairment ◽  
Cognitive Deficits ◽  
Daily Living ◽  
Functional Disability ◽  
Motor Behavior ◽  
Regression Analyses ◽  
Behavioral Variant Frontotemporal Dementia ◽  
Everyday Function

BackgroundBehavioral variant frontotemporal dementia (bvFTD) has profound consequences on patients and their families. In this multicenter study, we investigated the contribution of cognitive and neuropsychiatric factors to everyday function at different levels of overall functional impairment.MethodsIn a retrospective cross-sectional study, 109 patients with bvFTD from 4 specialist frontotemporal dementia centers (Australia, England, India, and Brazil) were included. The measures administered evaluated everyday function (Disability Assessment for Dementia [DAD]), dementia staging (Clinical Dementia Rating [CDR]), general cognition (Addenbrooke's Cognitive Examination–revised [ACE-R]), and neuropsychiatric symptoms (Neuropsychiatric Inventory [NPI]). Patients were then subdivided according to functional impairment on the DAD into mild, moderate, severe, and very severe subgroups. Three separate multiple linear regression analyses were run, where (1) total DAD, (2) basic activities of daily living (BADL), and (3) instrumental activities of daily living (IADL) scores were dependent variables; ACE-R total score and selected NPI domains (agitation/aggression, euphoria, apathy, disinhibition, irritability, aberrant motor behavior) were used as independent variables. Age, sex, education, and country of origin were controlled for in the analyses.ResultsCognitive deficits were similar across the mild, moderate, and severe subgroups but significantly worse in the very severe subgroup. NPI domain scores (agitation/aggression, euphoria, apathy, disinhibition, irritability, aberrant motor behavior) did not differ across the DAD subgroups. In the multiple regression analyses, a model including ACE-R and NPI apathy explained 32.5% of the variance for total DAD scores. For IADL, 35.6% of the variance was explained by the ACE-R only. No model emerged for BADL scores.ConclusionsCognitive deficits and apathy are key contributors to functional disability in bvFTD but factors underlying impairment in BADLs remain unclear. Treatments targeting reduction of disability need to address apathy and cognitive impairment to ensure greater efficacy, especially in regards to IADLs.

scholarly journals Impaired β-glucocerebrosidase activity and processing in frontotemporal dementia due to progranulin mutations

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Andrew E. Arrant ◽  
Jonathan R. Roth ◽  
Nicholas R. Boyle ◽  
Shreya N. Kashyap ◽  
Madelyn Q. Hoffmann ◽  
...  
Keyword(s):  
Frontotemporal Dementia ◽  
Posttranslational Modifications ◽  
Neuronal Ceroid Lipofuscinosis ◽  
Inferior Frontal Gyrus ◽  
Lysosomal Storage ◽  
Loss Of Function ◽  
Wild Type ◽  
Metabolizing Enzymes ◽  
Dementia Patients ◽  
The Brain

AbstractLoss-of-function mutations in progranulin (GRN) are a major autosomal dominant cause of frontotemporal dementia. Most pathogenic GRN mutations result in progranulin haploinsufficiency, which is thought to cause frontotemporal dementia in GRN mutation carriers. Progranulin haploinsufficiency may drive frontotemporal dementia pathogenesis by disrupting lysosomal function, as patients with GRN mutations on both alleles develop the lysosomal storage disorder neuronal ceroid lipofuscinosis, and frontotemporal dementia patients with GRN mutations (FTD-GRN) also accumulate lipofuscin. The specific lysosomal deficits caused by progranulin insufficiency remain unclear, but emerging data indicate that progranulin insufficiency may impair lysosomal sphingolipid-metabolizing enzymes. We investigated the effects of progranulin insufficiency on sphingolipid-metabolizing enzymes in the inferior frontal gyrus of FTD-GRN patients using fluorogenic activity assays, biochemical profiling of enzyme levels and posttranslational modifications, and quantitative neuropathology. Of the enzymes studied, only β-glucocerebrosidase exhibited impairment in FTD-GRN patients. Brains from FTD-GRN patients had lower activity than controls, which was associated with lower levels of mature β-glucocerebrosidase protein and accumulation of insoluble, incompletely glycosylated β-glucocerebrosidase. Immunostaining revealed loss of neuronal β-glucocerebrosidase in FTD-GRN patients. To investigate the effects of progranulin insufficiency on β-glucocerebrosidase outside of the context of neurodegeneration, we investigated β-glucocerebrosidase activity in progranulin-insufficient mice. Brains from Grn−/− mice had lower β-glucocerebrosidase activity than wild-type littermates, which was corrected by AAV-progranulin gene therapy. These data show that progranulin insufficiency impairs β-glucocerebrosidase activity in the brain. This effect is strongest in neurons and may be caused by impaired β-glucocerebrosidase processing.

scholarly journals 2432 The relationship between cognitive functioning and abnormal eating behavior in behavioral variant frontotemporal dementia

2018 ◽  
Vol 2 (S1) ◽  
pp. 49-49
Author(s):  
Vidyulata Kamath ◽  
Grace-Anna Chaney ◽  
Chiadi Onyike
Keyword(s):  
Feeding Behavior ◽  
Frontotemporal Dementia ◽  
Cognitive Dysfunction ◽  
Eating Behavior ◽  
Processing Speed ◽  
Group Differences ◽  
Behavioral Variant Frontotemporal Dementia ◽  
Abnormal Eating ◽  
Abnormal Eating Behavior

OBJECTIVES/SPECIFIC AIMS: Abnormal eating behavior is a core and distinguishing diagnostic feature of behavioral variant frontotemporal dementia (bvFTD) that differentiates it from other neurodegenerative disorders and late-life psychiatric conditions. Though it has been proposed that hyperphagia in bvFTD results from cognitive dysfunction, the observation of altered sweet preferences and food foraging indicate that bvFTD is accompanied by fundamental dietary changes associated with hypothalamic and insular atrophy. In the current study, we examined how cognitive dysfunction contributes to abnormal feeding behavior in bvFTD. METHODS/STUDY POPULATION: We analyzed first-visit eating and neuropsychological data from the National Alzheimer’s Coordinating Center database (7 centers; September 2017 data freeze) in a subset of bvFTD patients with clinician-rated characterization of disturbed feeding severity. Group differences in cognitive domains of attention, processing speed, language, memory, and executive functioning were examined between patients with abnormal eating behavior (n=59) and a demographically-matched sample of patients with normal feeding behavior (n=60). Group differences in informant-reported empathy, behavioral inhibition, and depressive symptoms were also examined. RESULTS/ANTICIPATED RESULTS: Cognitive profiles in bvFTD patients did not vary as a function of disturbed feeding behavior. In a subset of cases pathologically-confirmed at autopsy, processing speed was better in cases with abnormal feeding behavior. No significant group differences were found for behavioral indices. DISCUSSION/SIGNIFICANCE OF IMPACT: These findings suggest that cognitive dysfunction is not the sole driver of abnormal eating behavior in bvFTD. Future studies with comprehensive characterization of feeding behavior, cognition and physiological/neuroimaging indices are warranted.

scholarly journals Structural and effective brain connectivity underlying biological motion detection

2018 ◽  
Vol 115 (51) ◽  
pp. E12034-E12042 ◽  
Author(s):  
Arseny A. Sokolov ◽  
Peter Zeidman ◽  
Michael Erb ◽  
Philippe Ryvlin ◽  
Karl J. Friston ◽  
...  
Keyword(s):  
Biological Motion ◽  
Effective Connectivity ◽  
Inferior Frontal Gyrus ◽  
Functional Integration ◽  
Temporal Cortex ◽  
Causal Modeling ◽  
High Angular Resolution ◽  
Wide Range ◽  
Crus I ◽  
The Right

The perception of actions underwrites a wide range of socio-cognitive functions. Previous neuroimaging and lesion studies identified several components of the brain network for visual biological motion (BM) processing, but interactions among these components and their relationship to behavior remain little understood. Here, using a recently developed integrative analysis of structural and effective connectivity derived from high angular resolution diffusion imaging (HARDI) and functional magnetic resonance imaging (fMRI), we assess the cerebro-cerebellar network for processing of camouflaged point-light BM. Dynamic causal modeling (DCM) informed by probabilistic tractography indicates that the right superior temporal sulcus (STS) serves as an integrator within the temporal module. However, the STS does not appear to be a “gatekeeper” in the functional integration of the occipito-temporal and frontal regions: The fusiform gyrus (FFG) and middle temporal cortex (MTC) are also connected to the right inferior frontal gyrus (IFG) and insula, indicating multiple parallel pathways. BM-specific loops of effective connectivity are seen between the left lateral cerebellar lobule Crus I and right STS, as well as between the left Crus I and right insula. The prevalence of a structural pathway between the FFG and STS is associated with better BM detection. Moreover, a canonical variate analysis shows that the visual sensitivity to BM is best predicted by BM-specific effective connectivity from the FFG to STS and from the IFG, insula, and STS to the early visual cortex. Overall, the study characterizes the architecture of the cerebro-cerebellar network for BM processing and offers prospects for assessing the social brain.

Eating Disorders in Frontotemporal Dementia and Alzheimer’s Disease: Evaluation of Brain Perfusion Correlates Using 99mTc-HMPAO SPECT with Brodmann Areas Analysis

2021 ◽  
pp. 1-11
Author(s):  
Varvara Valotassiou ◽  
Nikolaos Sifakis ◽  
Chara Tzavara ◽  
Evi Lykou ◽  
Niki Tsinia ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Eating Disorders ◽  
Frontotemporal Dementia ◽  
Inferior Frontal Gyrus ◽  
Photon Emission ◽  
Temporal Cortex ◽  
Emission Computed Tomography ◽  
Brodmann Areas ◽  
Duration Of Disease

Background: Eating disorders (ED) in dementia represent a significant impairment affecting patients’ and caregivers’ lives. In frontotemporal dementia (FTD), ED include overeating, sweet food preference hyperorality, stereotypical eating, and hyperorality, while in Alzheimer’s disease (AD), anorexia and appetite loss are the most common ED. Objective: The aim of our study was to highlight Brodmann areas (BAs) implicated specifically in the appearance of ED in FTD and AD. Methods: We studied 141 patients, 75 with FTD and 66 with AD. We used the NeuroGamTM software on the reconstructed single photon emission computed tomography-SPECT data for the automated comparison of BAs perfusion on the left (L) and right (R) hemisphere with perfusion in corresponding BAs of a normal database. Results: The FTD group included 27 men and 48 women, age (mean±SD) 65.8±8.5 years, duration of disease 3.4±3.3 years, Mini-Mental State Examination (MMSE) 17.9±8.6, ED score on Neuropsychiatric Inventory (NPI) 4.7±8.5. ED in FTD were correlated with hypoperfusion in right anterior and dorsolateral prefrontal cortices (BAs 10R, 46R), left orbitofrontal cortex (BA 12L), orbital part of the right inferior frontal gyrus (BA 47R), and left parahippocampal gyrus (BA 36L). The AD group included 21 men and 45 women, age (mean±SD) 70.2±8.0 years, duration of disease 3.3±2.4 years, MMSE 20.2±6, ED-NPI score 2.7±3.9. ED in AD were correlated with hypoperfusion in left inferior temporal cortex (BA 20L). Conclusion: SPECT imaging with automated mapping of brain cortex could contribute to the understanding of the neural networks involved in the manifestation of ED in dementia.

scholarly journals Barking up the right tree: Univariate and multivariate fMRI analyses of homonym comprehension

2019 ◽  
Author(s):  
Paul Hoffman ◽  
Andres Tamm
Keyword(s):  
Semantic Processing ◽  
Control Function ◽  
Semantic Representation ◽  
Inferior Frontal Gyrus ◽  
Temporal Cortex ◽  
Unrelated Word ◽  
Test Case ◽  
Neuroimaging Data ◽  
The Right

AbstractHomonyms are a critical test case for investigating how the brain resolves ambiguity in language and, more generally, how context influences semantic processing. Previous neuroimaging studies have associated processing of homonyms with greater engagement of regions involved in executive control of semantic processing. However, the precise role of these areas and the involvement of semantic representational regions in homonym comprehension remain elusive. We addressed this by combining univariate and multivariate fMRI analyses of homonym processing. We tested whether multi-voxel activation patterns could discriminate between presentations of the same homonym in different contexts (e.g., bark following tree vs. bark following dog). The ventral anterior temporal lobe, implicated in semantic representation but not previously in homonym comprehension, showed this meaning-specific coding, despite not showing increased mean activation for homonyms. Within inferior frontal gyrus (IFG), a key site for semantic control, there was a dissociation between pars orbitalis, which also showed meaning-specific coding, and pars triangularis, which discriminated more generally between semantically related and unrelated word pairs. IFG effects were goal-dependent, only occurring when the task required semantic decisions, in line with a top-down control function. Finally, posterior middle temporal cortex showed a hybrid pattern of responses, supporting the idea that it acts as an interface between semantic representations and the control system. The study provides new evidence for context-dependent coding in the semantic system and clarifies the role of control regions in processing ambiguity. It also highlights the importance of combining univariate and multivariate neuroimaging data to fully elucidate the role of a brain region in semantic cognition.

scholarly journals Cognitive Indicators of Preclinical Behavioral Variant Frontotemporal Dementia in MAPT Carriers

2018 ◽  
Vol 25 (2) ◽  
pp. 184-194 ◽  
Author(s):  
Gayathri Cheran ◽  
Liwen Wu ◽  
Seonjoo Lee ◽  
Masood Manoochehri ◽  
Sarah Cines ◽  
...  
Keyword(s):  
Executive Function ◽  
Social Cognition ◽  
Frontotemporal Dementia ◽  
Spatial Ability ◽  
Fixed Effects ◽  
Memory Storage ◽  
Group Differences ◽  
Carrier Status ◽  
Mixed Effect ◽  
Behavioral Variant Frontotemporal Dementia

AbstractObjectives: The cognitive indicators of preclinical behavioral variant Frontotemporal Dementia (bvFTD) have not been identified. To investigate these indicators, we compared cross-sectional performance on a range of cognitive measures in 12 carriers of pathogenic MAPT mutations not meeting diagnostic criteria for bvFTD (i.e., preclinical) versus 32 demographically-matched familial non-carriers (n = 44). Studying preclinical carriers offers a rare glimpse into emergent disease, environmentally and genetically contextualized through comparison to familial controls. Methods: Evaluating personnel blinded to carrier status administered a standardized neuropsychological battery assessing attention, speed, executive function, language, memory, spatial ability, and social cognition. Results from mixed effect modeling were corrected for multiplicity of comparison by the false discovery rate method, and results were considered significant at p < .05. To control for potential interfamilial variation arising from enrollment of six families, family was treated as a random effect, while carrier status, age, gender, and education were treated as fixed effects. Results: Group differences were detected in 17 of 31 cognitive scores and spanned all domains except spatial ability. As hypothesized, carriers performed worse on specific measures of executive function, and social cognition, but also on measures of attention, speed, semantic processing, and memory storage and retrieval. Conclusions: Most notably, group differences arose on measures of memory storage, challenging long-standing ideas about the absence of amnestic features on neuropsychological testing in early bvFTD. Current findings provide important and clinically relevant information about specific measures that may be sensitive to early bvFTD, and advance understanding of neurocognitive changes that occur early in the disease. (JINS, 2019, 25, 184–194)

scholarly journals Functional connectivity of the right inferior frontal gyrus and orbitofrontal cortex in depression

2020 ◽  
Vol 15 (1) ◽  
pp. 75-86 ◽  
Author(s):  
Edmund T Rolls ◽  
Wei Cheng ◽  
Jingnan Du ◽  
Dongtao Wei ◽  
Jiang Qiu ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Orbitofrontal Cortex ◽  
Inferior Frontal Gyrus ◽  
Temporal Cortex ◽  
Cingulate Cortex ◽  
Posterior Cingulate Cortex ◽  
Angular Gyrus ◽  
Parahippocampal Gyrus ◽  
The Right ◽  
And Behavior

Abstract The orbitofrontal cortex extends into the laterally adjacent inferior frontal gyrus. We analyzed how voxel-level functional connectivity of the inferior frontal gyrus and orbitofrontal cortex is related to depression in 282 people with major depressive disorder (125 were unmedicated) and 254 controls, using FDR correction P &lt; 0.05 for pairs of voxels. In the unmedicated group, higher functional connectivity was found of the right inferior frontal gyrus with voxels in the lateral and medial orbitofrontal cortex, cingulate cortex, temporal lobe, angular gyrus, precuneus, hippocampus and frontal gyri. In medicated patients, these functional connectivities were lower and toward those in controls. Functional connectivities between the lateral orbitofrontal cortex and the precuneus, posterior cingulate cortex, inferior frontal gyrus, ventromedial prefrontal cortex and the angular and middle frontal gyri were higher in unmedicated patients, and closer to controls in medicated patients. Medial orbitofrontal cortex voxels had lower functional connectivity with temporal cortex areas, the parahippocampal gyrus and fusiform gyrus, and medication did not result in these being closer to controls. These findings are consistent with the hypothesis that the orbitofrontal cortex is involved in depression, and can influence mood and behavior via the right inferior frontal gyrus, which projects to premotor cortical areas.

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