*Departments of Neurology ∥Pathology, University of California, San Francisco, CA †Department of Neurology, National Yang-Ming University, School of Medicine ‡Taipei Veterans General Hospital, Taipei, Taiwan §Department of Pathology, University of Pennsylvania, Philadelphia, PA.
Behavioral variant frontotemporal dementia and semantic dementia have been associated with striatal degeneration, but few studies have delineated striatal subregion volumes in vivo or related them to the clinical phenotype. We traced caudate, putamen, and nucleus accumbens on magnetic resonance images to quantify volumes of these structures in behavioral variant frontotemporal dementia, semantic dementia, Alzheimer disease, and healthy controls (n=12 per group). We further related these striatal volumes to clinical deficits and neuropathologic findings in a subset of patients. Behavioral variant frontotemporal dementia and semantic dementia showed significant overall striatal atrophy compared with controls. Moreover, behavioral variant frontotemporal dementia showed panstriatal degeneration, whereas semantic dementia featured a more focal pattern involving putamen and accumbens. Right-sided striatal atrophy, especially in the putamen, correlated with the overall behavioral symptom severity and with specific behavioral domains. At autopsy, patients with behavioral variant frontotemporal dementia and semantic dementia showed striking and severe tau or TAR DNA-binding protein of 43 kDa pathology, especially in ventral parts of the striatum. These results demonstrate that ventral striatum degeneration is a prominent shared feature in behavioral variant frontotemporal dementia and semantic dementia and may contribute to the social-emotional deficits common to both disorders.
"This prevents optimization of behavior or decision-making. In frontotemporal dementia patients, for example, in which the salient network – that includes the Acb has degenerated, there is a tendency not to make decisions based on contexts relating to moral and sociality , . Such decisions mismatched with context may, as a result, increase the frequency of stress for the patient. "
[Show abstract][Hide abstract] ABSTRACT: In recent years, the study of resting state neural activity has received much attention. To better understand the roles of different brain regions in the regulation of behavioral activity in an arousing or a resting period, we developed a novel behavioral paradigm (8-arm food-foraging task; 8-arm FFT) using the radial 8-arm maze and examined how AcbC lesions affect behavioral execution and learning. Repetitive training on the 8-arm FFT facilitated motivation of normal rats to run quickly to the arm tips and to the center platform before the last-reward collection. Importantly, just after this point and before confirmation of no reward at the next arm traverse, locomotor activity decreased. This indicates that well-trained rats can predict the absence of the reward at the end of food seeking and then start another behavior, namely planned resting. Lesions of the AcbC after training selectively impaired this reduction of locomotor activity after the last-reward collection without changing activity levels before the last-reward collection. Analysis of arm-selection patterns in the lesioned animals suggests little influence of the lesion in the ability to predict the reward absence. AcbC lesions did not change exploratory locomotor activity in an open-field test in which there were no rewards. This suggests that the AcbC controls the activity level of planned resting behavior shaped by the 8-arm FFT. Rats receiving training after AcbC lesioning showed a reduction in motivation for reward seeking. Thus, the AcbC also plays important roles not only in controlling the activity level after the last-reward collection but also in motivational learning for setting the activity level of reward-seeking behavior.
PLoS ONE 04/2014; 9(4):e95941. DOI:10.1371/journal.pone.0095941 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The pace of discovery in frontotemporal dementia (FTD) has accelerated dramatically with the discovery of new genetic causes and pathological substrates of the disease. MAPT/tau, GRN/progranulin, and C9ORF72 have emerged as common FTD genes, and TARDBP/TDP-43, VCP, FUS, and CHMP2B have been identified as less common genetic causes. TDP-43 and FUS have joined tau as common neuropathological substrates of the disease. Mouse models provide an important tool for understanding the role of these molecules in FTD pathogenesis. Here, we review recent progress with mouse models based on tau, TDP-43, progranulin, VCP, and CHMP2B. We also consider future prospects for FTD models, including developing new models to address unanswered questions. There are also opportunities for capitalizing on conservation of the salience network, which is selectively vulnerable in FTD, and the availability of FTD-related behavioral paradigms to analyze mouse models of the disease. Ann Neurol ANN NEUROL 2012;72:837-849.
Annals of Neurology 12/2012; 72(6):837-49. DOI:10.1002/ana.23722 · 9.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Investigations of cognitive and behavioural changes in neurodegeneration have been mostly focussed on how cortical changes can explain these symptoms. In the proposed review, we will argue that the striatum has been overlooked as a critical nexus in understanding the generation of such symptoms. Although the striatum is historically more associated with motor dysfunction, there is increasing evidence from functional neuroimaging studies in the healthy that striatal regions modulate behaviour and cognition. This should not be surprising, as the striatum has strong anatomical connections to many cortical regions including the frontal, temporal and insula lobes, as well as some subcortical regions (amygdala, hippocampus). To date, however, it is largely unclear to what extent striatal regions are affected in many neurodegenerative conditions-and if so, how striatal dysfunction can potentially influence cognition and behaviour. The proposed review will examine the existing evidence of striatal changes across selected neurodegenerative conditions (Parkinson's disease, progressive supranuclear palsy, Huntington's disease, motor neuron disease, frontotemporal dementia and Alzheimer's disease), and will document their link with the cognitive and behavioural impairments observed. Thus, by reviewing the varying degrees of cortical and striatal changes in these conditions, we can start outlining the contributions of the striatal nexus to cognitive and behavioural symptoms. In turn, this knowledge will inform future studies investigating corticostriatal networks and also diagnostic strategies, disease management and future therapeutics of neurodegenerative conditions.
Journal of neurology, neurosurgery, and psychiatry 07/2013; 85(4). DOI:10.1136/jnnp-2012-304558 · 6.81 Impact Factor
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