The brain correlates of behavioral disturbances in frontotemporal dementia

Abstract. Dyslexia is a phenomenon for which the brain correlates have been studied since the beginning of the 20th century. Simultaneously, the field of education has also been studying dyslexia and its remediation, mainly through behavioral data. The last two decades have seen a growing interest in integrating neuroscience and education. This article provides a quick overview of pertinent scientific literature involving neurophysiological data on functional brain differences in dyslexia and discusses their very limited influence on the development of reading remediation for dyslexic individuals. Nevertheless, it appears that if certain conditions are met – related to the key elements of educational neuroscience and to the nature of the research questions – conceivable benefits can be expected from the integration of neurophysiological data with educational research. When neurophysiological data can be employed to overcome the limits of using behavioral data alone, researchers can both unravel phenomenon otherwise impossible to document and raise new questions.

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The Limits of Emotion

10.1093/oso/9780198811572.003.0002 ◽

2018 ◽

Author(s):

Joshua May

Keyword(s):

Moral Judgment ◽

Frontotemporal Dementia ◽

Empirical Research ◽

Emotional Processing ◽

Moral Cognition ◽

Moral Norms ◽

Moral Concepts ◽

Integral Role ◽

The Brain

Empirical research apparently suggests that emotions play an integral role in moral judgment. The evidence for sentimentalism is diverse, but it is rather weak and has generally been overblown. There is no evidence that our moral concepts themselves are partly composed of or necessarily dependent on emotions. While the moral/conventional distinction may partly characterize the essence of moral judgment, moral norms needn’t be backed by affect in order to transcend convention. Priming people with incidental emotions like disgust doesn’t make them moralize actions. Finally, moral judgment can only be somewhat impaired by damage to areas of the brain that are generally associated with emotional processing (as in acquired sociopathy and frontotemporal dementia). While psychopaths exhibit both emotional and rational deficits, the latter alone can explain any minor defects in moral cognition.

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Magnetoencephalography and the Cortical Dynamics of Language Processing

The Oxford Handbook of Neurolinguistics ◽

10.1093/oxfordhb/9780190672027.013.6 ◽

2019 ◽

pp. 114-153

Author(s):

Riitta Salmelin ◽

Jan Kujala ◽

Mia Liljeström

Keyword(s):

Language Processing ◽

Language Disorders ◽

Scientific Data ◽

Neural Processing ◽

Powerful Method ◽

Cortical Dynamics ◽

Brain Correlates ◽

Adults And Children ◽

The Brain ◽

Selection Of

When seeking to uncover the brain correlates of language processing, timing and location are of the essence. Magnetoencephalography (MEG) offers them both, with the highest sensitivity to cortical activity. MEG has shown its worth in revealing cortical dynamics of reading, speech perception, and speech production in adults and children, in unimpaired language processing as well as developmental and acquired language disorders. The MEG signals, once recorded, provide an extensive selection of measures for examination of neural processing. Like all other neuroimaging tools, MEG has its own strengths and limitations of which the user should be aware in order to make the best possible use of this powerful method and to generate meaningful and reliable scientific data. This chapter reviews MEG methodology and how MEG has been used to study the cortical dynamics of language.

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Stuck in a State of Inattention? Functional Hyperconnectivity as an Indicator of Disturbed Intrinsic Brain Dynamics in Adolescents With Concussion: A Pilot Study

ASN NEURO ◽

10.1177/1759091417753802 ◽

2018 ◽

Vol 10 ◽

pp. 175909141775380 ◽

Cited By ~ 7

Author(s):

Angela M. Muller ◽

Naznin Virji-Babul

Keyword(s):

Diffusion Tensor Imaging ◽

Pilot Study ◽

Resting State ◽

Diffusion Tensor ◽

Brain Dynamics ◽

Public Health Issue ◽

Brain Correlates ◽

Brain States ◽

The Brain ◽

Structural Brain

Sports-related concussion in youth is a major public health issue. Evaluating the diffuse and often subtle changes in structure and function that occur in the brain, particularly in this population, remains a significant challenge. The goal of this pilot study was to evaluate the relationship between the intrinsic dynamics of the brain using resting-state functional magnetic resonance imaging (rs-fMRI) and relate these findings to structural brain correlates from diffusion tensor imaging in a group of adolescents with sports-related concussions ( n = 6) and a group of healthy adolescent athletes ( n = 6). We analyzed rs-fMRI data using a sliding windows approach and related the functional findings to structural brain correlates by applying graph theory analysis to the diffusion tensor imaging data. Within the resting-state condition, we extracted three separate brain states in both groups. Our analysis revealed that the brain dynamics in healthy adolescents was characterized by a dynamic pattern, shifting equally between three brain states; however, in adolescents with concussion, the pattern was more static with a longer time spent in one brain state. Importantly, this lack of dynamic flexibility in the concussed group was associated with increased nodal strength in the left middle frontal gyrus, suggesting reorganization in a region related to attention. This preliminary report shows that both the intrinsic brain dynamics and structural organization are altered in networks related to attention in adolescents with concussion. This first report in adolescents will be used to inform future studies in a larger cohort.

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How the Brain Moves the Eyes

Eye Movement Disorders in Clinical Practice ◽

10.1093/med/9780199921805.003.0001 ◽

2014 ◽

pp. 1-25

Author(s):

Shirley H. Wray

Keyword(s):

Cardiac Surgery ◽

Eye Movements ◽

Progressive Supranuclear Palsy ◽

Disease Progression ◽

Frontotemporal Dementia ◽

Smooth Pursuit ◽

Cortical Areas ◽

Initial Symptoms ◽

The Brain ◽

Symptoms And Signs

discusses the brain’s visual architecture for directing and controlling of eye movements:the striate, frontal and parietal cortical areas; and the eye movements themselves—saccades, smooth pursuit, and vergence. The susceptibility to disorders of these systems is illustrated in four detailed cases that follow disease progression from initial symptoms and signs to diagnosis and treatment. The case studies and video displays include a patient with Pick’s disease (frontotemporal dementia), another with Alzheimer’s dementia, and two examples of rare saccadic syndromes, one a patient with the slow saccade syndrome due to progressive supranuclear palsy and one with selective saccadic palsy following cardiac surgery.

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Network analysis of the brain proteome of GRN knockout mice reveals pathogenic mechanisms shared in human frontotemporal dementia caused by GRN mutations

Alzheimer s & Dementia ◽

10.1002/alz.047569 ◽

2020 ◽

Vol 16 (S3) ◽

Author(s):

Thomas Kukar ◽

Meixiang Huang ◽

Erica S Modeste ◽

Eric B Dammer ◽

Christopher J Holler ◽

...

Keyword(s):

Network Analysis ◽

Frontotemporal Dementia ◽

Knockout Mice ◽

Pathogenic Mechanisms ◽

Brain Proteome ◽

The Brain

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

Acta Neuropathologica Communications ◽

10.1186/s40478-019-0872-6 ◽

2019 ◽

Vol 7 (1) ◽

Cited By ~ 4

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.

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Behavioral Disturbances in the Course of Frontotemporal Dementia

Dementia and Geriatric Cognitive Disorders ◽

10.1159/000095625 ◽

2006 ◽

Vol 22 (4) ◽

pp. 352-357 ◽

Cited By ~ 30

Author(s):

J. Diehl-Schmid ◽

C. Pohl ◽

R. Perneczky ◽

H. Förstl ◽

A. Kurz

Keyword(s):

Frontotemporal Dementia ◽

Behavioral Disturbances

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The inhibition of the kynurenine pathway prevents behavioral disturbances and oxidative stress in the brain of adult rats subjected to an animal model of schizophrenia

Progress in Neuro-Psychopharmacology and Biological Psychiatry ◽

10.1016/j.pnpbp.2017.10.009 ◽

2018 ◽

Vol 81 ◽

pp. 55-63 ◽

Cited By ~ 15

Author(s):

Gislaine Z. Réus ◽

Indianara R.T. Becker ◽

Giselli Scaini ◽

Fabricia Petronilho ◽

Jean P. Oses ◽

...

Keyword(s):

Oxidative Stress ◽

Animal Model ◽

Kynurenine Pathway ◽

Behavioral Disturbances ◽

Adult Rats ◽

The Brain ◽

And Oxidative Stress

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Premonitory Urges and Sensorimotor Processing in Tourette Syndrome

Behavioural Neurology ◽

10.1155/2013/984836 ◽

2013 ◽

Vol 27 (1) ◽

pp. 65-73 ◽

Cited By ~ 34

Author(s):

Sangeerthana Rajagopal ◽

Stefano Seri ◽

Andrea Eugenio Cavanna

Keyword(s):

Tourette Syndrome ◽

Preliminary Evidence ◽

Sensorimotor Processing ◽

Sensory Experiences ◽

Brain Correlates ◽

Clinical Phenomenology ◽

The Brain ◽

Insight Into ◽

Syndrome Report

Most patients with Tourette syndrome report characteristic sensory experiences (premonitory urges) associated with the expression of tic symptoms. Despite the central role of these experiences to the clinical phenomenology of Tourette syndrome, little is known about their underlying brain processes. In the present article we present the results of a systematic literature review of the published studies addressing the pathophysiological mechanisms of premonitory urges. We identified some preliminary evidence for specific alterations in sensorimotor processing at both cortical and subcortical levels. A better insight into the brain correlates of premonitory urges could lead to the identification of new targets to treat the sensory initiators of tics in patients with Tourette syndrome.

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