Visual perception in prediagnostic and early stage Huntington's disease

O’Donnell, Brian F.; Blekher, Tanya; Weaver, Marjorie; White, Kerry; Marshall, Jessica; Beristaín, Xabier; Stout, Julie C.; Gray, Jacqueline S.; Wojcieszek, Joanne; Foroud, Tatiana

doi:10.1017/s1355617708080405

Cited by 22 publications

(28 citation statements)

References 42 publications

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“…170–172 Even with normal aging, cumulative insults of mitochondrial DNA with reactive oxygen species (ROS) increases the incidence of mutations in each mitochondrion and the prevalence of defective mitochondria in each organ. 173 Respiratory control normally limits the production of ROS, but if the allosteric inhibition of cytochrome c oxidase at high ATP:ADP ratio is switched off under various forms of stress, increased mitochondrial membrane potential and cellular ROS can result, leading to degenerative diseases.…”

Section: Disorders Of the Visual Systemmentioning

confidence: 99%

Energy metabolism of the visual system

Wong‐Riley¹

2010

364

323

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The visual system is one of the most energetically demanding systems in the brain. The currency of energy is ATP, which is generated most efficiently from oxidative metabolism in the mitochondria. ATP supports multiple neuronal functions. Foremost is repolarization of the membrane potential after depolarization. Neuronal activity, ATP generation, blood flow, oxygen consumption, glucose utilization, and mitochondrial oxidative metabolism are all interrelated. In the retina, phototransduction, neurotransmitter utilization, and protein/organelle transport are energy-dependent, yet repolarization-after-depolarization consumes the bulk of the energy. Repolarization in photoreceptor inner segments maintains the dark current. Repolarization by all neurons along the visual pathway following depolarizing excitatory glutamatergic neurotransmission preserves cellular integrity and permits reactivation. The higher metabolic activity in the magno- versus the parvo-cellular pathway, the ON- versus the OFF-pathway in some (and the reverse in other) species, and in specialized functional representations in the visual cortex all reflect a greater emphasis on the processing of specific visual attributes. Neuronal activity and energy metabolism are tightly coupled processes at the cellular and even at the molecular levels. Deficiencies in energy metabolism, such as in diabetes, mitochondrial DNA mutation, mitochondrial protein malfunction, and oxidative stress can lead to retinopathy, visual deficits, neuronal degeneration, and eventual blindness.

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Section: Disorders Of the Visual Systemmentioning

confidence: 99%

Energy metabolism of the visual system

Wong‐Riley¹

2010

364

323

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“…Our design is limited due to the cross-sectional nature; however, it could be possible that future prospective studies may show that loss of PDE10A expression in the insula and occipital fusiform gyrus are associated with the risk of developing cognitive and behavioural issues in manifest HD. Furthermore, in HD the affected extra-striatal regions could play a role in visuomotor (37), visuospatial (38) and oculomotor (39,40), as well as facial expression deficits (41,42). In the present study we did not examine visual function or face recognition.…”

Section: Discussionmentioning

confidence: 82%

Loss of extra-striatal phosphodiesterase 10A expression in early premanifest Huntington's disease gene carriers

Wilson

Niccolini

Haider

et al. 2016

Journal of the Neurological Sciences

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Huntington's disease (HD) is a monogenic neurodegenerative disorder with an underlying pathology involving the toxic effect of mutant huntingtin protein primarily in striatal and cortical neurons. Phosphodiesterase 10A (PDE10A) regulates intracellular signalling cascades, thus having a key role in promoting neuronal survival. Using positron emission tomography (PET) with [(11)C]IMA107, we investigated the in vivo extra-striatal expression of PDE10A in 12 early premanifest HD gene carriers. Image processing and kinetic modelling was performed using MIAKAT™. Parametric images of [(11)C]IMA107 non-displaceable binding potential (BPND) were generated from the dynamic [(11)C]IMA107 scans using the simplified reference tissue model with the cerebellum as the reference tissue for nonspecific binding. We set a threshold criterion for meaningful quantification of [(11)C]IMA107 BPND at 0.30 in healthy control data; regions meeting this criterion were designated as regions of interest (ROIs). MRI-based volumetric analysis showed no atrophy in ROIs. We found significant differences in mean ROIs [(11)C]IMA107 BPND between HD gene carriers and healthy controls. HD gene carriers had significant loss of PDE10A within the insular cortex and occipital fusiform gyrus compared to healthy controls. Insula and occipital fusiform gyrus are important brain areas for the regulation of cognitive and limbic function that is impaired in HD. Our findings suggest that dysregulation of PDE10A-mediated intracellular signalling could be an early phenomenon in the course of HD with relevance also for extra-striatal brain areas.

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“…These tasks have been used to study schizophrenia and schizotypal personality disorder, Huntington's disease, and autism (Brenner, et al, 2003; Davis, Bockbrader, Murphy, Hetrick, & O'Donnell, 2006; O'Donnell et al, 2006; O'Donnell et al, 2008). …”

Section: Discussionmentioning

confidence: 99%

Psychometrically matched tasks evaluating differential fMRI activation during form and motion processing.

et al. 2011

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Objective-Deficits in visual perception and working memory are commonly observed in neuropsychiatric disorders and have been investigated using functional MRI. However, interpretation of differences in brain activation may be confounded with differences in task performance between groups. Differences in task difficulty across conditions may also pose interpretative issues in studies of visual processing in healthy subjects.Method-In order to address these concerns, the present study characterized brain activation in tasks which were psychometrically matched for difficulty. Functional magnetic resonance imaging (fMRI) was used to assess brain activation in ten healthy subjects during discrimination and working memory judgments for static and moving stimuli. For all task conditions, performance accuracy was matched at 70.7%.Results-Areas associated with V2 and V5 in the dorsal stream were activated during motion processing tasks and V4 in the ventral stream were activated during form processing tasks. Frontoparietal areas associated with working memory were also statistically significant during the working memory tasks.Conclusions-Application of psychophysical methods to equate task demands provides a practical method to equate performance levels across conditions in fMRI studies, and to compare healthy and cognitively impaired groups at comparable levels of effort. These psychometrically matched tasks can be applied to patients with a variety of cognitive disorders to investigate dysfunction of multiple a priori defined brain regions. Measuring the changes in typical activation (Drzezga, 2008;Sperling, 2007;Wierenga & Bondi, 2007), and Parkinson's disease (Dagher & Nagano-Saito, 2007;van Eimeren & Siebner, 2006). A major aim of this approach is to characterize differences in the amount, location, or connectivity of brain activity between the control and patient groups. However, the interpretation of such differences is often confounded by performance differences between groups, since patients with brain dysfunction often perform more poorly than healthy subjects on cognitive tasks. Individual differences in performance may reflect differences in perceptual processing, attention, learning efficiency, effort, or cognitive strategies. More generally, comparison of fMRI activation between conditions may also be influenced by individual differences in performance. In the visual modality, for example, parametric manipulation of stimulus detectability, decision certainty or effort can have marked effects on activation. Huang et al. (Huang, Xiang, & Cao, 2006) varied the visibility of a target stimulus in a masking paradigm, and found that activation in V1 decreased with decreased stimulus visibility. Volz et al. (Volz, Schubotz, & von Cramon, 2005) showed that increasing uncertainty in a decision making task increased activation within the posterior frontal median cortex. Haynes et al. (Haynes, Driver, & Rees, 2005) reported that the psychometric visibility for target stimuli in a metacontrast paradigm affected...

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Visual perception in prediagnostic and early stage Huntington's disease

Cited by 22 publications

References 42 publications

Energy metabolism of the visual system

Energy metabolism of the visual system

Loss of extra-striatal phosphodiesterase 10A expression in early premanifest Huntington's disease gene carriers

Psychometrically matched tasks evaluating differential fMRI activation during form and motion processing.

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