scholarly journals Planning deficits in Huntington’s disease: A brain structural correlation by voxel-based morphometry

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0249144
Author(s):  
Jesus Calderon-Villalon ◽  
Gabriel Ramirez-Garcia ◽  
Juan Fernandez-Ruiz ◽  
Fernanda Sangri-Gil ◽  
Aurelio Campos-Romo ◽  
...  

Introduction Early Huntington’s disease (HD) patients begin to show planning deficits even before motor alterations start to manifest. Generally, planning ability is associated with the functioning of anterior brain areas such as the medial prefrontal cortex. However, early HD neuropathology involves significant atrophy in the occipital and parietal cortex, suggesting that more posterior regions could also be involved in these planning deficits. Objective To identify brain regions associated with planning deficits in HD patients at an early clinical stage. Materials and methods Twenty-two HD-subjects genetically confirmed with incipient clinical manifestation and twenty healthy subjects were recruited. All participants underwent MRI T1 image acquisition as well as testing in the Stockings of Cambridge (SOC) task to measure planning ability. First, group comparison of SOC measures were performed. Then, correlation voxel-based morphometry analyses were done between gray matter degeneration and SOC performance in the HD group. Results Accuracy and efficiency planning scores correlated with gray matter density in right lingual gyrus, middle temporal gyrus, anterior cingulate gyrus, and paracingulate gyrus. Conclusions Our results suggest that planning deficits exhibited by early HD-subjects are related to occipital and temporal cortical degeneration in addition to the frontal areas deterioration.

2015 ◽  
Vol 357 ◽  
pp. e216-e217
Author(s):  
P.C. Azevedo ◽  
R.P. Guimarães ◽  
C. Piccinin ◽  
B. Campos ◽  
L.G. Piovesana ◽  
...  

2008 ◽  
Vol 35 (S 01) ◽  
Author(s):  
M Mühlau ◽  
A Wohlschläger ◽  
C Gaser ◽  
M Valet ◽  
S Nunnemann ◽  
...  

2021 ◽  
Author(s):  
Audrey E. De Paepe ◽  
Alberto Ara ◽  
Clara Garcia‐Gorro ◽  
Saül Martinez‐Horta ◽  
Jesus Perez‐Perez ◽  
...  

2019 ◽  
Vol 51 (8) ◽  
pp. 1827-1843 ◽  
Author(s):  
Gabriel Ramirez‐Garcia ◽  
Víctor Galvez ◽  
Rosalinda Diaz ◽  
Leo Bayliss ◽  
Juan Fernandez‐Ruiz ◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
Aldo Alberto Conti ◽  
Alexander Mario Baldacchino

Introduction: Impairments in the multifaceted neuropsychological construct of cognitive impulsivity are a main feature of chronic tobacco smokers. According to the literature, these cognitive impairments are relevant for the initiation and maintenance of the smoking behavior. However, the neuroanatomical correlates of cognitive impulsivity in chronic smokers remain under-investigated.Methods: A sample of 28 chronic smokers (mean age = 28 years) not affected by polysubstance dependence and 24 matched non-smoker controls was recruited. Voxel Based Morphometry (VBM) was employed to assess Gray Matter (GM) volume differences between smokers and non-smokers. The relationships between GM volume and behavioral manifestations of impulsive choices (5 trial adjusting delay discounting task, ADT-5) and risky decision making (Cambridge Gambling Task, CGT) were also investigated.Results: VBM results revealed GM volume reductions in cortical and striatal brain regions of chronic smokers compared to non-smokers. Additionally, smokers showed heightened impulsive choices (p < 0.01, Cohen's f = 0.50) and a riskier decision- making process (p < 0.01, Cohen's f = 0.40) compared to non-smokers. GM volume reductions in the left Anterior Cingulate Cortex (ACC) correlated with impaired impulsive and risky choices, while GM volume reductions in the left Ventrolateral Prefrontal Cortex (VLPFC) and Caudate correlated with heightened impulsive choices. Reduced GM volume in the left VLPFC correlated with younger age at smoking initiation (mean = 16 years).Conclusion: Smokers displayed significant GM volume reductions and related cognitive impulsivity impairments compared to non-smoker individuals. Longitudinal studies would be required to assess whether these impairments underline neurocognitive endophenotypes or if they are a consequence of tobacco exposure on the adolescent brain.


2019 ◽  
Author(s):  
Gabriel Ramirez‐Garcia ◽  
Víctor Galvez ◽  
Rosalinda Diaz ◽  
Leo Bayliss ◽  
Juan Fernandez‐Ruiz ◽  
...  

2019 ◽  
Vol 29 (2) ◽  
pp. 216-227
Author(s):  
Sheridan L Roberts ◽  
Tracey Evans ◽  
Yi Yang ◽  
Yuhua Fu ◽  
Robert W Button ◽  
...  

Abstract Huntington’s disease (HD) is a neurodegenerative disorder caused by an expanded polyglutamine tract in the huntingtin (HTT) protein. Mutant HTT (mHTT) toxicity is caused by its aggregation/oligomerization. The striatum is the most vulnerable region, although all brain regions undergo neuronal degeneration in the disease. Here we show that the levels of Bim, a BH3-only protein, are significantly increased in HD human post-mortem and HD mouse striata, correlating with neuronal death. Bim reduction ameliorates mHTT neurotoxicity in HD cells. In the HD mouse model, heterozygous Bim knockout significantly mitigates mHTT accumulation and neuronal death, ameliorating disease-associated phenotypes and lifespan. Therefore, Bim could contribute to the progression of HD.


2020 ◽  
Vol 21 (15) ◽  
pp. 5412 ◽  
Author(s):  
Johannes Burtscher ◽  
Alba Di Pardo ◽  
Vittorio Maglione ◽  
Christoph Schwarzer ◽  
Ferdinando Squitieri

Mitochondrial dysfunction is crucially involved in aging and neurodegenerative diseases, such as Huntington’s Disease (HD). How mitochondria become compromised in HD is poorly understood but instrumental for the development of treatments to prevent or reverse resulting deficits. In this paper, we investigate whether oxidative phosphorylation (OXPHOS) differs across brain regions in juvenile as compared to adult mice and whether such developmental changes might be compromised in the R6/2 mouse model of HD. We study OXPHOS in the striatum, hippocampus, and motor cortex by high resolution respirometry in female wild-type and R6/2 mice of ages corresponding to pre-symptomatic and symptomatic R6/2 mice. We observe a developmental shift in OXPHOS-control parameters that was similar in R6/2 mice, except for cortical succinate-driven respiration. While the LEAK state relative to maximal respiratory capacity was reduced in adult mice in all analyzed brain regions, succinate-driven respiration was reduced only in the striatum and cortex, and NADH-driven respiration was higher as compared to juvenile mice only in the striatum. We demonstrate age-related changes in respirational capacities of different brain regions with subtle deviations in R6/2 mice. Uncovering in situ oxygen conditions and potential substrate limitations during aging and HD disease progression are interesting avenues for future research to understand brain-regional vulnerability in HD.


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