An fMRI study indicating increased cortical recruitment during a cognitive interference task in Huntington's disease patients

We used an event related fMRI design to study the BOLD response in Huntington’s disease (HD) patients during performance of a Simon interference task. We hypothesised that HD patients will demonstrate significantly slower RTs than controls, and that there will be significant differences in the pattern of brain activation between groups. Seventeen HD patients and 15 age and sex matched controls were scanned using 3T GE scanner (FOV = 24 cm2; TE = 40 ms; TR = 3 s; FA = 60°; slice thickness = 6 mm; in-plane resolution = 1.88x1.88 mm2). The task involved two activation conditions, namely congruent (for example, left pointing arrow appearing on the left side of the screen) and incongruent (for example, left pointing arrow appearing on the right side of the screen), and a baseline condition. Each stimulus was presented for 2500 ms followed by a blank screen for 500 ms. Subjects were instructed to press a button using the same hand as indicated by the direction of the arrow head and were given 3000 ms to respond. Data analysis was performed using SPM2 with a random effects analysis model. For each subject parameter estimates for combined task conditions (congruent and incongruent combined) were calculated. Comparisons such as these, based on block designs, have superior statistical power for detecting subtle changes in the BOLD response anywhere in the brain. The activations reported are significant at PFDR_corr

An event-related fMRI study of cognitive deficits in Huntington's disease

The BOLD contrast signal history determined by lagged Unear correlation has a significant contribution to functional connectivity in activation data sets. It has been demonstrated that in resting state fMRI data, the major contribution to synchronous correlation between functionally connected areas arises from low frequency contributions (

Impairments of movement kinematics in patients with Huntington's disease: A comparison with and without a concurrent task

This study aimed to quantify the efficiency and smoothness of voluntary movement in Huntington's disease (HD) by the use of a graphics tablet that permits analysis of movement profiles. In particular, we aimed to ascertain whether a concurrent task (digit span) would affect the kinematics of goal-directed movements. Twelve patients with HD and their matched controls performed 12 vertical zig-zag movements, with both left and right hands (with and without the concurrent task), to large or small circular targets over long or short extents. The concurrent task was associated with shorter movement times and reduced right-hand superiority. Patients with HD were overall slower, especially with long strokes, and had similar peak velocities for both small and large targets, so that controls could better accommodate differences in target size. Patients with HD spent more time decelerating, especially with small targets, whereas controls allocated more nearly equal proportions of time to the acceleration and deceleration phases of movement, especially with large targets. Short strokes were generally less force inefficient than were long strokes, especially so for either hand in either group in the absence of the concurrent task, and for the right hand in its presence. With the concurrent task, however, the left hand's behavior changed differentially for the two groups; for patients with HD, it became more force efficient with short strokes and even less efficient with long strokes, whereas for controls, it became more efficient with long strokes. Controls may be able to divert attention away from the inferior left hand, increasing its automaticity, whereas patients with HD, because of disease, may be forced to engage even further online visual control under the demands of a concurrent task. Patients with HD may perhaps become increasingly reliant on terminal visual guidance, which indicates an impairment in constructing and refining an internal representation of the movement necessary for its. effective execution. Basal ganglia dysfunction may impair the ability to use internally generated cues to guide movement.

Use of the frontal assessment battery in evaluating executive dysfunction in patients with Huntington`s disease

The frontal assessment battery (FAB) is a bedside cognitive scale designed to measure executive functions. Huntington`s disease (HD) is a neurodegenerative disorder characterized by motor, behavioral, and cognitive dysfunction. The aim of this study was to check the validity of the FAB for the evaluation of cognitive impairment in patients with HD. Forty-one patients diagnosed with HD and 53 healthy controls matched by education, sex and age were evaluated with a validated Brazilian version of the UHDRS, the VFT, the SDMT, the SIT, the MMSE, and the FAB. The diagnosis of HD was made by DNA analysis. FAB scores were lower in patients than in the controls (p < 0.001) and had significant correlations with the VFT (r = 0.79; p < 0.05), the SDMT (r = 0.80; p < 0.05), the SIT (r = 0.72; p < 0.05), the MMSE (r = 0.83; p < 0.05), the FCS (r = 0.79; p < 0.05) and the motor section of the UHDRS (r = -0.80; p < 0.05). The FAB differentiated between HD patients in the initial and later stages of the disease. The one-year longitudinal evaluation revealed a global trend toward a worsening in the second score of the FAB. The results demonstrate that the FAB presents good internal consistency and also convergent and discriminative validity; therefore it is a useful scale to assess executive functions and to evaluate cognitive impairment in patients with HD.

Huntington`s Disease-Like 2 in Brazil-Report of 4 Patients

Huntington`s disease-like 2 (HDL2) is a neurodegenerative disorder found in people of African ancestry with clinical, radiological, and neuropathological manifestations similar to Huntington`s disease (HD). HDL2 is caused by a pathological expansion of CAG/CTG triplets in exon 2A of the JPH3 gene. We describe four cases of HDL2 from four unrelated families, and discuss their clinical findings. HDL2 should be considered in every patient with an HD-like phenotype who tests negative for the HD mutation, even if African ancestry is not immediately apparent. (C) 2008 Movement Disorder Society

Complex language functions and subcortical mechanisms: evidence from Huntington's disease and patients with non-thalamic subcortical lesions

The neuropathological changes associated with Huntington's disease (HD) are most marked in the head of the caudate nucleus and, to a lesser extent, in the putamen and globus pallidus, suggesting that at least part of the language impairments found in patients with HD may result from non-thalamic subcortical (NTS) pathology. The present study aimed to test the hypothesis that a signature profile of impaired language functions is found in patients who have sustained damage to the non-thalamic subcortex, either focally induced or resulting from neurodegenerative pathology. The language abilities of a group of patients with Huntington's disease (n=13) were compared with those of an age- and education-matched group of patients with chronic NTS lesions following stroke (n=13) and a non-neurologically impaired control group (n=13). The three groups were compared on language tasks that assessed both primary and more complex language abilities. The primary language battery consisted of The Western Aphasia Battery and The Boston Naming Test, whilst the more complex cognitive-linguistic battery employed selected subtests from The Test of Language Competence-Expanded, The Test of Word Knowledge and The Word Test-Revised. On many of the tests of primary language function from the Western Aphasia Battery, both the HD and NTS participants performed in a similar manner to the control participants. The language performances of the HD participants were significantly more impaired (p<0.05 using modified Bonferroni adjustments) than the control group, however, on various lexico-semantic tasks (e. g. the Boston Naming Test and providing definitions), on both single-word and sentence-level generative tasks (e. g. category fluency and formulating sentences), and on tasks which required interpretation of ambiguous, figurative and inferential meaning. The difficulties that patients with HD experienced with tasks assessing complex language abilities were strikingly similar, both qualitatively and quantitatively, to the language profile produced by NTS participants. The results provide evidence to suggest that a signature language profile is associated with damage to the non-thalamic subcortex resulting from either focal neurological insult or a degenerative disease.

Role of sirtuin 3 on mitochondrial dynamics in Huntington's disease striatal cells

Dissertação de mestrado em Genética Molecular

Nacionalismo e identidad nacional en Corea, 1876-1945

Este trabajo de investigación tiene como objetivo el análisis de las circunstancias sociopolíticas que propiciaron la aparición y consolidación del nacionalismo como paradigma dominante en la creación de una nueva identidad colectiva coreana. El nacionalismo ha sido, en las últimas décadas, el discurso dominante dentro de la sociedad y la política coreana. De la derecha a la izquierda, pasando por los conservadores y los radicales, el pueblo coreano ha acogido de manera análoga el discurso nacionalista, siendo un instrumento utilizado abiertamente por las diferentes fuerzas gubernamentales para su propia legitimación política y moral tanto en el norte como en el sur.

Placebo effect characteristics observed in a single, international, longitudinal study in Huntington's disease.

BACKGROUND: Classically, clinical trials are based on the placebo-control design. Our aim was to analyze the placebo effect in Huntington's disease. METHODS: Placebo data were obtained from an international, longitudinal, placebo-controlled trial for Huntington's disease (European Huntington's Disease Initiative Study Group). One-hundred and eighty patients were evaluated using the Unified Huntington Disease Rating Scale over 36 months. A placebo effect was defined as an improvement of at least 50% over baseline scores in the Unified Huntington Disease Rating Scale, and clinically relevant when at least 10% of the population met it. RESULTS: Only behavior showed a significant placebo effect, and the proportion of the patients with placebo effect ranged from 16% (first visit) to 41% (last visit). Nondepressed patients with better functional status were most likely to be placebo-responders over time. CONCLUSIONS: In Huntington's disease, behavior seems to be more vulnerable to placebo than overall motor function, cognition, and function

S. P. Huntington : identitats i geopolítica

Aquest treball té com a propòsit esbrinar quina política internacional legitima S. P. Huntington, i quin paper hi adjudica als Estats Units. En aquest sentit, s'analitza el contingut de la teoria del "xoc de civilitzacions" i es treuen conclusions a partir de l'associació que realitza el politòleg nord-americà entre política internacional i les identitats cultural i religiosa en un món que ell considera marcadament hobbesià o d'esperit agonista.

Lentiviral-mediated gene transfer of siRNAs for the treatment of Huntington's disease.

This chapter describes the potential use of viral-mediated gene transfer in the central nervous system for the silencing of gene expression using RNA interference in the context of Huntington's disease (HD). Protocols provided here describe the design of small interfering RNAs, their encoding in lentiviral vectors (LVs) and viral production, as well as procedures for their stereotaxic injection in the rodent brain.

Neuroprotective gene therapy for Huntington's disease, using polymer-encapsulated cells engineered to secrete human ciliary neurotrophic factor: results of a phase I study.

Huntington's disease (HD) is a monogenic neurodegenerative disease that affects the efferent neurons of the striatum. The protracted evolution of the pathology over 15 to 20 years, after clinical onset in adulthood, underscores the potential of therapeutic tools that would aim at protecting striatal neurons. Proteins with neuroprotective effects in the adult brain have been identified, among them ciliary neurotrophic factor (CNTF), which protected striatal neurons in animal models of HD. Accordingly, we have carried out a phase I study evaluating the safety of intracerebral administration of this protein in subjects with HD, using a device formed by a semipermeable membrane encapsulating a BHK cell line engineered to synthesize CNTF. Six subjects with stage 1 or 2 HD had one capsule implanted into the right lateral ventricle; the capsule was retrieved and exchanged for a new one every 6 months, over a total period of 2 years. No sign of CNTF-induced toxicity was observed; however, depression occurred in three subjects after removal of the last capsule, which may have correlated with the lack of any future therapeutic option. All retrieved capsules were intact but contained variable numbers of surviving cells, and CNTF release was low in 13 of 24 cases. Improvements in electrophysiological results were observed, and were correlated with capsules releasing the largest amount of CNTF. This phase I study shows the safety, feasibility, and tolerability of this gene therapy procedure. Heterogeneous cell survival, however, stresses the need for improving the technique.

Les Crisis asiàtiques i el procés de globalització : el cas de Corea del Sud

Corea del Sud ha vist en els últims 50 anys com la seva economia creixia a unsritmes espectaculars fins arribar a situar-se entre les primeres del món. El seu ascenssemblava imparable fins que l’any 1997, de forma inesperada per la majoria, esclatà lacrisis. En aquells moments, Corea del Sud s’havia convertit en la undècima economiadel planeta i la sisena potència comercial, sent el primer productor de vaixells imemòries DRAM, el quart de béns electrònics de consum, el cinquè d’automòbils i deproductes petroquímics, els sisè d’acer i el setè de productes tèxtils,A mitjans dels anys 50 el país tenia una economia agrària afectada per unapobresa massiva, la seva renta per càpita era inferior a les d’Angola o Moçambic, peròentre 1962 i 1996 el seu PNB per càpita passà de 87 dòlars a més de 12.000 i el seuPIB es multiplicà per 12, amb una taxa anual mitja de creixement del 8%, convertint-seen un país industrial avançat. A més, durant els anys 70 i 80 havia resistitsorprenentment bé les perturbacions (energètiques, monetàries i comercials) externes,malgrat el seu model de creixement depenia molt de les importacions de petroli, deldeute extern (fins mitjans dels 80) i de les exportacions de manufactures als mercatsoccidentals, i havia superat bé els problemes de deute extern que afectaren a altrespaïsos en vies de desenvolupament.Durant els anys 90 el procés de globalització financera contribuí, aparentment,a sostenir aquest creixement, amb l’entrada d’una quantitat ingent de fluxos de capitalestranger i la integració cada cop més plena dins dels mercats mundials de la mà d’unprocés de liberalització financera i comercial, arribant a aconseguir a finals de 1996 laseva admissió a la Organització de Cooperació i Desenvolupament Econòmic (OCDE).Però aquests factors que contribuïren al creixement li passarien factura, al propiciaruna sèrie de vulnerabilitats macroeconòmiques que acabarien sortint a la llum en elcontext de la crisis asiàtica del 97 i mostrarien la necessitat d’un canvi en el model dedesenvolupament, tan exitós durant anys, però incapaç d’adaptar-se per si sol alsnous paràmetres de l’economia globalitzada.2Com a continuació es veurà, la crisis coreana té unes característiques concretes,que la diferencien de la patida per la resta de països afectats per la crisis asiàtica del97, però comparteix també elements en comú. La crisis coreana s’entén millor dins elmarc en què es produí, el de les crisis asiàtiques. Però encara podem anar més lluny, jaque per molts experts les crisis del 97 han estat les primeres grans crisis de laglobalització i per tant és des d’aquí que s’ha d’analitzar, fins arribar al cas concret deCorea del Sud, incomprensible sense tot el context general.Les debilitats estructurals de les diferents economies asiàtiques afectadespoden explicar parcialment la gènesis de la crisis, però es tracta per molts d’una crisissistèmica global, que s’insereix en un context molt més ampli. Per això s’ha dividit elsegüent anàlisi en tres parts: els efectes de la globalització en general, les crisisasiàtiques i finalment el cas concret de Corea del Sud.