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1.
Proc Natl Acad Sci U S A ; 115(3): E536-E545, 2018 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-29284747

RESUMO

Attention control (or executive control) is a higher cognitive function involved in response selection and inhibition, through close interactions with the motor system. Here, we tested whether influences of attention control are also seen on lower level motor functions of dexterity and strength-by examining relationships between attention control and motor performance in healthy-aged and hemiparetic-stroke subjects (n = 93 and 167, respectively). Subjects undertook simple-tracking, precision-hold, and maximum force-generation tasks, with each hand. Performance across all tasks correlated strongly with attention control (measured as distractor resistance), independently of factors such as baseline performance, hand use, lesion size, mood, fatigue, or whether distraction was tested during motor or nonmotor cognitive tasks. Critically, asymmetric dissociations occurred in all tasks, in that severe motor impairment coexisted with normal (or impaired) attention control whereas normal motor performance was never associated with impaired attention control (below a task-dependent threshold). This implies that dexterity and force generation require intact attention control. Subsequently, we examined how motor and attention-control performance mapped to lesion location and cerebral functional connectivity. One component of motor performance (common to both arms), as well as attention control, correlated with the anatomical and functional integrity of a cingulo-opercular "salience" network. Independently of this, motor performance difference between arms correlated negatively with the integrity of the primary sensorimotor network and corticospinal tract. These results suggest that the salience network, and its attention-control function, are necessary for virtually all volitional motor acts while its damage contributes significantly to the cardinal motor deficits of stroke.


Assuntos
Atenção/fisiologia , Função Executiva , Atividade Motora/fisiologia , Desempenho Psicomotor/fisiologia , Acidente Vascular Cerebral/fisiopatologia , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Memória/fisiologia , Pessoa de Meia-Idade
2.
Mult Scler ; 25(11): 1462-1471, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30141723

RESUMO

BACKGROUND: Progression is the major driver of disability and cost in multiple sclerosis (MS). However, the search for treatments in progressive multiple sclerosis (PMS) has not mirrored the success in relapsing MS. OBJECTIVES: To assess changes in PMS trials over time. METHODS: PubMed, MEDLINE and Embase were searched to identify randomised, double-blind, placebo-controlled trials in PMS. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used, study quality was assessed and trends were examined by regression. RESULTS: Placebo groups of 43 studies published between 1988 and 2018 were included. The mean age at trial entry increased by 9.8 years per decade (95% confidence interval (CI): [2.7; 4.9]; p < 0.001). Mean baseline Expanded Disability Status Scale (EDSS) scores increased by 0.36 points (95% CI: [0.09; 0.62]; p = 0.009) and disease durations at baseline were prolonged by 1.8 years (95% CI: [0.7; 2.9]; p = 0.003) per decade. The trials became larger, specifically placebo groups increased by about 222 patients (95% CI: [36; 409]; p = 0.021) and 88 patients (95% CI: [12; 165]; p = 0.025) per decade for primary progressive multiple sclerosis (PPMS) and secondary progressive multiple sclerosis (SPMS), respectively. The proportion of patients on placebo experiencing disability progression within 24 months decreased by 7.6 percentage points (95% CI: [1.2; 14.1]; p = 0.022) per year. CONCLUSION: Over three decades, PMS trial populations changed and are now older, with a longer disease duration and more disability, with lower on-trial progression rates.


Assuntos
Esclerose Múltipla Crônica Progressiva/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Distribuição por Idade , Progressão da Doença , Definição da Elegibilidade/tendências , Humanos , Esclerose Múltipla Crônica Progressiva/epidemiologia , Esclerose Múltipla Crônica Progressiva/fisiopatologia , Índice de Gravidade de Doença
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