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1.
Br J Haematol ; 204(3): 1005-1016, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38083818

RESUMO

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare condition caused by severe ADAMTS13 deficiency, leading to platelet aggregation and thrombosis. Despite treatment, patients are prone to cognitive impairment and depression. We investigated brain changes in iTTP patients during remission using advanced magnetic resonance imaging (MRI) techniques, correlating these changes with mood and neurocognitive tests. Twenty iTTP patients in remission (30 days post-haematological remission) were compared with six healthy controls. MRI scans, including standard and specialized sequences, were conducted to assess white matter health. Increased T1 relaxation times were found in the cingulate cortex (p < 0.05), and elevated T2 relaxation times were observed in the cingulate cortex, frontal, parietal and temporal lobes (p < 0.05). Pathological changes in these areas are correlated with impaired cognitive and depressive scores in concentration, short-term memory and verbal memory. This study highlights persistent white matter damage in iTTP patients, potentially contributing to depression and cognitive impairment. Key regions affected include the frontal lobe and cingulate cortex. These findings have significant implications for the acute and long-term management of iTTP, suggesting a need for re-evaluation of treatment approaches during both active phases and remission. Further research is warranted to enhance our understanding of these complexities.


Assuntos
Disfunção Cognitiva , Púrpura Trombocitopênica Trombótica , Substância Branca , Humanos , Púrpura Trombocitopênica Trombótica/terapia , Proteína ADAMTS13
2.
Neurobiol Learn Mem ; 161: 135-142, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30986532

RESUMO

Sleep is known to be beneficial to the strengthening of two distinct forms of procedural memory: memory for novel, cognitively simple series of motor movements, and memory for novel, cognitively complex strategies required to solve problems. However, these two types of memory are intertwined, since learning a new cognitive procedural strategy occurs through practice, and thereby also requires the execution of a series of simple motor movements. As a result, it is unclear whether the benefit of sleep results from the enhancement of the cognitive strategy, or the motor skills required to execute the solution. To disentangle the role of sleep in these aspects of procedural memory, we employed two tasks: (1) the Tower of Hanoi (ToH), and, (2) a modified version of the ToH, akin to an implicit Motor Sequence Learning (MSL) task. The MSL task involved the identical series of motor movements as the ToH, but without access to the information necessary to execute the task according to the underlying cognitive procedural strategy. Participants (n = 28) were trained on the 3-disk ToH, then retested on 5-disk versions of both ToH and MSL tasks. Half (n = 15) were trained and immediately tested at 8 PM and retested at 8 AM after a night of sleep. They were retested again at 8 PM after a day of wake (PM-AM-PM condition). The other half (n = 13) were trained and immediately tested at 8 AM, retested at 8 PM after a day of wake, and retested again at 8 AM after a night of sleep (AM-PM-AM condition). ToH performance only improved following a period of sleep. There was no benefit of sleep to implicit MSL. Our results show that sleep, but not wake, allowed individuals to extrapolate what was learned on a simpler 3-disk version of the task to the larger 5-disk problem, which included new elements to which they had not yet been exposed. Here, we isolate the specific role sleep plays for cognitive procedural memory: sleep benefits the cognitive strategy, rather than strengthening implicitly acquired motor sequences required to learn and execute the underlying strategy itself.


Assuntos
Função Executiva/fisiologia , Consolidação da Memória/fisiologia , Destreza Motora/fisiologia , Aprendizagem Seriada/fisiologia , Sono/fisiologia , Adulto , Feminino , Humanos , Masculino , Prática Psicológica , Adulto Jovem
3.
BMC Med ; 16(1): 134, 2018 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-30097009

RESUMO

The original article [1] contains an error affecting the actigraphy time-stamps throughout the article, particularly in Table 1.

4.
Cereb Cortex ; 23(2): 361-9, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22351648

RESUMO

A key mechanism by which the prefrontal cortex (PFC) supports goal-oriented behaviors is attentional set formation: the formation and maintenance of an attentional bias toward relevant features. It has previously been proposed that a common single nucleotide polymorphism (val158met) in the gene that codes for the catechol O-methyltransferase (COMT) enzyme may affect an individual's ability to form and maintain an attentional set by modulating PFC dopamine (DA) levels. Here, we present data from a functional magnetic resonance imaging study that investigated the effect of this polymorphism on the tendency for older adults to display set-like behavior, and we compare these results to preexisting data from Parkinson's Disease (PD) patients. Our results demonstrate that putatively different levels of PFC DA predict both attentional set formation and right dorsolateral PFC (DLPFC) activation. More specifically, while for PD patients, val homozygotes showed heightened DLPFC activation and increased set-like behavior, for healthy older adults, the opposite pattern of results was observed. This interaction between COMT genotype and PD accords well with previous studies that have shown an excess of DA in the PFC in early PD patients and, furthermore, supports the hypothesis that there is an inverted-U shaped functional relationship between PFC DA levels and attentional set formation.


Assuntos
Catecol O-Metiltransferase/genética , Cognição/fisiologia , Dopamina/metabolismo , Córtex Pré-Frontal/metabolismo , Idoso , Atenção/fisiologia , Dopamina/genética , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/genética , Doença de Parkinson/psicologia , Polimorfismo de Nucleotídeo Único , Córtex Pré-Frontal/química
5.
Clin Neurophysiol ; 132(1): 45-55, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33248433

RESUMO

OBJECTIVE: The current study investigated the behavioral, cognitive, and electrophysiological impact of mild (only a few hours) and acute (one night) sleep loss via simultaneously recorded behavioural and physiological measures of vigilance. METHODS: Participants (N = 23) came into the lab for two testing days where their brain activity and vigilance were recorded and assessed. The night before the testing session, participants either slept from 12am to 9am (Normally Rested), or from 1am to 6am (Sleep Restriction). RESULTS: Vigilance was reduced and sleepiness was increased in the Sleep Restricted vs. Normally Rested condition, and this was exacerbated over the course of performing the vigilance task. As well, sleep restriction resulted in more intense alpha bursts. Lastly, EEG spectral power differed in Sleep Restricted vs. Normally Rested conditions as sleep onset progressed, particularly for frequencies reflecting arousal (e.g., delta, alpha, beta). CONCLUSIONS: The findings of this study suggest that only one night of mild sleep loss significantly increases sleepiness and, importantly, reduces vigilance. In addition, this sleep loss has a clear impact on the physiology of the brain in ways that reflect reduced arousal. SIGNIFICANCE: Understanding the neural correlates and cognitive processes associated with loss of sleep may lead to important advancements in identifying and preventing deleterious or potentially dangerous, sleep-related lapses in vigilance.


Assuntos
Nível de Alerta/fisiologia , Cognição/fisiologia , Eletroencefalografia , Privação do Sono/fisiopatologia , Sonolência , Adulto , Ritmo alfa/fisiologia , Análise de Variância , Ritmo beta/fisiologia , Eletroencefalografia/métodos , Feminino , Humanos , Masculino , Desempenho Psicomotor/fisiologia , Tempo de Reação/fisiologia , Latência do Sono/fisiologia , Adulto Jovem
6.
Neuroimage ; 52(3): 1015-26, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20056151

RESUMO

Dynamic causal modelling (DCM) of functional magnetic resonance imaging (fMRI) data offers new insights into the pathophysiology of neurological disease and mechanisms of effective therapies. Current applications can be used both to identify the most likely functional brain network underlying observed data and estimate the networks' connectivity parameters. We examined the reproducibility of DCM in healthy subjects (young 18-48 years, n=27; old 50-80 years, n=15) in the context of action selection. We then examined the effects of Parkinson's disease (50-78 years, Hoehn and Yahr stage 1-2.5, n=16) and dopaminergic therapy. Forty-eight models were compared, for each of 90 sessions from 58 subjects. Model-evidences clustered according to sets of structurally similar models, with high correlations over two sessions in healthy older subjects. The same model was identified as most likely in healthy controls on both sessions and in medicated patients. In this most likely network model, the selection of action was associated with enhanced coupling between prefrontal cortex and the pre-supplementary motor area. However, the parameters for intrinsic connectivity and contextual modulation in this model were poorly correlated across sessions. A different model was identified in patients with Parkinson's disease after medication withdrawal. In "off" patients, action selection was associated with enhanced connectivity from prefrontal to lateral premotor cortex. This accords with independent evidence of a dopamine-dependent functional disconnection of the SMA in Parkinson's disease. Together, these results suggest that DCM model selection is robust and sensitive enough to study clinical populations and their pharmacological treatment. For critical inferences, model selection may be sufficient. However, caution is required when comparing groups or drug effects in terms of the connectivity parameter estimates, if there are significant posterior covariances among parameters.


Assuntos
Encéfalo/fisiopatologia , Interpretação de Imagem Assistida por Computador/métodos , Modelos Neurológicos , Rede Nervosa/fisiopatologia , Doença de Parkinson/fisiopatologia , Idoso , Teorema de Bayes , Encéfalo/efeitos dos fármacos , Dopaminérgicos/uso terapêutico , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Rede Nervosa/efeitos dos fármacos , Doença de Parkinson/tratamento farmacológico , Reprodutibilidade dos Testes
7.
Brain ; 132(Pt 9): 2541-52, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19710182

RESUMO

Clinical audits have highlighted the many challenges and dilemmas faced by clinicians assessing persons with disorders of consciousness (vegetative state and minimally conscious state). The diagnostic decision-making process is highly subjective, dependent upon the skills of the examiner and invariably dictated by the patients' ability to move or speak. Whilst a considerable amount has been learnt since Jennett and Plum coined the term 'vegetative state', the assessment process remains largely unchanged; conducted at the bedside, using behavioural assessment tools, which are susceptible to environmental and physiological factors. This has created a situation where the rate of misdiagnosis is unacceptably high (up to 43%). In order to address these problems, various functional brain imaging paradigms, which do not rely upon the patient's ability to move or speak, have been proposed as a source of additional information to inform the diagnostic decision making process. Although accumulated evidence from brain imaging, particularly functional magnetic resonance imaging (fMRI), has been encouraging, the empirical evidence is still based on relatively small numbers of patients. It remains unclear whether brain imaging is capable of informing the diagnosis beyond the behavioural assessment and whether brain imaging has any prognostic utility. In this study, we describe the functional brain imaging findings from a group of 41 patients with disorders of consciousness, who undertook a hierarchical speech processing task. We found, contrary to the clinical impression of a specialist team using behavioural assessment tools, that two patients referred to the study with a diagnosis of vegetative state did in fact demonstrate neural correlates of speech comprehension when assessed using functional brain imaging. These fMRI findings were found to have no association with the patient's behavioural presentation at the time of investigation and thus provided additional diagnostic information beyond the traditional clinical assessment. Notably, the utility of brain imaging was further underlined by the finding that the level of auditory processing revealed by functional brain imaging, correlated strongly (rs = 0.81, P < 0.001) with the patient's subsequent behavioural recovery, 6 months after the scan, suggesting that brain imaging may also provide valuable prognostic information. Although further evidence is required before consensus statements can be made regarding the use of brain imaging in clinical decision making for disorders of consciousness, the results from this study clearly highlight the potential of imaging to inform the diagnostic decision-making process for persons with disorders of consciousness.


Assuntos
Encéfalo/fisiopatologia , Transtornos da Consciência/diagnóstico , Estimulação Acústica/métodos , Adolescente , Adulto , Idoso , Estudos de Coortes , Compreensão , Transtornos da Consciência/etiologia , Transtornos da Consciência/psicologia , Tomada de Decisões , Feminino , Escala de Coma de Glasgow , Humanos , Idioma , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Estado Vegetativo Persistente/diagnóstico , Estado Vegetativo Persistente/etiologia , Estado Vegetativo Persistente/psicologia , Prognóstico , Percepção da Fala/fisiologia , Adulto Jovem
8.
Neuroimage Clin ; 28: 102477, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33395970

RESUMO

Children who have been diagnosed with autism spectrum disorder (ASD) often show a marked deficit in measures of social cognition. In autistic adults, measures of social cognition have been shown to relate to differences in brain synchronization (as measured by fMRI) when individuals are processing naturalistic stimuli, such as movies. However, whether children who differ in their degree of autistic traits, with or without a diagnosis of ASD, differ in their neural responses to movies has not yet been investigated. In the current study, neural synchrony, measured using fMRI, was examined in three groups of children aged 7 to 12, who differed with respect to scores on a measure of autistic traits associated with social impairment and whether or not they had been diagnosed with ASD. While watching the movie 'Despicable Me', those diagnosed with ASD had significantly less neural synchrony in areas that have been previously shown to be associated with social cognition (e.g. areas related to 'theory of mind'), and plot following (e.g. the lateral prefrontal cortex), than those who did not have an ASD diagnosis. In contrast, two groups who differed in their degree of autistic traits, but did not have a diagnosis of ASD, showed no significant differences in neural synchrony across the whole brain. These results shed some light on how autistic traits may contribute to an individual's conscious experience of the world, and how, for children with ASD, that experience may differ markedly from that of those without ASD.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Adulto , Transtorno do Espectro Autista/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Criança , Humanos , Imageamento por Ressonância Magnética , Filmes Cinematográficos
9.
Clin Neurophysiol ; 131(11): 2736-2765, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32917521

RESUMO

The analysis of spontaneous EEG activity and evoked potentialsis a cornerstone of the instrumental evaluation of patients with disorders of consciousness (DoC). Thepast few years have witnessed an unprecedented surge in EEG-related research applied to the prediction and detection of recovery of consciousness after severe brain injury,opening up the prospect that new concepts and tools may be available at the bedside. This paper provides a comprehensive, critical overview of bothconsolidated and investigational electrophysiological techniquesfor the prognostic and diagnostic assessment of DoC.We describe conventional clinical EEG approaches, then focus on evoked and event-related potentials, and finally we analyze the potential of novel research findings. In doing so, we (i) draw a distinction between acute, prolonged and chronic phases of DoC, (ii) attempt to relate both clinical and research findings to the underlying neuronal processes and (iii) discuss technical and conceptual caveats.The primary aim of this narrative review is to bridge the gap between standard and emerging electrophysiological measures for the detection and prediction of recovery of consciousness. The ultimate scope is to provide a reference and common ground for academic researchers active in the field of neurophysiology and clinicians engaged in intensive care unit and rehabilitation.


Assuntos
Transtornos da Consciência/diagnóstico , Eletroencefalografia/métodos , Potenciais Evocados/fisiologia , Estado de Consciência/fisiologia , Transtornos da Consciência/fisiopatologia , Humanos , Prognóstico
10.
J Neurol Neurosurg Psychiatry ; 80(11): 1202-5, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19286742

RESUMO

BACKGROUND: An fMRI study is described in which a postencephalitic woman with amnesia used a wearable camera which takes photographs passively, without user intervention, to record and review recent autobiographical events. "SenseCam" generates hundreds of images which can subsequently be reviewed quickly or one by one. RESULTS: Memory for a significant event was improved substantially when tested after 4.5 weeks, if the patient viewed SenseCam images of the event every 2 days for 3 weeks. In contrast, after only 3.5 weeks, her memory was at chance levels for a similarly significant event which was reviewed equally often, but using a written diary. During the fMRI scan, the patient viewed images of these two events, plus images of an unrehearsed event and images from a novel "control" event that she had never experienced. There was no difference in behavioural responses or in activation when the unrehearsed and novel conditions were compared. Relative to the written-rehearsed condition, successful recognition of the images in the SenseCam-rehearsed condition was associated with activation of frontal and posterior cortical regions associated with normal episodic memory. CONCLUSION: SenseCam images may provide powerful cues that trigger the recall and consolidation of stored but inaccessible memories.


Assuntos
Amnésia/terapia , Córtex Cerebral/fisiopatologia , Encefalite Límbica/complicações , Psicoterapia/métodos , Idoso , Amnésia/complicações , Amnésia/fisiopatologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Fotografação
11.
Brain ; 131(Pt 8): 2094-105, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18577547

RESUMO

Cognitive deficits are very common in Parkinson's disease particularly for 'executive functions' associated with frontal cortico-striatal networks. Previous work has identified deficits in tasks that require attentional control like task-switching, and reward-based tasks like gambling or reversal learning. However, there is a complex relationship between the specific cognitive problems faced by an individual patient, their stage of disease and dopaminergic treatment. We used a bimodality continuous performance task during fMRI to examine how patients with Parkinson's disease represent the prospect of reward and switch between competing task rules accordingly. The task-switch was not separately cued but was based on the implicit reward relevance of spatial and verbal dimensions of successive compound stimuli. Nineteen patients were studied in relative 'on' and 'off' states, induced by dopaminergic medication withdrawal (Hoehn and Yahr stages 1-4). Patients were able to successfully complete the task and establish a bias to one or other dimension in order to gain reward. However the lateral prefrontal cortex and caudate nucleus showed a non-linear U-shape relationship between motor disease severity and regional brain activation. Dopaminergic treatment led to a shift in this U-shape function, supporting the hypothesis of differential neurodegeneration in separate motor and cognitive cortico-striato-thalamo-cortical circuits. In addition, anterior cingulate activation associated with reward expectation declined with more severe disease, whereas activation following actual rewards increased with more severe disease. This may facilitate a change in goal-directed behaviours from deferred predicted rewards to immediate actual rewards, particularly when on dopaminergic treatment. We discuss the implications for investigation and optimal treatment of this common condition at different stages of disease.


Assuntos
Dopaminérgicos/uso terapêutico , Levodopa/uso terapêutico , Doença de Parkinson/psicologia , Idoso , Estudos de Casos e Controles , Núcleo Caudado/patologia , Cognição , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Movimento , Testes Neuropsicológicos , Doença de Parkinson/patologia , Córtex Pré-Frontal/patologia , Desempenho Psicomotor , Tempo de Reação , Recompensa
12.
Cereb Cortex ; 18(10): 2275-85, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18234684

RESUMO

The human capacity for voluntary action is one of the major contributors to our success as a species. In addition to choosing actions themselves, we can also voluntarily choose behavioral codes or sets of rules that can guide future responses to events. Such rules have been proposed to be superordinate to actions in a cognitive hierarchy and mediated by distinct brain regions. We used event-related functional magnetic resonance imaging to study novel tasks of rule-based and voluntary action. We show that the voluntary selection of rules to govern future responses to events is associated with activation of similar regions of prefrontal and parietal cortex as the voluntary selection of an action itself. The results are discussed in terms of hierarchical models and the adaptive coding potential of prefrontal neurons and their contribution to a global workspace for nonautomatic tasks. These tasks include the choices we make about our behavior.


Assuntos
Comportamento de Escolha/fisiologia , Imageamento por Ressonância Magnética , Lobo Parietal/anatomia & histologia , Lobo Parietal/fisiologia , Córtex Pré-Frontal/anatomia & histologia , Córtex Pré-Frontal/fisiologia , Adulto , Mapeamento Encefálico , Cognição/fisiologia , Tomada de Decisões/fisiologia , Feminino , Humanos , Masculino , Vias Neurais/fisiologia , Volição/fisiologia , Adulto Jovem
13.
Sci Adv ; 5(2): eaat7603, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30775433

RESUMO

Adopting the framework of brain dynamics as a cornerstone of human consciousness, we determined whether dynamic signal coordination provides specific and generalizable patterns pertaining to conscious and unconscious states after brain damage. A dynamic pattern of coordinated and anticoordinated functional magnetic resonance imaging signals characterized healthy individuals and minimally conscious patients. The brains of unresponsive patients showed primarily a pattern of low interareal phase coherence mainly mediated by structural connectivity, and had smaller chances to transition between patterns. The complex pattern was further corroborated in patients with covert cognition, who could perform neuroimaging mental imagery tasks, validating this pattern's implication in consciousness. Anesthesia increased the probability of the less complex pattern to equal levels, validating its implication in unconsciousness. Our results establish that consciousness rests on the brain's ability to sustain rich brain dynamics and pave the way for determining specific and generalizable fingerprints of conscious and unconscious states.


Assuntos
Encéfalo/fisiologia , Conectoma , Estado de Consciência , Vias Neurais , Adulto , Mapeamento Encefálico , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem
14.
Curr Biol ; 8(23): R850-2, 1998 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-9822574

RESUMO

Memory depends upon a network of interconnected and functionally related cortical and subcortical areas including, at the very least, the prefrontal cortex and the medial temporal lobe structures. Evidence is now emerging to relate these neuroanatomical regions to specific aspects of mnemonic processing.


Assuntos
Encéfalo/fisiologia , Memória/fisiologia , Animais , Humanos
15.
Trends Neurosci ; 23(10): 475-83, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11006464

RESUMO

Though many neuroscientific methods have been brought to bear in the search for functional specializations within prefrontal cortex, little consensus has emerged. To assess the contribution of functional neuroimaging, this article reviews patterns of frontal-lobe activation associated with a broad range of different cognitive demands, including aspects of perception, response selection, executive control, working memory, episodic memory and problem solving. The results show a striking regularity: for many demands, there is a similar recruitment of mid-dorsolateral, mid-ventrolateral and dorsal anterior cingulate cortex. Much of the remainder of frontal cortex, including most of the medial and orbital surfaces, is largely insensitive to these demands. Undoubtedly, these results provide strong evidence for regional specialization of function within prefrontal cortex. This specialization, however, takes an unexpected form: a specific frontal-lobe network that is consistently recruited for solution of diverse cognitive problems.


Assuntos
Mapeamento Encefálico , Cognição/fisiologia , Lobo Frontal/fisiologia , Animais , Atenção/fisiologia , Discriminação Psicológica/fisiologia , Lobo Frontal/ultraestrutura , Giro do Cíngulo/fisiologia , Haplorrinos/fisiologia , Humanos , Imageamento por Ressonância Magnética , Memória/fisiologia , Testes Neuropsicológicos , Percepção/fisiologia , Córtex Pré-Frontal/fisiologia , Córtex Pré-Frontal/ultraestrutura , Desempenho Psicomotor/fisiologia , Semântica , Comportamento Espacial/fisiologia
16.
Prog Neurobiol ; 53(4): 431-50, 1997 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9421831

RESUMO

In recent years, considerable progress has been made in understanding the cognitive and neuroanatomical basis of high-level planning behaviour through a combination of neuropsychological, neuropharmacological and functional neuroimaging approaches. In this article, early evidence suggesting a relationship between planning impairments and damage to the frontal lobe is reviewed and several contemporary studies of planning behaviour in patients with circumscribed frontal lobe excisions are described in detail. These neuropsychological investigations, together with recent functional neuroimaging studies of normal control subjects, have identified a specific area within the mid-dorsolateral frontal cortex of humans which appears to be critically involved in the cognitive processes that mediate efficient planning. The functions of this region, both in cognitive planning and in related functions such as working memory, are then discussed in the context of a general theoretical framework for understanding the functional organization of "executive" processes within the human lateral frontal cortex. In the final sections, the relationship between the planning deficits observed after intrinsic frontal lobe damage and those exhibited by patients with neuropathology of primarily sub-cortical origin, such as Parkinson's disease, is discussed. A central model for much of this work has been the concept of cortico-striatal circuitry which emphasizes the relationship between the neocortex and the striatum. The combined evidence from comparative studies in patients and from functional neuroimaging studies on Parkinson's disease suggests that altered cortico-striatal interactions may disrupt normal planning function at a number of levels, possibly consequent upon intrinsic striatal pathology on the one hand and the partial loss of (frontal) cortical input to the basal ganglia on the other.


Assuntos
Encéfalo/anatomia & histologia , Encéfalo/fisiologia , Cognição/efeitos dos fármacos , Cognição/fisiologia , Processos Mentais/efeitos dos fármacos , Processos Mentais/fisiologia , Química Encefálica/efeitos dos fármacos , Humanos
17.
Cancer Res ; 50(1): 193-6, 1990 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-2293555

RESUMO

The effect of treatment with the aromatase inhibitor, 4-hydroxyandrostenedione (4-OHA) on the peripheral conversion of androstenedione to estrone has been examined in eight postmenopausal women with advanced breast cancer. Before treatment conversion of androstenedione to estrone ([p]AEIBB) ranged from 0.81 to 3.7% and was almost completely inhibited after treatment with 4-OHA (two doses of 500 mg i.m. with an interval of 12 days between doses). Transfer constants were also measured by the urinary method ([p]AEIBU) for some subjects and decreased from 2.3 +/- 0.52% to 0.24 +/- 0.11% after treatment, a mean reduction of 90%. Mean plasma concentration of estradiol (37.4 +/- 16.6 pmol/liter) and estrone (99.0 +/- 32.2 pmol/liter) decreased significantly (P less than 0.01) to 15.7 +/- 4.6 pmol/liter and 52.4 +/- 8.9 pmol/liter, respectively, after treatment. Aromatase and DNA polymerase alpha (a marker of cell proliferation) activities were measured in seven samples of breast tumor tissue obtained before and after treatment. For three samples there was a marked (67 +/- 17%) decrease in tumor aromatase activity after treatment, for two, little change occurred, while tumor aromatase activity in the other two samples appeared to be resistant to the effect of 4-OHA. The correlation between tumor aromatase and DNA polymerase alpha activities (r = 0.45) failed to reach a significant level.


Assuntos
Androstenodiona/análogos & derivados , Androstenodiona/metabolismo , Antineoplásicos/uso terapêutico , Aromatase/metabolismo , Neoplasias da Mama/tratamento farmacológico , Estrona/metabolismo , Idoso , Androstenodiona/uso terapêutico , Neoplasias da Mama/enzimologia , Neoplasias da Mama/metabolismo , DNA Polimerase II/metabolismo , Feminino , Humanos , Cinética , Taxa de Depuração Metabólica
18.
Prog Brain Res ; 228: 241-91, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27590972

RESUMO

The disorders of consciousness refer to clinical conditions that follow a severe head injury. Patients diagnosed as in a vegetative state lack awareness, while patients diagnosed as in a minimally conscious state retain fluctuating awareness. However, it is a challenge to accurately diagnose these disorders with clinical assessments of behavior. To improve diagnostic accuracy, neuroimaging-based approaches have been developed to detect the presence or absence of awareness in patients who lack overt responsiveness. For the small subset of patients who retain awareness, brain-computer interfaces could serve as tools for communication and environmental control. Here we review the existing literature concerning the sensory and cognitive abilities of patients with disorders of consciousness with respect to existing brain-computer interface designs. We highlight the challenges of device development for this special population and address some of the most promising approaches for future investigations.


Assuntos
Ondas Encefálicas/fisiologia , Interfaces Cérebro-Computador , Transtornos da Consciência/reabilitação , Neurorretroalimentação/métodos , Transtornos da Consciência/diagnóstico por imagem , Bases de Dados Bibliográficas/estatística & dados numéricos , Eletroencefalografia , Humanos , Intenção , Imageamento por Ressonância Magnética
19.
J Neurosci ; 20(7): 2649-56, 2000 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-10729345

RESUMO

Research with animals suggests that structures within the amygdaloid nuclear complex (ANC) are critical for acquiring associations between rewarding events and neutral stimuli, a form of conditioning often manifested in a subsequent preference for those (conditioned) stimuli. In this study, we investigated the relationship between the ANC and preference learning in humans. Three abstract monochrome patterns were presented to each subject over 180 trials in the context of a counting task requiring working memory. One pattern was paired with food reward on 90% of the trials in which it was presented and with no food reward on the other 10% of trials. The other patterns were similarly reinforced, but at ratios of 50:50% and 10:90% with reward and nonreward, respectively. Subsequently, a group of 21 normal participants preferred the pattern paired most often with reward to that paired least often with reward, and they did not explicitly relate their preferences to the conditioning procedure, but instead attributed them to the characteristics of the patterns themselves. Unlike the normal controls, a group of patients with unilateral surgical lesions that included the ANC (15 left, 18 right) did not show conditioned preferences, but performed normally on a measure of working memory. In contrast, 13 patients with unilateral damage confined to frontal cortex exhibited normal conditioned preferences but were impaired on the working memory task. This double dissociation provides clear evidence that, in humans as in other animals, reward-related learning (conditioned reward) critically depends on a circuit involving inferotemporal cortex and the ANC.


Assuntos
Comportamento de Escolha/fisiologia , Condicionamento Psicológico/fisiologia , Lobo Temporal/fisiologia , Adolescente , Adulto , Tonsila do Cerebelo/fisiologia , Mapeamento Encefálico , Neoplasias Encefálicas/cirurgia , Epilepsia/cirurgia , Feminino , Lateralidade Funcional , Humanos , Masculino , Pessoa de Meia-Idade
20.
J Neurosci ; 20(6): RC65, 2000 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-10704519

RESUMO

The indirect catecholamine agonist methylphenidate (Ritalin) is the drug treatment of choice in attention deficit/hyperactivity disorder (AD/HD), one of the most common behavioral disorders of childhood (DSM-IV), although symptoms may persist into adulthood. Methylphenidate can enhance cognitive performance in adults and children diagnosed with AD/HD (Kempton et al., 1999; Riordan et al., 1999) and also in normal human volunteers on tasks sensitive to frontal lobe damage, including aspects of spatial working memory (SWM) performance (Elliott et al., 1997). The present study investigated changes in regional cerebral blood flow (rCBF) induced by methylphenidate during performance of a self-ordered SWM task to define the neuroanatomical loci of the beneficial effect of the drug. The results show that the methylphenidate-induced improvements in working memory performance occur with task-related reductions in rCBF in the dorsolateral prefrontal cortex and posterior parietal cortex. The beneficial effects of methylphenidate on working memory were greatest in the subjects with lower baseline working memory capacity. This is to our knowledge the first demonstration of a localization of a drug-induced improvement in SWM performance in humans and has relevance for understanding the treatment of AD/HD.


Assuntos
Inibidores da Captação Adrenérgica/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Inibidores da Captação de Dopamina/farmacologia , Lobo Frontal/efeitos dos fármacos , Memória de Curto Prazo/efeitos dos fármacos , Metilfenidato/farmacologia , Lobo Parietal/efeitos dos fármacos , Adulto , Circulação Cerebrovascular/efeitos dos fármacos , Lobo Frontal/irrigação sanguínea , Lobo Frontal/fisiologia , Lateralidade Funcional , Humanos , Masculino , Memória de Curto Prazo/fisiologia , Lobo Parietal/irrigação sanguínea , Lobo Parietal/fisiologia , Tomografia Computadorizada de Emissão
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