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1.
Mult Scler ; 25(2): 246-255, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29172994

RESUMO

BACKGROUND: Recent basic and clinical evidence suggests amiloride may be neuroprotective in multiple sclerosis (MS) through the blockade of the acid sensing ion channel (ASIC). OBJECTIVE: To examine the neuroprotective efficacy of amiloride in acute optic neuritis (ON). METHODS: A total of 48 patients were recruited to a phase 2, double blind, single site, randomised controlled trial. Scanning laser polarimetry (GDx) at 6 months was the primary outcome measure and optical coherence tomography (OCT) and visual and electrophysiological measures were secondary outcome measures. Participants aged 18-55 years, ≤28 days of onset of first episode unilateral ON, were randomised to amiloride (10 mg daily for 5 months) or placebo ( clinicaltrials.gov , NCT 01802489). RESULTS: Intention-to-treat (ITT) cohort consisted of 43 patients; 23 placebo and 20 amiloride. No significant drug-related adverse events occurred. No significant differences were found in GDx ( p = 0.840). Visual evoked potentials (VEP) were significantly prolonged in the amiloride group compared to placebo ( p = 0.004). All other secondary outcome measures showed no significant difference. Baseline analysis of OCT data demonstrated a significant pre-randomisation thinning of ganglion cell layer. CONCLUSION: Amiloride has not demonstrated any neuroprotective benefit within this trial paradigm, but future neuroprotective trials in ON should target the window of opportunity to maximise potential neuroprotective benefit.


Assuntos
Amilorida/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Neurite Óptica/tratamento farmacológico , Retina/efeitos dos fármacos , Adulto , Método Duplo-Cego , Potenciais Evocados Visuais/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neurite Óptica/patologia , Retina/patologia
2.
Brain ; 140(5): 1212-1219, 2017 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-28369215

RESUMO

Magnetic resonance imaging has linked chronic voltage-gated potassium channel (VGKC) complex antibody-mediated limbic encephalitis with generalized hippocampal atrophy. However, autoantibodies bind to specific rodent hippocampal subfields. Here, human hippocampal subfield (subiculum, cornu ammonis 1-3, and dentate gyrus) targets of immunomodulation-treated LGI1 VGKC-complex antibody-mediated limbic encephalitis were investigated using in vivo ultra-high resolution (0.39 × 0.39 × 1.0 mm3) 7.0 T magnetic resonance imaging [n = 18 patients, 17 patients (94%) positive for LGI1 antibody and one patient negative for LGI1/CASPR2 but positive for VGKC-complex antibodies, mean age: 64.0 ± 2.55 years, median 4 years post-limbic encephalitis onset; n = 18 controls]. First, hippocampal subfield quantitative morphometry indicated significant volume loss confined to bilateral CA3 [F(1,34) = 16.87, P < 0.0001], despite hyperintense signal evident in 5 of 18 patients on presentation. Second, early and later intervention (<3 versus >3 months from symptom onset) were associated with CA3 atrophy. Third, whole-brain voxel-by-voxel morphometry revealed no significant grey matter loss. Fourth, CA3 subfield atrophy was associated with severe episodic but not semantic amnesia for postmorbid autobiographical events that was predicted by variability in CA3 volume. The results raise important questions about the links with histopathology, the impact of the observed focal atrophy on other CA3-mediated reconstructive and episodic mechanisms, and the role of potential antibody-mediated pathogenicity as part of the pathophysiology cascade in humans.


Assuntos
Região CA3 Hipocampal/patologia , Encefalite Límbica/patologia , Canais de Potássio de Abertura Dependente da Tensão da Membrana/imunologia , Proteínas/imunologia , Adulto , Idoso , Amnésia/complicações , Amnésia/patologia , Atrofia/complicações , Atrofia/patologia , Autoanticorpos/imunologia , Estudos de Casos e Controles , Feminino , Substância Cinzenta/patologia , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Encefalite Límbica/complicações , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Adulto Jovem
3.
Ophthalmology ; 124(10): 1556-1564, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28651813

RESUMO

PURPOSE: Acquired nystagmus, a highly symptomatic consequence of damage to the substrates of oculomotor control, often is resistant to pharmacotherapy. Although heterogeneous in its neural cause, its expression is unified at the effector-the eye muscles themselves-where physical damping of the oscillation offers an alternative approach. Because direct surgical fixation would immobilize the globe, action at a distance is required to damp the oscillation at the point of fixation, allowing unhindered gaze shifts at other times. Implementing this idea magnetically, herein we describe the successful implantation of a novel magnetic oculomotor prosthesis in a patient. DESIGN: Case report of a pilot, experimental intervention. PARTICIPANT: A 49-year-old man with longstanding, medication-resistant, upbeat nystagmus resulting from a paraneoplastic syndrome caused by stage 2A, grade I, nodular sclerosing Hodgkin's lymphoma. METHODS: We designed a 2-part, titanium-encased, rare-earth magnet oculomotor prosthesis, powered to damp nystagmus without interfering with the larger forces involved in saccades. Its damping effects were confirmed when applied externally. We proceeded to implant the device in the patient, comparing visual functions and high-resolution oculography before and after implantation and monitoring the patient for more than 4 years after surgery. MAIN OUTCOME MEASURES: We recorded Snellen visual acuity before and after intervention, as well as the amplitude, drift velocity, frequency, and intensity of the nystagmus in each eye. RESULTS: The patient reported a clinically significant improvement of 1 line of Snellen acuity (from 6/9 bilaterally to 6/6 on the left and 6/5-2 on the right), reflecting an objectively measured reduction in the amplitude, drift velocity, frequency, and intensity of the nystagmus. These improvements were maintained throughout a follow-up of 4 years and enabled him to return to paid employment. CONCLUSIONS: This work opens a new field of implantable therapeutic devices-oculomotor prosthetics-designed to modify eye movements dynamically by physical means in cases where a purely neural approach is ineffective. Applied to acquired nystagmus refractory to all other interventions, it is shown successfully to damp pathologic eye oscillations while allowing normal saccadic shifts of gaze.


Assuntos
Campos Magnéticos , Nistagmo Patológico/cirurgia , Músculos Oculomotores/cirurgia , Próteses e Implantes , Movimentos Oculares/fisiologia , Humanos , Masculino , Metais Terras Raras , Pessoa de Meia-Idade , Nistagmo Patológico/fisiopatologia , Músculos Oculomotores/fisiopatologia , Desenho de Prótese , Implantação de Prótese , Visão Ocular/fisiologia , Acuidade Visual/fisiologia
4.
J Neurosci ; 35(21): 8201-13, 2015 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-26019336

RESUMO

When the human primary visual cortex (V1) is damaged, the dominant geniculo-striate pathway can no longer convey visual information to the occipital cortex. However, many patients with such damage retain some residual visual function that must rely on an alternative pathway directly to extrastriate occipital regions. This residual vision is most robust for moving stimuli, suggesting a role for motion area hMT+. However, residual vision also requires high-contrast stimuli, which is inconsistent with hMT+ sensitivity to contrast in which even low-contrast levels elicit near-maximal neural activation. We sought to investigate this discrepancy by measuring behavioral and neural responses to increasing contrast in patients with V1 damage. Eight patients underwent behavioral testing and functional magnetic resonance imaging to record contrast sensitivity in hMT+ of their damaged hemisphere, using Gabor stimuli with a spatial frequency of 1 cycle/°. The responses from hMT+ of the blind hemisphere were compared with hMT+ and V1 responses in the sighted hemisphere of patients and a group of age-matched controls. Unlike hMT+, neural responses in V1 tend to increase linearly with increasing contrast, likely reflecting a dominant parvocellular channel input. Across all patients, the responses in hMT+ of the blind hemisphere no longer showed early saturation but increased linearly with contrast. Given the spatiotemporal parameters used in this study and the known direct subcortical projections from the koniocellular layers of the lateral geniculate nucleus to hMT+, we propose that this altered contrast sensitivity in hMT+ could be consistent with input from the koniocellular pathway.


Assuntos
Cegueira/diagnóstico , Cegueira/fisiopatologia , Sensibilidades de Contraste , Estimulação Luminosa/métodos , Córtex Visual/fisiopatologia , Adulto , Sensibilidades de Contraste/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade
5.
J Neurosci ; 35(46): 15353-68, 2015 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-26586822

RESUMO

Repetitive transcranial magnetic stimulation (rTMS) applied over the right posterior parietal cortex (PPC) in healthy participants has been shown to trigger a significant rightward shift in the spatial allocation of visual attention, temporarily mimicking spatial deficits observed in neglect. In contrast, rTMS applied over the left PPC triggers a weaker or null attentional shift. However, large interindividual differences in responses to rTMS have been reported. Studies measuring changes in brain activation suggest that the effects of rTMS may depend on both interhemispheric and intrahemispheric interactions between cortical loci controlling visual attention. Here, we investigated whether variability in the structural organization of human white matter pathways subserving visual attention, as assessed by diffusion magnetic resonance imaging and tractography, could explain interindividual differences in the effects of rTMS. Most participants showed a rightward shift in the allocation of spatial attention after rTMS over the right intraparietal sulcus (IPS), but the size of this effect varied largely across participants. Conversely, rTMS over the left IPS resulted in strikingly opposed individual responses, with some participants responding with rightward and some with leftward attentional shifts. We demonstrate that microstructural and macrostructural variability within the corpus callosum, consistent with differential effects on cross-hemispheric interactions, predicts both the extent and the direction of the response to rTMS. Together, our findings suggest that the corpus callosum may have a dual inhibitory and excitatory function in maintaining the interhemispheric dynamics that underlie the allocation of spatial attention. SIGNIFICANCE STATEMENT: The posterior parietal cortex (PPC) controls allocation of attention across left versus right visual fields. Damage to this area results in neglect, characterized by a lack of spatial awareness of the side of space contralateral to the brain injury. Transcranial magnetic stimulation over the PPC is used to study cognitive mechanisms of spatial attention and to examine the potential of this technique to treat neglect. However, large individual differences in behavioral responses to stimulation have been reported. We demonstrate that the variability in the structural organization of the corpus callosum accounts for these differences. Our findings suggest novel dual mechanism of the corpus callosum function in spatial attention and have broader implications for the use of stimulation in neglect rehabilitation.


Assuntos
Atenção/fisiologia , Corpo Caloso/fisiologia , Percepção Espacial/fisiologia , Estimulação Magnética Transcraniana , Adulto , Mapeamento Encefálico , Movimentos Oculares , Feminino , Lateralidade Funcional , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Estimulação Luminosa , Tempo de Reação/fisiologia , Campos Visuais/fisiologia , Adulto Jovem
6.
J Neurosci ; 35(38): 13043-52, 2015 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-26400935

RESUMO

The frontal cortex and basal ganglia form a set of parallel but mostly segregated circuits called cortico-basal ganglia loops. The oculomotor loop controls eye movements and can direct relatively simple movements, such as reflexive prosaccades, without external help but needs input from "higher" loops for more complex behaviors. The antisaccade task requires the dorsolateral prefrontal cortex, which is part of the prefrontal loop. Information flows from prefrontal to oculomotor circuits in the striatum, and directional errors in this task can be considered a measure of failure of prefrontal control over the oculomotor loop. The antisaccadic error rate (AER) is increased in Parkinson's disease (PD). Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has no effect on the AER, but a previous case suggested that DBS of the globus pallidus interna (GPi) might. Our aim was to compare the effects of STN DBS and GPi DBS on the AER. We tested eye movements in 14 human DBS patients and 10 controls. GPi DBS substantially reduced the AER, restoring lost higher control over oculomotor function. Interloop information flow involves striatal neurons that receive cortical input and project to pallidum. They are normally silent when quiescent, but in PD they fire randomly, creating noise that may account for the degradation in interloop control. The reduced AER with GPi DBS could be explained by retrograde stimulation of striatopallidal axons with consequent activation of inhibitory collaterals and reduction in background striatal firing rates. This study may help explain aspects of PD pathophysiology and the mechanism of action of GPi DBS. Significance statement: Parkinson's disease causes symptoms including stiffness, slowness of movement, and tremor. Electrical stimulation of specific areas deep in the brain can effectively treat these symptoms, but exactly how is not fully understood. Part of the cause of such symptoms may be impairments in the way information flows from one circuit within the brain to another, as a result of overactivity of certain nerve cells. By demonstrating that stimulation of an area called the globus pallidus interna partially reverses deficits in voluntary control of eye movements, this study shows that stimulation can improve information flow between circuits, probably by calming down the overactive cells.


Assuntos
Estimulação Encefálica Profunda/métodos , Globo Pálido/fisiologia , Transtornos da Motilidade Ocular/etiologia , Transtornos da Motilidade Ocular/terapia , Doença de Parkinson/complicações , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Orientação , Doença de Parkinson/terapia , Estimulação Luminosa , Núcleo Subtalâmico/fisiologia , Resultado do Tratamento
7.
Brain ; 138(Pt 1): 164-78, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25433915

RESUMO

Motion area V5/MT+ shows a variety of characteristic visual responses, often linked to perception, which are heavily influenced by its rich connectivity with the primary visual cortex (V1). This human motion area also receives a number of inputs from other visual regions, including direct subcortical connections and callosal connections with the contralateral hemisphere. Little is currently known about such alternative inputs to V5/MT+ and how they may drive and influence its activity. Using functional magnetic resonance imaging, the response of human V5/MT+ to increasing the proportion of coherent motion was measured in seven patients with unilateral V1 damage acquired during adulthood, and a group of healthy age-matched controls. When V1 was damaged, the typical V5/MT+ response to increasing coherence was lost. Rather, V5/MT+ in patients showed a negative trend with coherence that was similar to coherence-related activity in V1 of healthy control subjects. This shift to a response-pattern more typical of early visual cortex suggests that in the absence of V1, V5/MT+ activity may be shaped by similar direct subcortical input. This is likely to reflect intact residual pathways rather than a change in connectivity, and has important implications for blindsight function. It also confirms predictions that V1 is critically involved in normal V5/MT+ global motion processing, consistent with a convergent model of V1 input to V5/MT+. Historically, most attempts to model cortical visual responses do not consider the contribution of direct subcortical inputs that may bypass striate cortex, such as input to V5/MT+. We have shown that the signal change driven by these non-striate pathways can be measured, and suggest that models of the intact visual system may benefit from considering their contribution.


Assuntos
Lesões Encefálicas/patologia , Percepção de Movimento/fisiologia , Transtornos da Percepção/etiologia , Córtex Visual/fisiopatologia , Adulto , Idoso , Cegueira/patologia , Cegueira/fisiopatologia , Lesões Encefálicas/complicações , Estudos de Casos e Controles , Movimentos Oculares , Feminino , Lateralidade Funcional/fisiologia , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estimulação Luminosa , Campos Visuais/fisiologia , Vias Visuais/fisiopatologia
8.
J Neurosci ; 34(33): 10844-52, 2014 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-25122887

RESUMO

The cortico-basal-ganglia circuit plays a critical role in decision making on the basis of probabilistic information. Computational models have suggested how this circuit could compute the probabilities of actions being appropriate according to Bayes' theorem. These models predict that the subthalamic nucleus (STN) provides feedback that normalizes the neural representation of probabilities, such that if the probability of one action increases, the probabilities of all other available actions decrease. Here we report the results of an experiment testing a prediction of this theory that disrupting information processing in the STN with deep brain stimulation should abolish the normalization of the neural representation of probabilities. In our experiment, we asked patients with Parkinson's disease to saccade to a target that could appear in one of two locations, and the probability of the target appearing in each location was periodically changed. When the stimulator was switched off, the target probability affected the reaction times (RT) of patients in a similar way to healthy participants. Specifically, the RTs were shorter for more probable targets and, importantly, they were longer for the unlikely targets. When the stimulator was switched on, the patients were still faster for more probable targets, but critically they did not increase RTs as the target was becoming less likely. This pattern of results is consistent with the prediction of the model that the patients on DBS no longer normalized their neural representation of prior probabilities. We discuss alternative explanations for the data in the context of other published results.


Assuntos
Estimulação Encefálica Profunda , Doença de Parkinson/fisiopatologia , Tempo de Reação/fisiologia , Movimentos Sacádicos/fisiologia , Núcleo Subtalâmico/fisiopatologia , Idoso , Teorema de Bayes , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/terapia , Desempenho Psicomotor/fisiologia
9.
J Cogn Neurosci ; 27(2): 377-86, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25203274

RESUMO

When briefly presented with pairs of words, skilled readers can sometimes report words with migrated letters (e.g., they report hunt when presented with the words hint and hurt). This and other letter migration phenomena have been often used to investigate factors that influence reading such as letter position coding. However, the neural basis of letter migration is poorly understood. Previous evidence has implicated the right posterior parietal cortex (PPC) in processing visuospatial attributes and lexical properties during word reading. The aim of this study was to assess this putative role by combining an inhibitory TMS protocol with a letter migration paradigm, which was designed to examine the contributions of visuospatial attributes and lexical factors. Temporary interference with the right PPC led to three specific effects on letter migration. First, the number of letter migrations was significantly increased only in the group with active stimulation (vs. a sham stimulation group or a control group without stimulation), and there was no significant effect on other error types. Second, this effect occurred only when letter migration could result in a meaningful word (migration vs. control context). Third, the effect of active stimulation on the number of letter migrations was lateralized to target words presented on the left. Our study thus demonstrates that the right PPC plays a specific and causal role in the phenomenon of letter migration. The nature of this role cannot be explained solely in terms of visuospatial attention, rather it involves an interplay between visuospatial attentional and word reading-specific factors.


Assuntos
Lobo Parietal/fisiologia , Reconhecimento Visual de Modelos/fisiologia , Leitura , Adulto , Atenção/fisiologia , Feminino , Lateralidade Funcional/fisiologia , Humanos , Testes de Linguagem , Linguística , Masculino , Estimulação Luminosa , Tempo de Reação , Estimulação Magnética Transcraniana , Adulto Jovem
10.
Mov Disord ; 30(6): 843-7, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25600361

RESUMO

BACKGROUND: Cognitive impairment is well recognized in Parkinson's disease (PD), but when it begins to develop is unclear. The aim of this study was to identify early signs of cognitive impairment along with abnormalities in saccadic behavior in newly diagnosed unmedicated PD patients. METHODS: Nineteen drug-naive PD patients and 20 controls were examined using a battery of tests, including an antisaccade task, phonemic and semantic verbal fluencies, and a switching and rule finding task. RESULTS: With simple tasks, no differences were found between the two groups. However, cognitive performance of the two groups diverged with more complex tasks, occurring independently of PD-related motor impairment. Patients exhibited higher antisaccadic error rates and switch costs in the task switching test, and performed significantly worse in the rule finding task. CONCLUSIONS: Certain cognitive domains and saccadic parameters are already significantly impoverished in newly diagnosed Parkinson's patients, even before the initiation of medication.


Assuntos
Transtornos Cognitivos/diagnóstico , Função Executiva , Doença de Parkinson/fisiopatologia , Doença de Parkinson/psicologia , Movimentos Sacádicos , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Transtornos Cognitivos/psicologia , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Desempenho Psicomotor
11.
J Neurol Neurosurg Psychiatry ; 85(4): 379-86, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24163431

RESUMO

BACKGROUND: The existence of transsynaptic retrograde degeneration (TRD) in the human visual system has been established, however the dependence of TRD on different factors such as lesion location, size and manner of lesion acquisition has yet to be quantified. METHODS: We obtained T1-weighted structural and diffusion-weighted images for 26 patients with adult-acquired or congenital hemianopia and 12 age-matched controls. The optic tract (OT) was defined and measured in the structural and diffusion-weighted images, and degeneration assessed by comparing the integrity of tracts in the lesioned and in the undamaged hemisphere. RESULTS: OT degeneration was found in all patients with established lesions, regardless of lesion location. In patients with acquired lesions, the larger the initial lesion, the greater is the resulting TRD. However, this was not the case for congenital patients, who generally showed greater degeneration than would be predicted by lesion size. A better predictor of TRD was the size of the visual field deficit, which was correlated with degeneration across all patients. Interestingly, although diffusion-weighted imaging (DWI) is more frequently used to examine white matter tracts, in this study the T1-weighted scans gave a better indication of the extent of tract degeneration. CONCLUSIONS: We conclude that TRD of the OT occurs in acquired and congenital hemianopia, is correlated with visual field loss, and is most severe in congenital cases. Understanding the pattern of TRD may help to predict effects of any visual rehabilitation training.


Assuntos
Hemianopsia/patologia , Degeneração Retrógrada/patologia , Vias Visuais/patologia , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuroimagem , Testes de Campo Visual
12.
Cogn Neurosci ; 15(2): 27-55, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38384107

RESUMO

Learning regularities in the environment is a fundament of human cognition, which is supported by a network of brain regions that include the hippocampus. In two experiments, we assessed the effects of selective bilateral damage to human hippocampal subregion CA3, which was associated with autobiographical episodic amnesia extending ~50 years prior to the damage, on the ability to recognize complex, deterministic event sequences presented either in a spatial or a non-spatial configuration. In contrast to findings from related paradigms, modalities, and homologue species, hippocampal damage did not preclude recognition memory for an event sequence studied and tested at four spatial locations, whereas recognition memory for an event sequence presented at a single location was at chance. In two additional experiments, recognition memory for novel single-items was intact, whereas the ability to recognize novel single-items in a different location from that presented at study was at chance. The results are at variance with a general role of the hippocampus in the learning and recognition of complex event sequences based on non-adjacent spatial and temporal dependencies. We discuss the impact of the results on established theoretical accounts of the hippocampal contributions to implicit sequence learning and episodic memory.


Assuntos
Região CA3 Hipocampal , Reconhecimento Psicológico , Humanos , Reconhecimento Psicológico/fisiologia , Masculino , Feminino , Região CA3 Hipocampal/fisiologia , Região CA3 Hipocampal/fisiopatologia , Região CA3 Hipocampal/diagnóstico por imagem , Pessoa de Meia-Idade , Aprendizagem/fisiologia , Memória Episódica , Idoso , Adulto , Testes Neuropsicológicos
13.
Hum Brain Mapp ; 34(3): 519-29, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22102212

RESUMO

TRACK-HD is a multicentre longitudinal observational study investigating the use of clinical assessments and 3-Tesla magnetic resonance imaging as potential biomarkers for future therapeutic trials in Huntington's disease (HD). The cross-sectional data from this large well-characterized dataset provide the opportunity to improve our knowledge of how the underlying neuropathology of HD may contribute to the clinical manifestations of the disease across the spectrum of premanifest (PreHD) and early HD. Two hundred and thirty nine gene-positive subjects (120 PreHD and 119 early HD) from the TRACK-HD study were included. Using voxel-based morphometry (VBM), grey and white matter volumes were correlated with performance in four domains: quantitative motor (tongue force, metronome tapping, and gait); oculomotor [anti-saccade error rate (ASE)]; cognition (negative emotion recognition, spot the change and the University of Pennsylvania smell identification test) and neuropsychiatric measures (apathy, affect and irritability). After adjusting for estimated disease severity, regionally specific associations between structural loss and task performance were found (familywise error corrected, P < 0.05); impairment in tongue force, metronome tapping and ASE were all associated with striatal loss. Additionally, tongue force deficits and ASE were associated with volume reduction in the occipital lobe. Impaired recognition of negative emotions was associated with volumetric reductions in the precuneus and cuneus. Our study reveals specific associations between atrophy and decline in a range of clinical modalities, demonstrating the utility of VBM correlation analysis for investigating these relationships in HD.


Assuntos
Mapeamento Encefálico , Encéfalo/patologia , Doença de Huntington/complicações , Doença de Huntington/patologia , Adulto , Atrofia/etiologia , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/patologia , Estudos de Coortes , Progressão da Doença , Feminino , Transtornos Neurológicos da Marcha/etiologia , Transtornos Neurológicos da Marcha/patologia , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Transtornos da Motilidade Ocular/etiologia , Transtornos da Motilidade Ocular/patologia , Transtornos Psicomotores/etiologia , Transtornos Psicomotores/patologia , Língua/fisiopatologia
14.
Nat Rev Neurosci ; 9(11): 856-69, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18843271

RESUMO

The supplementary motor complex consists of the supplementary motor area, the supplementary eye field and the pre-supplementary motor area. In recent years, these areas have come under increasing scrutiny from cognitive neuroscientists, motor physiologists and clinicians because they seem to be crucial for linking cognition to action. However, theories regarding their function vary widely. This Review brings together the data regarding the supplementary motor regions, highlighting outstanding issues and providing new perspectives for understanding their functions.


Assuntos
Córtex Motor/fisiologia , Córtex Visual/fisiologia , Animais , Cognição/fisiologia , Humanos , Vias Neurais/fisiologia , Córtex Somatossensorial/fisiologia , Campos Visuais/fisiologia
15.
J Neurol Neurosurg Psychiatry ; 84(12): 1392-9, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23813743

RESUMO

OBJECTIVE: The effects of 4-aminopyridine (4-AP) on downbeat nystagmus (DBN) were analysed in terms of slow-phase velocity (SPV), stance, locomotion, visual acuity (VA), patient satisfaction and side effects using standardised questionnaires. METHODS: Twenty-seven patients with DBN received 5 mg 4-AP four times a day or placebo for 3 days and 10 mg 4-AP four times a day or placebo for 4 days. Recordings were done before the first, 60 min after the first and 60 min after the last drug administration. RESULTS: SPV decreased from 2.42 deg/s at baseline to 1.38 deg/s with 5 mg 4-AP and to 2.03 deg/s with 10 mg 4-AP (p<0.05; post hoc: 5 mg 4-AP: p=0.04). The rate of responders was 57%. Increasing age correlated with a 4-AP-related decrease in SPV (p<0.05). Patients improved in the 'get-up-and-go test' with 4-AP (p<0.001; post hoc: 5 mg: p=0.025; 10 mg: p<0.001). Tandem-walk time (both p<0.01) and tandem-walk error (4-AP: p=0.054; placebo: p=0.059) improved under 4-AP and placebo. Posturography showed that some patients improved with the 5 mg 4-AP dose, particularly older patients. Near VA increased from 0.59 at baseline to 0.66 with 5 mg 4-AP (p<0.05). Patients with idiopathic DBN had the greatest benefit from 4-AP. There were no differences between 4-AP and placebo regarding patient satisfaction and side effects. CONCLUSIONS: 4-AP reduced SPV of DBN, improved near VA and some locomotor parameters. 4-AP is a useful medication for DBN syndrome, older patients in particular benefit from the effects of 5 mg 4-AP on nystagmus and postural stability.


Assuntos
4-Aminopiridina/farmacologia , 4-Aminopiridina/uso terapêutico , Movimentos Oculares/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Nistagmo Patológico/tratamento farmacológico , Equilíbrio Postural/efeitos dos fármacos , 4-Aminopiridina/efeitos adversos , Adulto , Fatores Etários , Idoso , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Avaliação de Sintomas , Acuidade Visual/efeitos dos fármacos
16.
Brain ; 135(Pt 11): 3426-39, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22831781

RESUMO

Left-sided spatial neglect is a common neurological syndrome following right-hemispheric stroke. The presence of spatial neglect is a powerful predictor of poor rehabilitation outcome. In one influential account of spatial neglect, interhemispheric inhibition is impaired and leads to a pathological hyperactivity in the contralesional hemisphere, resulting in a biased attentional allocation towards the right hemifield. Inhibitory transcranial magnetic stimulation can reduce the hyperactivity of the contralesional, intact hemisphere and thereby improve spatial neglect symptoms. However, it is not known whether this improvement is also relevant to the activities of daily living during spontaneous behaviour. The primary aim of the present study was to investigate whether the repeated application of continuous theta burst stimulation trains could ameliorate spatial neglect on a quantitative measure of the activities of daily living during spontaneous behaviour. We applied the Catherine Bergego Scale, a standardized observation questionnaire that can validly and reliably detect the presence and severity of spatial neglect during the activities of daily living. Eight trains of continuous theta burst stimulation were applied over two consecutive days on the contralesional, left posterior parietal cortex in patients suffering from subacute left spatial neglect, in a randomized, double-blind, sham-controlled design, which also included a control group of neglect patients without stimulation. The results showed a 37% improvement in the spontaneous everyday behaviour of the neglect patients after the repeated application of continuous theta burst stimulation. Remarkably, the improvement persisted for at least 3 weeks after stimulation. The amelioration of spatial neglect symptoms in the activities of daily living was also generally accompanied by significantly better performance in the neuropsychological tests. No significant amelioration in symptoms was observed after sham stimulation or in the control group without stimulation. These results provide Class I evidence that continuous theta burst stimulation is a viable add-on therapy in neglect rehabilitation that facilitates recovery of normal everyday behaviour.


Assuntos
Atividades Cotidianas/psicologia , Mapeamento Encefálico/psicologia , Transtornos da Percepção/psicologia , Transtornos da Percepção/reabilitação , Estimulação Magnética Transcraniana/psicologia , Mapeamento Encefálico/métodos , Avaliação da Deficiência , Método Duplo-Cego , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos/estatística & dados numéricos , Lobo Parietal/patologia , Lobo Parietal/fisiologia , Transtornos da Percepção/complicações , Transtornos da Percepção/patologia , Índice de Gravidade de Doença , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/psicologia , Reabilitação do Acidente Vascular Cerebral , Estimulação Magnética Transcraniana/métodos
18.
Stereotact Funct Neurosurg ; 90(2): 124-9, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22398800

RESUMO

We report a case of induced oscillopsia caused by deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN). Recent reports have described involuntary oscillopsia during DBS of the PPN that patients have described as trembling vision. Here we substantiate this observation using infra-red eye tracking. It has been suggested that this phenomenon might be used as an indicator of accurate targeting of the PPN with DBS. Our observations suggest that this phenomenon may not be related to a constricted anatomical structure and therefore such practise may be unwise. Scrutiny has led us to believe that the oscillopsia in our patient is not caused by direct stimulation of the oculomotor nerve as suggested in a previous report, but by stimulation of fibres in the uncinate fasciculus of the cerebellum and the superior cerebellar peduncle, which in turn stimulate the saccadic pre-motor neurones in the brainstem.


Assuntos
Estimulação Encefálica Profunda/efeitos adversos , Transtornos da Motilidade Ocular/etiologia , Doença de Parkinson/terapia , Núcleo Tegmental Pedunculopontino/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos da Motilidade Ocular/fisiopatologia , Doença de Parkinson/fisiopatologia
19.
Pract Neurol ; 12(3): 147-53, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22661344

RESUMO

We review the latest literature on the neuropharmacological treatments for acquired nystagmus.Nystagmus may have a significant [corrected] impact on health, yet there is little scientific evidence on which to make firm recommendations for treatment. Acquired pendular nystagmus may respond to gabapentin or memantine; downbeat and upbeat nystagmus to aminopyridines; and periodic alternating nystagmus to baclofen. To improve treatment we need multi-centre, randomised controlled trials using standardised techniques in reporting objective outcomes, with good follow-up duration and careful reporting of side effects.


Assuntos
Nistagmo Patológico/tratamento farmacológico , Aminas/uso terapêutico , Aminopiridinas/uso terapêutico , Baclofeno/uso terapêutico , Ácidos Cicloexanocarboxílicos/uso terapêutico , Gabapentina , Humanos , Memantina/uso terapêutico , Nistagmo Congênito/diagnóstico , Nistagmo Congênito/tratamento farmacológico , Nistagmo Patológico/diagnóstico , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Resultado do Tratamento , Ácido gama-Aminobutírico/uso terapêutico
20.
Neuron ; 54(5): 697-711, 2007 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-17553420

RESUMO

Within the medial frontal cortex, the supplementary eye field (SEF), supplementary motor area (SMA), and pre-SMA have been implicated in the control of voluntary action, especially during motor sequences or tasks involving rapid choices between competing response plans. However, the precise roles of these areas remain controversial. Here, we study two extremely rare patients with microlesions of the SEF and SMA to demonstrate that these areas are critically involved in unconscious and involuntary motor control. We employed masked-prime stimuli that evoked automatic inhibition in healthy people and control patients with lateral premotor or pre-SMA damage. In contrast, our SEF/SMA patients showed a complete reversal of the normal inhibitory effect--ocular or manual--corresponding to the functional subregion lesioned. These findings imply that the SEF and SMA mediate automatic effector-specific suppression of motor plans. This automatic mechanism may contribute to the participation of these areas in the voluntary control of action.


Assuntos
Lobo Frontal/fisiologia , Córtex Motor/fisiologia , Movimento/fisiologia , Inibição Neural/fisiologia , Volição/fisiologia , Idoso , Dano Encefálico Crônico/fisiopatologia , Mapeamento Encefálico , Estado de Consciência/fisiologia , Sinais (Psicologia) , Feminino , Lobo Frontal/anatomia & histologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Córtex Motor/anatomia & histologia , Transtornos dos Movimentos/etiologia , Transtornos dos Movimentos/fisiopatologia , Testes Neuropsicológicos , Transtornos da Motilidade Ocular/etiologia , Transtornos da Motilidade Ocular/fisiopatologia , Estimulação Luminosa , Desempenho Psicomotor/fisiologia , Reflexo/fisiologia , Movimentos Sacádicos/fisiologia , Inconsciente Psicológico
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