RESUMO
Instability of simple DNA repeats has been known as a common cause of hereditary ataxias for over 20 years. Routine genetic diagnostics of these phenotypically similar diseases still rely on an iterative workflow for quantification of repeat units by PCR-based methods of limited precision. We established and validated clinical nanopore Cas9-targeted sequencing, an amplification-free method for simultaneous analysis of 10 repeat loci associated with clinically overlapping hereditary ataxias. The method combines target enrichment by CRISPR-Cas9, Oxford Nanopore long-read sequencing and a bioinformatics pipeline using the tools STRique and Megalodon for parallel detection of length, sequence, methylation and composition of the repeat loci. Clinical nanopore Cas9-targeted sequencing allowed for the precise and parallel analysis of 10 repeat loci associated with adult-onset ataxia and revealed additional parameter such as FMR1 promotor methylation and repeat sequence required for diagnosis at the same time. Using clinical nanopore Cas9-targeted sequencing we analysed 100 clinical samples of undiagnosed ataxia patients and identified causative repeat expansions in 28 patients. Parallel repeat analysis enabled a molecular diagnosis of ataxias independent of preconceptions on the basis of clinical presentation. Biallelic expansions within RFC1 were identified as the most frequent cause of ataxia. We characterized the RFC1 repeat composition of all patients and identified a novel repeat motif, AGGGG. Our results highlight the power of clinical nanopore Cas9-targeted sequencing as a readily expandable workflow for the in-depth analysis and diagnosis of phenotypically overlapping repeat expansion disorders.
Assuntos
Ataxia Cerebelar , Degenerações Espinocerebelares , Adulto , Humanos , Ataxia/genética , Ataxia Cerebelar/genética , Biologia Computacional , Sequenciamento de Nucleotídeos em Larga Escala , Proteína do X Frágil da Deficiência IntelectualRESUMO
The diagnosis of ocular motor disorders and the different forms of a nystagmus is based on a systematic clinical examination of all types of eye movements: eye position, spontaneous nystagmus, range of eye movements, smooth pursuit, saccades, gaze-holding function, vergence, optokinetic nystagmus, as well as testing of the function of the vestibulo-ocular reflex (VOR) and visual fixation suppression of the VOR. Relevant anatomical structures are the midbrain, pons, medulla, cerebellum, and cortex. There is a simple clinical rule: vertical and torsional eye movements are generated in the midbrain, horizontal in the pons. The cerebellum is relevant for almost all types of eye movements; typical pathological findings are saccadic smooth pursuit, gaze-evoked nystagmus or dysmetric saccades.Nystagmus is defined as a rhythmic, most often involuntary eye movement. It normally consists of a slow (pathological) drift of the eyes and a fast central compensatory movement of the eyes back to the primary position (re-fixation saccade). There are three major categories: first, spontaneous nystagmus, i. e. nystagmus which occurs in the gaze straight ahead position as upbeat or downbeat nystagmus; second, nystagmus that becomes visible at eccentric gaze only and third, nystagmus which can be elicited by certain maneuvers, e. g. head-shaking, head positioning, air pressure or hyperventilation, most of which are of peripheral vestibular origin. The most frequent central types of spontaneous nystagmus are downbeat and upbeat, infantile, pure torsional, pendular fixation, periodic alternating, and seesaw nystagmus. Many types of central nystagmus allow a precise neuroanatomical localization: for instance, downbeat nystagmus, which is most often caused by a bilateral floccular lesion or dysfunction, or upbeat nystagmus, which is caused by a lesion in the mesencephalon or medulla oblongata. Examples of pharmacotherapy are the use of 4-aminopyridine for downbeat and upbeat nystagmus, memantine or gabapentin for fixation pendular nystagmus or baclofen for periodic alternating nystagmus.
Assuntos
Nistagmo Patológico , Reflexo Vestíbulo-Ocular , Humanos , Nistagmo Patológico/diagnóstico , Nistagmo Patológico/fisiopatologia , Reflexo Vestíbulo-Ocular/fisiologia , Transtornos da Motilidade Ocular/fisiopatologia , Transtornos da Motilidade Ocular/diagnóstico , Transtornos da Motilidade Ocular/terapia , Movimentos Sacádicos/fisiologiaRESUMO
BACKGROUND: After a transient ischemic attack (TIA) or minor stroke, the long-term risk of stroke and other vascular events is not well known. In this follow-up to a report on 1-year outcomes from a registry of TIA clinics in 21 countries that enrolled 4789 patients with a TIA or minor ischemic stroke from 2009 through 2011, we examined the 5-year risk of stroke and vascular events. METHODS: We evaluated patients who had had a TIA or minor stroke within 7 days before enrollment in the registry. Among 61 sites that participated in the 1-year outcome study, we selected 42 sites that had follow-up data on more than 50% of their enrolled patients at 5 years. The primary outcome was a composite of stroke, acute coronary syndrome, or death from cardiovascular causes (whichever occurred first), with an emphasis on events that occurred in the second through fifth years. In calculating the cumulative incidence of the primary outcome and secondary outcomes (except death from any cause), we treated death as a competing risk. RESULTS: A total of 3847 patients were included in the 5-year follow-up study; the median percentage of patients with 5-year follow-up data per center was 92.3% (interquartile range, 83.4 to 97.8). The composite primary outcome occurred in 469 patients (estimated cumulative rate, 12.9%; 95% confidence interval [CI], 11.8 to 14.1), with 235 events (50.1%) occurring in the second through fifth years. At 5 years, strokes had occurred in 345 patients (estimated cumulative rate, 9.5%; 95% CI, 8.5 to 10.5), with 149 of these patients (43.2%) having had a stroke during the second through fifth years. Rates of death from any cause, death from cardiovascular causes, intracranial hemorrhage, and major bleeding were 10.6%, 2.7%, 1.1%, and 1.5%, respectively, at 5 years. In multivariable analyses, ipsilateral large-artery atherosclerosis, cardioembolism, and a baseline ABCD2 score for the risk of stroke (range, 0 to 7, with higher scores indicating greater risk) of 4 or more were each associated with an increased risk of subsequent stroke. CONCLUSIONS: In a follow-up to a 1-year study involving patients who had a TIA or minor stroke, the rate of cardiovascular events including stroke in a selected cohort was 6.4% in the first year and 6.4% in the second through fifth years. (Funded by AstraZeneca and others.).
Assuntos
Isquemia Encefálica/complicações , Ataque Isquêmico Transitório/complicações , Acidente Vascular Cerebral/etiologia , Adulto , Idoso , Anti-Hipertensivos/uso terapêutico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/mortalidade , Feminino , Seguimentos , Fármacos Hematológicos/uso terapêutico , Humanos , Hipolipemiantes/uso terapêutico , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mortalidade , Análise Multivariada , Recidiva , Sistema de Registros , Risco , Acidente Vascular Cerebral/epidemiologiaRESUMO
In the neglect syndrome, the perceptual deficit for contra-lesional hemi-space is increasingly viewed as a dysfunction of fronto-parietal cortical networks, the disruption of which has been described in neuroanatomical and hemodynamic studies. Here we exploit the superior temporal resolution of electroencephalography (EEG) to study dynamic transient connectivity of fronto-parietal circuits at early stages of visual perception in neglect. As reflected by inter-regional phase synchronization in a full-field attention task, two functionally distinct fronto-parietal networks, in beta (15-25Hz) and theta (4-8Hz) frequency bands, were related to stimulus discrimination within the first 200 ms of visual processing. Neglect pathology was specifically associated with significant suppressions of both beta and theta networks engaging right parietal regions. These connectivity abnormalities occurred in a pattern that was distinctly different from what was observed in right-hemisphere lesion patients without neglect. Also, both beta and theta abnormalities contributed additively to visual awareness decrease, quantified in the Behavioural Inattention Test. These results provide evidence for the impairment of fast dynamic fronto-parietal interactions during early stages of visual processing in neglect pathology. Also, they reveal that different modes of fronto-parietal dysfunction contribute independently to deficits in visual awareness at the behavioural level.
Assuntos
Conscientização/fisiologia , Ritmo beta , Sincronização Cortical , Lobo Frontal/fisiopatologia , Lobo Parietal/fisiopatologia , Transtornos da Percepção/fisiopatologia , Ritmo Teta , Percepção Visual/fisiologia , Idoso , Eletroencefalografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vias Neurais/fisiopatologiaRESUMO
Cranial pachymeningitis is a poorly understood syndrome, defined by leptomeningeal thickening and typical gadolinium enhanced MRI. The heterogeneous clinical and aetiological features of five patients with both focal and diffuse pachymeningitis are presented. The initial symptoms included headache (n=3), sensory Jackson seizures (n=1), hemiparesis (n=1), episodes of short lasting hemiataxia (n=1), hemihypaesthesia (n=1), aphasia (n=1) and confusion (n=2). MRI scans revealed focal (n=3) or diffuse (n=2) leptomeningeal gadolinium enhancement and cortical swelling (n=4). In addition, one case presented with a subarachnoid and a second with an intracerebral haemorraghe. CSF findings were variable and showed clear lymphomonocytic pleocytosis in 3/5 cases. Infectious diseases were extensively excluded in all cases. Leptomeningeal biopsies of two cases revealed perivascular inflammation, indicating central nervous system vasculitis. In the cases presented, pachymeningitis was caused by primary central nervous system vasculitis (n=2) and rheumatoid arthritis (n=2). In one case, the cause remained unclear.
Assuntos
Meningite/etiologia , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/patologia , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/patologia , Biópsia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patologia , Artérias Cerebrais/patologia , Córtex Cerebral/irrigação sanguínea , Córtex Cerebral/patologia , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Angiografia por Ressonância Magnética , Imageamento por Ressonância Magnética , Masculino , Meninges/irrigação sanguínea , Meninges/patologia , Meningite/diagnóstico , Meningite/patologia , Exame Neurológico , Síndromes Paraneoplásicas/diagnóstico , Síndromes Paraneoplásicas/patologia , Vasculite do Sistema Nervoso Central/diagnóstico , Vasculite do Sistema Nervoso Central/patologiaRESUMO
The usefulness of brain imaging studies in dizzy patients presenting to the emergency department (ED) is controversial. We aimed to assess the 'real-world' probability of ischemic stroke and other acute brain lesions (ABLs) in these patients to create an algorithm that helps decision-making on whether which and when brain imaging is needed. By reviewing medical records, we identified 610 patients presenting with dizziness, vertigo or imbalance to our university hospital's ED and receiving neurological workup. We collected timing/triggers of symptoms, ABCD2 score, focal neurological abnormalities, HINTS (head impulse, nystagmus, test-of-skew) and other central oculomotor signs. ABLs were extracted from CT/MRI reports. Uni-/multivariate logistic regression analyses investigated associations between clinical parameters and ABLs. Finally, the likelihood of ABLs was assessed for different clinically defined subgroups ('dizziness syndromes'). Early CT (day 1) was performed in 539 (88%) and delayed MR imaging (median: day 4) in 299 (49%) patients. ABLs (89% ischemic stroke) were revealed in 75 (24%) of 318 patients with adequate imaging (MRI or lesion-positive CT). The risk for ABLs increased with the presence of central oculomotor signs (odds ratio 2.8, 95% confidence interval 1.5-5.2) or focal abnormalities (OR 3.3, 95% CI 1.8-6.2). The likelihood of ABLs differed between dizziness syndromes, e.g., HINTS-negative acute vestibular syndrome: 0%, acute imbalance syndrome with ABCD2-score ≥ 4: 50%. We propose a clinical pathway, according to which patients with HINTS-negative acute vestibular syndrome should not receive brain imaging, whereas imaging is suggested in dizzy patients with acute imbalance, central oculomotor signs or focal abnormalities.
Assuntos
Nistagmo Patológico , Acidente Vascular Cerebral , Encéfalo/diagnóstico por imagem , Tontura/diagnóstico por imagem , Tontura/epidemiologia , Tontura/etiologia , Serviço Hospitalar de Emergência , Humanos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/epidemiologia , Vertigem/diagnóstico por imagem , Vertigem/epidemiologiaRESUMO
Selective spatial attention is a crucial cognitive process that guides us to the behaviorally relevant objects in a complex visual world by using exploratory eye movements. The spatial location of objects, their (bottom-up) saliency and (top-down) relevance is assumed to be encoded in one "attentional priority map" in the brain, using different egocentric (eye-, head- and trunk-centered) spatial reference frames. In patients with hemispatial neglect, this map is supposed to be imbalanced, leading to a spatially biased exploration of the visual environment. As a proof of concept, we altered the visual saliency (and thereby attentional priority) of objects in a naturalistic scene along a left-right spatial gradient and investigated whether this can induce a bias in the exploratory eye movements of healthy humans (n = 28; all right-handed; mean age: 23 years, range 19-48). We developed a computerized mask, using high-end "gaze-contingent display (GCD)" technology, that immediately and continuously reduced the saliency of objects on the left-"left" with respect to the head (body-centered) and the current position on the retina (eye-centered). In both experimental conditions, task-free viewing and goal-driven visual search, this modification induced a mild but significant bias in visual exploration similar to hemispatial neglect. Accordingly, global eye movement parameters changed (reduced number and increased duration of fixations) and the spatial distribution of fixations indicated an attentional bias towards the right (rightward shift of first orienting, fixations favoring the scene's outmost right over left). Our results support the concept of an attentional priority map in the brain as an interface between perception and behavior and as one pathophysiological ground of hemispatial neglect.
RESUMO
Focal brain lesions may induce dysfunctions in distant brain regions leading to behavioral impairments. Based on this concept of 'diaschisis', spatial neglect following stroke has been related to structural damage of the right-lateralized ventral attention network (VAN) and disrupted inter-hemispheric functional connectivity (FC) in the bilateral dorsal attention network (DAN). We questioned whether neglect-related behavioral deficits may be determined by local dysfunction of a specific region within these brain networks. We investigated acute right-hemisphere stroke patients with left hemispatial neglect using resting-state functional MRI, neuropsychological tests of spatial attention and clinical assessment of neglect-related functional disability. In addition to conventional FC analyses between different cortical regions of interest (ROIs) in the DAN/VAN, we extracted the fractional amplitude of low frequency fluctuations (fALFF) from each ROI as a marker of regional spontaneous neuronal activity. Although DAN regions (as opposed to the VAN regions) were largely spared from structural brain damage, they exhibited a significant reduction of inter-hemispheric FC. However, significant fMRI-behavior correlations were revealed specifically for the fALFF of one DAN-ROI in the right superior parietal lobule (SPL): the smaller the fALFF in the right posterior intraparietal sulcus, the more severe the patient's pathological attention bias and neglect-related functional impairment. In line with 'diaschisis', our findings confirm a crucial role of the non-lesioned but dysfunctional right SPL for the emergence of spatial neglect and its behavioral consequences. They further support targeting the SPL dysfunction by non-invasive brain stimulation in neglect rehabilitation.
Assuntos
Viés de Atenção/fisiologia , Córtex Cerebral/fisiopatologia , Lateralidade Funcional/fisiologia , Neuroimagem Funcional , Rede Nervosa/fisiopatologia , Lobo Parietal/fisiopatologia , Transtornos da Percepção/fisiopatologia , Percepção Espacial/fisiologia , Idoso , Córtex Cerebral/diagnóstico por imagem , Conectoma , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Transtornos da Percepção/etiologia , Acidente Vascular Cerebral/complicaçõesRESUMO
BACKGROUND AND PURPOSE: Numerous preclinical findings and a clinical pilot study suggest that recombinant human erythropoietin (EPO) provides neuroprotection that may be beneficial for the treatment of patients with ischemic stroke. Although EPO has been considered to be a safe and well-tolerated drug over 2 decades, recent studies have identified increased thromboembolic complications and/or mortality risks on EPO administration to patients with cancer or chronic kidney disease. Accordingly, the double-blind, placebo-controlled, randomized German Multicenter EPO Stroke Trial (Phase II/III; ClinicalTrials.gov Identifier: NCT00604630) was designed to evaluate efficacy and safety of EPO in stroke. METHODS: This clinical trial enrolled 522 patients with acute ischemic stroke in the middle cerebral artery territory (intent-to-treat population) with 460 patients treated as planned (per-protocol population). Within 6 hours of symptom onset, at 24 and 48 hours, EPO was infused intravenously (40,000 IU each). Systemic thrombolysis with recombinant tissue plasminogen activator was allowed and stratified for. RESULTS: Unexpectedly, a very high number of patients received recombinant tissue plasminogen activator (63.4%). On analysis of total intent-to-treat and per-protocol populations, neither primary outcome Barthel Index on Day 90 (P=0.45) nor any of the other outcome parameters showed favorable effects of EPO. There was an overall death rate of 16.4% (n=42 of 256) in the EPO and 9.0% (n=24 of 266) in the placebo group (OR, 1.98; 95% CI, 1.16 to 3.38; P=0.01) without any particular mechanism of death unexpected after stroke. CONCLUSIONS: Based on analysis of total intent-to-treat and per-protocol populations only, this is a negative trial that also raises safety concerns, particularly in patients receiving systemic thrombolysis.
Assuntos
Isquemia Encefálica/tratamento farmacológico , Eritropoetina/administração & dosagem , Eritropoetina/efeitos adversos , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/efeitos adversos , Acidente Vascular Cerebral/tratamento farmacológico , Doença Aguda/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/fisiopatologia , Método Duplo-Cego , Esquema de Medicação , Interações Medicamentosas/fisiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/fisiopatologia , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Mortalidade , Seleção de Pacientes , Efeito Placebo , Proteínas Recombinantes/administração & dosagem , Acidente Vascular Cerebral/fisiopatologia , Ativador de Plasminogênio Tecidual/administração & dosagem , Ativador de Plasminogênio Tecidual/efeitos adversos , Resultado do Tratamento , Adulto JovemRESUMO
Objective. Leftward optokinetic stimulation (OKS) is a promising therapeutic approach for right-hemisphere stroke patients with left hemispatial neglect. We questioned whether the putative neural basis is an activation of frontoparietal brain regions involved in the control of eye movements and spatial attention. Methods. We used functional magnetic resonance imaging to investigate brain activations during OKS in acute right-hemisphere stroke patients (RHS, n = 19) compared with healthy control subjects (HC, n = 9). Based on neuropsychological testing we determined the ipsilesional attention bias in all RHS patients, 11 showed manifest hemispatial neglect. Results. In HC subjects, OKS in either direction led to bilateral activation of the visual cortex (V1-V4), frontal (FEF) and supplementary (SEF) eye fields, intraparietal sulcus (IPS), basal ganglia, and thalamus. RHS patients' activations were generally reduced compared with HC. Nevertheless, leftward OKS bilaterally activated the visual cortex (V1-V4), FEF, SEF, IPS, and thalamus. The neural response to OKS was negatively correlated with patients' behavioral impairment: The greater the individual attention bias/neglect the weaker the brain activations. Conclusion. In RHS patients, leftward OKS activates frontoparietal regions (FEF, IPS) that are spared from structural brain damage and functionally involved in both oculomotor control and spatial attention. This may provide a neural basis for the known therapeutic effects of OKS on hemispatial neglect. In acute stroke stages, reduced activation levels correlating with neglect severity indicate functional downregulation of the underlying dorsal attention network. Therefore, chronic RHS patients with less severe neglect after recovery of network disturbances may be more suitable candidates for OKS rehabilitation.
Assuntos
Atenção/fisiologia , Mapeamento Encefálico , Movimentos Oculares/fisiologia , Lobo Frontal/fisiopatologia , Nistagmo Optocinético/fisiologia , Lobo Parietal/fisiopatologia , Transtornos da Percepção/reabilitação , Percepção Espacial/fisiologia , Acidente Vascular Cerebral/terapia , Idoso , Feminino , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Lobo Parietal/diagnóstico por imagem , Lobo Parietal/patologia , Transtornos da Percepção/diagnóstico por imagem , Transtornos da Percepção/etiologia , Transtornos da Percepção/patologia , Estimulação Física , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/patologiaRESUMO
Sleep has been found to enhance consolidation of many different forms of memory. However in most procedural tasks, a sleep-independent, fast learning component interacts with slow, sleep-dependent improvements. Here, we show that in humans a visuo-motor saccade learning task shows no improvements during training, but only during a delayed recall testing after a period of sleep. Subjects were trained in a prosaccade task (saccade to a visual target). Performance was tested in the prosaccade and the antisaccade task (saccade to opposite direction of the target) before training, after a night of sleep or sleep deprivation, after a night of recovery sleep, and finally in a follow-up test 4 weeks later. We found no immediate improvement in saccadic reaction time (SRT) during training, but a delayed reduction in SRT, indicating a slow-learning process. This reduction occurred only after a period of sleep, i.e. after the first night in the sleep group and after recovery sleep in the sleep deprivation group. This improvement was stable during the 4-week follow-up. Saccadic training can thus induce covert changes in the saccade generation pathway. During the following sleep period, these changes in turn bring about overt performance improvements, presuming a learning effect based on synaptic tagging.
Assuntos
Aprendizagem/fisiologia , Desempenho Psicomotor/fisiologia , Tempo de Reação , Movimentos Sacádicos/fisiologia , Sono/fisiologia , Vigília/fisiologia , Adulto , Eletroencefalografia , Eletromiografia , Eletroculografia , Feminino , Lateralidade Funcional , Humanos , Masculino , Adulto JovemRESUMO
In obsessive-compulsive disorder (OCD), a dysfunction of neuronal circuits involving prefrontal areas and the basal ganglia is discussed that implies specific oculomotor deficits. Performance during reflexive and predictive saccades, antisaccades and predictive smooth pursuit was compared between patients with OCD (n=22), patients with schizophrenia (n=21) and healthy subjects (n=24). Eye movements were recorded by infrared reflection oculography. In both patient groups, higher frequencies of anticipatory saccades with reduced amplitudes in the predictive saccade task were observed. Additionally, reduced smooth pursuit eye velocity and increased frequencies of saccadic intrusions during smooth pursuit as well as increased error rates in the antisaccade task were demonstrated for patients suffering from schizophrenia. Patients with OCD and schizophrenia revealed different patterns of oculomotor impairment: whereas increased anticipation of predictive saccades provides evidence for a dysfunction of the circuit between the frontal eye field and the basal ganglia in both groups, results from the antisaccade task imply additional deficits involving the dorsolateral prefrontal cortex in schizophrenic patients. Furthermore, the cortical network for smooth pursuit (especially the frontal eye field) is also assumed to be disturbed in schizophrenia.
Assuntos
Corpo Estriado/fisiopatologia , Lobo Frontal/fisiopatologia , Rede Nervosa/fisiopatologia , Transtorno Obsessivo-Compulsivo/diagnóstico , Transtorno Obsessivo-Compulsivo/fisiopatologia , Movimentos Sacádicos/fisiologia , Adulto , Gânglios da Base/fisiopatologia , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Córtex Pré-Frontal/fisiopatologia , Esquizofrenia/diagnóstico , Esquizofrenia/fisiopatologia , Campos Visuais/fisiologiaRESUMO
STUDY OBJECTIVES: This study was designed to show the influence of sleep deprivation on different types of saccadic eye movements. DESIGN: Performance of saccadic eye movements was compared after normal sleep and sleep deprivation in a randomized, within-subjects paradigm. Parameters of voluntary and reflexive saccades were measured before and after experimental nights and after a night of recovery sleep. Additionally, subjects spent 1 adaptation night in the laboratory before the experiments. SETTING: Experiments took place under controlled laboratory conditions. PARTICIPANTS: Fifteen healthy male volunteers (aged 19-30 years). INTERVENTIONS: Each subject participated in 1 night of sleep deprivation followed by a night of recovery sleep and, on another occasion, in 2 successive nights of undisturbed sleep. MEASUREMENTS AND RESULTS: Horizontal prosaccades, antisaccades, and memory-guided saccades were recorded by means of electrooculography. They were analysed semiautomatically with respect to accuracy, peak velocity, and latency. Peak velocity was significantly reduced in all saccade tasks after 1 night of sleep deprivation but recovered after another night of sleep. Latency was prolonged after sleep deprivation only for memory-guided saccades; accuracy showed a decrease after 1 night without sleep only for prosaccades. CONCLUSIONS: Sleep deprivation has a general impairing effect on the peak velocity of saccades, reflecting possible dysfunction at the level of the brainstem reticular formation. Deficits of accuracy and latency point to dysfunction of specific brain sites such as the supplementary eye field and cerebellum, whereas the cardinal functions of the frontal and parietal eye fields were not affected. These results suggest the possibility of measuring fatigue by means of saccadic parameters, especially saccadic peak velocity.
Assuntos
Privação do Sono/fisiopatologia , Adulto , Encéfalo/anatomia & histologia , Encéfalo/fisiopatologia , Tronco Encefálico/fisiopatologia , Eletroculografia , Fixação Ocular , Humanos , Masculino , Memória/fisiologia , Polissonografia , Formação Reticular/fisiopatologia , Movimentos Sacádicos/fisiologia , Privação do Sono/diagnósticoRESUMO
Recent studies have discussed the role of the cerebellum in not only motor but also cognitive functions, and in particular, fronto-executive operations. Similar to a previous study on hemineglect patients, we recorded eye movements during a visual search task to investigate patients with isolated infarction of the cerebellum compared with controls. Patients showed longer search durations, associated with mild saccadic dysmetria, longer single fixation durations and a higher number of repeated fixations of items. Systematic search strategies were preserved, but less frequent in patients. In conclusion, though basic mechanisms of visual search including spatial memory were not affected by cerebellar lesions, patients' search behaviour was slower and less efficient, indicating a mild deficit of visual attention and motor planning.
Assuntos
Infarto Encefálico/fisiopatologia , Doenças Cerebelares/fisiopatologia , Desempenho Psicomotor/fisiologia , Percepção Visual/fisiologia , Adolescente , Adulto , Fatores Etários , Idoso , Feminino , Fixação Ocular/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estimulação Luminosa , Movimentos Sacádicos/fisiologiaRESUMO
Adaptation of saccade amplitude in response to intra-saccadic target displacement is a type of implicit motor learning which is required to compensate for physiological changes in saccade performance. Once established trials without intra-saccadic target displacement lead to de-adaptation or extinction, which has been attributed either to extra-retinal mechanisms of spatial constancy or to the influence of the stable visual surroundings. Therefore we investigated whether visual deprivation ("Ganzfeld"-stimulation or sleep) can partially maintain this motor learning compared to free viewing of the natural surroundings. Thirty-five healthy volunteers performed two adaptation blocks of 100 inward adaptation trials - interspersed by an extinction block - which were followed by a two-hour break with or without visual deprivation (VD). Using additional adaptation and extinction blocks short and long (4 weeks) term memory of this implicit motor learning were tested. In the short term, motor memory tested immediately after free viewing was superior to adaptation performance after VD. In the long run, however, effects were opposite: motor memory and relearning of adaptation was superior in the VD conditions. This could imply independent mechanisms that underlie the short-term ability of retrieving learned saccadic gain and its long term consolidation. We suggest that subjects mainly rely on visual cues (i.e., retinal error) in the free viewing condition which makes them prone to changes of the visual stimulus in the extinction block. This indicates the role of a stable visual array for resetting adapted saccade amplitudes. In contrast, visual deprivation (GS and sleep), might train subjects to rely on extra-retinal cues, e.g., efference copy or prediction to remap their internal representations of saccade targets, thus leading to better consolidation of saccadic adaptation.
Assuntos
Adaptação Fisiológica , Consolidação da Memória , Memória de Longo Prazo , Movimentos Sacádicos , Adulto , Feminino , Humanos , Masculino , Adulto JovemRESUMO
The response delay to left target stimuli preceded by right-side cues, first described by Posner et al. [J. Neurosci. 4 (1984) 1863-1874] appears to be a stable marker of right-parietal injury. However, only few studies compared patients' performance to age-matched controls. Furthermore, only few studies compared visual and auditory stimuli in this task. Therefore, two groups of right-hemisphere stroke patients, with and without left visual hemineglect, and a healthy control group were studied in three versions of Posner's paradigm. Visual or auditory target stimuli were presented to the subject's left or right, following a visual or auditory cue by 150 ms. The classical 'extinction-type' effect, an increase in missing responses for right visual cue/left visual target, was specifically observed in neglect patients. In the same condition, an 'extinction-type' response delay was present in patients with neglect and in those without neglect. No such delay occurred in any group when cues were auditory. Specifically in neglect patients, response times were generally longer for left than for right visual targets, regardless of cue side and of cue modality. Response times were generally prolonged in neglect patients regardless of target modality. This suggests that three components impair neglect patients' performance in this paradigm: a non-spatial, supramodal deficit, a global, neglect-type deficit of the contralesional hemi-field, and the extinction-type impairment. The latter two deficits appear to be most marked within the visual domain.
Assuntos
Extinção Psicológica/fisiologia , Lateralidade Funcional/fisiologia , Transtornos da Percepção/psicologia , Percepção Espacial/fisiologia , Acidente Vascular Cerebral/psicologia , Estimulação Acústica , Adulto , Idoso , Sinais (Psicologia) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estimulação Luminosa , Desempenho Psicomotor/fisiologia , Tempo de Reação/fisiologia , Localização de Som/fisiologia , Acidente Vascular Cerebral/complicaçõesRESUMO
Patients with hemispatial neglect are severely impaired in orienting their attention to contralesional hemispace. Although motion is one of the strongest attentional cues in humans, it is still unknown how neglect patients visually explore their moving real-world environment. We therefore recorded eye movements at bedside in 19 patients with hemispatial neglect following acute right hemisphere stroke, 14 right-brain damaged patients without neglect and 21 healthy control subjects. Videos of naturalistic real-world scenes were presented first in a free viewing condition together with static images, and subsequently in a visual search condition. We analyzed number and amplitude of saccades, fixation durations and horizontal fixation distributions. Novel computational tools allowed us to assess the impact of different scene features (static and dynamic contrast, colour, brightness) on patients' gaze. Independent of the different stimulus conditions, neglect patients showed decreased numbers of fixations in contralesional hemispace (ipsilesional fixation bias) and increased fixation durations in ipsilesional hemispace (disengagement deficit). However, in videos left-hemifield fixations of neglect patients landed on regions with particularly high dynamic contrast. Furthermore, dynamic scenes with few salient objects led to a significant reduction of the pathological ipsilesional fixation bias. In visual search, moving targets in the neglected hemifield were more frequently detected than stationary ones. The top-down influence (search instruction) could neither reduce the ipsilesional fixation bias nor the impact of bottom-up features. Our results provide evidence for a strong impact of dynamic bottom-up features on neglect patients' scanning behaviour. They support the neglect model of an attentional priority map in the brain being imbalanced towards ipsilesional hemispace, which can be counterbalanced by strong contralateral motion cues. Taking into account the lack of top-down control in neglect patients, bottom-up stimulation with moving real-world stimuli may be a promising candidate for future neglect rehabilitation schemes.
Assuntos
Encéfalo/fisiopatologia , Medições dos Movimentos Oculares/psicologia , Percepção de Movimento/fisiologia , Reconhecimento Visual de Modelos/fisiologia , Transtornos da Percepção/fisiopatologia , Idoso , Medições dos Movimentos Oculares/instrumentação , Movimentos Oculares/fisiologia , Feminino , Fixação Ocular/fisiologia , Lateralidade Funcional/fisiologia , Humanos , Imageamento por Ressonância Magnética/instrumentação , Imageamento por Ressonância Magnética/métodos , Masculino , Transtornos da Percepção/etiologia , Movimentos Sacádicos/fisiologiaRESUMO
Patients with homonymous hemianopia due to occipital brain lesions show disorders of visual search. In everyday life this leads to difficulties in reading and spatial orientation. It is a matter of debate whether these disorders are due to the brain lesion or rather reflect compensatory eye movement strategies developing over time. For the first time, eye movements of acute hemianopic patients (n= 9) were recorded during the first days following stroke while they performed an exploratory visual-search task. Compared to age-matched control subjects their search duration was prolonged due to increased fixations and refixations, that is, repeated scanning of previously searched locations. Saccadic amplitudes were smaller in patients. Right hemianopic patients were more impaired than left hemianopic patients. The number of fixations and refixations did not differ significantly between both hemifields in the patients. Follow-up of one patient revealed changes of visual search over 18 months. By using more structured scanpaths with fewer saccades his search duration decreased. Furthermore, he developed a more efficient eye-movement strategy by making larger but less frequent saccades toward his blind side. In summary, visual-search behavior of acute hemianopic patients differs from healthy control subjects and from chronic hemianopic patients. We conclude that abnormal visual search in acute hemianopic patients is related to the brain lesion. We provide some evidence for adaptive eye-movement strategies developed over time. These adaptive strategies make the visual search more efficient and may help to compensate for the persisting visual-field loss.
Assuntos
Adaptação Fisiológica , Hemianopsia/fisiopatologia , Transtornos da Visão/fisiopatologia , Doença Aguda , Idoso , Doença Crônica , Feminino , Hemianopsia/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estimulação Luminosa , Transtornos da Visão/patologiaRESUMO
Patients with homonymous visual field defects (HVFD) are often crucially disabled during self-guided visual exploration of their natural environment. Abnormal visual search may be related to the sensory deficit, deficient spatial orientation or compensatory eye movements. We tested the hypothesis that visual search in HVFD is purely determined by the visual-sensory deficit by comparing nine patients with HVFD due to occipital stroke in an acute stage to nine healthy subjects with technically simulated "virtual" homonymous visual field defects (vHVFD) and to nine controls with normal visual fields. The simulated gaze-contingent visual field defects in vHVFD subjects were individually matched to the patients' HVFD with respect to their size and side. Eye movements were recorded while subjects searched for targets among distractors and indicated target detection by clicks. All patients, in particular those with lesions involving the inferior occipito-temporal (fusiform) gyrus, but also those with small lesions restricted to the visual cortex, showed longer search durations than vHVFD subjects. This was tightly related to the higher number of fixations and particularly "re-fixations" (repeated scanning of fixated items). Working memory across saccades during the search was intact (no increased "re-clicks"). Scanpath strategies were similar in patients and vHVFD subjects. For both groups amplitude and frequency of saccades did not differ between the hemifields. In HVFD patients with acute occipital brain lesions, visual input failure does not fully account for abnormal visual search. It might either result from disconnections of the primary visual cortex to associated occipital and temporal brain areas or reflect an early stage of compensatory eye movements which differ from chronic HVFD patients.
Assuntos
Oftalmopatias/etiologia , Movimentos Sacádicos/fisiologia , Escotoma/fisiopatologia , Campos Visuais/fisiologia , Adulto , Idoso , Estudos de Casos e Controles , Infarto Cerebral/fisiopatologia , Percepção de Cores , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Lobo Occipital/fisiopatologia , Tempo de ReaçãoRESUMO
We studied how physical and instructed embedding of features in gestalts affects perceptual selection. Four ovals on the horizontal midline were either unconnected or pairwise connected by circles, forming ears of left and right heads (gestalts). Relevant to responding was the position of one colored oval, either within its pair or relative to fixation ("object-based" or "fixation-based" instruction). Responses were faster under fixation- than object-based instruction, less so with gestalts. Previously reported increases of N1 when evoked by features within objects were replicated for fixation-based instruction only. There was no effect of instruction on N2pc. However P1 increased under the adequate instruction, object-based for gestalts, fixation-based for unconnected items, which presumably indicated how foci of attention were set by expecting specific stimuli under instructions that specified how to bind these stimuli to objects.