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Corollary discharge signals are found in the nervous systems of many animals, where they serve a large variety of functions related to the integration of sensory and motor signals. In humans, an important corollary discharge signal is generated by oculomotor structures and communicated to sensory systems in concert with the execution of each saccade. This signal is thought to serve a number of purposes related to the maintenance of accurate visual perception. The properties of the oculomotor corollary discharge can be probed by asking subjects to localize stimuli that are flashed briefly around the time of a saccade. The results of such experiments typically reveal large errors in localization. Here, we have exploited these well-known psychophysical effects to assess the potential dysfunction of corollary discharge signals in people with schizophrenia. In a standard perisaccadic localization task, we found that, compared with controls, patients with schizophrenia exhibited larger errors in localizing visual stimuli. The pattern of errors could be modeled as an overdamped corollary discharge signal that encodes instantaneous eye position. The dynamics of this signal predicted symptom severity among patients, suggesting a possible mechanistic basis for widely observed behavioral manifestations of schizophrenia.
Assuntos
Transtornos da Percepção/etiologia , Movimentos Sacádicos/fisiologia , Esquizofrenia/complicações , Percepção Espacial/fisiologia , Adulto , Feminino , Humanos , Masculino , Modelos Biológicos , Estimulação Luminosa , Escalas de Graduação Psiquiátrica , Psicofísica , Tempo de ReaçãoRESUMO
The past three decades have seen multiple reports of people with neurodegenerative disorders, or other forms of changes in their brains, who also show putative changes in how they approach and produce visual art. Authors argue that these cases may provide a unique body of evidence, so-called 'artistic signatures' of neurodegenerative diseases, that might be used to understand disorders, provide diagnoses, be employed in treatment, create patterns of testable hypotheses for causative study, and also provide unique insight into the neurobiological linkages between the mind, brain, body, and the human penchant for art-making itself. However-before we can begin to meaningfully build from such emerging findings, much less formulate applications-not only is such evidence currently quite disparate and in need of systematic review, almost all case reports and artwork ratings are entirely subjective, based on authors' personal observations or a sparse collection of methods that may not best fit underlying research aims. This leads to the very real question of whether we might actually find patterns of systematic change if fit to a rigorous review-Can we really 'read' art to illuminate possible changes in the brain? How might we best approach this topic in future neuroscientific, clinical, and art-related research? This paper presents a review of this field and answer to these questions. We consider the current case reports for seven main disorders-Alzheimer's and Parkinson's disease, frontotemporal and Lewy body dementia, corticobasal degeneration, aphasia, as well as stroke-consolidating arguments for factors and changes related to art-making and critiquing past methods. Taking the published artworks from these papers, we then conduct our own assessment, employing computerized and human-rater-based approaches, which we argue represent best practice to identify stylistic or creativity/quality changes. We suggest, indeed, some evidence for systematic patterns in art-making for specific disorders and also find that case authors showed rather high agreement with our own assessments. More important, through opening this topic and past evidence to a systematic review, we hope to open a discussion and provide a theoretical and empirical foundation for future application and research on the intersection of art-making and the neurotypical, the changed, and the artistic brain.
Assuntos
Arte , Doença por Corpos de Lewy , Doenças Neurodegenerativas , Humanos , Encéfalo , CriatividadeRESUMO
In primates, inspection of a visual scene is typically interrupted by frequent gaze shifts, occurring at an average rate of three to five times per second. Perceptually, these gaze shifts are accompanied by a compression of visual space toward the saccade target, which may be attributed to an oculomotor signal that transiently influences visual processing. While previous studies of compression have focused exclusively on saccadic eye movements made with the head artificially immobilized, many brain structures involved in saccade generation also encode combined eye-head gaze shifts. Thus, in order to understand the interaction between gaze motor and visual signals, we studied perception during eye-head gaze shifts and found a powerful compression of visual space that was spatially directed toward the intended gaze (and not the eye movement) target location. This perceptual compression was nearly constant in duration across gaze shift amplitudes, suggesting that the signal that triggers compression is largely independent of the size and kinematics of the gaze shift. The spatial pattern of results could be captured by a model that involves interactions, on a logarithmic map of visual space, between two loci of neural activity that encode the gaze shift vector and visual stimulus position relative to the fovea.
Assuntos
Modelos Neurológicos , Movimentos Sacádicos/fisiologia , Percepção Espacial/fisiologia , Colículos Superiores/fisiologia , Visão Binocular/fisiologia , Animais , Fenômenos Biomecânicos/fisiologia , Fixação Ocular/fisiologia , Fóvea Central/fisiologia , Cabeça , Humanos , Imobilização/métodos , Masculino , Estimulação Luminosa/métodos , Primatas , Desempenho Psicomotor/fisiologiaRESUMO
Our ability to explore our surroundings requires a combination of high-resolution vision and frequent rotations of the visual axis toward objects of interest. Such gaze shifts are themselves a source of powerful retinal stimulation, and so the visual system appears to have evolved mechanisms to maintain perceptual stability during movements of the eyes in space. The mechanisms underlying this perceptual stability can be probed in the laboratory by briefly presenting a stimulus around the time of a saccadic eye movement and asking subjects to report its position. Under such conditions, there is a systematic misperception of the probes toward the saccade end point. This perisaccadic compression of visual space has been the subject of much research, but few studies have attempted to relate it to specific brain mechanisms. Here, we show that the magnitude of perceptual compression for a wide variety of probe stimuli and saccade amplitudes is quantitatively predicted by a simple heuristic model based on the geometry of retinotopic representations in the primate brain. Specifically, we propose that perisaccadic compression is determined by the distance between the probe and saccade end point on a map that has a logarithmic representation of visual space, similar to those found in numerous cortical and subcortical visual structures. Under this assumption, the psychophysical data on perisaccadic compression can be appreciated intuitively by imagining that, around the time of a saccade, the brain confounds nearby oculomotor and sensory signals while attempting to localize the position of objects in visual space.
Assuntos
Modelos Neurológicos , Movimentos Sacádicos , Percepção Visual , Adulto , Algoritmos , Encéfalo/fisiologia , Medições dos Movimentos Oculares , Humanos , Masculino , Estimulação Luminosa , Psicofísica , Percepção Espacial , Fatores de TempoRESUMO
Recent psychophysical work has shown that performance on a direction discrimination task decreases with increasing stimulus size, provided the stimulus is high in contrast. This psychophysical surround suppression has been linked to the inhibitory spatial surrounds that have been observed throughout the primate visual system. In this work we have examined a temporal factor that may also contribute to psychophysical surround suppression. Consistent with previous work, we found that psychophysical surround suppression is strongest when a high-contrast motion stimulus is presented very briefly so that the appearance of the stimulus coincided with its motion. However, when a brief delay was inserted between the stimulus onset and the onset of motion, the counterintuitive effects of stimulus size disappeared. The effect of the motion onset asynchrony (MOA) was strongest when the stationary stimulus immediately preceded the stimulus motion and when stimulus orientation during the MOA was very similar to that during the motion presentation. We conclude that psychophysical surround suppression is partially linked to the temporal structure of the stimulus, more precisely to a masking effect caused by sudden stimulus onsets (and to a smaller degree stimulus offsets).
Assuntos
Percepção de Movimento/fisiologia , Inibição Neural/fisiologia , Psicofísica , Tempo de Reação/fisiologia , Retina/fisiologia , Adulto , Sensibilidades de Contraste/fisiologia , Humanos , Masculino , Orientação/fisiologia , Mascaramento Perceptivo/fisiologia , Estimulação Luminosa/métodos , Limiar Sensorial/fisiologia , Percepção Espacial/fisiologiaRESUMO
Deutetrabenazine (DTBZ) is a US FDA-approved treatment for chorea in Huntington's disease. The substitution of deuterium for hydrogen at specific positions imparts a longer half-life on DTBZ, allowing for less-frequent daily dosing. As a reversible vesicular monoamine transporter Type 2 inhibitor, DTBZ depletes monoamines at presynaptic nerve terminals. DTBZ significantly improved chorea in Huntington's disease patients compared with placebo. This effect continued in an ongoing open-label extension study in the cohort who switched from tetrabenazine to DTBZ. Whereas there are currently no head-to-head studies to adequately compare safety profiles between tetrabenazine and DTBZ, an indirect comparison study suggested that the tolerability profile of DTBZ was similar to placebo. In fact, there are currently no direct comparisons between vesicular monoamine transporter Type 2 inhibitors in humans. This review will explore DTBZ's pharmacological properties, drug interactions, administration and efficacy.
Assuntos
Inibidores da Captação Adrenérgica/farmacologia , Doença de Huntington/tratamento farmacológico , Tetrabenazina/análogos & derivados , Inibidores da Captação Adrenérgica/administração & dosagem , Interações Medicamentosas , Humanos , Tetrabenazina/administração & dosagem , Tetrabenazina/farmacologia , Resultado do TratamentoRESUMO
Chorea-acanthocytosis (ChAc) is a rare autosomal recessive neurodegenerative disease due to mutation of the VPS13A gene encoding the protein chorein. ChAc is a slowly progressive disorder that typically presents in early adulthood, and whose clinical features include chorea and dystonia with involuntary lip, cheek, and tongue biting. Some patients also have seizures. Treatment for ChAc is symptomatic. A small number of ChAc patients have been treated with bilateral deep brain stimulation (DBS) of the globus pallidus interna (GPi), and we now present an additional case. Patient chart, functional measures, and laboratory findings were reviewed from the time of ChAc diagnosis until 6 months after DBS surgery. Here, we present a case of ChAc in a 31-year-old male positive for VPS13A gene mutations who presented with chorea, tongue biting, dysarthria, weight loss, and mild cognitive dysfunction. DBS using monopolar stimulation with placement slightly lateral to the GPi was associated with significant improvement in chorea and dysarthria. This case adds to the current state of knowledge regarding the efficacy and safety of bilateral GPi-DBS for symptomatic control of drug-resistant hyperkinetic movements seen in ChAc. Controlled trials are needed to better assess the impact and ideal target of DBS in ChAc.
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BACKGROUND: In the Canadian context, health literacy has been shown to depend on place of birth, education level, socioeconomic status, language spoken and geographic location. This study seeks to determine whether currently available advance directive documentation in Canada is written in accordance with the average reading level of the population and to assess whether recommendations for health literacy are currently being met. METHODS: A cross-sectional study design was used. Patient-oriented English-language advance directive documents (brochures and/or forms) were obtained from the health agency websites of all Canadian provinces and territories and analyzed for readability using the Flesch-Kincaid Grade Level and Flesch Readability Ease scales. RESULTS: Advance directives in Canada are distinct from one another and surpass the recommended reading level by 4.5 ± 1.4 grade levels on average (95% confidence interval 8.7-10.3) with the hardest-to-read documents existing in Ontario, Quebec and Alberta. INTERPRETATION: These results demonstrate that the provincial and territorial governments issuing advance directive documentation have fallen short of their fiduciary responsibility to provide documents that facilitate health literacy. Addressing this shortcoming can result in increased patient engagement in advance directive completion while promoting patient autonomy.
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Amblyopia is characterised by visual deficits in both spatial vision and motion perception. While the spatial deficits are thought to result from deficient processing at both low and higher level stages of visual processing, the deficits in motion perception appear to result primarily from deficits involving higher level processing. Specifically, it has been argued that the motion deficit in amblyopia occurs when local motion information is pooled spatially and that this process is abnormally susceptible to the presence of noise elements in the stimulus. Here we investigated motion direction discrimination for abruptly presented two-frame Gabor stimuli in a group of five strabismic amblyopes and five control observers. Motion direction discrimination for this stimulus is inherently noisy and relies on the signal/noise processing of motion detectors. We varied viewing condition (monocular vs. binocular), stimulus size (5.3-18.5°) and stimulus contrast (high vs. low) in order to assess the effects of binocular summation, spatial summation and contrast on task performance. No differences were found for the high contrast stimuli; however the low contrast stimuli revealed differences between the control and amblyopic groups and between fellow fixing and amblyopic eyes. Control participants exhibited pronounced binocular summation for this task (on average a factor of 3.7), whereas amblyopes showed no such effect. In addition, the spatial summation that occurred for control eyes and the fellow eye of amblyopes was significantly attenuated for the amblyopic eyes relative to fellow eyes. Our results support the hypothesis that pooling of local motion information from amblyopic eyes is abnormal and highly sensitive to noise.
Assuntos
Ambliopia/fisiopatologia , Discriminação Psicológica/fisiologia , Percepção de Movimento/fisiologia , Estrabismo/fisiopatologia , Visão Binocular/fisiologia , Visão Monocular/fisiologia , Adulto , Análise de Variância , Sensibilidades de Contraste/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Percepção de Tamanho/fisiologia , Adulto JovemRESUMO
BACKGROUND: Although the induction of behavioural unconsciousness during sleep and general anaesthesia has been shown to involve overlapping brain mechanisms, sleep involves cyclic fluctuations between different brain states known as active (paradoxical or rapid eye movement: REM) and quiet (slow-wave or non-REM: nREM) stages whereas commonly used general anaesthetics induce a unitary slow-wave brain state. METHODOLOGY/PRINCIPAL FINDINGS: Long-duration, multi-site forebrain field recordings were performed in urethane-anaesthetized rats. A spontaneous and rhythmic alternation of brain state between activated and deactivated electroencephalographic (EEG) patterns was observed. Individual states and their transitions resembled the REM/nREM cycle of natural sleep in their EEG components, evolution, and time frame ( approximately 11 minute period). Other physiological variables such as muscular tone, respiration rate, and cardiac frequency also covaried with forebrain state in a manner identical to sleep. The brain mechanisms of state alternations under urethane also closely overlapped those of natural sleep in their sensitivity to cholinergic pharmacological agents and dependence upon activity in the basal forebrain nuclei that are the major source of forebrain acetylcholine. Lastly, stimulation of brainstem regions thought to pace state alternations in sleep transiently disrupted state alternations under urethane. CONCLUSIONS/SIGNIFICANCE: Our results suggest that urethane promotes a condition of behavioural unconsciousness that closely mimics the full spectrum of natural sleep. The use of urethane anaesthesia as a model system will facilitate mechanistic studies into sleep-like brain states and their alternations. In addition, it could also be exploited as a tool for the discovery of new molecular targets that are designed to promote sleep without compromising state alternations.