Age at onset as stratifier in idiopathic Parkinson’s disease – effect of ageing and polygenic risk score on clinical phenotypes

Several phenotypic differences observed in Parkinson’s disease (PD) patients have been linked to age at onset (AAO). We endeavoured to find out whether these differences are due to the ageing process itself by using a combined dataset of idiopathic PD (n = 430) and healthy controls (HC; n = 556) excluding carriers of known PD-linked genetic mutations in both groups. We found several significant effects of AAO on motor and non-motor symptoms in PD, but when comparing the effects of age on these symptoms with HC (using age at assessment, AAA), only positive associations of AAA with burden of motor symptoms and cognitive impairment were significantly different between PD vs HC. Furthermore, we explored a potential effect of polygenic risk score (PRS) on clinical phenotype and identified a significant inverse correlation of AAO and PRS in PD. No significant association between PRS and severity of clinical symptoms was found. We conclude that the observed non-motor phenotypic differences in PD based on AAO are largely driven by the ageing process itself and not by a specific profile of neurodegeneration linked to AAO in the idiopathic PD patients

Perceptual Encoding Efficiency in Visual Search

The authors present 10 experiments that challenge some central assumptions of the dominant theories of visual search. Their results reveal that the complexity (or redundancy) of nontarget items is a crucial but overlooked determinant of search efficiency. The authors offer a new theoretical outline that emphasizes the importance of nontarget encoding efficiency, and they test this proposal using dot pattern stimuli adapted from W. R. Garner and D. E. Clement (1963). The results provide converging support for the importance of nontarget encoding efficiency in accounting for visual search performance

No representation without awareness in the lateral occipital cortex

Recent research has shown that four small dots presented in the vicinity of, but not adjacent to, a target stimulus can banish that stimulus from conscious awareness. It is thought that the mental representation of the masked stimulus is "erased" by the trailing quartet of dots. Using functional magnetic resonance adaptation, we show that there is no persisting neural representation of the successfully masked stimulus in lateral occipital cortex, a region that has been implicated in the processing of object structure. This finding rules out the alternative interpretation that a lingering neural representation is merely rendered inaccessible to consciousness, as is the fate, for example, of monocular information under conditions of binocular rivalry.5 page(s

New objects dominate luminance transients in setting attentional priority

Both the sudden appearance of an object and sudden changes in existing object features influence priority in visual search. However, direct comparisons of these influences have not been made under controlled conditions. In 5 visual search experiments, new object onsets were compared directly with changes in the luminance of old objects. Factors included the luminance contrast of items against the background, the magnitude of luminance change, and the probability that these changes were associated with the target item. New objects were consistently more effective in guiding search, such that a new item with very low luminance contrast was equivalent to an old item undergoing a large change in luminance. An important exception was an old item changing in contrast and polarity, which was as effective as the appearance of a new object. This indicates that search priority is biased toward object rather than situational changes. The human visual system is confronted with a bewildering array of choices each time a new scene is encountered. Which features, objects, and relations among objects should be processed first? The answer to this question depends on complex interactions between the behavioral goals of the observer (Folk & Annett, 1994; Folk

The evolution of dystonia-like movements in TOR1A rats after transient nerve injury is accompanied by dopaminergic dysregulation and abnormal oscillatory activity of a central motor network

TOR1A is the most common inherited form of dystonia with still unclear pathophysiology and reduced penetrance of 30–40%. ∆ETorA rats mimic the TOR1A disease by expression of the human TOR1A mutation without presenting a dystonic phenotype. We aimed to induce dystonia-like symptoms in male ∆ETorA rats by peripheral nerve injury and to identify central mechanism of dystonia development. Dystonia-like movements (DLM) were assessed using the tail suspension test and implementing a pipeline of deep learning applications. Neuron numbers of striatal parvalbumin+, nNOS+, calretinin+, ChAT+ interneurons and Nissl+ cells were estimated by unbiased stereology. Striatal dopaminergic metabolism was analyzed via in vivo microdialysis, qPCR and western blot. Local field potentials (LFP) were recorded from the central motor network. Deep brain stimulation (DBS) of the entopeduncular nucleus (EP) was performed. Nerve-injured ∆ETorA rats developed long-lasting DLM over 12 weeks. No changes in striatal structure were observed. Dystonic-like ∆ETorA rats presented a higher striatal dopaminergic turnover and stimulus-induced elevation of dopamine efflux compared to the control groups. Higher LFP theta power in the EP of dystonic-like ∆ETorA compared to wt rats was recorded. Chronic EP-DBS over 3 weeks led to improvement of DLM. Our data emphasizes the role of environmental factors in TOR1A symptomatogenesis. LFP analyses indicate that the pathologically enhanced theta power is a physiomarker of DLM. This TOR1A model replicates key features of the human TOR1A pathology on multiple biological levels and is therefore suited for further analysis of dystonia pathomechanism