De novo loss of function mutations in STXBP1 are a relatively common cause of epilepsy and intellectual disability (ID). However, little is known about the types and severities of behavioural ...features associated with this genetic diagnosis.
To address this, we collected systematic phenotyping data encompassing neurological, developmental, and behavioural characteristics. Participants were 14 individuals with STXBP1-associated neurodevelopmental disorder, ascertained from clinical genetics and neurology services UK-wide. Data was collected via standardised questionnaires administered to parents at home, supplemented by researcher observations. To isolate discriminating phenotypes, the STXBP1 group was compared to 33 individuals with pathogenic mutations in other ID-associated genes (ID group). To account for the potential impact of global cognitive impairment, a secondary comparison was made to an ability-matched subset of the ID group (low-ability ID group).
The STXBP1 group demonstrated impairments across all assessed domains. In comparison to the ID group, the STXBP1 group had more severe global adaptive impairments, fine motor difficulties, and hyperactivity. In comparison to the low-ability ID group, severity of receptive language and social impairments discriminated the STXBP1 group. A striking feature of the STXBP1 group, with reference to both comparison groups, was preservation of social motivation.
De novo mutations in STXBP1 are associated with complex and variable neurodevelopmental impairments. Consistent features, which discriminate this disorder from other monogenic causes of ID, are severe language impairment and difficulties managing social interactions, despite strong social motivation. Future work could explore the physiological mechanisms linking motor, speech, and social development in this disorder. Understanding the developmental emergence of behavioural characteristics can help to focus clinical assessment and management after genetic diagnosis, with the long-term aim of improving outcomes for patients and families.
Extended practice on a particular cognitive task can boost the performance of other tasks, even though they themselves have not been practised. This transfer of benefits appears to be specific, ...occurring most when tasks are very similar to those being trained. But what type of similarity is most important for predicting transfer? This question is addressed with a tightly controlled randomised design, with a relatively large sample (N = 175) and an adaptive control group. We created a hierarchical set of nested assessment tasks. Participants then trained on two of the tasks: one was relatively “low” in the hierarchy requiring just simultaneous judgements of shapes’ spikiness, whereas the other was relatively “high” requiring delayed judgements of shapes’ spikiness or number of spikes in a switching paradigm. Using the full complement of nested tasks before and after training, we could then test whether and how these “low” and “high” training effects cascade through the hierarchy. For both training groups, relative to the control, whether or not an assessment task shared a single specific feature was the best predictor of transfer patterns. For the low-level training group, the overall proportion of feature overlap also significantly predicted transfer, but the same was not true for the high-level training group. Finally, pre-training between-task correlations were not predictive of the pattern of transfer for either group. Together these findings provide an experimental exploration of the specificity of transfer and establish the nature of task overlap that is crucial for the transfer of performance improvements.
The formation of large-scale brain networks, and their continual refinement, represent crucial developmental processes that can drive individual differences in cognition and which are associated with ...multiple neurodevelopmental conditions. But how does this organization arise, and what mechanisms drive diversity in organization? We use generative network modeling to provide a computational framework for understanding neurodevelopmental diversity. Within this framework macroscopic brain organization, complete with spatial embedding of its organization, is an emergent property of a generative wiring equation that optimizes its connectivity by renegotiating its biological costs and topological values continuously over time. The rules that govern these iterative wiring properties are controlled by a set of tightly framed parameters, with subtle differences in these parameters steering network growth towards different neurodiverse outcomes. Regional expression of genes associated with the simulations converge on biological processes and cellular components predominantly involved in synaptic signaling, neuronal projection, catabolic intracellular processes and protein transport. Together, this provides a unifying computational framework for conceptualizing the mechanisms and diversity in neurodevelopment, capable of integrating different levels of analysis-from genes to cognition.
Difficulties with attention are common following stroke, particularly in patients with frontal and parietal damage, and are associated with poor outcome. Home-based online cognitive training may have ...the potential to provide an efficient and effective way to improve attentional functions in such patients. Little work has been carried out to assess the efficacy of this approach in stroke patients, and the lack of studies with active control conditions and rigorous evaluations of cognitive functioning pre and post-training means understanding is limited as to whether and how such interventions may be effective. Here, in a feasibility pilot study, we compare the effects of 20 days of cognitive training using either novel Selective Attention Training (SAT) or commercial Working Memory Training (WMT) programme, versus a waitlist control on a range of attentional and working memory tasks. We demonstrate separable effects of each training condition, with SAT leading to improvements in spatial and non-spatial aspects of attention and WMT leading to improvements on closely related working memory tasks. In addition, both training groups reported improvements in everyday functioning, which were associated with improvements in attention, suggesting that improving attention may be of particular importance in maximising functional improvements in this patient group.
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Dostopno za:
BFBNIB, DOBA, FSPLJ, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Early adversity can change educational, cognitive, and mental health outcomes. However, the neural processes through which early adversity exerts these effects remain largely unknown. We used ...generative network modeling of the mouse connectome to test whether unpredictable postnatal stress shifts the constraints that govern the organization of the structural connectome. A model that trades off the wiring cost of long‐distance connections with topological homophily (i.e., links between regions with shared neighbors) generated simulations that successfully replicate the rodent connectome. The imposition of early life adversity shifted the best‐performing parameter combinations toward zero, heightening the stochastic nature of the generative process. Put simply, unpredictable postnatal stress changes the economic constraints that reproduce rodent connectome organization, introducing greater randomness into the development of the simulations. While this change may constrain the development of cognitive abilities, it could also reflect an adaptive mechanism that facilitates effective responses to future challenges.
The impact of socioeconomic status (SES) on early child development is well-established, but the mediating role of parental mental health is poorly understood. Data were obtained from The Avon ...Longitudinal Study of Parents and Children (ALSPAC;
n
= 13,855), including measures of early SES (age 8 months), key aspects of development during mid-late childhood (ages 7–8 years), and maternal mental health during early childhood (ages 0–3 years). In the first year of life, better maternal mental health was shown to weaken the negative association between SES and child mental health. Better maternal mental health was additionally shown to weaken the association between SES and child cognitive ability. These findings highlight the variability and complexity of the mediating role of parental mental health on child development. They further emphasise the importance of proximal factors in the first year of life, such as parental mental health, in mediating key developmental outcomes.
Visual short-term memory (VSTM) is limited in the quantity and quality of items that can be retained over time. Importantly, these two mnemonic parameters interact: increasing the number of items in ...VSTM reduces the quality with which they are represented. Here, we ask whether this trade-off is under top-down control. Specifically, we test whether participants can strategically optimise the trade-off between quality and quantity for VSTM according to task demands. We manipulated strategic trade-off by varying expectations about the number of to-be-remembered items (Experiments 1-2) or the precision required for the memory-based judgement (Experiment 3). In a final experiment, we manipulated both variables in a complementary way to maximise the motivation to strategically control the balance between number and the quality of items encoded into VSTM. In different blocks, performance would benefit most either by encoding a large number of items with low precision or by encoding a small number of items with high precision (Experiment 4). In all experiments, we compared VSTM performance on trials matched for mnemonic demand, but within contexts emphasising the quality or quantity of VSTM representations. Across all four experiments, we found no evidence to suggest that participants use this contextual information to bias the balance between the number and precision of items in VSTM. Rather, our data suggest that the trade-off may be determined primarily by stimulus-driven factors at encoding.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cognitive difficulties are common following stroke and can have widespread impacts on everyday functioning. Technological advances offer the possibility of individualized cognitive training for ...patients at home, potentially providing a low-cost, low-intensity adjunct to rehabilitation services. Using this approach, we have previously demonstrated post-training improvements in attention and everyday functioning in fronto-parietal stroke patients. Here we examine whether these benefits are observed more broadly in a community stroke sample. Eighty patients were randomized to either 4 weeks of online adaptive attention training (SAT), working memory training (WMT) or waitlist (WL). Cognitive and everyday function measures were collected before and after the intervention, and after 3 months. During training, weekly measures of patients' subjective functioning were collected. The training was well received and compliance good. No differences in our primary end-point, spatial bias, or other cognitive functions were observed. However, on patient-reported outcomes, SAT participants showed greater levels of improvement in everyday functioning than WMT or WL participants. In line with our previous work, everyday functioning improvements were greatest for patients with spatial impairments and those who received SAT training. Whether attention training can be recommended for stroke survivors depends on whether cognitive test performance or everyday functioning is considered more relevant.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, FSPLJ, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Attention is important for effectively comparing incoming perceptual information with the contents of visual short-term memory (VSTM), such that any differences can be detected. However, how ...attentional mechanisms operate upon these comparison processes remains largely unknown. Here we investigate the underlying neural mechanisms by which attention modulates the comparisons between VSTM and perceptual representations using functional magnetic resonance imaging (fMRI). Participants performed a cued change detection task. Spatial cues were presented to orient their attention either to the location of an item in VSTM prior to its comparison (retro-cues), or simultaneously (simultaneous-cues) with the probe array. A no-cue condition was also included. When attention cannot be effectively deployed in advance (i.e. following the simultaneous-cues), we observed a distributed and extensive activation pattern in the prefrontal and parietal cortices in support of successful change detection. This was not the case when participants can deploy their attention in advance (i.e. following the retro-cues). The region-of-interest analyses confirmed that neural responses for successful change detection versus correct rejection in the visual and parietal regions were significantly different for simultaneous-cues compared to retro-cues. Importantly, we found enhanced functional connectivity between prefrontal and parietal cortices when detecting changes on the simultaneous-cue trials. Moreover, we demonstrated a close relationship between this functional connectivity and d' scores. Together, our findings elucidate the attentional and neural mechanisms by which items held in VSTM are compared with incoming perceptual information.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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