Development of the human cerebral cortex: Boulder Committee revisited.

In 1970 the Boulder Committee described the basic principles of the development of the CNS, derived from observations on the human embryonic cerebrum. Since then, numerous studies have significantly advanced our knowledge of the timing, sequence and complexity of developmental events, and revealed important inter-species differences. We review current data on the development of the human cerebral cortex and update the classical model of how the structure that makes us human is formed.

Intersecting distributed networks support convergent linguistic functioning across different languages in bilinguals.

How bilingual brains accomplish the processing of more than one language has been widely investigated by neuroimaging studies. The assimilation-accommodation hypothesis holds that both the same brain neural networks supporting the native language and additional new neural networks are utilized to implement second language processing. However, whether and how this hypothesis applies at the finer-grained levels of both brain anatomical organization and linguistic functions remains unknown. To address this issue, we scanned Chinese-English bilinguals during an implicit reading task involving Chinese words, English words and Chinese pinyin. We observed broad brain cortical regions wherein interdigitated distributed neural populations supported the same cognitive components of different languages. Although spatially separate, regions including the opercular and triangular parts of the inferior frontal gyrus, temporal pole, superior and middle temporal gyrus, precentral gyrus and supplementary motor areas were found to perform the same linguistic functions across languages, indicating regional-level functional assimilation supported by voxel-wise anatomical accommodation. Taken together, the findings not only verify the functional independence of neural representations of different languages, but show co-representation organization of both languages in most language regions, revealing linguistic-feature specific accommodation and assimilation between first and second languages.

Synaesthetic perception of colour and visual space in a blind subject: an fMRI case study.

In spatial sequence synaesthesia (SSS) ordinal stimuli are perceived as arranged in peripersonal space. Using fMRI, we examined the neural bases of SSS and colour synaesthesia for spoken words in a late-blind synaesthete, JF. He reported days of the week and months of the year as both coloured and spatially ordered in peripersonal space; parts of the days and festivities of the year were spatially ordered but uncoloured. Words that denote time-units and triggered no concurrents were used in a control condition. Both conditions inducing SSS activated the occipito-parietal, infero-frontal and insular cortex. The colour area hOC4v was engaged when the synaesthetic experience included colour. These results confirm the continued recruitment of visual colour cortex in this late-blind synaesthetes. Synaesthesia also involved activation in inferior frontal cortex, which may be related to spatial memory and detection, and in the insula, which might contribute to audiovisual integration related to the processing of inducers and concurrents.

The impact of multiple non-pharmaceutical interventions on controlling COVID-19 outbreak without lockdown in Hong Kong: A modelling study.

BACKGROUND: The 'third wave' of COVID-19 in Hong Kong, China was suppressed by non-pharmaceutical interventions (NPIs). Although social distancing regulations were quickly strengthened, the outbreak continued to grow, causing increasing delays in tracing and testing. Further regulations were introduced, plus 'targeted testing' services for at-risk groups. Estimating the impact of individual NPIs could provide lessons about how outbreaks can be controlled without radical lockdown. However, the changing delays in confirmation time challenge current modelling methods. We used a novel approach aimed at disentangling and quantifying the effects of individual interventions. METHODS: We incorporated the causes of delays in tracing and testing (i.e. load-efficiency relationship) and the consequences from such delays (i.e. the proportion of un-traced cases and the proportion of traced-cases with confirmation delay) into a deterministic transmission model, which was fitted to the daily number of cases with and without an epi­link (an indication of being contact-traced). The effect of each NPI was then calculated. FINDINGS: The model estimated that after earlier relaxation of regulations, Re rose from 0.7 to 3.2. Restoration of social distancing to the previous state only reduced Re to 1.3, because of increased delay in confirmation caused by load on the contact-tracing system. However, Re decreased by 20.3% after the introduction of targeted testing and by 17.5% after extension of face-mask rules, reducing Re to 0.9 and suppressing the outbreak. The output of the model without incorporation of delay failed to capture important features of transmission and Re. INTERPRETATION: Changing delay in confirmation has a significant impact on disease transmission and estimation of transmissibility. This leads to a clear recommendation that delay should be monitored and mitigated during outbreaks, and that delay dynamics should be incorporated into models to assess the effects of NPIs. FUNDING: City University of Hong Kong and Health and Medical Research Fund.

The impact of contact tracing and testing on controlling COVID-19 outbreak without lockdown in Hong Kong: An observational study.

BACKGROUND: Maintaining effective contact tracing to control COVID-19 is challenging. Rapid growth in the number of infected cases can overload tracing and testing capacity, resulting in failure to trace contacts and delays in confirming an infection until after symptom onset (confirmation delay), hence increasing transmissibility. A substantial outbreak in Hong Kong, which was suppressed with non-pharmaceutical interventions (NPIs), provided an opportunity to assess the impact of overloading contact tracing and of efforts to improve its efficiency. METHODS: Using epidemiological-link (epi-link) data, we calculated the probability and duration of confirmation delay for cases with and without an epi-link, among all 3,148 confirmed cases between 5 July and 15 August 2020. Logistic regression was performed to determine the relationship between the number of recently confirmed infections and the probability of confirmation delay for epi-linked (contact-traced) cases. We estimated the impact on this relationship of targeted testing of at-risk groups. FINDINGS: The probability and duration of confirmation delay were associated with the rise in daily case number during growth of the outbreak. The proportion with confirmation delay among contact-traced cases increased from about 60 % to nearly 85 % as the number of cases grew from 1 to 50 per day (p-value = 0.003). The subsequent introduction of testing services for at-risk groups substantially reduced the proportion and it did not approach 85 % again until the daily number of cases exceeded 125. This 2.5-fold improvement in capacity contributed crucially to suppression of the outbreak. INTERPRETATION: The number of recently confirmed infections is an indicator of the load on the contact-tracing system, the consequence of which can be assessed by the probability of confirmation delay. Measures to monitor and improve contact-tracing efficiency, alongside social distancing interventions, can enable outbreaks to be controlled without lockdown. FUNDING: City University of Hong Kong and Health and Medical Research Fund.

New treatment for amblyopia based on rules of synaptic plasticity: a randomized clinical trial.

Amblyopia resulting from early deprivation of vision or defocus in one eye reflects an imbalance of input from the eyes to the visual cortex. We tested the hypothesis that asynchronous stimulation of the two eyes might induce synaptic plasticity and rebalance input. Experiments on normal adults showed that repetitive brief exposure of grating stimuli, with the onset of each stimulus delayed by 8.3 ms in one eye, results in a shift in perceptual eye dominance. Clinical studies (Clinical trial registration number: ChiCTR2100049130), using popular 3D movies with similar asynchrony between the two eyes (amblyopic eye stimulated first) to treat anisometropic amblyopia, established that just 10.5 h of conditioning over <3 weeks produced improvement that met criteria for successful treatment. The benefits of asynchronous conditioning accumulate over 20-30 45 min sessions, and are maintained for at least 2 years. Finally, we demonstrate that asynchronous binocular treatment alone is more effective than patching only. This novel treatment is popular with children and is some 50 times more efficient than patching alone.

Spatial attention changes excitability of human visual cortex to direct stimulation.

Conscious perception depends not only on sensory input, but also on attention [1, 2]. Recent studies in monkeys [3-6] and humans [7-12] suggest that influences of spatial attention on visual awareness may reflect top-down influences on excitability of visual cortex. Here we tested this specifically, by providing direct input into human visual cortex via cortical transcranial magnetic stimulation (TMS) to produce illusory visual percepts, called phosphenes. We found that a lower TMS intensity was needed to elicit a conscious phosphene when its apparent spatial location was attended, rather than unattended. Our results indicate that spatial attention can enhance visual-cortex excitability, and visual awareness, even when sensory signals from the eye via the thalamic pathway are bypassed.

The first neurons of the human cerebral cortex.

We describe a distinctive, widespread population of neurons situated beneath the pial surface of the human embryonic forebrain even before complete closure of the neural tube. These 'predecessor' cells include the first neurons seen in the primordium of the cerebral cortex, before the onset of local neurogenesis. Morphological analysis, combined with the study of centrosome location, regional transcription factors and patterns of mitosis and neurogenesis, indicates that predecessor cells invade the cortical primordium by tangential migration from the subpallium. These neurons, described here for the first time, precede all other known cell types of the developing cortex.

I haven't a clue! Expectations based on repetitions and hints facilitate perceptual experience of ambiguous images.

In recent years, the role of top-down expectations on perception has been extensively researched within the framework of predictive coding. However, less attention has been given to the different sources of expectations, how they differ, and how they interact. In this article, we examined the effects of informative hints on perceptual experience and how these interact with repetition-based expectations to create a long-lasting effect. Over 7 experiments, we used verbal hints and multiple presentations of ambiguous 2-tone images. We found that vividness ratings increased from 1 presentation to the next, even after the object in the image had been identified. In addition, vividness ratings significantly increased when images were introduced with a hint, and this boost was greater for more detailed hints. However, the initial increase in vividness did not always carry over to the next presentation. When recognition of the image in the presentation was hard because of memory load, inconsistent presentation, or noise level of the image, the initial advantage in vividness was attenuated. This was most apparent when participants were primed with a grayscale version of the 2-tone image. A computational model based on evidence accumulation was able to recover these patterns of perceptual experience, suggesting that the effect of hints is short lived if it cannot be encoded in memory for future presentations. This notion highlights the different contributions of attention, memory, and their interactions on forming expectations for perception. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Seeing a Work of Art Indirectly: When a Reproduction Is Better Than an Indirect View, and a Mirror Better Than a Live Monitor.

Visiting a museum and seeing an original artwork can be a special experience. We use a survey and a set of hypothetical questions to explore how such experience would be affected by changes in how the artwork is seen. In a first study, participants imagined that they had traveled to see a painting that they particularly like. They discover that it is impossible to directly see the original painting. Three alternatives are offered: seeing an optical reflection (using a mirror), seeing a video screening (a closed-circuit camera), or seeing a reproduction. In all cases, it is made clear that the size, brightness, and resolution will match that of the original. In addition, these options could be within the same room as the original, in the room next door, or in a different building. Results show that physical distance did not affect significantly the responses. However, there was an overall preference for seeing a reproduction as opposed to an optical or digital image. Contrary to the idea that the original is always superior to a copy, many people felt that a direct view of a copy is a preferable experience than an indirect view. The second study was focused directly on the comparison between a mirror and a monitor. Here we highlighted the fact that for the mirror light coming from the mirror originated from the painting. Data were collected in Britain and in China. In both cases, there was a clear preference for the mirror over the monitor.

Development of a rational scale to assess the harm of drugs of potential misuse.

Drug misuse and abuse are major health problems. Harmful drugs are regulated according to classification systems that purport to relate to the harms and risks of each drug. However, the methodology and processes underlying classification systems are generally neither specified nor transparent, which reduces confidence in their accuracy and undermines health education messages. We developed and explored the feasibility of the use of a nine-category matrix of harm, with an expert delphic procedure, to assess the harms of a range of illicit drugs in an evidence-based fashion. We also included five legal drugs of misuse (alcohol, khat, solvents, alkyl nitrites, and tobacco) and one that has since been classified (ketamine) for reference. The process proved practicable, and yielded roughly similar scores and rankings of drug harm when used by two separate groups of experts. The ranking of drugs produced by our assessment of harm differed from those used by current regulatory systems. Our methodology offers a systematic framework and process that could be used by national and international regulatory bodies to assess the harm of current and future drugs of abuse.

Wheel running from a juvenile age delays onset of specific motor deficits but does not alter protein aggregate density in a mouse model of Huntington's disease.

BACKGROUND: Huntington's disease (HD) is a neurodegenerative disorder predominantly affecting the cerebral cortex and striatum. Transgenic mice (R6/1 line), expressing a CAG repeat encoding an expanded polyglutamine tract in the N-terminus of the huntingtin protein, closely model HD. We have previously shown that environmental enrichment of these HD mice delays the onset of motor deficits. Furthermore, wheel running initiated in adulthood ameliorates the rear-paw clasping motor sign, but not an accelerating rotarod deficit. RESULTS: We have now examined the effects of enhanced physical activity via wheel running, commenced at a juvenile age (4 weeks), with respect to the onset of various behavioral deficits and their neuropathological correlates in R6/1 HD mice. HD mice housed post-weaning with running wheels only, to enhance voluntary physical exercise, have delayed onset of a motor co-ordination deficit on the static horizontal rod, as well as rear-paw clasping, although the accelerating rotarod deficit remains unaffected. Both wheel running and environmental enrichment rescued HD-induced abnormal habituation of locomotor activity and exploratory behavior in the open field. We have found that neither environment enrichment nor wheel running ameliorates the shrinkage of the striatum and anterior cingulate cortex (ACC) in HD mice, nor the overall decrease in brain weight, measured at 9 months of age. At this age, the density of ubiquitinated protein aggregates in the striatum and ACC is also not significantly ameliorated by environmental enrichment or wheel running. CONCLUSION: These results indicate that enhanced voluntary physical activity, commenced at an early presymptomatic stage, contributes to the positive effects of environmental enrichment. However, sensory and cognitive stimulation, as well as motor stimulation not associated with running, may constitute major components of the therapeutic benefits associated with enrichment. Comparison of different environmental manipulations, performed in specific time windows, can identify critical periods for the induction of neuroprotective 'brain reserve' in animal models of HD and related neurodegenerative diseases.

The site of saccadic suppression.

During rapid eye movements, or saccades, stable vision is maintained by active reduction of visual sensitivity. The site of this saccadic suppression remains uncertain. Here we show that phosphenes--small illusory visual perceptions--induced by transcranial magnetic stimulation (TMS) to the human occipital cortex are immune to saccadic suppression, whereas phosphenes induced by retinal stimulation are not, thus providing direct physiological evidence that saccadic suppression occurs between the retina and the occipital visual cortex.

Public health failure in the prevention of neural tube defects: time to abandon the tolerable upper intake level of folate.

The neural tube defects anencephaly and spina bifida are two of the most common serious congenital malformations. Most cases can be prevented by consuming sufficient folic acid immediately before pregnancy and in early pregnancy. Fortification of flour with folic acid to prevent these defects has been implemented in 81 countries without public objection or indication of harm. An obstacle to the wider adoption of fortification arises from the creation of a "tolerable upper intake level" for folate (which includes natural food folate as well as synthetic folic acid), and which has been set at 1 mg/day, thereby proscribing higher folate intakes. Increasing the intake of folic acid in a population will necessarily increase the number of people with a folate intake greater than 1 mg per day, and this concern is obstructing folic acid fortification. This paper shows that the scientific basis for setting any upper limit, let alone one at 1 mg/day, is flawed. An upper intake level is therefore unnecessary and should be removed, thus allaying unjustified concerns about folic acid fortification. As a result, the full global opportunity to prevent two serious fatal or disabling disorders can and should be realized.

Olfactory abnormalities in Huntington's disease: decreased plasticity in the primary olfactory cortex of R6/1 transgenic mice and reduced olfactory discrimination in patients.

Reduced neuronal plasticity in the striatum, hippocampus, and neocortex is a common feature of transgenic mouse models of Huntington's disease (HD). Doublecortin (DCX) and polysialylated neural cell adhesion molecule (PSA-NCAM) are associated with structural plasticity in the adult mammalian brain, are markers of newly formed neurons in the dentate gyrus of the adult hippocampus, and are highly expressed in primary olfactory (piriform) cortex. Animal studies have demonstrated that a reduction in plasticity in the piriform cortex is associated with a selective impairment in odour discrimination. Therefore, the number of DCX and PSA-NCAM immunoreactive cells in the piriform cortex were quantified as measures of plasticity in early stage (fifteen week old) R6/1 transgenic HD mice. The transgenic mice had a large reduction in the number of DCX and PSA-NCAM immunoreactive cells in the piriform cortex, similar to that previously reported in the R6/2 mice. We also tested whether odour discrimination, as well as identification and detection, were impaired in HD patients and found that patients (at a similar disease stage as the mice) had an impairment in odour discrimination and identification, but not odour detection. These results suggest that olfactory impairments observed in HD patients may be the result of reduced plasticity in the primary olfactory cortex.

Building Bridges through Science.

Science is ideally suited to connect people from different cultures and thereby foster mutual understanding. To promote international life science collaboration, we have launched "The Science Bridge" initiative. Our current project focuses on partnership between Western and Middle Eastern neuroscience communities.

Tangential networks of precocious neurons and early axonal outgrowth in the embryonic human forebrain.

We used a combination of immunohistochemistry and carbocyanine dye tracing to study neurons and their processes in the human embryonic forebrain, 4-7 weeks after conception, before the onset of synaptogenesis. We discovered a widespread network of precocious MAP2 (microtubule-associated protein 2)-immunoreactive cells, with long, nonaxonal processes, before the appearance of the cortical plate and the establishment of thalamocortical connectivity. Dye tracing revealed that the processes of these precocious cells form tangential links between intermediate zones of the thalamus, ganglionic eminence, hypothalamus, and cortical preplate. The spatiotemporal distribution and morphology of the precocious neurons in the cortical preplate suggest that they are generated outside the cerebral wall rather than in the local ventricular zone. The first thalamocortical axons and axons of preplate cells extend across diencephalo-telencephalic and striatocortical boundaries before the arrival of the first cortical plate neurons. Precocious cells may provide initial communication between subdivisions of the embryonic brain as well as guidance cues for navigation of growing axons and/or transverse neuronal migration.