The impact of area level mental health interventions on outcomes for secondary school pupils: Evidence from the HeadStart programme in England.

In light of the dramatic rise in mental health disorders amongst adolescents seen in the past decade across the world, there is an urgent need for robust evidence on what works to combat this trend. This paper provides the first robust evaluation of the impacts on school outcomes of 6-year funding programme (HeadStart) for area-level mental health interventions for adolescents. Exploiting educational administrative data on ten cohorts of state-educated secondary school students, we use the synthetic control method to construct counterfactual outcomes for areas that received the funding. We show that the funding did not affect students' absenteeism or academic attainment, but it prevented around 800 students (c. 10% of students typically excluded yearly) from being excluded in its first year. The transient nature of this effect suggests that sustained funding for intervention may be a necessary but not sufficient condition to maintain programme effectiveness over time.

Inequality in mortality between Black and White Americans by age, place, and cause and in comparison to Europe, 1990 to 2018.

Although there is a large gap between Black and White American life expectancies, the gap fell 48.9% between 1990 and 2018, mainly due to mortality declines among Black Americans. We examine age-specific mortality trends and racial gaps in life expectancy in high- and low-income US areas and with reference to six European countries. Inequalities in life expectancy are starker in the United States than in Europe. In 1990, White Americans and Europeans in high-income areas had similar overall life expectancy, while life expectancy for White Americans in low-income areas was lower. However, since then, even high-income White Americans have lost ground relative to Europeans. Meanwhile, the gap in life expectancy between Black Americans and Europeans decreased by 8.3%. Black American life expectancy increased more than White American life expectancy in all US areas, but improvements in lower-income areas had the greatest impact on the racial life expectancy gap. The causes that contributed the most to Black Americans' mortality reductions included cancer, homicide, HIV, and causes originating in the fetal or infant period. Life expectancy for both Black and White Americans plateaued or slightly declined after 2012, but this stalling was most evident among Black Americans even prior to the COVID-19 pandemic. If improvements had continued at the 1990 to 2012 rate, the racial gap in life expectancy would have closed by 2036. European life expectancy also stalled after 2014. Still, the comparison with Europe suggests that mortality rates of both Black and White Americans could fall much further across all ages and in both high-income and low-income areas.

Inequalities in Children's Experiences of Home Learning during the COVID-19 Lockdown in England.

This paper combines novel data on the time use, home-learning practices and economic circumstances of families with children during the COVID-19 lockdown with pre-lockdown data from the UK Time Use Survey to characterise the time use of children and how it changed during lockdown, and to gauge the extent to which changes in time use and learning practices during this period are likely to reinforce the already large gaps in educational attainment between children from poorer and better-off families. We find considerable heterogeneity in children's learning experiences - amount of time spent learning, activities undertaken during this time and availability of resources to support learning. Concerningly, but perhaps unsurprisingly, this heterogeneity is strongly associated with family income and in some instances more so than before lockdown. Furthermore, our analysis suggests that any impacts of inequalities in time spent learning between poorer and richer children are likely to be compounded by inequalities not only in learning resources available at home, but also in those provided by schools.

Sound Induces Change in Orientation Preference of V1 Neurons: Audio-Visual Cross-Influence.

In the cortex, demarcated unimodal sensory regions often respond to unforeseen sensory stimuli and exhibit plasticity. The goal of the current investigation was to test evoked responses of primary visual cortex (V1) neurons when an adapting auditory stimulus is applied in isolation. Using extracellular recordings in anesthetized cats, we demonstrate that, unlike the prevailing observation of only slight modulations in the firing rates of the neurons, sound imposition in isolation entirely shifted the peaks of orientation tuning curves of neurons in both supra- and infragranular layers of V1. Our results suggest that neurons specific to either layer dynamically integrate features of sound and modify the organization of the orientation map of V1. Intriguingly, these experiments present novel findings that the mere presentation of a prolonged auditory stimulus may drastically recalibrate the tuning properties of the visual neurons and highlight the phenomenal neuroplasticity of V1 neurons.

Comparative effects of adaptation on layers II-III and V-VI neurons in cat V1.

V1 is fundamentally grouped into columns that descend from layers II-III to V-VI. Neurons inherent to visual cortex are capable of adapting to changes in the incoming stimuli that drive the cortical plasticity. A principle feature called orientation selectivity can be altered by the presentation of non-optimal stimulus called 'adapter'. When triggered, LGN cells impinge upon layer IV and further relay the information to deeper layers via layers II-III. Using different adaptation protocols, neuronal plasticity can be investigated. Superficial neurons in area V1 are well acknowledged to exhibit attraction and repulsion by shifting their tuning peaks when challenged by a non-optimal stimulus called 'adapter'. Layers V-VI neurons in spite of partnering layers II-III neurons in cortical computation have not been explored simultaneously toward adaptation. We believe that adaptation not only affects cells specific to a layer but modifies the entire column. In this study, through simultaneous multiunit recordings in anesthetized cats using a multichannel depth electrode, we show for the first time how layers V-VI neurons (1000-1200 µm) along with layers II-III neurons (300-500 µm) exhibit plasticity in response to adaptation. Our results demonstrate that superficial and deeper layer neurons react synonymously toward adapter by exhibiting similar behavioral properties. The neurons displayed similar amplitude of shift and maintained equivalent sharpness of Gaussian tuning peaks before and the following adaptation. It appears that a similar mechanism, belonging to all layers, is responsible for the analog outcome of the neurons' experience with adapter.

Functional synchrony and stimulus selectivity of visual cortical units: Comparison between cats and mice.

In spite of the fact that the functional organization of primary visual cortices (V1) differs across species, the dynamic of orientation selectivity is highly structured within neuronal populations. In fact, neurons functionally connect each other in an organized Hebbian process, wherein their wiring and firing are intimately related. Moreover, neuronal ensembles have been suggested to be strongly implicated in sensory processing. Within these ensembles, neurons may be sharply or broadly tuned in relation to the stimulus. Therefore, it is important to determine the relationship between the response selectivity of neurons and their functional connectivity pattern across species. In the present investigation, we sought to compare the stimulus-evoked functional connectivity between the broadly tuned and the sharply tuned neurons in two species exhibiting different cortical organization for orientation selectivity: cats (columnar-organized) and mice (salt-and-pepper organization). In addition, we examined the distribution of connectivity weights within cell-assemblies in the visual cortex during visual adaptation. First, we report that the sharply tuned neurons exhibited higher synchrony index than the broadly tuned cells in the cat visual cortex. On the contrary, in mice, the broadly tuned cells displayed higher connectivity index. Second, a significant correlation was found between the connectivity strength and the difference of preferred orientations of neurons for both species. Finally, we observed a systematic adjustment of the connectivity weights within neuronal ensembles in mouse primary visual cortex similarly to the cat V1.

Interplay of orientation selectivity and the power of low- and high-gamma bands in the cat primary visual cortex.

Gamma oscillations are ubiquitous in brain and are believed to be inevitable for information processing in brain. Here, we report that distinct bands (low, 30-40Hz and high gamma, 60-80Hz) of stimulus-triggered gamma oscillations are systematically linked to the orientation selectivity index (OSI) of neurons in the cat primary visual cortex. The gamma-power is high for the highly selective neurons in the low-gamma band, whereas it is high for the broadly selective neurons in the high-gamma band. We suggest that the low-gamma band is principally implicated in feed-forward excitatory flow, whereas the high-gamma band governs the flow of this excitation.

High noise correlation between the functionally connected neurons in emergent V1 microcircuits.

Neural correlations (noise correlations and cross-correlograms) are widely studied to infer functional connectivity between neurons. High noise correlations between neurons have been reported to increase the encoding accuracy of a neuronal population; however, low noise correlations have also been documented to play a critical role in cortical microcircuits. Therefore, the role of noise correlations in neural encoding is highly debated. To this aim, through multi-electrodes, we recorded neuronal ensembles in the primary visual cortex of anaesthetized cats. By computing cross-correlograms, we divulged the functional network (microcircuit) between neurons within an ensemble in relation to a specific orientation. We show that functionally connected neurons systematically exhibit higher noise correlations than functionally unconnected neurons in a microcircuit that is activated in response to a particular orientation. Furthermore, the mean strength of noise correlations for the connected neurons increases steeply than the unconnected neurons as a function of the resolution window used to calculate noise correlations. We suggest that neurons that display high noise correlations in emergent microcircuits feature functional connections which are inevitable for information encoding in the primary visual cortex.

Network-selectivity and stimulus-discrimination in the primary visual cortex: cell-assembly dynamics.

Visual neurons coordinate their responses in relation to the stimulus; however, the complex interplay between a stimulus and the functional dynamics of an assembly still eludes neuroscientists. To this aim, we recorded cell assemblies from multi-electrodes in the primary visual cortex of anaesthetized cats in response to randomly presented sine-wave drifting gratings whose orientation tilted in 22.5° steps. Cross-correlograms revealed the functional connections at all the tested orientations. We show that a cell-assembly discriminates between orientations by recruiting a 'salient' functional network at every presented orientation, wherein the connections and their strengths (peak-probabilities in the cross-correlogram) change from one orientation to another. Within these assemblies, closely tuned neurons exhibited increased connectivity and connection-strengths compared with differently tuned neurons. Minimal connectivity between untuned neurons suggests the significance of neuronal selectivity in assemblies. This study reflects upon the dynamics of functional connectivity, and brings to the fore the importance of a 'signature' functional network in an assembly that is strictly related to a specific stimulus. It appears that an assembly is the major 'functional unit' of information processing in cortical circuits, rather than the individual neurons.

Summation of connectivity strengths in the visual cortex reveals stability of neuronal microcircuits after plasticity.

BACKGROUND: Within sensory systems, neurons are continuously affected by environmental stimulation. Recently, we showed that, on cell-pair basis, visual adaptation modulates the connectivity strength between similarly tuned neurons to orientation and we suggested that, on a larger scale, the connectivity strength between neurons forming sub-networks could be maintained after adaptation-induced-plasticity. In the present paper, based on the summation of the connectivity strengths, we sought to examine how, within cell-assemblies, functional connectivity is regulated during an exposure-based adaptation. RESULTS: Using intrinsic optical imaging combined with electrophysiological recordings following the reconfiguration of the maps of the primary visual cortex by long stimulus exposure, we found that within functionally connected cells, the summed connectivity strengths remain almost equal although connections among individual pairs are modified. Neuronal selectivity appears to be strongly associated with neuronal connectivity in a "homeodynamic" manner which maintains the stability of cortical functional relationships after experience-dependent plasticity. CONCLUSIONS: Our results support the "homeostatic plasticity concept" giving new perspectives on how the summation in visual cortex leads to the stability within labile neuronal ensembles, depending on the newly acquired properties by neurons.

Electrophysiological and firing properties of neurons: Categorizing soloists and choristers in primary visual cortex.

Visual processing in the cortex involves various aspects of neuronal properties such as morphological, electrophysiological and molecular. In particular, the neural firing pattern is an important indicator of dynamic circuitry within a neuronal population. Indeed, in microcircuits, neurons act as soloists or choristers wherein the characteristical activity of a 'soloist' differs from the firing pattern of a 'chorister'. Both cell types correlate their respective firing rate with the global populational activity in a unique way. In the present study, we sought to examine the relationship between the spike shape (thin spike neurons and broad spike neurons) of cortical neurons recorded from V1, their firing levels and their propensity to act as soloists or choristers. We found that thin spike neurons, which exhibited higher levels of firing, generally correlate their activity with the neuronal population (choristers). On the other hand, broad spike neurons showed lower levels of firing and demonstrated weak correlations with the assembly (soloists). A major consequence of the present study is: estimating the correlation of neural spike trains with their neighboring population is a predictive indicator of spike waveforms and firing level. Indeed, we found a continuum distribution of coupling strength ranging from weak correlation-strength (attributed to low-firing neurons) to high correlation-strength (attributed to high-firing neurons). The tendency to exhibit high- or low-firing is conducive to the spike shape of neurons. Our results offer new insights into visual processing by showing how high-firing rate neurons (mostly thin spike neurons) could modulate the neuronal responses within cell-assemblies.

Stimulus-dependent augmented gamma oscillatory activity between the functionally connected cortical neurons in the primary visual cortex.

Neuronal assemblies typically synchronise within the gamma oscillatory band (30-80 Hz) and are fundamental to information processing. Despite numerous investigations, the exact mechanisms and origins of gamma oscillations are yet to be known. Here, through multiunit recordings in the primary visual cortex of cats, we show that the strength of gamma power (20-40 and 60-80 Hz) is significantly stronger between the functionally connected units than between the unconnected units within an assembly. Furthermore, there is increased frequency coherence in the gamma band between the connected units than between the unconnected units. Finally, the higher gamma rhythms (60-80 Hz) are mostly linked to the fast-spiking neurons. These results led us to postulate that gamma oscillations are intrinsically generated between the connected units within cell assemblies (microcircuits) in relation to the stimulus within an emergent '50-ms temporal window of opportunity'.

Reprogramming of orientation columns in visual cortex: a domino effect.

Cortical organization rests upon the fundamental principle that neurons sharing similar properties are co-located. In the visual cortex, neurons are organized into orientation columns. In a column, most neurons respond optimally to the same axis of an oriented edge, that is, the preferred orientation. This orientation selectivity is believed to be absolute in adulthood. However, in a fully mature brain, it has been established that neurons change their selectivity following sensory experience or visual adaptation. Here, we show that after applying an adapter away from the tested cells, neurons whose receptive fields were located remotely from the adapted site also exhibit a novel selectivity in spite of the fact that they were not adapted. These results indicate a robust reconfiguration and remapping of the orientation domains with respect to each other thus removing the possibility of an orientation hole in the new hypercolumn. These data suggest that orientation columns transcend anatomy, and are almost strictly functionally dynamic.

Comparative analysis of orientation maps in areas 17 and 18 of the cat primary visual cortex following adaptation.

Object orientations in the visual field are columned into specific orientation domains in the primary visual cortex [area 17 (A17) and area 18 (A18)] of cats. At the single-cell level, adapting A17 neurons to a non-preferred orientation (adaptor) shifts their preferred orientation either towards the adaptor (attractive shift) or away from it (repulsive shift). As A17 and A18 are reciprocally connected, we sought to determine how changes in preferred orientations in A18 neurons are correlated with changes recorded in A17 anesthetised cats. To this end, we simultaneously traced populations of neurons in A17 and A18, using intrinsic optical imaging, before and after long (12 min) and short (3 min) adaptations. The comparison of A17 and A18 maps pre-adaptation and post-adaptation showed that variance in shift amplitudes is greater in A18 than A17 for short adaptations. Our results indicate a rapid reconfiguration of functional maps that may spread to many cortical areas.

Adaptation shifts preferred orientation of tuning curve in the mouse visual cortex.

In frontalized mammals it has been demonstrated that adaptation produces shift of the peak of the orientation tuning curve of neuron following frequent or lengthier presentation of a non-preferred stimulus. Depending on the duration of adaptation the shift is attractive (toward the adapter) or repulsive (away from the adapter). Mouse exhibits a salt-and-pepper cortical organization of orientation maps, hence this species may respond differently to adaptation. To examine this question, we determined the effect of twelve minutes of adaptation to one particular orientation on neuronal orientation tuning curves in V1 of anesthetized mice. Multi-unit activity of neurons in V1 was recorded in a conventional fashion. Cells were stimulated with sine-wave drifting gratings whose orientation tilted in steps. Results revealed that similarly to cats and monkeys, majority of cells shifted their optimal orientation in the direction of the adapter while a small proportion exhibited a repulsive shift. Moreover, initially untuned cells showing poor tuning curves reacted to adaptation by displaying sharp orientation selectivity. It seems that modification of the cellular property following adaptation is a general phenomenon observed in all mammals in spite of the different organization pattern of the visual cortex. This study is of pertinence to comprehend the mechanistic pathways of brain plasticity.

Fluoxetine and serotonin facilitate attractive-adaptation-induced orientation plasticity in adult cat visual cortex.

Neurons in V1 display orientation selectivity by responding optimally to a preferred orientation edge when it is presented within their receptive fields. Orientation plasticity in striate cortex occurs either by ocular deprivation or by imposition of a non-preferred stimulus for several minutes. Adaptation of neurons to a non-optimal orientation induces shifts of tuning curves towards the adapting orientation (attractive shift) or away from it (repulsive shift). Here, we investigated the effects of the neurotransmitter serotonin and antidepressant fluoxetine (a selective serotonin reuptake inhibitor) on the modulation of adaptation-induced orientation plasticity. We show that serotonin and fluoxetine promote mostly attractive shifts. Attractive shifts augmented in magnitude towards adapter, whereas repulsive neurons reversed their behavior in the direction of the forced orientation. Furthermore, neurons which retained their original preferred orientation expressed plasticity by shifting their tuning curves after drug administration mostly towards adapter. Our data suggest a pre-eminent role of fluoxetine by inducing and facilitating short-term plasticity in V1.