Value-guided remapping of sensory cortex by lateral orbitofrontal cortex.

Adaptive behaviour crucially depends on flexible decision-making, which in mammals relies on the frontal cortex, specifically the orbitofrontal cortex (OFC)1-9. How OFC encodes decision variables and instructs sensory areas to guide adaptive behaviour are key open questions. Here we developed a reversal learning task for head-fixed mice, monitored the activity of neurons of the lateral OFC using two-photon calcium imaging and investigated how OFC dynamically interacts with primary somatosensory cortex (S1). Mice learned to discriminate 'go' from 'no-go' tactile stimuli10,11 and adapt their behaviour upon reversal of stimulus-reward contingency ('rule switch'). Imaging individual neurons longitudinally across all behavioural phases revealed a distinct engagement of S1 and lateral OFC, with S1 neural activity reflecting initial task learning, whereas lateral OFC neurons responded saliently and transiently to the rule switch. We identified direct long-range projections from lateral OFC to S1 that can feed this activity back to S1 as value prediction error. This top-down signal updated sensory representations in S1 by functionally remapping responses in a subpopulation of neurons that was sensitive to reward history. Functional remapping crucially depended on top-down feedback as chemogenetic silencing of lateral OFC neurons disrupted reversal learning, as well as plasticity in S1. The dynamic interaction of lateral OFC with sensory cortex thus implements computations critical for value prediction that are history dependent and error based, providing plasticity essential for flexible decision-making.

Edible oil based optical clearing for optical coherence tomography angiography imaging.

In optical imaging, optical clearing agents are commonly used to enhance the structural details of a sample. The current study investigates how to use it to improve the data obtained by an optical coherence tomography angiography system. A natural edible oil with no chemical base has been used for optical clearing. In-vivo testing on mice and humans yielded excellent optical clearing. Using computational techniques, the improvement in angiography signal caused by the optical clearing agent is investigated qualitatively and quantitatively. Compared to the control group, applying the edible oil-based optical clearing agent demonstrated improved vessel percentage and refined vascular signal intensity along depth.

Climate uncertainty and vulnerability of urban flooding associated with regional risk using multi-criteria analysis in Mumbai, India.

The study made a comprehensive effort to examine climatic uncertainties at both yearly and monthly scales, along with mapping flood risks based on different land use categories. Recent studies have progressively been engrossed in demonstrating regional climate variations and associated flood probability to maintain the geo-ecological balance at micro to macro-regions. To carry out this investigation, various historical remote sensing record, reanalyzed and in-situ data sets were acquired with a high level of spatial precision using the Google Earth Engine (GEE) web-based remote sensing platform. Non-parametric techniques and multi-layer integration methods were then employed to illustrate the fluctuations in climate factors alongside creating maps indicating the susceptibility to floods. The study reveals an increased pattern in LST (Land Surface Temperature) (0.03 °C/year), albeit marginal declined in southern coastal regions (-0.15 °C/year) along with uneven rainfall patterns (1.42 mm/year). Moreover, long-term LULC change estimation divulges increased trends of urbanization (16.4 km2/year) together with vegetation growth (8.7 km2/year) from 2002 to 2022. Furthermore, this inquiry involves numerous environmental factors that influence the situation (elevation data, topographic wetness index, drainage density, proximity to water bodies, slope, and soil properties) as well as socio-economic attributes (population) to assess flood risk areas through the utilization of Analytical Hierarchy Process and overlay methods with assigned weights. The outcomes reveal nearly 55 percent of urban land is susceptible to flood in 2022, which were 45 and 37 percent in 2012 and 2002 separately. Additionally, 106 km2 of urban area is highly susceptible to inundation, whereas vegetation also occupies a significant proportion (52 km2). This thorough exploration offers a significant chance to formulate flood management and mitigation strategies tailored to specific regions during the era of climate change.

Bacteria populating freshly appeared supraglacial lake possess metals and antibiotic-resistant genes.

Antibiotic resistance (AR) has been extensively studied in natural habitats and clinical applications. AR is mainly reported with the use and misuse of antibiotics; however, little is known about its presence in antibiotic-free remote supraglacial lake environments. This study evaluated bacterial strains isolated from supraglacial lake debris and meltwater in Dook Pal Glacier, northern Pakistan, for antibiotic-resistant genes (ARGs) and metal-tolerant genes (MTGs) using conventional PCR. Several distinct ARGs were reported in the bacterial strains isolated from lake debris (92.5%) and meltwater (100%). In lake debris, 57.5% of isolates harbored the blaTEM gene, whereas 58.3% of isolates in meltwater possessed blaTEM and qnrA each. Among the ARGs, qnrA was dominant in debris isolates (19%), whereas in meltwater isolates, qnrA (15.2%) and blaTEM (15.2%) were dominant. ARGs were widely distributed among the bacterial isolates and different bacteria shared similar types of ARGs. Relatively greater number of ARGs were reported in Gram-negative bacterial strains. In addition, 92.5% of bacterial isolates from lake debris and 83.3% of isolates from meltwater harbored MTGs. Gene copA was dominant in meltwater isolates (50%), whereas czcA was greater in debris bacterial isolates (45%). Among the MTGs, czcA (18.75%) was dominant in debris strains, whereas copA (26.0%) was greater in meltwater isolates. This presents the co-occurrence and co-selection of MTGs and ARGs in a freshly appeared supraglacial lake. The same ARGs and MTGs were present in different bacteria, exhibiting horizontal gene transfer (HGT). Both positive and negative correlations were determined between ARGs and MTGs. The research provides insights into the existence of MTGs and ARGs in bacterial strains isolated from remote supraglacial lake environments, signifying the need for a more detailed study of bacteria harboring ARGs and MTGs in supraglacial lakes.

Temperature-dependent transformation of microbial community: A systematic approach to analyzing functional microbes and biogas production.

The stability and effectiveness of the anaerobic digestion (AD) system are significantly influenced by temperature. While majority research has focused on the composition of the microbial community in the AD process, the relationships between functional gene profile deduced from gene expression at different temperatures have received less attention. The current study investigates the AD process of potato peel waste and explores the association between biogas production and microbial gene expression at 15, 25, and 35 °C through metatranscriptomic analysis. The production of total biogas decreased with temperature at 15 °C (19.94 mL/g VS), however, it increased at 35 °C (269.50 mL/g VS). The relative abundance of Petrimonas, Clostridium, Aminobacterium, Methanobacterium, Methanothrix, and Methanosarcina were most dominant in the AD system at different temperatures. At the functional pathways level 3, α-diversity indices, including Evenness (Y = 5.85x + 8.85; R2 = 0.56), Simpson (Y = 2.20x + 2.09; R2 = 0.33), and Shannon index (Y = 1.11x + 4.64; R2 = 0.59), revealed a linear and negative correlation with biogas production. Based on KEGG level 3, several dominant functional pathways associated with Oxidative phosphorylation (ko00190) (25.09, 24.25, 24.04%), methane metabolism (ko00680) (30.58, 32.13, and 32.89%), and Carbon fixation pathways in prokaryotes (ko00720) (27.07, 26.47, and 26.29%), were identified at 15 °C, 25 °C and 35 °C. The regulation of biogas production by temperature possibly occurs through enhancement of central function pathways while decreasing the diversity of functional pathways. Therefore, the methanogenesis and associated processes received the majority of cellular resources and activities, thereby improving the effectiveness of substrate conversion to biogas. The findings of this study illustrated the crucial role of central function pathways in the effective functioning of these systems.

Evaluating the relative influence of climate and human activities on recent vegetation dynamics in West Bengal, India.

Assessing the relative importance of climate change and human activities is important in developing sustainable management policies for regional land use. In this study, multiple remote sensing datasets, i.e. CHIRPS (Climate Hazard Group InfraRed Precipitation with Station Data) precipitation, MODIS Land Surface Temperature (LST), Enhanced Vegetation Index (EVI), Potential Evapotranspiration (PET), Soil Moisture (SM), WorldPop, and nighttime light have been analyzed to investigate the effect that climate change (CC) and regional human activities (HA) have on vegetation dynamics in eastern India for the period 2000 to 2022. The relative influence of climate and anthropogenic factors is evaluated on the basis of non-parametric statistics i.e., Mann-Kendall and Sen's slope estimator. Significant spatial and elevation-dependent variations in precipitation and LST are evident. Areas at higher elevations exhibit increased mean annual temperatures (0.22 °C/year, p < 0.05) and reduced winter precipitation over the last two decades, while the northern and southwest parts of West Bengal witnessed increased mean annual precipitation (17.3 mm/year, p < 0.05) and a slight cooling trend. Temperature and precipitation trends are shown to collectively impact EVI distribution. While there is a negative spatial correlation between LST and EVI, the relationship between precipitation and EVI is positive and stronger (R2 = 0.83, p < 0.05). Associated hydroclimatic parameters are potent drivers of EVI, whereby PET in the southwestern regions leads to markedly lower SM. The relative importance of CC and HA on EVI also varies spatially. Near the major conurbation of Kolkata, and confirmed by nighttime light and population density data, changes in vegetation cover are very clearly dominated by HA (87%). In contrast, CC emerges as the dominant driver of EVI (70-85%) in the higher elevation northern regions of the state but also in the southeast. Our findings inform policy regarding the future sustainability of vulnerable socio-hydroclimatic systems across the entire state.

NaYF4:Ho3+/Yb3+@NaGdF4 core@shell upconversion nanoparticles for contrast enhancement in bimodal in-vitro OCT imaging.

Contrast enhancement is explored in optical coherence tomography images using core NaYF4:Ho3+/Yb3+ and core@shell NaYF4:Ho3+/Yb3+@NaGdF4 nanoparticles. Under 980 nm excitation, core@shell nanoparticles exhibited 2.8 and 3.3 times enhancement at 541 nm and 646 nm emission wavelengths of Ho3+ ions compared to core nanoparticles. Photo-thermal conversion efficiencies were 32% and 20% for core and core@shell nanoparticles. In swept-source optical coherence tomography (SSOCT), core@shell nanoparticles have shown superior contrast, while in photo-thermal optical coherence tomography (PTOCT) core nanoparticles have excelled due to their higher photo-thermal conversion efficiency. The enhancement in contrast to noise ratio obtained is 58 dB. Comparative assessments of scattering coefficients and contrast-to-noise ratios were conducted, providing insights into nanoparticle performance for contrast enhancement in optical coherence tomography.

Search for Ultralight Dark Matter with Spectroscopy of Radio-Frequency Atomic Transitions.

The effects of scalar and pseudoscalar ultralight bosonic dark matter (UBDM) were searched for by comparing the frequency of a quartz oscillator to that of a hyperfine-structure transition in ^{87}Rb, and an electronic transition in ^{164}Dy. We constrain linear interactions between a scalar UBDM field and standard-model (SM) fields for an underlying UBDM particle mass in the range 1×10^{-17}-8.3×10^{-13} eV and quadratic interactions between a pseudoscalar UBDM field and SM fields in the range 5×10^{-18}-4.1×10^{-13} eV. Within regions of the respective ranges, our constraints on linear interactions significantly improve on results from previous, direct searches for oscillations in atomic parameters, while constraints on quadratic interactions surpass limits imposed by such direct searches as well as by astrophysical observations.

Control of Andreev Bound States Using Superconducting Phase Texture.

Andreev bound states with opposite phase-inversion asymmetries are observed in local tunneling spectra at the two ends of a superconductor-semiconductor-superconductor planar Josephson junction in the presence of a perpendicular magnetic field, while the nonlocal spectra remain phase symmetric. Spectral signatures agree with a theoretical model, yielding a physical picture in which phase textures in superconducting leads localize and control the position of Andreev bound states in the junction, demonstrating a simple means of controlling the position and size of Andreev states within a planar junction.

Phase Asymmetry of Andreev Spectra from Cooper-Pair Momentum.

In analogy to conventional semiconductor diodes, the Josephson diode exhibits superconducting properties that are asymmetric in applied bias. The effect has been investigated in a number of systems recently, and requires a combination of broken time-reversal and inversion symmetries. We demonstrate a dual of the usual Josephson diode effect, a nonreciprocal response of Andreev bound states to a superconducting phase difference across the normal region of a superconductor-normal-superconductor Josephson junction, fabricated using an epitaxial InAs/Al heterostructure. Phase asymmetry of the subgap Andreev spectrum is absent in the absence of in-plane magnetic field and reaches a maximum at 0.15 T applied in the plane of the junction transverse to the current direction. We interpret the phase diode effect in this system as resulting from finite-momentum Cooper pairing due to orbital coupling to the in-plane magnetic field. At higher magnetic fields, we observe a sign reversal of the diode effect that appears together with a reopening of the spectral gap. Within our model, the sign reversal of the diode effect at higher fields is correlated with a topological phase transition that requires Zeeman and spin-orbit interactions in addition to orbital coupling.

Exploring the Effect of Size Variability on Efficiency of Upconversion Nanoparticles as Optical Contrast Agents.

The current works explores the optical contrast property and nanaotheranostic capabilities of the rare earth based Upconversion nanoparticles. Optical coherence tomography (OCT) has been used to explore the particles ability to increase contrast and improve signal intensity. Photo thermal OCT, a function extension of OCT has been used to gauge the photo thermal potential of the nanoparticles. The nanoparticles successfully improved contrast and information from the deeper layers of the sample. The particles also showed excellent capability for use as photo thermal agents.

Region-Specific KCC2 Rescue by rhIGF-1 and Oxytocin in a Mouse Model of Rett Syndrome.

Rett syndrome (RTT) is characterized by dysfunction in neuronal excitation/inhibition (E/I) balance, potentially impacting seizure susceptibility via deficits in K+/Cl- cotransporter 2 (KCC2) function. Mice lacking the Methyl-CpG binding protein 2 (MeCP2) recapitulate many symptoms of RTT, and recombinant human insulin-like growth factor-1 (rhIGF-1) restores KCC2 expression and E/I balance in MeCP2 KO mice. However, clinical trial outcomes of rhIGF-1 in RTT have been variable, and increasing its therapeutic efficacy is highly desirable. To this end, the neuropeptide oxytocin (OXT) is promising, as it also critically modulates KCC2 function during early postnatal development. We measured basal KCC2 expression levels in MeCP2 KO mice and identified 3 key frontal brain regions showing KCC2 alterations in young adult mice, but not in postnatal P10 animals. We hypothesized that deficits in an IGF-1/OXT signaling crosstalk modulating KCC2 may occur in RTT during postnatal development. Consistently, we detected alterations of IGF-1 receptor and OXT receptor levels in those brain areas. rhIGF-1 and OXT treatments in KO mice rescued KCC2 expression in a region-specific and complementary manner. These results suggest that region-selective combinatorial pharmacotherapeutic strategies could be most effective at normalizing E/I balance in key brain regions subtending the RTT pathophysiology.

Quantifying climate variability and regional anthropogenic influence on vegetation dynamics in northwest India.

To explore the spatio-temporal dynamics and mechanisms underlying vegetation cover in Haryana State, India, and implications thereof, we obtained MODIS EVI imagery together with CHIRPS rainfall and MODIS LST at annual, seasonal and monthly scales for the period spanning 2000 to 2022. Additionally, MODIS Potential Evapotranspiration (PET), Ground Water Storage (GWS), Soil Moisture (SM) and nighttime light datasets were compiled to explore their spatial relationships with vegetation and other selected environmental parameters. Non-parametric statistics were applied to estimate the magnitude of trends, along with correlation and residual trend analysis to quantify the relative influence of Climate Change (CC) and Human Activities (HA) on vegetation dynamics using Google Earth Engine algorithms. The study reveals regional contrasts in trends that are evidently related to elevation. An annual increasing trend in rainfall (21.3 mm/decade, p < 0.05), together with augmented vegetation cover and slightly cooler (-0.07 °C/decade) LST is revealed in the high-elevation areas. Meanwhile, LST in the plain regions exhibit a warming trend (0.02 °C/decade) and decreased in vegetation and rainfall, accompanied by substantial reductions in GWS and SM related to increased PET. Linear regression demonstrates a strongly significant relationship between rainfall and EVI (R2 = 0.92), although a negative relationship is apparent between LST and vegetation (R2 = -0.83). Additionally, increased LST in the low-elevation parts of the study area impacted PET (R2 = 0.87), which triggered EVI loss (R2 = 0.93). Moreover, increased HA resulted in losses of 25.5 mm GSW and 1.5 mm SM annually. The relative contributions of CC and HA are shown to vary with elevation. At higher elevations, CC and HA contribute respectively 85% and 15% to the increase in EVI. However, at lower elevations, reduced EVI is largely (79%) due to human activities. This needs to be considered in managing the future of vulnerable socio-ecological systems in the state of Haryana.

High prevalence of antibiotic-resistant and metal-tolerant cultivable bacteria in remote glacier environment.

Studies of antibiotic-resistant bacteria (ARB) have mainly originated from anthropic-influenced environments, with limited information from pristine environments. Remote cold environments are major reservoirs of ARB and have been determined in polar regions; however, their abundance in non-polar cold habitats is underexplored. This study evaluated antibiotics and metals resistance profiles, prevalence of antibiotic resistance genes (ARGs) and metals tolerance genes (MTGs) in 38 ARB isolated from the glacier debris and meltwater from Baishui Glacier No 1, China. Molecular identification displayed Proteobacteria (39.3%) predominant in debris, while meltwater was dominated by Actinobacteria (30%) and Proteobacteria (30%). Bacterial isolates exhibited multiple antibiotic resistance index values > 0.2. Gram-negative bacteria displayed higher resistance to antibiotics and metals than Gram-positive. PCR amplification exhibited distinct ARGs in bacteria dominated by ß-lactam genes blaCTX-M (21.1-71.1%), blaACC (21.1-60.5%), tetracycline-resistant gene tetA (21.1-60.5%), and sulfonamide-resistant gene sulI (18.4-52.6%). Moreover, different MTGs were reported in bacterial isolates, including mercury-resistant merA (21.1-63.2%), copper-resistant copB (18.4-57.9%), chromium-resistant chrA (15.8-44.7%) and arsenic-resistant arsB (10.5-44.7%). This highlights the co-selection and co-occurrence of MTGs and ARGs in remote glacier environments. Different bacteria shared same ARGs, signifying horizontal gene transfer between species. Strong positive correlation among ARGs and MTGs was reported. Metals tolerance range exhibited that Gram-negative and Gram-positive bacteria clustered distinctly. Gram-negative bacteria were significantly tolerant to metals. Amino acid sequences of blaACC,blaCTX-M,blaSHV,blaampC,qnrA, sulI, tetA and blaTEM revealed variations. This study presents promising ARB, harboring ARGs with variations in amino acid sequences, highlighting the need to assess the transcriptome study of glacier bacteria conferring ARGs and MTGs.

Improved Bounds on Ultralight Scalar Dark Matter in the Radio-Frequency Range.

We present a search for fundamental constant oscillations in the range 20 kHz-100 MHz that may arise within models for ultralight dark matter (UDM). Using two independent optical-spectroscopy apparatuses, we achieve up to ×1000 greater sensitivity in the search relative to previous work [D. Antypas et al., Phys. Rev. Lett. 123, 141102 (2019).PRLTAO0031-900710.1103/PhysRevLett.123.141102]. We report no observation of UDM and thus constrain respective couplings to electrons and photons within the investigated UDM particle mass range 8×10^{-11}-4×10^{-7} eV. The constraints significantly exceed previously set bounds from atomic spectroscopy and, as we show, may surpass in future experiments those provided by equivalence-principle (EP) experiments in a specific case regarding the combination of UDM couplings probed by the EP experiments.

Towards a better diagnosis and treatment of Rett syndrome: a model synaptic disorder.

With the recent 50th anniversary of the first publication on Rett syndrome, and the almost 20 years since the first report on the link between Rett syndrome and MECP2 mutations, it is important to reflect on the tremendous advances in our understanding and their implications for the diagnosis and treatment of this neurodevelopmental disorder. Rett syndrome features an interesting challenge for biologists and clinicians, as the disorder lies at the intersection of molecular mechanisms of epigenetic regulation and neurophysiological alterations in synapses and circuits that together contribute to severe pathophysiological endophenotypes. Genetic, clinical, and neurobiological evidences support the notion that Rett syndrome is primarily a synaptic disorder, and a disease model for both intellectual disability and autism spectrum disorder. This review examines major developments in both recent neurobiological and preclinical findings of Rett syndrome, and to what extent they are beginning to impact our understanding and management of the disorder. It also discusses potential applications of knowledge on synaptic plasticity abnormalities in Rett syndrome to its diagnosis and treatment.

Restoring Superconductivity in the Quantum Metal Phase of NbSe2 Using Dissipative Coupling.

Localization arguments forbid the appearance of a metallic ground state in two dimensions. Yet, a large variety of disordered superconductors are known to manifest an anomalous metal phase in the zero temperature limit. While previous observations were confined to noncrystalline "dirty" superconductors, the recent observation of the so-called Bose metal phase in crystalline thin flakes of NbSe2 has sparked off intense debate. While the exact nature of this phase remains unknown, it is thought that quantum fluctuations play a decisive role in Bose metal physics. In this work, we study the response of the anomalous metal phase in thin flakes of NbSe2 to dissipative coupling. We evince a dramatic quenching of the Bose metal phase when dissipative coupling is strong, fully restoring a zero resistance superconducting state in the entire region of the magnetic field (H)-temperature (T) phase diagram where the Bose metal phase is otherwise observed. The suppression of the Bose metal phase by dissipative coupling is possible only in a quantum system where dissipation can directly affect system thermodynamics. Our observation of a dissipative phase transition in two-dimensional NbSe2 firmly establishes the quantum nature of the anomalous metal phase in this class of "clean" superconductors.

Nitrogenase-mimic iron-containing chalcogels for photochemical reduction of dinitrogen to ammonia.

A nitrogenase-inspired biomimetic chalcogel system comprising double-cubane [Mo2Fe6S8(SPh)3] and single-cubane (Fe4S4) biomimetic clusters demonstrates photocatalytic N2 fixation and conversion to NH3 in ambient temperature and pressure conditions. Replacing the Fe4S4 clusters in this system with other inert ions such as Sb(3+), Sn(4+), Zn(2+) also gave chalcogels that were photocatalytically active. Finally, molybdenum-free chalcogels containing only Fe4S4 clusters are also capable of accomplishing the N2 fixation reaction with even higher efficiency than their Mo2Fe6S8(SPh)3-containing counterparts. Our results suggest that redox-active iron-sulfide-containing materials can activate the N2 molecule upon visible light excitation, which can be reduced all of the way to NH3 using protons and sacrificial electrons in aqueous solution. Evidently, whereas the Mo2Fe6S8(SPh)3 is capable of N2 fixation, Mo itself is not necessary to carry out this process. The initial binding of N2 with chalcogels under illumination was observed with in situ diffuse-reflectance Fourier transform infrared spectroscopy (DRIFTS). (15)N2 isotope experiments confirm that the generated NH3 derives from N2 Density functional theory (DFT) electronic structure calculations suggest that the N2 binding is thermodynamically favorable only with the highly reduced active clusters. The results reported herein contribute to ongoing efforts of mimicking nitrogenase in fixing nitrogen and point to a promising path in developing catalysts for the reduction of N2 under ambient conditions.

Jointly reduced inhibition and excitation underlies circuit-wide changes in cortical processing in Rett syndrome.

Rett syndrome (RTT) arises from loss-of-function mutations in methyl-CpG binding protein 2 gene (Mecp2), but fundamental aspects of its physiological mechanisms are unresolved. Here, by whole-cell recording of synaptic responses in MeCP2 mutant mice in vivo, we show that visually driven excitatory and inhibitory conductances are both reduced in cortical pyramidal neurons. The excitation-to-inhibition (E/I) ratio is increased in amplitude and prolonged in time course. These changes predict circuit-wide reductions in response reliability and selectivity of pyramidal neurons to visual stimuli, as confirmed by two-photon imaging. Targeted recordings reveal that parvalbumin-expressing (PV+) interneurons in mutant mice have reduced responses. PV-specific MeCP2 deletion alone recapitulates effects of global MeCP2 deletion on cortical circuits, including reduced pyramidal neuron responses and reduced response reliability and selectivity. Furthermore, MeCP2 mutant mice show reduced expression of the cation-chloride cotransporter KCC2 (K+/Cl- exporter) and a reduced KCC2/NKCC1 (Na+/K+/Cl- importer) ratio. Perforated patch recordings demonstrate that the reversal potential for GABA is more depolarized in mutant mice, but is restored by application of the NKCC1 inhibitor bumetanide. Treatment with recombinant human insulin-like growth factor-1 restores responses of PV+ and pyramidal neurons and increases KCC2 expression to normalize the KCC2/NKCC1 ratio. Thus, loss of MeCP2 in the brain alters both excitation and inhibition in brain circuits via multiple mechanisms. Loss of MeCP2 from a specific interneuron subtype contributes crucially to the cell-specific and circuit-wide deficits of RTT. The joint restoration of inhibition and excitation in cortical circuits is pivotal for functionally correcting the disorder.