BackgroundAttention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder, often—but not always—characterized by inattention, hyperactivity/impulsivity, and deficits in executive functions (EFs); some individuals may also exhibit sensorimotor dysfunction. While SMN dysfunction has been implicated in ADHD, the patterns of SMN functional connectivity (FC) and their relationships with clinical symptoms and EFs remain inconsistent, partly due to methodological heterogeneity.MethodsThe study included 62 medication-naïve patients with ADHD (aged 6–15 years) and 46 healthy controls matched for age, sex, and IQ. Clinical symptoms and EFs were assessed using CPRS, IVA-CPT, and Stroop tests. Resting-state fMRI data were acquired, and ROIs within SMN, SN, DMN, and FPN were selected from the Dosenbach atlas. FC was analyzed using Network-Based Statistics (NBS). Partial correlations explored FC–behavior relationships in the ADHD group, controlling for age, sex, and IQ.ResultsThe ADHD group showed significantly higher CPRS hyperactivity/impulsivity scores and poorer IVA-CPT and Stroop performance. Compared to controls, ADHD showed increased FC within SMN (right posterior insula to left precentral gyrus/parietal lobe), between SMN–DMN (precentral gyrus, dorsal frontal cortex, temporal lobe, angular gyrus, posterior cingulate cortex, and precuneus), and SMN–SN (middle insula, superior parietal lobule, superior temporal gyrus, basal ganglia, and fusiform gyrus). Enhanced intra-SMN FC was negatively correlated with impulsivity/hyperactivity and hyperactivity index scores. Enhanced SMN–DMN FC was negatively correlated with hyperactivity symptoms and positively correlated with control quotients in IVA-CPT. Enhanced SMN–SN FC was negatively correlated with Stroop correct responses and positively correlated with omission errors.ConclusionsIn this medication-naïve pediatric sample, distinct SMN connectivity patterns differentially related to ADHD symptoms and executive function. However, given the cross-sectional design and modest sample size, these associations cannot establish causality; they require replication in longitudinal studies and larger cohorts to clarify whether they reflect developmental variation, neurobiological subtypes, or epiphenomena.
Autism-Like Traits in Mice Improved After Single Rapamycin Dose
The results of a preclinical study led by UCLA Health researchers suggest that inflammation during pregnancy in mice can trigger autism-like brain and behavior changes in offspring, and that the effects may be rapidly but temporarily reversible in adulthood with a short-term dose of the immunosuppressive drug rapamycin.
The study showed that a single dose of rapamycin rapidly improved changes including brain overactivity, seizure risk, sensory sensitivity, repetitive behaviors, and abnormal brain functional network organization. Rapamycin itself is not considered a viable candidate for human therapy, as the effects of the drug were found to be temporary, with repeated dosing losing efficacy, and repeated use also having the potential for toxicity. However, the researchers said the study findings indicate that some autism-related brain changes may still be treatable in adulthood, and point to possible therapeutic approaches that target the underlying pathway rather than only symptoms.
“These results reframe how autism-associated symptoms might be treated,” said Janel Le Belle, PhD, an associate professor in the UCLA Department of Neurosurgery. “If the adult brain remains capable of functional normalization, then some features of autism may be successfully addressed without needing to correct underlying structural differences.” Le Belle is first author of the researchers’ published paper in Nature Communications, titled “Acute rapamycin treatment reveals distinct mechanisms of dysfunction in a maternal inflammation mouse model.”
Neurodevelopmental disorders result from the disruption of brain development in utero or in early life, with genetic, environmental, epigenetic, and immunological factors all potential contributors to complex pathogenesis, the authors wrote. Previous studies have shown that offspring of mothers who experience inflammation while pregnant have a higher likelihood of developing autism-associated traits such as repetitive behaviors and difficulty with social interaction, as well as brain overgrowth and disrupted sensory processing that continue into adulthood. “Maternal inflammatory response (MIR) during early mouse gestation induces a cascade of physiological and behavioral changes associated with autism spectrum disorder (ASD),” they stated.
Rapamycin has been shown in previous mouse autism studies to improve symptoms by suppressing an overactive mTOR pathway that signals cell growth and proliferation. What has been less clear is whether these brain changes could still be modifiable in adulthood, and whether rapamycin’s benefits came from long-term structural repair or faster functional changes. “We wanted to understand the mechanisms that underlie the effects of adult mTOR inhibition, where treatment isn’t aimed at preventing or reversing structural brain abnormalities,” the team stated.
For their newly reported study the scientists exposed pregnant mice to a mild inflammatory trigger early in gestation at a dose that was too low to make the mothers significantly ill. The resulting offspring went on to develop chronic brain and body-wide inflammation, mild brain overgrowth, overactive cell-signaling in the mTOR pathway, disorganized brain functional network connectivity and behaviors associated with autism.
When researchers gave adult offspring a single dose of rapamycin they found rapid improvement across nearly every measure. Neurons that had been firing abnormally calmed down, susceptibility to seizures dropped, brain regions that had been miscommunicating reorganized into more typical patterns and repetitive behaviors and sensory over-responsivity eased. These changes occurred within roughly two hours of drug administration, which was too rapid to be explained by the kind of physical rewiring of brain synapses that typically takes longer.
“The level of functional normalization achieved over this short time suggests new mechanisms by which possible treatments may act,” said the study’s senior author Harley Kornblum, MD, PhD, director of the UCLA Intellectual and Developmental Disabilities Research Center in the Semel Institute for Neuroscience and Human Behavior. “It suggests the adult brain may be more adaptable than we assumed, even when the underlying structural changes from early development are still there. This points us toward the brain’s functional circuitry, not just its physical structure, as a target for future treatment approaches.”
To understand the mechanisms of rapid rapamycin effects, researchers examined gene activity in brain cells before and after treatment. They found that rapamycin reversed abnormal expression of genes tied to autism, epilepsy and ion channel function, particularly in excitatory neurons, suggesting the drug works by quickly rebalancing brain cell excitability rather than by repairing structural brain differences.
The findings suggest that mTOR pathway activity, brain network organization and neuronal excitation levels as potential targets for future therapies aimed at specific autism symptoms such as sensory over-responsivity, a common but difficult-to-treat symptom of autism. “Our findings demonstrate that mTOR dysregulation drives dysfunctional brain development in MIR offspring but the adult brain remains amenable to rapid functional normalization, rescuing core and comorbid ASD associated brain and behavior phenotypes,” the authors stated.
Co-senior author and professor in the UCLA Department of Neurosurgery, Neil Harris, PhD, cautioned that the results showed the treatment effects to be temporary and that daily dosing produced tolerance over several weeks. This, along with rapamycin’s high potential for toxicity and the fact that these studies were performed in mice, makes it unsuitable for broad use in humans. “This points toward new therapeutic targets like sensory circuit neuromodulation or balancing neuronal inhibition and excitation, rather than toward rapamycin itself as a treatment,” Harris said. As the authors further commented in their paper, “Restoring excitatory/inhibitory imbalance and sensory functional network modularity may be important targets for therapeutically addressing multiple ASD phenotypes.”
The post Autism-Like Traits in Mice Improved After Single Rapamycin Dose appeared first on GEN – Genetic Engineering and Biotechnology News.
Curvature-guided anisotropic noise injection for robust multimodal data processing in neuroscience and perception science
IntroductionLarge-batch training is widely used to scale multimodal neural networks that integrate heterogeneous inputs such as visual, textual, and physiological signals. However, increasing the batch size suppresses the stochastic fluctuations of mini-batch sampling, which can trap multimodal models in sharp, modality-dominant minima and produce a persistent generalization gap.MethodsTo address this problem, we propose Geometric Anisotropic Noise Injection (GANI), a curvature-aware optimization framework inspired by information geometry and multisensory integration. GANI decouples deterministic large-batch descent from stochastic geometric exploration. It approximates local curvature through an exponential moving average of first-order gradients and injects structured anisotropic noise during parameter updates, thereby restoring the geometry-aware exploration dynamics of small-batch stochastic gradient descent with linear computational complexity.ResultsTheoretical analysis shows that curvature-aligned stochasticity can accelerate escape from sharp modality-specific basins and guide parameters toward flatter regions. Experimental evaluations across multimodal benchmark settings and stress tests demonstrate that GANI reduces the generalization gap, improves convergence stability, bounds the maximum Hessian eigenvalue, and maintains stronger performance under visual noise and missing textual information than standard large-batch SGD and common adaptive optimizers.DiscussionBy linking optimization geometry with multimodal representation dynamics, GANI provides an efficient and interpretable mechanism for robust heterogeneous data processing. The framework offers potential value for uncertainty-aware multisensory integration, brain-inspired perception science, and scalable multimodal learning under noisy or incomplete sensory conditions.
Interpretable abstractions of artificial neural networks predict behavior and neural activity during human information gathering
Nature Neuroscience, Published online: 26 June 2026; doi:10.1038/s41593-026-02342-9
D’Ambrogio et al. combine deep learning and symbolic regression to report an interpretable equation of how humans value information. The equation predicts choices and neural activity in anterior insula, cingulate cortex and midbrain nuclei.
Gene Therapy Restores Brain Function and Behavior in Fragile X Syndrome
A University of California, Riverside-led research team has developed a gene therapy that restored production of a missing brain protein, corrected abnormalities in brain circuitry, and improved behavior in a mouse model of Fragile X syndrome (FXS). The study, published in the journal Molecular Therapy Nucleic Acids, tested an adeno-associated virus (AAV)-based therapy carrying a normal human version of the FMR1 gene to produce the Fragile X messenger ribonucleoprotein (FMRP) and found that early treatment normalized several measures of brain activity while improving social behavior, exploratory behavior, and cognitive flexibility.
“In a typical brain, FMRP acts like a brake or a volume control,” said senior author Iryna Ethell, PhD, a professor of biomedical sciences at the UC Riverside School of Medicine. “Without it, neural circuits become overactive and less efficient, which contributes to many of the developmental and behavioral challenges associated with FXS.”
FXS is the most common single-gene cause of autism spectrum disorder. According to the researchers, the disorder typically manifests from expansion of CGG repeats in the 5′ untranslated region of FMR1. The mutation causes methylation and silencing of the gene, leading to a major reduction or complete loss of FMRP, an RNA-binding protein that regulates numerous messenger RNAs involved in synapse formation, maturation, and function. Loss of the protein can lead to abnormal synaptic activity and increased cortical hyperexcitability.
FXS can produce sensory hypersensitivity, seizures, anxiety, intellectual disability, developmental delays, repetitive behaviors, and social communication difficulty. Current treatments for this syndrome don’t seek to cure it, rather they are aimed at managing the associated symptoms of anxiety, hyperactivity, irritability, aggression, depression, and seizures.
The therapy developed by the research team was designed to replace missing FMRP rather than repair the original mutation. To do this, the researchers used an AAV9 viral vector to deliver human FMR1 isoform 7, one of the most abundant forms of the protein found in the brain. The therapy was tested in newborn mice lacking FMRP via intracerebroventricular injections at either a low or high doses.
The work built on earlier research that explored the potential of AAV-mediated restoration of FMRP in rodent models. These prior studies used a range of viral serotypes, promoters, delivery routes, and FMRP isoforms and showed they could partially or completely correct specific biochemical, physiological, and behavioral abnormalities. The researchers noted that studies involving mouse and rat FMRP homologs had shown that restoring the protein could improve a range of Fragile X-related deficits.
The current study showed that high-dose treatment produced the strongest positive effects in the mouse models. Electroencephalography showed normalization of baseline gamma power, improvements in responses to sound, reduced background neural activity, and improved habituation to repeated auditory stimuli. The therapy also restored abnormal patterns of brain-wave coupling that have been associated with Fragile X-related dysfunction.
Behavioral testing showed that these improvements persisted into adulthood. Mice receiving the higher dose displayed normalized exploratory behavior, improved social preference, and better performance in probabilistic reversal learning, a measure of cognitive flexibility that requires adapting when previously rewarded behaviors stop producing rewards.
“Fragile X mice tend to persist with an old solution even after the rules change,” Ethell said. “After treatment, they became much better at adapting, performing similarly to mice with normal FMR1 function.”
The researchers noted that their work showed the importance of delivering at therapy for FXS early in its development. They said that widespread distribution of the potential new gene therapy throughout the brain was necessary to achieve a therapeutic benefit. There was a clear relationship between the proportion of neurons expressing the therapeutic gene and the degree of functional recovery, which indicated that restoring FMRP in a sufficient number of cortical cells is critical for correcting any behavioral deficits.
While a promising step, the investigators said that the work was a preclinical study and that future research will now focus on developing delivery methods that can of have broad distribution across the human brain. The team also believes their approach could have broader applications.
“Beyond FXS, the findings may provide a roadmap for treating other genetic neurodevelopmental disorders caused by the loss of a single critical protein,” Ethell said. “Our study shows it may be possible to restore function across complex brain networks by replacing a missing gene. That gives us reason to be optimistic about the future of genetic medicine.”
The post Gene Therapy Restores Brain Function and Behavior in Fragile X Syndrome appeared first on Inside Precision Medicine.
Longitudinal changes in MMN and P3 during emotional processing in adolescents who engage in NSSI: a 12-week follow-up study
BackgroundAdolescents with nonsuicidal self-injury (NSSI) often show deficits in negative emotion regulation. Within the dual-process framework of implicit and explicit emotion regulation, these deficits may reflect an automatic bias toward negative information and insufficient later-stage controlled regulation. Whether routine clinical intervention modifies both early automatic detection and later controlled evaluation of negative emotional information remains unclear.MethodsIn a longitudinal sample of 32 adolescents with NSSI, we examined changes in mismatch negativity (MMN) and P3 components elicited during an emotional oddball task before and after a 12-week clinical intervention. At baseline and Week 12, participants completed clinical assessments and a two-choice visual emotional oddball task containing neutral standards and negative, positive, and neutral deviants while EEG was recorded. MMN (Fz, 240–300 ms) and P3 (Pz, 450–650 ms) amplitudes were derived from deviant-minus-standard difference waves, indexing pre-attentive deviance detection and controlled evaluation, respectively.ResultsThe intervention selectively modulated neurocognitive processing of negative deviants. Self-injury ideation days (p = .036) and NSSI episode frequency (p = .007) both significantly decreased. MMN absolute amplitude to negative stimuli decreased significantly (p = .047), suggesting attenuated automatic salience detection, whereas P3 amplitude to negative stimuli increased significantly (p = .027), indicating enhanced controlled evaluation. Responses to positive and neutral conditions and behavioural performance remained stable. No baseline ERP–clinical correlations emerged; post-intervention, NSSI ideation days correlated with positive P3 (r = 0.380, p = .032), and episode frequency with neutral P3 (r = 0.461, p = .008).ConclusionsA 12-week intervention may attenuate automatic negative bias while enhancing controlled evaluative processing in adolescents with NSSI, consistent with the implicit–explicit framework. MMN and P3 may serve as candidate biomarkers and temporally sensitive tools for tracking intervention response when behavioural performance is stable.
Optical Pooled CRISPR Screen Reveals Regulators of NF-κB Dynamics in Human Cells
Tilmann Buerckstuemmer, PhD
CSO
Myllia Biotechnology
Panelist
Tilmann Buerckstuemmer, PhD
Tilmann Buerckstuemmer, PhD, is a CRISPR enthusiast since the early days of CRISPR. Originally trained as a biochemist, he joined Haplogen as principal scientist and later became their CSO. Following the acquisition by Horizon Discovery, Tilmann served as director of research and development and later as head of innovation, where he oversaw the company’s technology platform and innovation agenda. In 2018, he co-founded Myllia Biotechnology which focuses on single-cell CRISPR screens. He is also the CEO of bit.bio discovery, a joined venture between Vienna-based Myllia Biotechnology and Cambridge-based bit.bio. Tilmann is passionate about science and enjoys working with multi-disciplinary and multi-national teams.
Jens Durruthy Durruthy, PhD
Director of Product Management
Element Biosciences
Panelist
Jens Durruthy Durruthy, PhD
Jens Durruthy Durruthy, PhD, is the director of product management at Element Biosciences. Prior experience includes a decade at 10x Genomics, where he developed and oversaw the product portfolio for Chromium products. Jens held the position of LSA Bio/Genomics Fellow at Life Science Angels, conducting extensive research on investment opportunities in biotech and genomics startups, and has worked in various consulting roles, focusing on product development and market analysis. Educational credentials include a PhD in biomedical engineering from Stanford University and a diploma in medical biotechnology from Technische Universität Berlin.
Broadcast Date:
- Time:
Integrated pooled CRISPR screening linked to imaging readouts accelerate target identification and functional characterization of signaling pathways. A good example of this can be found in studies of NF-κB signaling, which is central to inflammatory responses and driven by rapid nuclear translocation of the p50/p65 complex to activate transcriptional programs following cytokine stimulation.
In this GEN webinar, Tilmann Buerckstuemmer, PhD, CSO at Myllia Biotechnology will show how high-throughput pooled CRISPR screening combined with cell painting readouts characterized important signaling pathways using NF-κB nuclear translocation as a case study. During the webinar, you will learn how the AVITI24
platform from Element Biosciences profiled ~440,000 cells in a pooled CRISPR screen targeting 195 genes. Linking genetic perturbations to p65 subcellular localization and cell painting features in a single workflow enabled identification of known pathway components, uncovered regulatory roles for chromatin-modifying complexes, and improved interpretation of phenotypic outcomes using morphological features.
Key takeaways include:
- Strategies for linking CRISPR perturbations to protein localization and morphological features at single-cell resolution
- Identification of hitherto poorly characterized chromatin modifying complexes in regulating NF-κB signaling
- The value of multimodal readouts, including morphology, in adding depth and confidence to recovered biology
- How this approach supports mechanism-of-action studies and enables identification of both positive and negative regulators of signaling pathways
A live Q&A session will follow the presentation offering you a chance to pose questions to our expert panelists.
Produced with support from:
The post Optical Pooled CRISPR Screen Reveals Regulators of NF-κB Dynamics in Human Cells appeared first on GEN – Genetic Engineering and Biotechnology News.
A novel music-based real-time fMRI neurofeedback interface modulates interhemispheric connectivity and enhances mood
IntroductionMusic is a universal language that transcends cultures and is deeply rooted in human evolutionary history. Its creation and appreciation recruit the limbic and reward systems, leading to the evocation of emotions ranging from happiness and sadness to tenderness and grief. Here, we investigate the potential of music as an interventional tool in a novel neurofeedback connectivity-based experiment. MethodsThis study proposes a musical interface for real-time functional magnetic resonance imaging neurofeedback that is adaptable to diverse experimental paradigms, namely the ones aiming at improving mood and other affective dimensions. Using a previously developed motor imagery connectivity-based approach, we evaluate its feasibility and efficacy by comparing the modulation of bilateral premotor cortex activity during functional runs with real versus sham (random) feedback in 22 healthy adults. We also assess its performance against a visual feedback interface. The experiment involves a 50-minute MRI session, including anatomical scans, a premotor cortex functional localizer run, and four neurofeedback runs (two with active feedback and two with sham feedback). Pre- and post-session questionnaires assess the neurobehavioral impact on mood, musical background (as a potential predictor of neurofeedback success), and subjective feedback experiences. During neurofeedback, participants perform motor imagery of finger-tapping, with feedback delivered as a dynamic, pre-validated chord progression that evolves or regresses based on the functional connectivity between left and right premotor cortex.ResultsWe found that our implementation of music-based feedback was successful, with participants managing to modulate their own connectivity using the proposed interface. The modulation performance was similar for active and sham runs, possibly due to the power of music to boost neuromodulation, but the network recruitment was stronger for active neurofeedback, including in the insula, putamen, and target regions of interest. Behaviorally, we found a decrease in tension and an improvement in the overall mood of the participants after the session. DiscussionWhen comparing our results to previous neurofeedback data with a visual interface, we found stronger brain activations, in particular in neurofeedback-relevant regions such as the insula and the putamen. This work shows that it is possible to directly modulate interhemispheric connectivity using a real-time functional magnetic resonance imaging musical interface with potential effects on mood and recruitment of saliency and learning networks.
Functional connectivity changes in the thalamocortical network due to neck pain and the multiscale regulatory effects of acupuncture: a cross-scale multi-omics neuroimaging study
BackgroundNeck pain correlates with multiscale brain abnormalities, but cross-scale mechanisms of acupuncture analgesia are unclear. This study aimed to: (1) Explore differential modulation of thalamic functional networks by verum vs. sham acupuncture; (2) Examine associations between functional connectivity changes and micro gene expression to unravel its multiscale mechanisms.MethodsA total of 130 participants were initially enrolled, and 100 eligible neck pain patients were randomized 1:1 to the verum (n = 50) or sham (n = 50) acupuncture groups. Finally, 49 patients in each group were included for the final analysis due to one case of exclusion in each group, with treatment administered twice a week for 2 weeks. Visual Analog Scale (VAS), resting-state functional magnetic resonance imaging (fMRI), and Allen Human Brain Atlas (AHBA) transcriptome data were analyzed via Partial Least Squares (PLS) regression.ResultsBoth groups showed reduced post-treatment VAS (p < 0.001), with the verum group exhibiting a superior effect (Z = −6.877, p < 0.001). Neuroimaging revealed that verum acupuncture (VA) specifically induced significant decreases in functional connectivity (FC) between the right thalamus and left anterior cingulate cortex (T = −4.498) as well as between the right thalamus and right Rolandic operculum (T = −4.532, voxel-level p < 0.01, cluster-level p < 0.05), an effect absent in the sham acupuncture group (SA). Gene- FC association analysis indicated that PLS2 component explained 39.83% of FC variance (Pspin: permutation test p < 0.05), with weight genes showing significant spatial correlation to connectivity changes (r = 0.445, Pspin = 0.0011). A total of 809 genes were enriched in the innate immune response and phosphorylation regulation pathways, whereas 1,222 genes were enriched in the GABA-ergic synapse and synaptic membrane-related pathways.ConclusionVA relieves pain via modulating thalamus-anterior cingulate cortex networks, involving immune-inflammation and neural inhibition, providing first multi-scale validation integrating neuroimaging and transcriptomics.Clinical trial registrationThis trial was registered with the International Traditional Medicine Clinical Trial Registry (registration number: ITMCTR2023000001) prior to participant enrollment.
Exploring neural mechanisms of Mandarin tone sandhi perception via fNIRS: the role of gesture in multimodal integration
IntroductionThe use of pitch gestures in teaching Mandarin tone (i.e., gesture-augmented instruction) has been reported to facilitate lexical tone acquisition. However, the neural mechanisms underlying how gestures aid the learning of complex phonological rules, such as tone sandhi, remain unclear. This study investigated whether gesture-based learning enhances tone sandhi perception primarily through multimodal integration or by promoting cognitive control.MethodsForty-four Vietnamese-speaking learners were randomly assigned to either a gesture training group or a no-gesture control group. Post-training, participants performed a disyllabic tone discrimination task while functional near-infrared spectroscopy (fNIRS) data and behavioral responses were recorded.ResultsResults revealed significantly greater neural responses in the left dorsolateral prefrontal cortex (L-DLPFC) in the gesture group compared to the control group. Moreover, enhanced L-DLPFC activation was positively correlated with improved behavioral discrimination accuracy. The gesture group also exhibited strengthened functional connectivity between the L-DLPFC and bilateral prefrontal cortices, accompanied by accelerated hemodynamic responses.DiscussionCollectively, these findings suggest that gesture-assisted learning facilitates tone sandhi mastery primarily by augmenting prefrontal executive control and fostering multisensory integration. This pattern aligns with a weak embodied cognition framework, in which gestures serve as distributed scaffolds that support, rather than replace, abstract tonal representations.