Brain-heart interaction (BHI) offers a systems-level framework for understanding major depressive disorder (MDD), yet reproducible cross-system markers remain unclear. We aimed to identify reproducible BHI impairments in MDD and clarify their physiological and clinical correlates.
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.
Pulvinar and total thalamus volumes are preserved following early monocular enucleation
BackgroundMonocular enucleation, the surgical removal of one eye, occurs early in life and leads to changes in visual, auditory, and audiovisual processing in adulthood. These changes can be observed behaviorally, as well as through cortical structure and white matter connectivity of visual and auditory pathways. Subcortically, the thalamus is a critical sensory processing structure that modulates both unisensory and multisensory stimuli, which are later processed in the cortex. Previous studies have shown that following monocular enucleation, the lateral geniculate nucleus (LGN) is reduced in volume, although this reduction is less than predicted. In contrast, the medial geniculate body (MGB) is asymmetric but maintains its volume. Together, this may support the auditory and audiovisual enhancements observed following early monocular enucleation. Another key subcortical thalamic nucleus, the pulvinar, plays a broad role in human visual information processing and sensorimotor integration.MethodsThe current study used structural MRI to anatomically localize and measure the total pulvinar and its subnuclei, as well as total thalamus volume, in individuals who had undergone early monocular enucleation during postnatal maturation compared to binocularly intact controls.ResultsOverall, people with one eye demonstrated preserved pulvinar and total thalamus volumes compared to binocularly intact controls.ConclusionThe preserved structural volume of the pulvinar and total thalamus may support the intact lower-level auditory and audiovisual processing previously observed in individuals with one eye. The absence of pulvinar volume changes in this broad-function supporting, subcortical region builds on previous studies regarding thalamic plasticity after early monocular enucleation. These findings provide evidence that not all thalamic nuclei show measurable long-term volumetric alterations and that neural plasticity is both regionally and functionally dependent.
Differences in brain functional connectivity between autonomous sensory meridian response and classical music
Autonomous sensory meridian response (ASMR) is a tingling sensation that originates in the occipital region and spreads along the neck and spine, elicited by specific audiovisual stimuli known as ASMR triggers. The characteristics of ASMR-related changes in brain activity relative to other external stimuli, and whether these changes are specific to ASMR, remain unclear. The aim of this study is to compare changes in functional connectivity during exposure to ASMR triggers and classical music, and to clarify the changes in connectivity that are more strongly associated with ASMR trigger listening. Forty-eight healthy adults without a history of psychiatric disorders underwent functional MRI under three conditions: resting state without auditory stimulation, listening to ASMR triggers, and listening to classical music. Functional connectivity during the ASMR and classical-music conditions was assessed relative to the resting state. As a result, functional connectivity between the medial prefrontal cortex and the right lateral parietal cortex increased during ASMR trigger listening compared to rest. Relative to classical music listening, ASMR trigger listening increased functional connectivity between the medial prefrontal cortex and the right lateral parietal cortex, between the left anterior insula and left supramarginal gyrus, and between the right rostral prefrontal cortex and the anterior cingulate cortex. No significant changes in functional connectivity were observed during classical music listening alone. These findings suggest that, compared with classical music listening, ASMR trigger listening is associated with stronger functional connectivity between specific ROI pairs involved in self-referential/internal evaluative processing and sensory integration.
The Sentinel Phenotype: a theoretical bioenergetic and neurobiological framework for high-fidelity predictive systems (HEPOE Theory)
The HEPOE Theory (High Entropy Predictive Organization Efficiency) proposes a novel conceptual framework for understanding Giftedness (HA/G), moving beyond academic performance-based models toward a biophysical and neuroscientific foundation. Through a theoretical synthesis grounded in the Free Energy Principle and Biological Thermodynamics, the gifted individual is redefined as a “Sentinel”: a high-fidelity sampling system specialized in the early detection of isomorphy and the reduction of systemic entropy. This framework reinterprets Charles Spearman’s general intelligence (g) as a macroscopic manifestation of hardware efficiency, where reasoning ability is proposed to be fundamentally constrained by working-memory capacity and the metabolic economy of ATP resynthesis. We hypothesize that the hardware operates under an “open sensory gating” regime and low latent inhibition, leading to high metabolic costs and chronic allostatic load. The paper introduces the original concept of Predictive Moral Injury to conceptualize the potential somatic damage resulting from the early perception of ethical-systemic collapses within low-resolution environments. The HEPOE Unification Matrix integrates decades of classical literature and proposes a rigorous differential diagnosis against the pathologization of ASD, ADHD, and PTSD. It hypothesizes that the Sentinel’s exhaustion is not a dysfunction, but a logistical byproduct of high predictive performance under entropy-saturated conditions.
Factors influencing the sensory profile in patients with autism spectrum disorder from 16 months to 14 years: results of an observational study
IntroductionSensory processing abnormalities represent a high-impact clinical feature in individuals with Autism Spectrum Disorder (ASD). Sensory alterations can be classified by modality and behavioral responses to stimuli. The literature presents conflicting results regarding the association between the sensory profile and other clinical elements. Therefore, this study aimed to characterize the clinical variables that influence sensory anomalies in subjects with ASD.MethodsThis single-center retrospective observational study selected 159 subjects with a confirmed ASD diagnosis, aged 16 months to 14 years. Data collected included clinical assessments (developmental profile, intelligence quotient, adaptive profile and autistic symptom severity) and sensory evaluations using the Sensory Profile-2. A Bayesian cumulative logit model was implemented to assess the impact of clinical variables on sensory profiles.ResultsThe analysis identifies adaptive functioning as the most consistent predictor of sensory outcomes, where higher functioning correlates with a reduction in atypical patterns, particularly sensory sensitivity. Conversely, autism severity and sex generally showed no significant impact, though higher cognitive functioning was specifically linked to increased sensory avoiding behaviors. Furthermore, the Bayesian analysis revealed a modifying effect of age on the sensory profile, characterized by a non-monotonic trend clustered around two distinct age peaks. The preschool period is characterized by a predominance of sensory seeking behaviors and auditory processing challenges, whereas the 8-to-12-year developmental window marks a significant shift toward hypersensitivity and avoidant patterns, particularly within the visual and oral modalities.DiscussionOverall, the analysis revealed that the adaptive profile has a significant impact on the sensory profile, consistent with existing literature. Age emerged as a key modifying factor with a non-monotonic trajectory, contrasting with previous studies that typically highlight either improvement or stability over time. Study main limitations include its retrospective and non-longitudinal nature. Therefore, further prospective longitudinal studies are necessary to explore these dynamic associations between the sensory profile and other clinical variables over time.
Functional brain alterations associated with acupuncture for chronic pain: a scoping review of fMRI studies
BackgroundChronic pain (CP) is a public health challenge recognized as involving large-scale functional brain dysregulation. Acupuncture is widely used as a non-pharmacological intervention for CP, yet its central mechanisms remain incompletely understood. fMRI provides an approach for investigating acupuncture-related brain alterations in CP.MethodsEight databases were searched from inception to March 27, 2025 for fMRI studies investigating acupuncture’s central effects in CP. Eligible studies included randomized controlled trials and observational studies involving migraine, knee osteoarthritis, fibromyalgia, sciatica, chronic shoulder pain, chronic neck pain, cervical spondylosis, chronic low back pain, and lumbar disk herniation. Data on characteristics, acupuncture protocols, neuroimaging findings, and outcomes were extracted and narratively synthesized. Reporting quality of acupuncture interventions was assessed using STRICTA, risk of bias of randomized controlled trials using RoB 2, and methodological quality of observational studies using the Newcastle–Ottawa Scale.ResultsA total of 64 studies were included. CP was characterized by widespread functional brain abnormalities, mainly involving the default mode network, sensorimotor network, and pain- and emotion-related regions such as the anterior cingulate cortex, precuneus, insula, and thalamus. Across longitudinal and controlled analyses, acupuncture-related brain changes were most consistently reflected in altered functional connectivity, local neural synchrony, and regional spontaneous activity. Functional connectivity findings suggested a potentially ACC-centered circuit pattern, whereas regional homogeneity findings revealed bidirectional modulation across multiple brain regions. Comparative evidence further indicated that VA, SA, and EEA may engage partially overlapping but distinct neural processes. Reporting of core acupuncture protocol components was generally adequate, whereas methodological quality remained heterogeneous.ConclusionCurrent fMRI evidence suggests that CP involves large-scale network-level functional imbalance and that acupuncture may be associated with modulation of key abnormal nodes and circuits related to pain perception, sensory processing, and emotional regulation. The available evidence supports a cautious interpretation that acupuncture-related brain effects may predominantly reflect a state-dependent recalibration of dysregulated brain networks. Future studies should prioritize large-sample, multicenter, longitudinal, and multimodal designs, together with rigorous control settings and more rigorous, externally validated machine learning-based prediction studies, to better distinguish differential central effects across intervention conditions and advance mechanism-informed personalized acupuncture in CP management.
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:
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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.
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.