生物学最新文献

This proof-of-concept study uses individualized functional magnetic resonance imaging neuromodulation (iNM) to explore the mechanisms that enhance BOLD signals in visuospatial perception (VP) networks that are crucial for navigation. Healthy participants (n = 8) performed a VP up- and down-direction discrimination task at full and subthreshold coherence through peripheral vision, and superimposed direction through visual imagery (VI) at central space under iNM and control conditions. iNM targets individualized anatomical and functional middle- and medial-superior temporal (MST) networks that control VP. We found that iNM engaged selective exteroceptive and interoceptive attention (SEIA) and motor planning (MP) networks. Specifically, iNM increased overall: (i) area under the curve of the BOLD magnitude: 100% in VP (but decreased for weak coherences), 21-47% in VI, 26-59% in MP and 48-76% in SEIA through encoding; and (ii) classification performance for each direction, coherence and network through decoding, predicting stimuli from brain maps. Our findings, derived from encoding and decoding models, suggest that mechanisms induced by iNM are causally linked in enhancing visuospatial networks and demonstrate iNM as a feasibility treatment for low-vision patients with cortical blindness or visuospatial impairments that precede cognitive decline.This article is part of the theme issue 'Neurofeedback: new territories and neurocognitive mechanisms of endogenous neuromodulation'.

Cells maintain homeostasis via dynamic regulation of stress response pathways. Stress pathways transiently induce response regulons via negative feedback loops, but the extent to which individual genes provide feedback has not been comprehensively measured for any pathway. Here, we disrupted the induction of each gene in the Saccharomyces cerevisiae heat shock response (HSR) and quantified cell growth and HSR dynamics following heat shock. The screen revealed a core feedback loop governing the expression of the chaperone Hsp70 reinforced by an auxiliary feedback loop controlling Hsp70 subcellular localization. Mathematical modeling and live imaging demonstrated that multiple HSR targets converge to promote Hsp70 nuclear localization via its release from cytosolic condensates. Following ethanol stress, a distinct set of factors similarly converged on Hsp70, suggesting that nonredundant subsets of the HSR regulon confer feedback under different conditions. Flexible spatiotemporal feedback loops may broadly organize stress response regulons and expand their adaptive capacity.

VPS13B/COH1 is the only known causative factor for Cohen syndrome, an early-onset autosomal recessive developmental disorder with intellectual inability, developmental delay, joint hypermobility, myopia, and facial dysmorphism as common features, but the molecular basis of VPS13B/COH1 in pathogenesis remains largely unclear. Here, we identify Sec23 interacting protein (Sec23IP) at the ER exit site (ERES) as a VPS13B adaptor that recruits VPS13B to ERES-Golgi interfaces. VPS13B interacts directly with Sec23IP via the VPS13 adaptor binding domain (VAB), and the interaction promotes the association between ERES and the Golgi. Disease-associated missense mutations of VPS13B-VAB impair the interaction with Sec23IP. Knockout of VPS13B or Sec23IP blocks the formation of tubular ERGIC, an unconventional cargo carrier that expedites ER-to-Golgi transport. In addition, depletion of VPS13B or Sec23IP delays ER export of procollagen, suggesting a link between procollagen secretion and joint laxity in patients with Cohen disease. Together, our study reveals a crucial role of VPS13B-Sec23IP interaction at the ERES-Golgi interface in the pathogenesis of Cohen syndrome.

Technological advances in fMRI including ultra-high magnetic fields (≥ 7 T) and acquisition methods that increase spatial specificity have paved the way for studies of the human cortex at the scale of layers and columns. This mesoscopic scale promises an improved mechanistic understanding of human cortical function so far only accessible to invasive animal neurophysiology. In recent years, an increasing number of studies have applied such methods to better understand the cortical function in perception and cognition. This future perspective article asks whether closed-loop fMRI studies could equally benefit from these methods to achieve layer and columnar specificity. We outline potential applications and discuss the conceptual and concrete challenges, including data acquisition and volitional control of mesoscopic brain activity. We anticipate an important role of fMRI with mesoscopic resolution for closed-loop fMRI and neurofeedback, yielding new insights into brain function and potentially clinical applications.This article is part of the theme issue 'Neurofeedback: new territories and neurocognitive mechanisms of endogenous neuromodulation'.

Perilipins (PLINs), the most abundant proteins on lipid droplets (LDs), display similar domain organization including amphipathic helices (AH). However, the five human PLINs bind different LDs, suggesting different modes of interaction. We established a minimal system whereby artificial LDs covered with defined polar lipids were transiently deformed to promote surface tension. Binding of purified PLIN3 and PLIN4 AH was strongly facilitated by tension but was poorly sensitive to phospholipid composition and to the presence of diacylglycerol. Accordingly, LD coverage by PLIN3 increased as phospholipid coverage decreased. In contrast, PLIN1 bound readily to LDs fully covered by phospholipids; PLIN2 showed an intermediate behavior between PLIN1 and PLIN3. In human adipocytes, PLIN3/4 were found in a soluble pool and relocated to LDs upon stimulation of fast triglyceride synthesis, whereas PLIN1 and PLIN2 localized to pre-existing LDs, consistent with the large difference in LD avidity observed in vitro. We conclude that the PLIN repertoire is adapted to handling LDs with different surface properties.

While neurofeedback represents a promising tool for neuroscience and a brain self-regulation approach to psychological rehabilitation, the field faces several problems and challenges. Current research has shown great variability and even failure among human participants in learning to self-regulate target features of brain activity with neurofeedback. A better understanding of cognitive mechanisms, psychological factors and neural substrates underlying self-regulation might help improve neurofeedback's scientific and clinical practices. This article reviews the current understanding of the neural mechanisms of brain self-regulation by drawing on findings from human and animal studies in neurofeedback, brain-computer/machine interfaces and neuroprosthetics. In this article, we look closer at the following topics: cognitive processes and psychophysiological factors affecting self-regulation, theoretical models and neural substrates underlying self-regulation, and finally, we provide an outlook on the outstanding gaps in knowledge and technical challenges. This article is part of the theme issue 'Neurofeedback: new territories and neurocognitive mechanisms of endogenous neuromodulation'.

During fMRI neurofeedback participants learn to self-regulate activity in relevant brain areas and networks based on ongoing feedback extracted from measured responses in those regions. This closed-loop approach has been successfully applied to reduce symptoms in mood disorders such as depression by showing participants a thermometer-like display indicating the strength of activity in emotion-related brain areas. The hitherto employed conventional neurofeedback is, however, 'blind' with respect to emotional content, i.e. patients instructed to engage in a specific positive emotion could drive the neurofeedback signal by engaging in a different (positive or negative) emotion. In this future perspective, we present a new form of neurofeedback that displays semantic information of emotions to the participant. Semantic information is extracted online using real-time representational similarity analysis of emotion-specific activity patterns. The extracted semantic information can be provided to participants in a two-dimensional semantic map depicting the current mental state as a point reflecting its distance to pre-measured emotional mental states (e.g. 'happy', 'content', 'sad', 'angry'). This new approach provides transparent feedback during self-regulation training, and it has the potential to enable more specific training effects for future therapeutic applications such as clinical interventions in mood disorders.This article is part of the theme issue 'Neurofeedback: new territories and neurocognitive mechanisms of endogenous neuromodulation'.

Excess dietary intake of saturated fatty acids (SFAs) induces glucose intolerance and metabolic disorders. In contrast, unsaturated fatty acids (UFAs) elicit beneficial effects on insulin sensitivity. However, it remains elusive how SFAs and UFAs signal differentially toward insulin signaling to influence glucose homeostasis. Here, using a croaker model, we report that dietary palmitic acid (PA), but not oleic acid or linoleic acid, leads to dysregulation of mTORC1, which provokes systemic insulin resistance. Mechanistically, we show that PA profoundly elevates acetyl-CoA derived from mitochondrial fatty acid β oxidation to intensify Tip60-mediated Rheb acetylation, which triggers mTORC1 activation by promoting the interaction between Rheb and FKBPs. Subsequently, hyperactivation of mTORC1 enhances IRS1 serine phosphorylation and inhibits TFEB-mediated IRS1 transcription, inducing impairment of insulin signaling. Collectively, our results reveal a conserved molecular insight into the mechanism by which Tip60-mediated Rheb acetylation induces mTORC1 activation and insulin resistance under the PA condition, which may provide therapeutic avenues to intervene in the development of T2D.

Executive function deficits, common in psychiatric disorders, hinder daily activities and may be linked to diminished neural plasticity, affecting treatment and training responsiveness. In this pioneering study, we evaluated the feasibility and preliminary efficacy of psilocybin-assisted frontal-midline theta neurofeedback (NF), a neuromodulation technique leveraging neuroplasticity, to improve executive functions (EFs). Thirty-seven eligible participants were randomized into an experimental group (n = 18) and a passive control group (n = 19). The experimental group underwent three microdose sessions and then three psilocybin-assisted NF sessions, without requiring psychological support, demonstrating the approach's feasibility. NF learning showed a statistical trend for increases in frontal-midline theta from session to session with a large effect size and non-significant but medium effect size dynamical changes within sessions. Placebo effects were consistent across groups, with no tasks-based EF improvements, but significant self-reported gains in daily EFs-working memory, shifting, monitoring and inhibition-showing medium and high effect sizes. The experimental group's significant gains in their key training goals underscored the approach's external relevance. A thorough study with regular sessions and an active control group is crucial to evaluate EFs improvement and their specificity in future. Psilocybin-enhanced NF could offer significant, lasting benefits across diagnoses, improving daily functioning. This article is part of the theme issue 'Neurofeedback: new territories and neurocognitive mechanisms of endogenous neuromodulation'.

With the spread of smartphones and computer games, concerns have escalated regarding the rising prevalence of gaming disorder. Patients often display attentional biases, unconsciously turning their attention towards gaming-related stimuli. However, attempts to discover and ameliorate these attentional deficits have yielded inconsistent outcomes, potentially due to the dynamic nature of attentional bias. This study investigated neural mechanisms underlying attentional bias state by combining neuroimaging (functional magnetic resonance imaging -fMRI) with an approach-avoidance task tailored to an individual's gaming preference. We conducted a multivariate pattern analysis of endogenous brain activity in 21 participants with probable gaming disorder. Our analyses revealed that activity patterns in the insula tracked temporal attentional bias states specific to gaming stimuli. A broad network of frontal and parietal regions instead appeared to predict a general temporal attentional bias state. Finally, we conducted a proof-of-concept study for 'just-in-time' attentional bias training through fMRI-decoded neurofeedback of insula activity patterns, named decoded attentional bias training (DecABT). Our preliminary results suggest that DecABT may help to decrease the attractiveness of gaming stimuli via a insula- and precuneus-based neural mechanism. This work provides new evidence for the insula as an endogenous regulator of attentional bias states in gaming disorder and a starting point to develop novel, individualized therapeutic approaches to treat addiction.This article is part of the theme issue 'Neurofeedback: new territories and neurocognitive mechanisms of endogenous neuromodulation'.