Current research in neurobiology最新文献

Studying higher brain function presents fundamental scientific challenges but has great potential for impactful translation to the clinic, supporting the needs of many patients suffering from conditions that relate to neuronal dysfunction. For many key questions relevant to human neurological conditions and clinical interventions, non-human primates (NHPs) remain the only suitable model organism and the only effective way to study the relationship between brain structure and function with the knowledge and tools currently available. Here we present three exemplary studies of current research yielding important findings that are directly translational to human clinical patients but which would be impossible without NHP studies. Our first example shows how studies of the NHP prefrontal cortex are leading to clinically relevant advances and potential new treatments for human neuropsychiatric disorders such as depression and anxiety. Our second example looks at the relevance of NHP research to our understanding of visual pathways and the visual cortex, leading to visual prostheses that offer treatments for otherwise blind patients. Finally, we consider recent advances in treatments leading to improved recovery of movement and motor control in stroke patients, resulting from our improved understanding of brain stem parallel pathways involved in movement in NHPs. The case for using NHPs in neuroscience research, and the direct benefits to human patients, is strong but has rarely been set out directly. This paper reviews three very different areas of neuroscience research, expressly highlighting the unique insights offered to each by NHP studies and their direct applicability to human clinical conditions.

The ability to engage into flexible behaviors is crucial in dynamic environments. We recently showed that in addition to the well described role of the orbitofrontal cortex (OFC), its thalamic input from the submedius thalamic nucleus (Sub) also contributes to adaptive responding during Pavlovian degradation. In the present study, we examined the role of the mediodorsal thalamus (MD) which is the other main thalamic input to the OFC. To this end, we assessed the effect of both pre- and post-training MD lesions in rats performing a Pavlovian contingency degradation task. Pre-training lesions mildly impeded the establishment of stimulus-outcome associations during the initial training of Pavlovian conditioning without interfering with Pavlovian degradation training when the sensory feedback provided by the outcome rewards were available to animals. However, we found that both pre- and post-training MD lesions produced a selective impairment during a test conducted under extinction conditions, during which only current mental representation could guide behavior. Altogether, these data suggest a role for the MD in the successful encoding and representation of Pavlovian associations.

IGF-1 and GLP-1 receptors are essential in all tissues, facilitating defense by upregulating anabolic processes. They are abundantly distributed throughout the central nervous system, promoting neuronal proliferation, survival, and differentiation. IGF-1/GLP-1 is a growth factor that stimulates neurons' development, reorganization, myelination, and survival. In primary and secondary brain injury, the IGF-1/GLP-1 receptors are impaired, resulting in further neuro complications such as cerebral tissue degradation, neuroinflammation, oxidative stress, and atrophy. Intracerebral hemorrhage (ICH) is a severe condition caused by a stroke for which there is currently no effective treatment. While some pre-clinical studies and medications are being developed as symptomatic therapies in clinical trials, there are specific pharmacological implications for improving post-operative conditions in patients with intensive treatment. Identifying the underlying molecular process and recognizing the worsening situation can assist researchers in developing effective therapeutic solutions to prevent post-hemorrhagic symptoms and the associated neural dysfunctions. As a result, in the current review, we have addressed the manifestations of the disease that are aggravated by the downregulation of IGF-1 and GLP-1 receptors, which can lead to ICH or other neurodegenerative disorders. Our review summarizes that IGF-1/GLP-1 activators may be useful for treating ICH and its related neurodegeneration.

Here we report meditative techniques, which modulate attentional control by arousal-driven influences and not by monitoring continuous thought processes as during mindfulness-related practices. We focus on Vajrayana (Tantric Buddhism) practices, during which a sequence of generation (self-visualization as a deity - Yidam) or completion with sign (inner heat -Tummo) stages necessarily precedes non-dual awareness (NDA) Tantric Mahamudra. We compared the electrocardiographic and electroencephalographic correlates of Mahamudra performed after rest (non-Tantric Mahamudra) with Mahamudra performed after Yidam (Tantric Mahamudra) in 16 highly experienced Vajrayana practitioners, 10 of whom also performed Tummo. Both Yidam and Tummo developed the state of PNS withdrawal (arousal) and phasic alertness, as reflected by HF HRV decreases and Alpha2 power increases, later neurophysiologically employed in Tantric Mahamudra. The latter led to the unique state of high cortical excitability, “non-selective” focused attention, and significantly reduced attentional control, quantified by power reductions in all frequency bands, except Theta. In contrast, similar to mindfulness-related practices, non-Tantric Mahamudra was performed in a state of PNS dominance (relaxation), tonic alertness, and active monitoring, as suggested by Alpha1 power increases and less pronounced decreases in other frequency bands. A neurobiological model of meditation is proposed, differentiating arousal-based and mindfulness-related practices.

Objective

This study aimed to clarify whether the glial fibrillary acidic protein (GFAP) and soluble protein-100β (S100β) can predict severe traumatic brain injury (TBI) in patients with severe multiple trauma.

Methods

This is a single-center retrospective observational study of 179 patients with severe multiple trauma. The GFAP and S100β were measured upon patient arrival at the hospital. We divided the patients into the severe TBI group (with a Traumatic Coma Data Bank classification of ≥III), the non-severe TBI group (non-TBI group [absence of abnormality on the computed tomography scan and extracranial injury], and the mild to moderate TBI group [TCDB classification I and II]). We compared biomarker levels between the two groups and then evaluated the accuracy of predicting severe TBI using a receiver operating characteristic curve.

Results

A total of 41 patients had severe TBI, and 138 had non-severe TBI. Mean GFAP levels were significantly higher in the severe TBI group (median, 6000 pg/mL; interquartile range [IQR], 651–15,548 pg/mL) than in the non-severe TBI group (median, 149 pg/mL; IQR, 0–695 pg/mL) (p < 0.0001). In contrast, there was no significant difference in S100β levels between the severe TBI group (median, 64 pg/mL; IQR, 0–536 pg/mL) and non-severe TBI group (median, 117 pg/mL; IQR, 0–403 pg/mL) (p = 0.637). The area under the receiver operating characteristic curve was 0.810 (p < 0.0001) for GFAP and 0.476 (p = 0.908) for S100β. For the GFAP, the optimal cutoff value for detecting severe TBI was 947 pg/mL (sensitivity, 75.6%; specificity, 78.3%).

Conclusions

In patients with severe multiple trauma, the GFAP level at hospital arrival could predict severe TBI, whereas the S100β level was not a useful predictor.

Listening to speech is difficult in noisy environments, and is even harder when the interfering noise consists of intelligible speech as compared to unintelligible sounds. This suggests that the competing linguistic information interferes with the neural processing of target speech. Interference could either arise from a degradation of the neural representation of the target speech, or from increased representation of distracting speech that enters in competition with the target speech. We tested these alternative hypotheses using magnetoencephalography (MEG) while participants listened to a target clear speech in the presence of distracting noise-vocoded speech. Crucially, the distractors were initially unintelligible but became more intelligible after a short training session. Results showed that the comprehension of the target speech was poorer after training than before training. The neural tracking of target speech in the delta range (1–4 Hz) reduced in strength in the presence of a more intelligible distractor. In contrast, the neural tracking of distracting signals was not significantly modulated by intelligibility. These results suggest that the presence of distracting speech signals degrades the linguistic representation of target speech carried by delta oscillations.

Research and developments based on nonhuman primate models have a specific place in biomedical sciences, and nonhuman primate species also have a specific place in the public opinion on the use of animal in research. While nonhuman primates are used in very limited number compared to other animal models, they are rightly the focus of deep ethical concerns. The importance of nonhuman primates in neuroscientific fundamental and preclinical discoveries together with the targeting of such research by activist groups well illustrate this fact. Nonhuman primates also highly contribute to other biomedical fields including immunology, virology, or metabolic and respiratory physiology. In all these fields, researchers, engineers and technicians face similar matters and share the same needs for optimal animal welfare, handling, and veterinary care, the same quest for first-rate research infrastructure and funding, and the same yearning for more public understanding and support. In this article, we give an overview of the evolution of human-animal relationships and public attitudes to animal research in France, and we recount the creation of BioSimia, France network for nonhuman primate biomedical research which now links all academic laboratories nationwide in all the domains for which nonhuman primates remain essential. We explain the principles as well as the outcomes of networking across disciplines. As a perspective, we outline the potential benefits of extending such network to a European scale.

In meditation practices that involve focused attention to a specific object, novice practitioners often experience moments of distraction (i.e., mind wandering). Previous studies have investigated the neural correlates of mind wandering during meditation practice through Electroencephalography (EEG) using linear metrics (e.g., oscillatory power). However, their results are not fully consistent. Since the brain is known to be a chaotic/nonlinear system, it is possible that linear metrics cannot fully capture complex dynamics present in the EEG signal. In this study, we assess whether nonlinear EEG signatures can be used to characterize mind wandering during breath focus meditation in novice practitioners. For that purpose, we adopted an experience sampling paradigm in which 25 participants were iteratively interrupted during meditation practice to report whether they were focusing on the breath or thinking about something else. We compared the complexity of EEG signals during mind wandering and breath focus states using three different algorithms: Higuchi's fractal dimension (HFD), Lempel-Ziv complexity (LZC), and Sample entropy (SampEn). Our results showed that EEG complexity was generally reduced during mind wandering relative to breath focus states. We conclude that EEG complexity metrics are appropriate to disentangle mind wandering from breath focus states in novice meditation practitioners, and therefore, they could be used in future EEG neurofeedback protocols to facilitate meditation practice.

Recent experimental evidence on patients with disorders of consciousness revealed that observing brain-heart interactions helps to detect residual consciousness, even in patients with absence of behavioral signs of consciousness. Those findings support hypotheses suggesting that visceral activity is involved in the neurobiology of consciousness, and sum to the existing evidence in healthy participants in which the neural responses to heartbeats reveal perceptual and self-consciousness. More evidence obtained through mathematical modeling of physiological dynamics revealed that emotion processing is prompted by an initial modulation from ascending vagal inputs to the brain, followed by sustained bidirectional brain-heart interactions. Those findings support long-lasting hypotheses on the causal role of bodily activity in emotions, feelings, and potentially consciousness. In this paper, the theoretical landscape on the potential role of heartbeats in cognition and consciousness is reviewed, as well as the experimental evidence supporting these hypotheses. I advocate for methodological developments on the estimation of brain-heart interactions to uncover the role of cardiac inputs in the origin, levels, and contents of consciousness. The ongoing evidence depicts interactions further than the cortical responses evoked by each heartbeat, suggesting the potential presence of non-linear, complex, and bidirectional communication between brain and heartbeat dynamics. Further developments on methodologies to analyze brain-heart interactions may contribute to a better understanding of the physiological dynamics involved in homeostatic-allostatic control, cognitive functions, and consciousness.

Ethical frameworks are the foundation for any research with humans or nonhuman animals. Human research is guided by overarching international ethical principles, such as those defined in the Helsinki Declaration by the World Medical Association. However, for nonhuman animal research, because there are several sets of ethical principles and national frameworks, it is commonly thought that there is substantial variability in animal research approaches internationally and a lack of an animal research ‘Helsinki Declaration’, or the basis for one. We first overview several prominent sets of ethical principles, including the 3Rs, 3Ss, 3Vs, 4Fs and 6Ps. Then using the 3Rs principles, originally proposed by Russell & Burch, we critically assess them, asking if they can be Replaced, Reduced or Refined. We find that the 3Rs principles have survived several replacement challenges, and the different sets of principles (3Ss, 3Vs, 4Fs and 6Ps) are complementary, a natural refinement of the 3Rs and are ripe for integration into a unified set of principles, as proposed here. We also overview international frameworks and documents, many of which incorporate the 3Rs, including the Basel Declaration on animal research. Finally, we propose that the available animal research guidance documents across countries can be consolidated, to provide a similar structure as seen in the Helsinki Declaration, potentially as part of an amended Basel Declaration on animal research. In summary, we observe substantially greater agreement on and the possibility for unification of the sets of ethical principles and documents that can guide animal research internationally.