Investigations into sensory coding in the visual system have typically relied on the use of either simple, unnatural visual stimuli, or natural images. Simple stimuli, such as Gabor patches, have been effective when looking at single neurons in early visual areas such as V1, but seldom produce large responses from mid-level visual neurons or neural populations with diverse tuning. Many types of “naturalistic” image models have been developed recently which bridge the gap between overly-simple stimuli and experimentally infeasible natural images. These stimuli can vary along a large number of feature dimensions, introducing new challenges when trying to map those features to neural activity. This “curse of dimensionality” is exacerbated when neural responses are themselves high-dimensional, such as when recording neural populations with implanted multielectrode arrays. We propose a method that searches high-dimensional stimulus spaces for characterizing neural population manifolds in a closed-loop experimental design. Stimuli were generated using a deep neural network in each block by using neural responses to previous stimuli to make predictions about the relationship between the latent space of the image model and neural responses. We found that these latent variables from the deep generative image model explained stronger linear relationships with neural activity than various alternative forms of image compression. This result reinforces the potential for deep generative image models for efficient characterization of high-dimensional tuning manifolds for visual neural populations.

Although the etio-pathogenesis of inflammatory bowel diseases (IBD) is not entirely clear, the interaction between genetic and adverse environmental factors may reduce the variety of the intestinal microbiota (dysbiosis), resulting in a chronic inflammation having effects on the large-scale brain network through the gut-brain axis. In this paper, we hypothesized the presence of inflammation-related changes in brain topology of IBD patients, regardless of the specific clinical form (ulcerative colitis (UC) or Crohn’s disease (CD)). To test this hypothesis, we analyzed source-reconstructed magnetoencephalography (MEG) signals in 25 IBD patients and 28 healthy controls (HC) in resting-state condition, and evaluated the brain network topology. Finally, to assess whether these changes were linked to IBD clinical evolution, we correlated brain topology to disease duration. We found that the betweenness centrality (BC) of the left hippocampus was higher in patients as compared to controls, in the gamma frequency band. BC is a nodal topological parameter indicating how much a brain region is involved in the flow of information through the brain network. Furthermore, the comparison among UC, CD and HC showed statistically significant differences between UC and HC and between CD and HC, but not between the two clinical forms. Our results demonstrated that the topological changes observed in IBD patients were not dependent on the specific clinical form, but due to the gastro-intestinal inflammatory process itself. However, although these findings are promising, we need to enlarge the sample size to monitor the brain involvement in IBD and to clarify the clinical impact.

Psychedelic drugs have profound effects on perception, cognition, and mood. How psychedelics affect neural signaling to produce these effects remains poorly understood. We investigated the effect of the classic psychedelic psilocybin on neural activity patterns and spatial encoding in the retrosplenial cortex of head-fixed mice navigating on a treadmill. The place specificity of neurons to distinct locations along the belt was reduced by psilocybin. Moreover, the stability of place-related activity across trials decreased. Psilocybin also reduced the functional connectivity among simultaneously recorded neurons. The 5-HT2AR (serotonin 2A receptor) antagonist ketanserin blocked the majority of these effects. These data are consistent with proposals that psychedelics increase the entropy of neural signaling, and provide a potential neural mechanism contributing to disorientation frequently reported by humans after taking psychedelics.

Alongside models and methods, concepts are one of the building blocks of neuroscientific inquiry. They help researchers to pursue various goals, such as describing novel patterns in the data, situate these patterns in existing models, formulate new models or build explanations, e.g., of how the brain processes sensory information. Often the formation of novel or reinterpretation of existing concepts can signal major shifts in how we understand the brain and investigate it scientifically. Yet not every novel concept or reinterpretation produces such a shift, which raises the question of when concepts succeed or fail to change our understanding of the brain. In this paper, we introduce analytical tools developed by philosophers of science and concepts of brain organization as examples to discuss when introducing novel, reinterpreting existing and replacing outdated neuroscientific concepts succeeds or fails. Our discussion opens up novel avenues for neuroscientists and philosophers to collaborate around the limits of old and prospects of new concepts describing how the brain is organized.

Abstract Objective: To summarize the clinical characteristics, radiological features, treatments, and prognosis of patients with myelin oligodendrocyte glycoprotein (MOG) antibody associated disease (MOGAD) overlapped with NMDA receptor (NMDAR) encephalitis. Methods: We retrospectively analyzed patients who exhibited dual positivity for MOG antibodies and NMDAR antibodies in serum/CSF from Jan 2018 to Jun 2023 Results: Ten patients with MOGAD and NMDAR encephalitis were enrolled. The median age of initial attacks was 23 (range: 10-43) years old. Common symptoms were cortical encephalopathies (8/10), focal neurological deficits (4/10), as well as other presentations including headache, fever, optic neuritis, and transverse myelitis. CSF pleocytosis was general (9/10, median 63.9 cells/μl). Lesions on brain MRI included brainstem (37.5%), cerebral cortex (33.3%), basal ganglia (25.0%), hippocampus (20.8%). The average follow-up duration was 25.4 months. 10/10 patients developed more than one relapse attacks, with MOG positivity before (10%), simultaneous (40%) or after anti-NMDAR encephalitis (50%). Most patients (7/10) had good response to first-line therapy, but experienced next relapse with an average interval of 6.7 (range: 2-14) months. We conducted initial analysis of lymphocyte subsets in these patients, which revealed CD3+ and CD4+ T cells increased after immunosuppressants medication (p < 0.01 and p < 0.05, respectively). Conclusion: MOGAD overlapping with NMDAR encephalitis presents a distinct clinical phenotype which differs from either MOGAD or NMDAR encephalitis. Brainstem in combination with cortical lesions might be warning signs for this overlapping syndrome. Due to the high recurrent rates, we recommend early diagnosis and timely treatment with high-efficiency immunosuppressants at onset.

For decades the external globus pallidus (GPe) has been viewed as a passive way-station in the indirect pathway of the cortico-basal ganglia-thalamic (CBGT) circuit, sandwiched between striatal inputs and basal ganglia outputs. According to this model, one-way descending striatal signals in the indirect pathway amplify the suppression of downstream thalamic nuclei by inhibiting GPe activity. Here we revisit this assumption, in light of new and emerging work on the cellular complexity, connectivity, and functional role of the GPe in behavior. We show how, according to this new circuit-level logic, the GPe is ideally positioned for relaying ascending and descending control signals within the basal ganglia. Focusing on the problem of inhibitory control, we illustrate how this bidirectional flow of information allows for the integration of reactive and proactive control mechanisms during action selection. Taken together, this new evidence points to the GPe as being a central hub in the CBGT circuit, participating in bidirectional information flow and linking multifaceted control signals to regulate behavior.

3,4-methylenedioxymethamphetamine (MDMA) has long been used non-medically, and it is currently under investigation for its potential therapeutic benefits. Both uses may be related to its ability to enhance empathy, sociability, emotional processing and its anxiolytic effects. However, the neural mechanisms underlying these effects, and their specificity to MDMA compared to other stimulants, are not yet fully understood. Here, using electroencephalography (EEG), we investigated the effects of MDMA and a prototypic stimulant, methamphetamine (MA), on early visual processing of socio-emotional stimuli in an oddball emotional faces paradigm. Specifically, we examined whether MDMA or MA enhance the processing of facial expressions, compared to placebo, during the early stages of visual perception. MDMA enhanced an event-related component that is sensitive to detecting faces (N170), specifically for happy and angry expressions compared to neutral faces. MA did not affect this measure, and neither drug altered other components of the response to emotional faces. These findings provide novel insights into the neural mechanisms underlying the effects of MDMA on socio-emotional processing and may have implications for the therapeutic use of MDMA in the treatment of social anxiety and other psychiatric disorders.

In the realm of neurointerventional treatment after ischemic stroke, ineffective reperfusion represents a significant challenge, with the integrity of the blood-brain barrier (BBB) serving as a pivotal determinant of outcomes. This review sheds light on the unique characteristics and roles of brain endothelial cells within the context of stroke with ineffective reperfusion. We address the distinctiveness of brain endothelial cells relative to their counterparts in different tissues, outlining their pathophysiological transformations, functional impairments, and inflammatory cascades post-stroke. The differential gene expression between brain endothelial cells and those from other organs provide a deeper understanding of their intrinsic roles in neuroprotective therapy. Looking ahead, exploring analogies between brain endothelial cells and those from organs with similar ischemia-reperfusion injury profiles could lead to innovative therapeutic strategies. This review highlights the paramount importance of understanding the nuanced roles of endothelial cells in mediating BBB dynamics, ultimately influencing reperfusion outcomes.

Tau hyperphosphorylation at Ser396/404 and its adverse neurological effects have been evident in animal models of cerebral malaria (CM). As a counter measure, quest for novel pharmacological therapeutics to ameliorate tau hyperphosphorylation in neurodegeneration and restore behavioural and cognitive functions with high efficacy in CM has been at the forefront of neurobiological studies. In this study, using experimental model of cerebral malaria (ECM), we administered four different polycyclitol derivatives, SR4 (01-04) as an adjunctive to ARM therapy resulting in alleviation of cdk5/p25 based tau signaling cascade and restoration of long-term memory. Limitations of scyllo-inositol and rational to synthesize these polycyclitols efficiently has also been captured in the backdrop. Initially, we studied long-term, short term memory and novelty based learning by conducting Barnes maze, T-maze and novel object recognition task in treated animal groups. The cognitive outcomes of SR4-02 (15) and SR4-04 (18) treated groups exhibited better learning and memory compared to SR4-01 (16) and SR4-03 (17) groups. We further evaluated cdk5/p25 and tau phosphorylation protein expression using western blotting, immunohistochemistry and Golgi-cox staining to study neuronal arborization pattern. Immunohistochemical analysis of hippocampal and cortical tissue regions showed reduced phospho tau expression in SR4-03 (17) and SR4-04 (18) groups compared to CM group. Similarly, Golgi-cox images showed increased neuronal density in Cornus Ammonis (CA1) and CA3 regions of hippocampus and cortex of SR4-02 (15), SR4-03 (17) and SR4-04 (18) treated mice. Overall, based on our findings, polycyclitol derivatives have the potential to alleviate tau levels and restore cognition in ECM.

The suprachiasmatic nucleus (SCN) and retrochiasmatic area (RCA) innervate the paraventricular nucleus of hypothalamus (PVH) that projects to the brainstem arousal parabrachial nucleus (PB), which may form a neural circuit regulating arousal, independent from the circadian control circuit of arousal. To test the hypothesis, we used DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) to activate these regions and examine wakefulness. We found that chemo-stimulation of the PVH, the SCN, the RCA, and the PVH-PB pathway all significantly promoted wakefulness, suggesting that a neural circuit consisting of these nodes regulating arousal.

The attention network test (ANT), developed based on the triple-network taxonomy by Posner and colleagues, has been widely used to examine the efficacy of alerting, orienting, and executive control in clinical and developmental neuroscience studies. Recent research suggests the imperfect reliability of the behavioral ANT and its variants. However, the classical ANT fMRI task’s test-retest reliability has received little attention. Moreover, it remains ambiguous whether the attention-related intrinsic network components, especially the dorsal attention, ventral attention, and frontoparietal network, manifest acceptable reliability. The present study approaches these issues by utilizing an openly available ANT fMRI dataset for participants with Parkinson’s disease and healthy elderly. The reproducibility of group-level activations across sessions and participant groups and the test-retest reliability at the individual level were examined at the voxel, region, and network levels. The intrinsic network was defined using the Yeo-Schaefer atlas. Our results reveal three critical facets: (1) The overlapping of the group-level contrast map between sessions and between participant groups was unsatisfactory; (2) The reliability of alerting, orienting, and executive, defined as contrast between conditions, was worse than estimates of specific conditions. (3) Dorsal attention, ventral attention, visual, and somatomotor networks showed acceptable reliability for the congruent and incongruent conditions. Our results suggest that specific condition estimates might be used instead of the contrast map for individual or group-difference studies.

Affective Touch plays a pivotal role in regulating emotions, fostering social bonds, and nurturing affiliations with others. Its emotional and arousing dimensions rely on specific features of tactile stimulations characterizing gentle human caresses, such as touch velocity and the nature of the stroking source. While previous research has examined the physiological responses to these individual features of Affective Touch, no study has explored how they interact to shape autonomic activity. In this study, we investigated whether and how both the nature of the touching effector (Human hand vs. Artificial hand) and touch type (Dynamic vs. Static) influenced the participants’ pupil dilation and their subjective experience during tactile stimulation. We observed that when participants received a dynamic touch, they displayed an increase in pupil dilation when the touch was promoted by a human compared to an artificial hand, and that such discrimination was absent for static touch. Also, dynamic touch promoted by a human hand invoked a supralinear enhancement of pupil dilation indicating that the combination of these two features induced a significantly stronger autonomic activation than the summed effects of each separately. Moreover, this specific type of touch was perceived as the most pleasant compared to all other tactile stimulations. Overall, our results suggest that pupil dilation could map the pleasant experience of human-to-human tactile interactions, supporting the notion that the autonomic nervous system encodes the emotional and hedonic aspects associated with Affective Touch as a complex and holistic social experience, rather than solely responding to its low-level sensory properties.

Most scientist agree that subjective tinnitus is the pathological result of an interaction of damage to the peripheral auditory system and central neuroplastic adaptations. Here we investigate such tinnitus related adaptations in the primary auditory cortex (AC) 13 days after noise trauma induction of tinnitus by quantifying the density of the extracellular matrix (ECM) in the AC of Mongolian gerbils (Meriones unguiculatus). The ECM density has been shown to be relevant for neuroplastic processes and synaptic stability within the cortex. We utilized a mild monaural acoustic noise trauma in 9 gerbils to induce tinnitus and a sham exposure in 3 control animals. Tinnitus was assessed by a behavioral response paradigm. Four of the trauma animals did show tinnitus 13 days after trauma (T), the remaining 5 trauma (NT) and the 3 control animals (C) did not show the percept. The ECM density 13 days after trauma was quantified using immunofluorescence luminance of Wisteria floribunda lectin-fluoresceine-5-isothiocyanate (WFA-FITC) on histological slices of the primary AC, relative to the non-auditory brainstem as a reference area. We found that the WFA-FITC luminance of the AC of NT animals was not significantly different from that of C animals. However, we found a significant increase of luminance in T animals’ ACs compared to NT or C animals’ cortices. This effect was found exclusively on the AC side contralateral to the trauma ear. These results point to a process of stabilization of synaptic connections in primary AC, which may be involved in the chronic manifestation of tinnitus.

Regulatory cells are critical for maintaining immune homeostasis in the central nervous system. Regulatory cell populations have been reported to control neuroinflammation in neurodegenerative conditions like Parkinson’s disease, multiple sclerosis, myasthenia gravis, encephalomyelitis, and Alzheimer’s disease by protecting neurons through different mechanisms, including the production of cytokines such as IL-10 and TGF-β, promoting the expression of inhibitory receptors (PD1, TIM3, LAG3), and inducing tolerance through cell-cell interactions by CTLA-4. Various phenotypes of CD4+ and CD8+ regulatory T cells, Bregs, MDCS, and tolDCs have been described and, despite the great interest in their function, few studies have focused on elucidating their role in neurodegenerative diseases. Therefore, this review aims to describe the mechanisms of regulation and suppression of effector cells in neurodegenerative diseases. The study of these mechanisms has led to the development of therapeutic approaches targeting molecules with suppressive or regulatory activity in severe neurological disorders.

Research groups use the single motion stimulus design of Dr. D.Tadin ​(Tadin, Lappin, Gilroy & Blake, 2003) that allows to putatively assess spatio-contrast excitatory and inhibitory effects from duration threshold data of motion perception. The present work presents the correct neurocomputational model for this experimental design and analyses issues related to data and model comparisons, among which: (1) once the full computational model that predicts the psychophysical results is properly defined, it is shown that two low-level models of how inhibition acts on neuronal activity, i.e. “divisive inhibition” and “subtractive inhibition”, predict exactly the same thresholds and cannot arguably be claimed that one is better than another one, (2) it is excitatory and inhibitory processes that are the mechanisms shaping threshold changes, i.e. perceptual “facilitation” and “suppression” in the behavioural domain, (3) that this experimental design allows a quantitative comparison and usage of such “contrast–size tuning” data, (4) that such studies must be carefully designed once the model is correctly understood and applied, because of the rather large parameter space (~10-12 variables) necessary to explain the behavioural measures even in such simple experiments.

A document by Takeru Okouchi. Click on the document to view its contents.

Should we stay or should we go – the ever-growing role of Twitter (X) in Neuroscience dissemination and a quandary of conscience for a field.Kenneth A. Foxe and John J. Foxe

Nutrient deficiency, excitotoxic injury, and oxidative stress caused by cerebral ischemia/reperfusion injury are important inducing factors of mitophagy and ferroptosis in neurons. Ferroptosis is an iron-dependent mode of cell death usually accompanied by a large accumulation of iron ions and lipid peroxides. Mitophagy is one of the forms of selective autophagy, which can maintain mitochondrial and cellular homeostasis by eliminating dysfunctional mitochondria. Mitophagy and ferroptosis are closely related to the pathological mechanism of ischemia/reperfusion injury. However, the function and mechanism of mitophagy in regulating ferroptosis are only beginning to be understood, and the relationship between mitophagy and ferroptosis after cerebral ischemia/reperfusion has not been elucidated. This article reviews the mechanism pathways of mitophagy and ferroptosis after cerebral ischemia/reperfusion, especially discusses the common regulatory factors of mitophagy and ferroptosis in cerebral reperfusion injury, and focuses on the therapeutic potential of mitophagy in regulating ferroptosis, in order to provide ideas for targeted treatment of cerebral ischemia/reperfusion injury.