bioRxiv Subject Collection: Neuroscience's Journal
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Saturday, June 1st, 2024
| Time |
Event |
| 5:35a |
Time-resolved coupling between connectome harmonics and subjective experience under the psychedelic DMT
Exploring the intricate relationship between brain's structure and function, and how this affects subjective experience is a fundamental pursuit in neuroscience. Psychedelic substances offer a unique insight into the influences of specific neurotransmitter systems on perception, cognition and consciousness. Specifically, their impact on brain function propagates across the structural connectome, a network of white matter pathways linking different regions. To comprehensively grasp the effects of psychedelic compounds on brain function, we used a theoretically rigorous framework known as connectome harmonic decomposition. This framework provides a robust method to characterize how brain function intricately depends on the organized network structure of the human connectome. We show that the connectome harmonic repertoire under DMT is reshaped in line with other reported psychedelic compounds; psilocybin, LSD and ketamine. Furthermore, we show that the repertoire entropy of connectome harmonics increases under DMT, as with those other psychedelics. Importantly, we demonstrate for the first time that measures of energy spectrum difference and repertoire entropy of connectome harmonics indexes the intensity of subjective experience of the participants in a time-resolved manner reflecting close coupling between connectome harmonics and subjective experience. | | 5:35a |
Congruency effects on object recognition persist when objects are placed in the wild: An AR and mobile EEG study
Objects in expected locations are recognised faster and more accurately than objects in incongruent environments. This congruency effect has a neural component, with increased activity for objects in incongruent environments. Studies have increasingly shown differences between neural processes in realistic environments and tasks, and neural processes in the laboratory. To what extent do findings obtained from a laboratory setting translate to neural processes elicited in real-world environments? We investigated how object recognition is modulated when objects are placed in real environments using augmented reality while recording mobile EEG. Participants approached, viewed, and rated how congruent they found the objects with the environment. We found significantly higher theta-band power for objects in incongruent contexts than objects in congruent contexts. This demonstrates that real-world contexts impact on how we recognize objects, and that mobile brain imaging and augmented reality are effective tools to study cognition in the wild. | | 11:15a |
Bilateral integration in somatosensory cortex is controlled by behavioral relevance
Sensory perception naturally requires processing stimuli from both sides of the body. Yet, how neurons bind stimulus features across the hemispheres to create a unified perceptual experience remains unknown. To address this question, we performed large-scale recordings from neurons in both somatosensory cortices (S1) while mice shared information between their hemispheres and discriminated between two categories of bilateral stimuli. When expert mice touched stimuli associated with reward, they moved their whiskers with greater bilateral symmetry. During this period, synchronous spiking and enhanced spike-field coupling emerged between the hemispheres. This coordinated activity was absent in stimulus-matched naive animals, indicating that interhemispheric (IH) binding was controlled by a goal-directed, internal process. In S1 neurons, the addition of ipsilateral touch primarily facilitated the contralateral, principal whisker response. This facilitation primarily emerged for reward-associated stimuli and was lost on trials where expert mice failed to respond. Taken together, these results reveal a novel state-dependent logic underlying bilateral integration in S1, where stimulus binding and facilitation are controlled by behavioral relevance. | | 11:15a |
Mapping and Modeling the Semantic Space of Math Concepts
Mathematics is an underexplored domain of human cognition. While many studies have focused on subsets of math concepts such as numbers, fractions, or geometric shapes, few have ventured beyond these elementary domains. Here, we attempted to map out the full space of math concepts and to answer two specific questions: can distributed semantic models, such a GloVe, provide a satisfactory fit to human semantic judgments in mathematics? And how does this fit vary with education? We first analyzed all of the French and English Wikipedia pages with math contents, and used a semi-automatic procedure to extract the 1,000 most frequent math terms in both languages. In a second step, we collected extensive behavioral judgments of familiarity and semantic similarity between them. About half of the variance in human similarity judgments was explained by vector embeddings that attempt to capture latent semantic structures based on cooccurence statistics. Participants' self-reported level of education modulated familiarity and similarity, allowing us to create a partial hierarchy among high-level math concepts. Our results converge onto the proposal of a map of math space, organized as a database of math terms with information about their frequency, familiarity, grade of acquisition, and entanglement with other concepts. | | 12:31p |
Running, Fast and Slow: The Dorsal Striatum Sets the Cost of Movement During Foraging
During reward-oriented behaviors, animals -including humans- spontaneously adjust the speeds of their decisions and movements based on dynamically changing costs and benefits. The mechanisms constraining these adaptive modulations remain unclear, especially in freely moving animals. Here, we developed a naturalistic foraging task in which rats decided when and how fast to run across a motorized treadmill to collect rewards. Model-based analyses explained why decision and movement speeds were coupled or decoupled as rats adapted to changes in reward value or motor cost, respectively. Moreover, lesions of the dorsal striatum increased the animals' sensitivity to motor cost, limiting their running speed in the most effortful conditions while sparing reward-related behavioral modulations. Altogether, our study describes how neuroeconomic constraints influence decision and movement speeds in foraging rats, and paves the way for a refined understanding of the role of the basal ganglia in motor control and decision-making. | | 12:31p |
Melanocortin 4 receptor-expressing neurons in the lateral stripe of the striatum are involved in affect regulation and motor control
The dopaminergic system is crucial for affect regulation. Melanocortin 4 receptors (MC4R) in the ventral striatum have been shown to be necessary for establishing aversive states. Here, we set out to functionally characterize MC4R-expressing striatal neurons. MC4Rs were enriched in atypical Dopamine receptor 1 (D1) neurons in the lateral stripe of the striatum (LSS), an understudied area in the ventrolateral striatum. Fiber photometry recordings showed that MC4R neuron activity and local dopamine release in the LSS were increased by rewarding as well as aversive stimuli. Moreover, MC4R neuronal activity and glutamate release correlated strongly to body movement. Optogenetic activation of MC4R-LSS neurons was rewarding in a real-time place preference test and a self-stimulation paradigm, increased locomotor activity and induced striatal dopamine release. Collectively, our findings suggest that MC4R-LSS neurons are activated by salient stimuli of both rewarding and aversive character and that they induce positive affect, dopamine release and locomotion. | | 12:31p |
Balancing Prior Knowledge and Sensory Data in a Predictive Coding Model: Insights into Coherent Motion Detection in Schizophrenia
This study introduces a biologically plausible computational model based on the predictive coding algorithm, providing insights into motion detection processes and potential deficiencies in schizophrenia. The model decomposes motion structures into individual and shared sources, highlighting a critical role of surround suppression in detecting global motion. This biologically plausible model sheds light on how the brain extracts the structure of motion and comprehends shared or coherent motion within the visual field. The results obtained from random dot stimuli underscore the delicate balance between sensory data and prior knowledge in coherent motion detection. Model testing across varying noise levels reveals increasing convergence time with higher noise, aligning with psychophysical experiments that show an increase in the response duration with an increase in the level of noise. The model suggests that an excessive emphasis on prior knowledge extends the convergence time in motion detection. Conversely, for faster convergence, the model requires a certain level of prior knowledge to prevent excessive disturbance due to noise. These findings contribute potential explanations for motion detection deficiencies observed in schizophrenia. | | 1:48p |
Cortex deviates from criticality during action and deep sleep: a temporal renormalization group approach
The hypothesis that the brain operates near criticality explains observations of complex, often scale-invariant, neural activity. However, the brain is not static, its dynamical state varies depending on what an organism is doing. Neurons often become more synchronized (ordered) during unconsciousness and more desynchronized (disordered) in highly active awake conditions. Are all these states equidistant from criticality; if not, which is closest? The fundamental physics of how systems behave near criticality came from renormalization group (RG) theory, but RG for neural systems remains largely undeveloped. Here we developed a temporal RG (tRG) theory for analysis of typical neuroscience data. We mathematically identified multiple types of criticality (tRG fixed points) and developed tRG-driven data analytic methods to assess proximity to each fixed point based on relatively short time series. Unlike traditional methods for studying criticality in neural systems, our tRG approach allows time-resolved measurements of distance from criticality in experiments at behaviorally relevant timescales. We apply our approach to recordings of spike activity in mouse visual cortex, showing that the relaxed, awake state is closest to criticality. When arousal shifts away from this state - either increasing in more active awake states or decreasing in deep sleep - cortical dynamics deviate from criticality. | | 4:33p |
Utilizing tACS to enhance memory confidence and EEG to predict individual differences in brain stimulation efficacy
The information transfer necessary for successful memory retrieval is believed to be mediated by theta and gamma oscillations. These oscillations have been linked to memory processes in electrophysiological studies, which were correlational in nature. In the current study, we used transcranial alternating current stimulation (tACS) to externally modulate brain oscillations to examine its direct effects on memory performance. Participants received sham, theta (4 Hz), and gamma (50 Hz) tACS over frontoparietal regions while retrieving information in a source memory paradigm. Linear regression models were used to investigate the direct effects of oscillatory non-invasive brain stimulation (NIBS) on memory accuracy and confidence. Our results indicate that both theta and gamma tACS altered memory confidence. Specifically, theta tACS seemed to lower the threshold for confidence in retrieved information, while gamma tACS appeared to alter the memory confidence bias. Furthermore, the individual differences in tACS effects could be predicted from electroencephalogram (EEG) measures recorded prior to stimulation, suggesting that EEG could be a useful tool for predicting individual variability in the efficacy of NIBS. | | 4:33p |
The functional and pathogenic consequences of fibrinogen on human oligodendroglia
Objective: Multiple sclerosis is an inflammatory demyelinating disorder associated with blood-brain-barrier breakdown, where myelin repair is reduced and ultimately fails. Our aim was to investigate the effect of a systemically circulating molecule fibrinogen, which is abnormally present in the central nervous system as a result of blood-brain barrier breakdown on human oligodendrocyte lineage cells. Methods: In situ immunofluorescence was performed using anti-fibrinogen and anti-SOX10 antibodies. Mature oligodendrocytes and late progenitors were derived from brain tissue from pediatric and adult donors. Early progenitors were generated from human induced pluripotent stem cells. Following fibrinogen addition to each of these cultures, cell viability and functional capacity was evaluated. Downstream signalling following fibrinogen exposure was confirmed by immunofluorescence microscopy and bulk RNA sequencing. Results: In situ studies showed fibrinogen on SOX10-positive oligodendrocytes in multiple sclerosis, both in plaques and normal-appearing white matter, and white matter in amyotrophic lateral sclerosis. In response to in vitro exposure to fibrinogen, mature oligodendrocytes showed increased ensheathment capacity and upregulation of lipid synthesis, whereas pediatric-age late oligodendrocyte precursors showed a decrease. Early precursors were unable to differentiate but expressed astrocytic markers and increased proliferation. Fibrinogen-exposed cells show bone morphogenetic protein signalling, more prominently in mature oligodendrocytes. Interpretation: We demonstrate that fibrinogen is deposited on oligodendrocytes in multiple sclerosis and has distinct functional consequences dependent on cell lineage stage. Our findings derived using human OL lineage cells suggest fibrinogen may be beneficial for myelin maintenance by mature oligodendrocytes, while preventing earlier lineage cells from differentiating and repairing multiple sclerosis lesions. | | 4:33p |
Accumulated reserves hold back age-related neural compensation in speech-in-noise perception
Recruitment of neural activity or functional connectivity is commonly observed in older adults but poorly understood. We measured brain activity with fMRI during speech-in-noise tasks and assessed whether accumulated reserve accrued through musical training bolsters or holds back age-related neural compensation. Older musicians exhibited less upregulation of task-induced functional connectivity than older non-musicians in dorsal regions, which predicted better behavioral performance in older musicians. The findings suggest that accumulated reserve may hold back neural recruitment. Besides functional connectivity strength, we also found that older musicians showed more youth-like fine spatial patterns of functional connectivity than older non-musicians. However, benefits from visual lip movements were not specific to either hypothesis. Aligning with enhanced benefits in behavioral performance, older musicians showed more extensive functional connectivity enhancement, specifically in the right hemisphere, than older non-musicians. Our findings enlightened the intricate interplay between accumulated reserve and age-related neural compensation during speech in noise perception. | | 4:33p |
Brain representation in conscious and unconscious vision
The development of robust frameworks to understand how the human brain represents conscious and unconscious perceptual contents is paramount to make progress in the neuroscience of consciousness. Recent functional MRI studies using multi-voxel pattern classification analyses showed that unconscious contents could be decoded from brain activity patterns. However, decoding does not imply a full understanding of neural representations. Here we re-analysed data from a high-precision fMRI study coupled with representational similarity analysis based on convolutional neural network models to provide a detailed information-based approach to neural representations of both unconscious and conscious perceptual content. The results showed that computer vision model representations strongly predicted brain responses in ventral visual cortex and in fronto-parietal regions to both conscious and unconscious contents. Moreover, this pattern of results generalised when the models were trained and tested with different participants. Remarkably, these observations results held even when the analysis was restricted to observers that showed null perceptual sensitivity. In light of the highly distributed brain representation of unconscious information, we suggest that the functional role of fronto-parietal cortex in conscious perception is unlikely to be related to the broadcasting of information, as proposed by the global neuronal workspace theory, and may instead relate to the generation of meta-representations as proposed by higher-order theories. | | 4:33p |
Different varieties of arousal converge on a shared cortical network
The term arousal is very often used, but with surprisingly few attempts at defining what arousal is and whether its usage in different domains relies on common grounds. The huge number of scientific articles using the term arousal (~50.000) highlights the importance of the concept, but also explains why such a vast literature had never been systematically reviewed so far. Here, we leverage the tools of natural language processing to probe the nature of arousal in a data-driven, comprehensive manner. We show that arousal comes in seven varieties: cognitive, emotional, physiological, sexual, related to stress disorders, to sleep, or to sleep disorders. Meta-analyses of the brain imaging literature further reveal that all varieties of arousal, except arousal in sleep disorders for lack of data, converge onto a domain-general cortical arousal network composed of the pre-supplementary motor area and the left and right dorsal anterior insula. More precisely, we found that dysgranular insular area 7, the region with highest convergence across varieties of arousal, also shows activation specific to arousal. Our results show that arousal corresponds to a construct at least partially shared across different domains of neuroscience. | | 4:33p |
Caffeine induces age-dependent increases in brain complexity and criticality during sleep
Caffeine is the most widely consumed psychoactive stimulant worldwide. Yet important gaps persist in understanding its effects on the brain, especially during sleep. We analyzed sleep EEG in 40 subjects, contrasting 200mg of caffeine against a placebo condition, utilizing inferential statistics and machine learning. We found that caffeine ingestion led to an increase in brain complexity, a widespread flattening of the power spectrum's 1/f-like slope, and a reduction in long-range temporal correlations. Being most prominent during non-REM sleep, these results suggest that caffeine shifts the brain towards a critical regime and more diverse neural dynamics. Interestingly, this was more pronounced in younger adults (20-27 years) compared to middle-aged participants (41-58 years) whose sleep brain dynamics were less affected by caffeine. Interpreting these data in the light of modeling and empirical work on EEG-derived measures of excitation-inhibition balance provides novel insights into the effects caffeine has on the sleeping brain. | | 6:30p |
Alpha Synuclein Induced Immune Response Triggers Parkinson's Disease Like Symptoms
Increasing evidence suggests that Parkinson's disease is an autoimmune disorder, with findings of elevated peripheral blood mononuclear cell in patients, and antigenic properties of alpha synuclein driving both the innate and adaptive immunity. Yet, how the interaction of alpha synuclein and a specific immune response participates to Parkinson's disease ontogenesis has remained unanswered. Here, we reveal that autoimmune response to an alpha synuclein antigen underlies Parkinson's disease. We demonstrate that autoimmunity mediated by CD4+T cell activation with alpha synuclein alpha syn61-75 antigen is required to lead to immune cell infiltration and localized inflammation in the substantia nigra, triggering dopaminergic cell neurodegeneration and deficits in locomotion and gait kinematics. This study offers the first immune-induced mouse model that recapitulates all features of Parkinson's disease to study the mechanisms triggering disease onset. It provides the basis for temporally tracking symptom development, exploring preventive strategies and prodromal therapeutic interventions in Parkinson's Disease. | | 6:30p |
Development and assessment of a new multichannel electrocutaneous device for non-invasive somatosensory stimulation for magnetic resonance applications
Electrocutaneous stimulation (ES) relies on the application of an electrical current flowing through the surface of the skin, eliciting a tactile percept. It can be applied for somatosensory mapping approaches at functional magnetic resonance imaging (fMRI) to obtain somatotopic maps illustrating the spatial patterns reflecting the functional organization of the primary somatosensory cortex (S1). However, its accessibility remains constrained, particularly in applications requiring multiple stimulation channels. Furthermore, the magnetic resonance (MR) environment poses several limitations in this regard. This study presents a prototype of a multichannel electrocutaneous stimulation device designed for somatosensory stimulation of the upper limbs of human participants in an MR environment in an inexpensive, safe, customizable, controlled, reproducible, and automated way. Our current-controlled, voltage-limited, stimulation device comprises 20 stimulation channels that can be individually configured to deliver various non-simultaneous combinations of personalized electrical pulses, depending on the subject, stimulation site, and stimulation paradigm. It can deliver a predefined electrical stimulus during fMRI acquisition, synchronized with the stimulation task design and triggered upon initiation of the acquisition sequence. Regarding device assessment, we conducted tests using an electrical circuit equivalent to the impedance of the human body and the electrode-skin interface to validate its feasibility. Then, we evaluated user acceptability by testing the device in human participants. Considering the stringent conditions of the MR environment, we performed a comprehensive set of safety and compatibility evaluations using a phantom. Lastly, we acquired structural and functional MR data from a participant during a somatosensory stimulation experiment to validate brain activity elicited by electric stimulation with our device. These assessments confirmed the device's safety in fMRI studies and its ability to elicit brain activity in the expected brain areas. The scope of application of our device includes fMRI studies focused on somatosensory mapping and brain-computer interfaces related to somatosensory feedback. |
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