Biology subjects

Castelo-Branco, M.

Publications and source records attributed to Castelo-Branco, M..

At least 19 recordsLinked to original sources

bioRxiv2026

All signals considered: Data quality partially explains inter-individual task differences in a large, open fNIRS dataset

Significance: High inter-subject variability and limited reproducibility in functional near-infrared spectroscopy (fNIRS) research may partly reflect global systemic physiology and signal quality differences, possibly distorting task-evoked hemodynamic responses. Aim: We investigate how signal quality relates to inter-subject variability in motor-task fNIRS responses and introduce a large, open, multi-task, near whole-head fNIRS dataset with extensive peripheral physiology and short-channel recordings. Approach: Fifty-seven participants completed resting-state, motor action, motor imagery, emotion recognition, visual, and auditory tasks during fNIRS recording. Peripheral measures included pulse oximetry, heart rate, blood oxygen saturation, respiration, room temperature, galvanic skin response, electrocardiogram, and electromyography. Signal quality was assessed using the scalp coupling index (SCI), coefficient of variation (CV), signal-to-noise ratio (SNR) and a spectral measure here coined the coupling SNR (cSNR). Results: Quality metrics were weakly to moderately correlated, except SNR and CV, which showed the expected inverse relationship. All quality metrics were significantly related to channel length and associated with task-related activation estimates. Group-level analyses validated activation in expected task-related regions. Conclusions: The assessed metrics capture complementary features of fNIRS signal quality and may help explain individual activation differences. The dataset provides a comprehensive, open resource enabling future evaluation of physiological correction methods and confound mitigation.

neuroscience↗

bioRxiv2026

Impaired Sensory-motor Reconfiguration and Pupil-linked Arousal in Aging

Mounting evidence indicates impairments of decision-making and brainstem arousal systems in aging. To shed light on the relationship between these phenomena, we compared behavior and dynamics of pupil-linked arousal between older and younger adults during compositionally structured tasks. The main task required continuous online inference about hidden changes in the stimulus-response mappings required for reporting a perceptual categorization judgment. Accuracy in that task was reduced in older compared to younger adults, impairment specifically reflecting objective and subjective difficulty in switching between stimulus-response mappings: there was no age difference in tasks requiring only the online inference or only the perceptual categorization under stable stimulus-response mappings. Participant[s] pupils reliably dilated during the categorization judgment as well as moments of high probability of switches in the online inference process in both age groups. But only when the switches prompted a change in stimulus-response association in the main task, were these pupil responses deteriorated in older compared to younger adults. We propose that impaired cognitive engagement of arousal in aging might limit the sensory-motor reconfigurations required for behavioral flexibility. SIGNIFICANCE STATEMENTAging affects decision-making, but the computational and physiological basis of these alterations are poorly understood. Here, we show that older people are impaired in switching the association between sensation and action to support flexible decision-making. This flexible switching process recruits pupil-linked arousal systems of the brainstem in a manner that is altered in older compared to younger individuals. By contrast, we find that several other computational processes required for complex decision-making, including rapid online inference about uncertain environments, and the associated pupil-linked arousal responses, are largely unaffected in older people. Our findings implicate an aberrant cognitive recruitment of brainstem arousal systems in age-related problems in decision-making.

neuroscience↗

bioRxiv2026

A Neurofeedback therapy of facial expression recognition in Autism shifts connectivity to higher levels within the third visual pathway in relation to clinical improvements

The mechanistic role of the third visual pathway in autism spectrum disorder (ASD) remains unknown. We previously developed a neurofeedback therapy for autism targeting the posterior superior temporal sulcus (pSTS), a region in this network that underlies the perception and imagery of emotional facial expressions, resulting in improvements in adaptive behavior and recognition of fear in facial expressions. Here, we investigated the impact of this 5-session therapy on the functional connectivity of that core region of the third visual pathway. We found evidence for a profound reorganization of this network with treatment-induced decreases in connectivity between low-level visual areas, the pSTS, and the posterior occipital face area (OFA), and increased connectivity with higher-level visual regions (fusiform face area - FFA), right middle STS (mSTS), and parietal cortex. These changes, suggesting the restoration of connectivity in regions known to be underconnected in ASD, such as mSTS and pSTS, and in a set of regions belonging to the temporoparietal junction and the ventral attention network, which are known to be involved in broader aspects of social cognition, were positively associated with clinical improvements. The demonstration of treatment response associated with network reconfiguration paves the way for multicentric trials to probe this observed reorganization as a treatment target.

neuroscience↗

bioRxiv2025

Inhibitory control and error processing in Obsessive-Compulsive Disorder: A mega-analysis of task-based fMRI data by the ENIGMA-OCD consortium

ObjectiveObsessive-compulsive disorder (OCD) is a chronic condition in which impaired inhibitory control and excessive error monitoring may contribute to the maintenance of obsessions and compulsions. This mega-analysis investigates neural activation during response inhibition and error processing using adult and pediatric data from the ENIGMA-OCD consortium and the ABCD study. MethodsIndividual participant data was uniformly processed using HALFpipe to extract statistical maps for response inhibition and error processing contrasts. Bayesian multilevel models were used to assess regional and whole-brain effects of OCD, with additional analyses examining the association between the OCD clinical profile and task-related activation. ResultsAcross inhibitory control tasks, both individuals with OCD and control participants showed robust activation in regions implicated in response inhibition and error processing. During response inhibition, compared to controls, adults with OCD showed stronger somatomotor cortex activation, while children with OCD showed stronger occipital cortex activation. Children with likely OCD from the ABCD cohort showed reduced activity in the frontoparietal network in the anterior insula/frontal operculum region. During error processing, relative to controls, adults with OCD showed weaker activation in fronto-striatal regions, while children with OCD showed stronger activation in frontoparietal and attention networks. Greater OCD symptom severity was associated with weaker task-related activation in adults and stronger activation in children during response inhibition. ConclusionCase-control differences in brain activation during inhibitory control varied by age group and task contrast. Symptom severity emerged as the main clinical correlate of activation during inhibition, suggesting that inhibitory control deficits in OCD may be both state-dependent and developmentally specific.

neuroscience↗

bioRxiv2025

The novel phenomenon of inter-retinal coupling predicts cortical neurovascular responses in health and disease

It has recently been discovered that physiological crosstalk exists between human retinas. Accordingly, visual stimulation of one retina elicited a neurovascular coupling (NVC) response of the contralateral retina in about 30% of individuals. The functional significance of this feature in health and disease remains unknown. Here, we asked the question whether inter-retina crosstalk predicts the nature of neurovascular coupling in the brain. To test this hypothesis, we assessed BOLD fMRI (blood-oxygen-level-dependent functional magnetic resonance imaging signal) in healthy individuals and a disease model of neurovascular coupling, type 1 diabetes. We used three visual paradigms: a Threshold speed and Sub-maximum speed discrimination tasks, and flicker stimulation. The presence or absence of inter-retinal coupling was predictive of the time course of the cortical hemodynamic response, either during the initial or late phases. The presence of interocular coupling predicted larger BOLD responses. Diabetic patients with interocular coupling showed a very similar profile to the healthy group. In sum, we identified a direct relationship between interocular physiological coupling and cortical hemodynamic responses, suggesting that this NVC response may serve as a disease biomarker in diabetes. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=80 SRC="FIGDIR/small/684136v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@74ae56org.highwire.dtl.DTLVardef@61a2ccorg.highwire.dtl.DTLVardef@7349dorg.highwire.dtl.DTLVardef@10f61b2_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2025

AAV-mediated allele-specific silencing alleviates neuropathology in a novel non-human primate model of Spinocerebellar ataxia type 3

Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD), is an autosomal dominant neurodegenerative disorder caused by an abnormal expansion of the cytosine-adenine-guanine (CAG) repeats in the ATXN3 gene. This mutation results in the production of an Ataxin-3 protein with an extended polyglutamine sequence, contributing to the diseases neuropathology. Currently, no treatment is available that can slow or halt the progression of SCA3. Gene-targeted therapies have gained significant attention for their potential to address the root cause of SCA3. Preliminary studies in transgenic mice using adeno-associated viral vector serotype 9 (AAV9) encoding artificial microRNAs targeting the mutant ATXN3 allele (AAV9-miR-ATXN3) have shown promising results. However, to advance this therapeutic approach toward clinical application, further studies in an animal model that more closely resembles human biology are essential. In this exploratory study, we assessed the biodistribution and target engagement of AAV9-miR-ATXN3 delivered via intracisterna magna (ICM) injection in non-human primates (NHPs). Using a lentiviral vector (LV) to introduce a mutant Ataxin-3 cDNA with 72 glutamines (LV-mutATXN3-Q72) into the NHP cerebellum, we successfully overexpressed SCA3 in the NHP brain. SCA3 NHP exhibited Ataxin-3 aggregation in the cerebellum, recruitment of inflammatory cells and reduced cerebellar volume. ICM administration of AAV9-miR-ATXN3 effectively directed transgene expression to key brain regions impacted by SCA3 pathology and enabled specific, dose-dependent silencing of mutant Ataxin-3. Furthermore, the therapeutic dose prevented the cerebellar morphological and biochemical alterations induced by the overexpression of mutant ATXN3. These proof-of-concept experiments are crucial, not only for advancing AAV9-miR-ATXN3 toward clinical use but also for establishing a valuable platform for validating future therapeutic interventions.

molecular biology↗

bioRxiv2025

Neural correlates of emotional responses to self-selected music: evidence from multivariate pattern analysis

Music is a uniquely powerful stimulus for evoking complex and deeply felt emotions. While previous research has identified neural correlates of music-evoked emotional responses, less is known about how these felt emotions are represented in the brain, particularly when elicited by familiar, personally meaningful music. Here, we used a personalized fMRI paradigm in which participants (N = 20) each selected musical excerpts corresponding to the nine emotion categories defined by the Geneva Emotional Music Scale. These self-selected excerpts were presented during functional MRI scanning. We first examined the neural correlates of music-evoked emotion by comparing brain activity during music listening to that during exposure to white noise. The maps were consistent with previous research, highlighting clusters in sensory and limbic regions. We then used multivoxel pattern analysis to decode emotion categories from whole-brain activation patterns. The results revealed that music-evoked emotions could be reliably discriminated based on distributed neural activity, with consistent involvement of the superior temporal gyrus, supplementary motor area, amygdala, and cerebellum, among other auditory, motor, and interoceptive regions. These findings provide new insight into the neural encoding of musical emotions and highlight the value of personalized, music-based paradigms for research in auditory and affective neuroscience.

neuroscience↗

bioRxiv2025

Music as a real-time fMRI neurofeedback interface for modulating interhemispheric connectivity: effects on mood and recruitment of the putamen and insula

Music is a universal language that transcends cultures and is deeply rooted in human evolutionary history. Its creation and appreciation recruit the limbic and reward systems, leading to the evocation of emotions ranging from happiness and sadness to tenderness and grief. Here, we investigate the potential of music as an interventional tool in a novel neurofeedback connectivity-based experiment. This study proposes a musical interface for real-time fMRI neurofeedback that is adaptable to diverse experimental paradigms, namely the ones aiming at improving mood and other affective dimensions. Using a previously developed motor imagery connectivity-based approach, we evaluate its feasibility and efficacy by comparing the modulation of bilateral premotor cortex (PMC) activity during functional runs with real versus sham (random) feedback in 22 healthy adults. We also assess its performance against a visual feedback interface. The experiment involves a 50-minute MRI session, including anatomical scans, a PMC functional localizer run, and four neurofeedback runs (two with active feedback and two with sham feedback). Pre- and post-session questionnaires assess the neurobehavioral impact on mood, musical background (as a potential predictor of NF success), and subjective feedback experiences. During neurofeedback, participants perform motor imagery of finger-tapping, with feedback delivered as a dynamic, pre-validated chord progression that evolves or regresses based on the functional connectivity between left and right PMC. We found that our implementation of music-based feedback was successful, with participants managing to modulate their own connectivity using the proposed interface. The modulation performance was similar for active and sham NF runs, possibly due to the power of music to boost neuromodulation, but the network recruitment was stronger for active NF, including in the insula, putamen, and target ROIs. Behaviorally, we found a decrease in tension and an improvement in the overall mood of the participants after the session. When comparing our results to previous NF data with a visual interface, we found stronger brain activations, in particular in NF-relevant regions such as the insula and the putamen. This work shows that it is possible to directly modulate interhemispheric connectivity using a rt-fMRI musical interface with direct effects on mood and recruitment of saliency and learning networks.

neuroscience↗

bioRxiv2024

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 devices 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.

neuroscience↗

bioRxiv2024

Joint contribution of adaptation and neuronal population recruitment to response level in visual area MT: a computational model

Adaptation is a form of short-term plasticity triggered by prolonged exposure to a stimulus, often resulting in altered perceptual sensitivity to stimulus features through a reduction in neuronal firing rates. Experimental studies have explored adaptation to bistable stimuli, specifically a stimulus comprising inward-moving plaids that can be perceived as either a grating moving coherently downward or two plaids moving incoherently through each other. Functional magnetic resonance imaging (fMRI) recordings have shown higher activity during incoherent perception and lower activity during coherent stimulus perception. There are two potential explanations for the underlying neural mechanisms: a weaker coherent stimulus response may result from stronger adaptation to coherent versus incoherent motion, or a stronger incoherent stimulus response could stem from the involvement of more neural populations to represent motion in more directions. Here, we employ a computational model of visual neurons with and without firing rate adaptation to test these hypotheses. By simulating the mean activity of a network of thirty-two columnar populations of visual area MT, each tuned to one direction of motion, we investigate the impact of firing rate adaptation on the blood-oxygen-level-dependent (BOLD) signal generated by the network in response to coherent and incoherent stimuli. Our results replicate the experimental curves both during and after stimulus presentation only when the model includes adaptation, highlighting the importance of this mechanism. However, our findings reveal that the response to incoherent motion is larger than the response to coherent motion for a wide variety of stimulus parameters and adaptation regimes, suggesting that the observed reduced response to coherent stimuli is most likely due to the activation of smaller neuronal populations, in alignment with the second hypothesis. Hence, adaptation and differential neuronal recruitment work together to give rise to the observed hemodynamic responses. This computational work sheds light on experimental results and enriches our understanding of the mechanisms involved in neural adaptation, particularly in the context of heterogeneous neuronal populations.

neuroscience↗

bioRxiv2024

Decoding Music-Evoked Valence and Arousal: Unraveling the Neural Correlates of Naturalistic Music Characteristics through fMRI

Music can convey basic emotions, such as joy and sadness, and more complex ones, such as tenderness or nostalgia. Its effects on emotion regulation and reward have attracted much attention in cognitive and affective neuroscience. Understanding the neural correlates of music-evoked emotions may guide the development of neurorehabilitation interventions based on music. Here, we used fMRI to examine the relationship between the classification of music excerpts regarding perceived valence and arousal and their neural correlates. Twenty participants were scanned while listening to 96 musical excerpts, which were classified beforehand into four categories as a function of valence (positive vs. negative) and arousal (high vs. low). Differences in valence and arousal modulated activity in cortical regions, most noticeably the music-specific subregions of the auditory cortex, but also in the thalamus and regions of the reward network such as the amygdala. Using multivoxel pattern analysis, we created a computational model able to decode the valence and arousal of the music excerpts significantly above chance. We further explored how a set of musical features relate to brain activity in valence-, arousal-, reward-, and auditory-related ROIs. The results emphasize the differential involvement of musical features in the brain, notably expressive features such as Vibrato and Tonal and Spectral dissonance in valence, arousal, and reward brain networks, while a broader set of features modulate sensory auditory networks. Using ecologically valid music stimuli, we contribute to the definition of the neural substrates of music listening and evoked emotions. Moreover, the definition of the musical features that modulate specific brain networks paves the way to developing novel music-based neurorehabilitation strategies.

neuroscience↗

bioRxiv2024

The cortical heartbeat-evoked potential is modulated by heart rate in a task and mental effort dependent manner

Cardiac cycle duration, or interbeat interval (IBI), is the period from one heartbeat to the next. IBI changes from cycle to cycle. Periods with longer IBI are associated with higher sensitivity to external sensory stimuli (exteroception). Warning cues induce a state of attentive anticipation characterized by an increase in IBI (anticipatory cardiac deceleration) and faster reaction times. Ageing reduces the increase in IBI induced by warning cues and response speed. However, it is unclear which mechanism, if any, connects IBI with reaction time. The heartbeat-evoked potential (HEP) is a cortical response evoked by the heartbeat, modulated by attention and associated with sensitivity to external sensory stimuli. HEP might be affected by IBI and mediate the association between cardiac output and cortical processing. We investigated if the HEP was affected by warning cues as well as spontaneous fluctuations in IBI. To explore the impact of age-related changes in cardiac responses, we included young and older people [N = 33/29; 26/23 women; mean age 23/61 years]. We analysed the electroencephalograms and electrocardiograms simultaneously acquired during auditory cued simple reaction time and go/no-go tasks. The warning cue did not induce significant changes in the HEP. Yet, fluctuations in IBI (not locked with the warning cue) affected the HEP and HEP amplitude was associated with average reaction time in the older group. However, on a trial-by-trial basis, reaction time was independent from IBI fluctuations. In conclusion, we found no evidence that the HEP mediates the effect of attention orienting on reaction time.

neuroscience↗

bioRxiv2023

Unmasking Hidden Systemic Effects of Neurodegenerative Diseases: A Two-Pronged Approach to Biomarker Discovery

Identification of reliable blood biomarkers for neurodegenerative diseases (NDs) is crucial for translational and clinical research. However, conventional omics struggle with blood samples complexity, hindering desired outcomes. In this work the potential of High Molecular Weight (HMW) fractionation under non-denaturing conditions as a complementary approach to the conventional proteomics for identifying serum biomarkers in NDs was explored. A cohort of 58 serum samples of Alzheimers disease (AD), Parkinsons disease (PD) patients and control (CT) individuals was used to compare the two proteomics strategies: i) direct analysis of whole serum and ii) non-denaturing fractionation using 300 kDa cut-off filters (HMW serum). Although both approaches quantified a similar set of proteins, each approach captured a distinct subset of differentially altered proteins, suggesting that HMW fractionation identified additional types of alterations beyond conventional protein level changes. A discriminant model combining altered proteins from both datasets effectively distinguished between the three groups (AUC = 0.999 and median sensitivity and specificity of 97.4% and 91.7%, respectively). Importantly, this performance surpassed that of any model created using each method individually. Altogether, this work demonstrated that HMW fractionation can be a valuable complementary method to direct serum analysis and could enhance biomarker discovery. The 10 proteins included in the model (5 from each strategy), comprise clear evidence for the contribution of apolipoproteins for the diagnosis of NDs, revealing potential changes within lipid metabolism and the organization of macromolecules and their complexes, thereby uncovering effects that remain hidden from a conventional serum proteome analysis.

biochemistry↗

bioRxiv2023

Kisspeptin modulates sex-like phenotypes in the neonatal period

In recent years, our understanding of the physiological role of kisspeptin (Kiss1) has evolved significantly, revealing its pivotal role in shaping sexual differentiation within the brain. Predominantly expressed in the hypothalamus, Kiss1 plays a crucial role in regulating release of the gonadotrophin-releasing hormone (GnRH). Kisspeptin 1 receptor (Kiss1R) exhibits sex-dependent expression in various brain regions, including the medial amygdala and preoptic area (POA) of the hypothalamus, regions underlying sexual development. Importantly, in the critical period for the sexual development in mammals occurs a synchronized surge of Kiss1 and testosterone, highlighting its importance in sexual dimorphism. It has been suggested that the neonatal Kiss1 surge is associated with the buildup of gender-linked social development. We investigated this hypothesis by testing the effect of neonatal blockage of Kiss1 signaling on the sex-like phenotype in rats. We postulate that Kiss1 actions are both time and region-dependent, particularly during the neonatal period, having lasting impact on social interactions. For that we injected intracerebroventricular (ICV) a Kiss1R antagonist, Kp234, in the first 24h of life. Our data showed, that neonatal Kiss1 is determinant in modulating physiological responses, such as weight and testis development in males (N: males Veh = 10; males Kp234 = 10). Also, we document, for the first time, that Kiss1 modulates the testosterone surge in males and inhibits it in females (N: males Vehicle = 3; males Kp234 = 4; females Vehicle = 3; females Kp234 = 4). Furthermore, neonatal Kiss1 blockade modulated the sexual drive in, while the sexual performance in both sexes is maintained males (N: males Vehicle = 8; males Kp234 = 9; females Vehicle = 7; females Kp234 = 8). In conclusion, this study underscores the significance of Kiss1 during the neonatal period, a critical phase for sexual differentiation and neuroplasticity. Neonatal Kiss1 emerges as a key player in the development of a sex-like phenotype in rats. Additionally, our findings show dimorphic patterns in Kiss1 influence. This work raises the intriguing possibility that the early influence of Kiss1 in brain circuitry is pivotal in the modulation of gender and plays a role in the social construction of the bimodality of gender identity.

neuroscience↗

bioRxiv2023

Mapping functional traces of opioid memories in the rat brain

Addiction to psychoactive substances is a maladaptive learned behavior. Contexts surrounding drug use integrate this aberrant mnemonic process and hold strong relapse triggering ability. Here we asked where context and salience might be concurrently represented in the brain, and found circuitry hubs specific to morphine-related contextual information storage. Starting with a classical rodent morphine-conditioned place preference (CPP) apparatus, we developed a CPP protocol that allows stimuli presentation inside a magnetic resonance imaging scanner, to allow the investigation of whole brain activity during retrieval of drug-context paired associations, as well as resting state functional connectivity under the effect of morphine conditioning. Using fMRI we found context-specific responses to stimulus onset in multiple brain regions, namely limbic, sensory, and striatal. Furthermore, we found increased functional connectivity of lateral septum with regions within and beyond a proposed limbic network, and of the lateral habenula with hippocampal CA1 region, in response to repeated pairings of drug and context. Subsequent exposure to either morphine or saline-conditioned contexts led to significant, context-specific, functional interconnectivity among amygdala, lateral habenula, and lateral septum. Resting-state connectivity of the lateral habenula and amygdala, and that during saline-paired context presentation significantly predicted inter-individual CPP score differences. In sum, our findings show that drug- and saline-paired contexts form distinct memory traces in overlapping functional brain microcircuits, and intrinsic connectivity of habenula, septum, and amygdala likely influences the maladaptive contextual learning in response to opioids. We identify functional mechanisms involved in the acquisition and retrieval of drug-related memories that might be behind the relapse-triggering ability of opioid-associated sensory/contextual cues. Graphical abstractTo investigate the brain-wide regional activity underlying drug addiction Gomes-Ribeiro et al. have developed a rodent morphine-induced CPP (conditioned place preference) protocol whose contextual cues can be consistently presented inside an MRI apparatus. The authors found a common circuitry supporting the neural mechanisms responsible for memorizing an association between distinct contexts, and morphine or the absence thereof, that includes regions involved in affect, reward, contextual perception and memory, with subtle, intriguing, functional specificities ultimately underlying the storage of distinct, individual, CPP memory engrams across the different animals. Animals that are more prone to strong emotional responses (as measured by the baseline resting state amygdala and habenula functional connectivity), exhibit a kind of neural circuit priming effect, and thus develop stronger connectivity patterns in anticipation of stronger morphine addiction behavior. These findings could help to clarify the inter-individual sensitivity to opioids in humans, since despite responding positively to the effects of opioids, many humans do not develop an addiction. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=138 SRC="FIGDIR/small/552221v2_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@1cd4989org.highwire.dtl.DTLVardef@96c76corg.highwire.dtl.DTLVardef@feadd0org.highwire.dtl.DTLVardef@4547b6_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2023

A human cortical adaptive mutual inhibition circuit underlying competition for perceptual decision and repetition suppression reversal

A model based on inhibitory coupling has been proposed to explain perceptual oscillations. This adapting reciprocal inhibition model postulates that it is the strength of inhibitory coupling that determines the fate of competition between percepts. Here, we used an fMRI-based adaptation technique to reveal the influence of neighboring neuronal populations, such as reciprocal inhibition, in motion-selective hMT+/V5. If reciprocal inhibition exists in this region, the following predictions should hold: 1. stimulus-driven response would not simply decrease, as predicted by simple repetition-suppression of neuronal populations, but instead increase due to the activity from adjacent populations; 2. perceptual decision involving competing representations, should reflect decreased reciprocal inhibition by adaptation; 3. neural activity for the competing percept should also later on increase upon adaptation. Our results confirm these three predictions, showing that a model of perceptual decision based on adapting reciprocal inhibition holds true. Finally, they also show that the well-known repetition suppression phenomenon can be reversed by this mechanism. Significance StatementfMRI-based adaptation has been developed as a tool to identify functional selectivity in the human brain. This is based on the notion that stimulus-selective adaptation leads to direct response suppression. In this study, we go a step further by showing that adaptation can also reveal the influence of neighboring neuronal populations. Our data reveals neural evidence for a disinhibition effect as a result of the adaptation of adjacent populations, which is in line with the adapting reciprocal inhibition model. Reciprocal inhibition can, thus, be tracked in the human brain using fMRI, adding to the understanding of human multistable perception and the neural coding of visual information. Moreover, our results also provide a mechanism for reversal of repetition suppression.

neuroscience↗

bioRxiv2023

Subtractive adaptation is a more effective and general mechanism in binocular rivalry than divisive adaptation

The activity of neurons is influenced by random fluctuations and can be strongly modulated by firing rate adaptation, especially in sensory systems. Still, there is an ongoing debate about the characteristics of neuronal noise and the mechanisms of adaptation, and even less is known about how exactly they affect perception. Noise and adaptation play central roles in binocular rivalry, a visual phenomenon where two images compete for perceptual dominance. Here, we investigated the effects of different noise processes and adaptation mechanisms on visual perception by simulating a model of binocular rivalry with Gaussian white noise, Ornstein-Uhlenbeck noise, and pink noise, in variants with divisive adaptation, subtractive adaptation, and without adaptation. By simulating the nine versions of the model for a wide range of parameter values, we find that white noise only produces rivalry when paired with subtractive adaptation and that subtractive adaptation reduces the influence of noise intensity on rivalry strength and introduces convergence of the mean percept duration, an important metric of binocular rivalry, across all noise processes. In sum, our results show that white noise is an insufficient description of background activity in the brain and that subtractive adaptation is a stronger and more general switching mechanism in binocular rivalry than divisive adaptation, with important noise-filtering properties. Author SummaryVisual neurons adapt to the environment by reducing the number of spikes evoked by a constant stimulus. They are also susceptible to random spikes produced by nearby neurons. These two phenomena, adaptation and noise, are essential features of brain activity and affect how we perceive the world. Although we know a great deal about the visual system, our understanding of the properties and mechanisms of neuronal noise and adaptation is still piecemeal, and even less is known about how these microscopic processes affect macroscopic behaviors. We shed light on this question by studying a bistable visual phenomenon called binocular rivalry, where two images compete for perception and where noise and adaptation play important roles. We simulated the activity of neurons involved in binocular rivalry to test different hypotheses about the statistics of neuronal noise and the mechanisms of adaptation. Our results reveal important differences between subtractive and divisive adaptation, suggesting that subtractive adaptation is a stronger switching mechanism in binocular rivalry and an effective noise filter. Our simulations also show the fundamental distinction between noise with and without temporal correlation, supporting the correlated noise hypothesis.

neuroscience↗

bioRxiv2022

Pilot MRI study of carbon monoxide (CO) against ischemic stroke in mice: blood brain barrier integrity and metabolic pattern

Although stroke is the main cause of brain damage worldwide, stroke therapies are based on blood reperfusion and do not target cerebral parenchyma. Ischemic stroke (representing 87% of all strokes) causes cerebral damage due to oxygen and tissue energy depletion, which lead to acidosis, inflammation, excitotoxicity and oxidative stress. Carbon monoxide (CO) is an endogenous gasotransmitter produced by heme oxygenase cleavage of the heme group. CO promotes cytoprotection by limiting inflammation and preventing cell death in several tissues including the brain. Previous studies have demonstrated the protective role of CO in the mouse ischemic stroke model, middle cerebral artery occlusion (MCAo) by histological analysis when CO is when applied before ischemia. Herein, there are two main novelties. First CO is administrated following stroke, which better mimics its potential future use as therapeutic drug. Secondly, imaging techniques were used to elucidate the effect of this gasotransmitter at the metabolic, vascular and anatomic levels. The putative neuroprotective effects of CO following MCAo were assessed by 3 i.p. injections of the CO-releasing molecule CORM-A1 (3 mg/kg), administered 6, 24 and 48h after reperfusion. Magnetic Resonance Imaging was performed 1 day and 7 days after reperfusion using T2-weighted, diffusion weighted images, proton spectroscopy (1H-MRS) and perfusion (dynamic contrast enhanced images). 1H-MRS also allowed the comparison between metabolite signatures at day 1 versus 7 day following MCAo. Furthermore, CORM-A1 limited the loss of blood-brain barrier (BBB) integrity as it reduced the edema formation. Furthermore, the CO donor minimized the metabolite load loss at an early stage after MCAo, both in striatum and cortex. In conclusion and based on MRI analysis, CO has a protective role in the recovery from stroke injury, mainly by acting on BBB integrity and brain metabolism.

neuroscience↗