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Garrido, M.

Publications and source records attributed to Garrido, M..

At least 19 recordsLinked to original sources

Predictability and controllability shape aversive learning and stress responses through independent computational mechanisms

BACKGROUND: An individual's adaptation to threatening environments under uncertainty is reflected in stress responses. Predictability (the ability to anticipate events) and controllability (the ability to control outcomes) are central to how one adapts, yet their joint influence on aversive learning remains unclear. METHODS: Thirty healthy adults completed a probabilistic aversive learning task in which cue-outcome contingencies varied across levels of predictability and controllability, i.e. whether shock intensity depended on prediction accuracy. Prediction accuracy, reaction time, subjective stress ratings, and skin conductance responses were recorded throughout. Trial-wise learning dynamics were estimated using the Volatile Kalman Filter. RESULTS: Prediction accuracy reduced as environments became less predictable and negatively associated with higher learning rates across predictability levels, with the strongest relationship observed in highly predictable blocks. Skin conductance responses showed that moderately predictable environments elicited responses like those in highly predictable environments when accurate predictions reduced shock intensity, but resembled responses in unpredictable environments when shock intensity was uncontrollable. Model comparison revealed a double dissociation between subjective stress ratings and skin conductance responses. Subjective ratings were best explained by model-derived volatility when prediction accuracy determined shock intensity and by belief uncertainty when it was independent of prediction accuracy, whereas skin conductance responses showed the reverse pattern. Reaction times were best explained by belief uncertainty when predictions influenced shock intensity. Higher anxiety was associated with elevated learning rates in highly and moderately predictable blocks when predictions did not control shock intensity.

neuroscience↗

Prior-Likelihood Metamers to Distinguish Strategies Underlying Human Bayesian Behaviour in Perception

Bayesian decision theory proposes that people make statistically rational decisions by combining prior knowledge with sensory information (likelihoods). This framework successfully explains many aspects of human behaviour. However, debate persists over whether people perform precise Bayesian computations (i.e., explicit Bayesian strategy) or rely on less demanding strategies - such as approximations or heuristics - that produce Bayesian-like behaviour (i.e., implicit Bayesian strategy). To address this, we examined people's sensitivity to metamers: different prior-likelihood combinations yielding identical optimal policies. An explicit Bayesian observer would show a temporary performance drop immediately after a switch of prior-likelihood combination, followed by recovery, reflecting prior updating. In two studies, we trained participants to estimate hidden target locations drawn from a Gaussian prior. On each trial, scattered dots provided likelihood information. Over time, participants learned the prior and combined it with likelihood information to infer target locations. We then covertly introduced an untrained prior-likelihood metamer. Unlike explicit Bayesian observers, participants' performance declined after the switch and persisted throughout the untrained pair presentation. This finding challenges strict Bayesian interpretations of task performance and suggests that participants rely instead on likelihood-sensitive strategy that is neither explicit Bayesian nor does it not fully integrate prior information. Our study demonstrates how metamer manipulations can distinguish behaviour that merely appears Bayesian, from behaviour genuinely produced by Bayesian computations, and calls for the use of metamers for ruling out alternative explanations of Bayesian-like behaviours.

neuroscience↗

Testing the Spatiotemporal Predictions of Global Neuronal Workspace Theory and Integrated Information Theory

The neural mechanisms underlying conscious perception remain contested, with global neuronal workspace theory (GNWT) and integrated information theory (IIT) offering divergent predictions about the spatiotemporal dynamics of conscious processing. The Cogitate Consortium (2025) recently conducted a large-scale adversarial collaboration to arbitrate between GNWT and IIT; however, some of their analyses yielded mixed findings. As the original study relied on functional connectivity, it could not assess the directed neural influences required to directly test the mechanistic claims of these theories. Here, we re-examined the Cogitate Consortiums MEG dataset (N = 100) using dynamic causal modelling (DCM) to test the effective connectivity profiles predicted by each theory during task-irrelevant face perception. We adopted a split discovery-validation procedure and an expanding time-window approach to track the temporal evolution of prototypical networks for each theory. Specifically, we evaluated GNWTs prediction of phasic prefrontal "ignition" by testing the necessity of PFC feedback to category-selective areas at stimulus onset and offset, and then tested IITs prediction of sustained posterior integration by testing extrinsic feedback and intrinsic connectivity within content-specific regions. We found support for both GNWT predictions of prefrontal ignition at stimulus onset and offset; noting that the latter was not previously observed in the original Cogitate analyses. For IIT, whilst feedback connectivity between the fusiform gyrus and primary visual cortex was not sustained throughout the stimulus duration, intrinsic fusiform gyrus connectivity was broadly consistent with IITs prediction of sustained processing within a content-specific substrate. However, a post-hoc validation analysis comparing face- and object-specific DCM networks did not yield strong evidence for face selectivity at any time window (pp< 0.95), warranting a conservative interpretation of the IIT findings in particular.

neuroscience↗

Weakening of subcortical and strengthening of cortical visual pathways across early adolescence

BackgroundMounting evidence suggests that amygdalar nuclei receive visual information via both a well-characterized cortical pathway through the inferior temporal cortex and a subcortical route through the superior colliculus and pulvinar. This subcortical pathway may facilitate rapid responses to salient visual stimuli and could explain phenomena such as blindsight. However, controversies remain about the organization of the subcortical pathway, its role in visual processing, and how the cortical and subcortical pathways mature across development. MethodsTo address these questions we used longitudinal diffusion magnetic resonance imaging (dMRI) data from 4361 participants in the Adolescent Brain Cognitive Development (ABCD) study, reconstructing every major segment of the cortical and subcortical amygdala pathways. We tested the existence of the subcortical pathway against null tractography models, characterized cortical and subcortical pathways development across early adolescence, and investigated their association with visual processing speed. ResultsWe provide evidence for the existence of bilateral pulvinar-amygdala pathways against a null model (all p < 0.001, corrected). While cortical tracts involving the primary and extrastriate visual cortex and the inferior-temporal cortex strengthened with chronological age and over pubertal development, we demonstrate that subcortical pulvinar-amygdala connectivity decreased over pubertal development. Greater connectivity strength of the right pulvinar-amygdala tract was associated with faster responses on a visual task for both emotional face and place stimuli, a relationship also seen for cortical tracts. ConclusionThis study provides evidence for the existence of pulvinar to amygdala tracts in the largest sample of adolescent participants studied to date. Greater connectivity in both cortical and subcortical tracts were associated with faster reaction time on a visual task, but further work will be needed to investigate the specificity of this association in terms of both task and tract. In line with the hypothesized importance of the subcortical pathway in early development, we show that the developmental trajectories of cortical and subcortical pathways diverge and highlight the influence of pubertal development, with cortical pathways generally strengthening and subcortical pathways weakening across early adolescence.

neuroscience↗

Movements and habitat use of the invasive blue crab Callinectes sapidus in a Mediterranean coastal lagoon

The Atlantic blue crab (Callinectes sapidus), an invasive and ecologically impactful decapod species, has rapidly proliferated across the Mediterranean Sea, prompting concerns over its effects on native ecosystems and local economies. Despite its growing presence, knowledge of its behavioural ecology in Mediterranean coastal systems remains limited. This study presents the first acoustic telemetry-based assessment of C. sapidus within its invasive range, focusing on movement patterns, activity levels, and habitat preferences in Biguglia Lagoon, Corsica (Northwestern Mediterranean). In 2023, 31 adult crabs (20 males, 11 females) were tagged and tracked over four months. Accelerometer data revealed distinct diel activity patterns, with females exhibiting significantly higher walking and swimming behaviours, while males were more sedentary, particularly at night. Salinity preferences varied by sex: females occupied higher-salinity zones, likely linked to reproductive behaviour, while males favoured lower salinity areas. Females also travelled greater distances and had larger, more variable home ranges, with some individuals extending into adjacent marine environments. Although no berried females were tagged, detections at sea suggest early seaward migrations by non-ovigerous and potentially ovigerous females. These findings underscore the species behavioural plasticity and sex-specific ecological strategies. The integration of telemetry and environmental data offers critical insights into the spatial ecology of C. sapidus, informing targeted management strategies. This research directly supported Corsicas first Territorial Control Plan for marine invasive species and provides a framework for adaptive management across other Mediterranean regions facing similar ecological challenges. HighlightsO_LIFirst telemetry study of blue crab in Mediterranean invasive range C_LIO_LIFemales showed higher activity and larger home ranges than males C_LIO_LICrabs displayed sex-specific salinity and depth preferences C_LIO_LISome females migrated to sea, suggesting early reproductive movement C_LIO_LIFindings informed Corsicas first invasive species control plan C_LI

ecology↗

Integrated multiomic profiling reveals SWI/SNF subunit-specific pathway alterations and targetable vulnerabilities

Mutations in subunits of the SWItch Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex occur in {approx}20% of cancers and represent a highly unmet medical need. To identify novel therapeutic approaches, we systematically characterized transcriptomic and proteomic changes caused by the loss of SWI/SNF subunits or other epigenetic enzymes in isogenic cell lines, which we subsequently integrated with high-throughput drug screening and independent genetic screens of the DepMap project. Using an optimized bioinformatics pipeline for pathway enrichment, we identified Metabolism of proteins as the most frequently dysregulated Reactome pathway category in SWI/SNF-defective cell lines. Drug screening and multiomic integration revealed multiple chemicals selectively cytotoxic for SWI/SNF-defective models, including CBP/EP300 or mitochondrial respiration inhibitors. A novel algorithm for the analysis of DepMap CRISPR screens independently identified synthetic lethality between SWI/SNF defects and EP300 or mitochondrial respiration genes, which we further revalidated in disease-relevant models. These results unravel novel genetic dependencies for SWI/SNF-defective cancers.

cancer biology↗

Evidence for adaptive myelination of subcortical shortcuts for visual motion perception in healthy adults

Conscious visual motion information follows a cortical pathway from the retina to the lateral geniculate nucleus (LGN) and on to the primary visual cortex (V1) before arriving at the middle temporal visual area (MT/V5). Alternative subcortical pathways that bypass V1 are thought to convey unconscious visual information. One flows from the retina to the pulvinar (PUL) and on to MT; while the other directly connects the LGN to MT. Evidence for these pathways comes from non-human primates and modest-sized studies in humans with brain lesions. Thus, the aim of the current study was to reconstruct these pathways in a large sample of neurotypical individuals and to determine the degree to which these pathways are myelinated, suggesting information flow is rapid. We used the publicly available 7T (N = 98; discovery) and 3T (N = 381; validation) diffusion MRI datasets from the Human Connectome Project to reconstruct the PUL-MT and LGN-MT pathways. We found more fibre tracts with greater density in the left hemisphere. Although the left PUL-MT path was denser, the bilateral LGN-MT tracts were more heavily myelinated, suggesting faster signal transduction. We suggest that this apparent discrepancy may be due to adaptive myelination caused by more frequent use of the LGN-MT pathway that leads to greater myelination and faster overall signal transmission.

neuroscience↗

People with nicotine dependence use-disorder exhibit more prefrontal activity during preparatory control but reduced anterior cingulate activity during reactive control

Reduced inhibitory control and a hypersensitivity to reward are key deficits in drug-dependents, however, they tend to be studied in isolation. Here we seek to understand the neural processes underlying control over reward and how this is different in people with a nicotine use disorder (pNUD). A novel variant of the monetary incentive delay task was performed by pNUD (n = 20) and non-smokers (n = 20), where we added a stop-signal component such that participants had to inhibit prepotent responses to earn a larger monetary reward. Brain activity was recorded using functional magnetic resonance imaging (fMRI). We estimated stop signal reaction times (SSRT), an indicator of impulsivity, and correlated these with brain activity. Inhibitory accuracy scores did not differ between the control group and pNUD. However, pNUD had slower SSRTs, suggesting that they may find it harder to inhibit responses. Brain data revealed that pNUD had greater preparatory control activity in the middle frontal gyrus and inferior frontal gyrus prior to successful inhibitions over reward. In contrast, non-smokers had greater reactive control associated with more activity in the anterior cingulate cortex during these successful inhibitions. SSRT-brain activity correlations revealed that pNUD engaged more control related prefrontal brain regions when SSRTs are slower. Overall, whilst the inhibition accuracy scores were similar between groups, differential neural processes and strategies were used to successfully inhibit a prepotent response. The findings suggest that increasing preparatory control in pNUD may be one possible treatment target in order to increase inhibitory control over reward.

neuroscience↗

Increased context adjustment is associated with auditory sensitivities but not with autistic traits

Bayesian models of autism suggest that disruptions in context-sensitive prediction error weighting may underpin sensory perceptual alterations, such as hypersensitivities. We used an auditory oddball paradigm with pure tones arising from high or low uncertainity contexts to determine whether autistic individuals display differences in context adjustment relative to neurotypicals. We did not find group differences in early prediction error responses indexed by mismatch negativity. However, the autism group had larger evoked responses to outliers, at 300ms latency suggesting a greater reorienting of attention to surprising sounds. A dimensional approach revealed a positive correlation between context-dependent prediction errors and auditory sensitivities, but not with autistic traits. These findings suggest that autism studies may benefit from accounting for sensory sensitivities in group comparisons. Lay SummaryWe find no differences in brain responses (EEG amplitudes) between autistic and neurotypical adults when listening to two contexts of tone patterns. However, we find a larger difference in the EEG amplitude when shifting between low to high uncertainity streams of tones, as sensory sensitivities (but not autistic traits) increase. These findings show that perceptual alterations maybe a function of sensory sensitivities, but not necessarily autistic traits. We suggest that future EEG studies in autism may benefit from accounting for sensory sensitivities.

neuroscience↗

Anxiety attenuates learning advantages conferred by statistical stability and induces loss of volatility-attuning in brain activity

Anxiety can alter an individuals perception of their external sensory environment. Previous studies suggest that anxiety can increase the magnitude of neural responses to unexpected (or surprising) stimuli. Additionally, surprise responses are reported to be boosted during stable compared to volatile environments. Few studies, however, have examined how learning is impacted by both threat and volatility. To investigate these effects, we used threat-of-shock to transiently increase subjective anxiety in healthy adults during an auditory oddball task, in which the regularity could be stable or volatile, while undergoing functional Magnetic Resonance Imaging (fMRI) scanning. We then used Bayesian Model Selection (BMS) mapping to pinpoint the brain areas where different models of anxiety displayed the highest evidence. Behaviourally, we found that threat-of-shock eliminated the accuracy advantage conferred by environmental stability over volatility in the task at hand. Neurally, we found that threat-of-shock led to both attenuation and loss of volatility-attuning of neural activity evoked by surprising sounds across most subcortical and limbic brain regions including the thalamus, basal ganglia, claustrum, insula, anterior cingulate, hippocampal gyrus and also the superior temporal gyrus. Conversely, within two small clusters in the left medial frontal gyrus and extrastriate area, threat-of-shock boosted the neural activity (relative to the safe and volatile condition) to the levels observed during the safe and stable condition, while also inducing a loss of volatility-attuning. Taken together, our findings suggest that threat eliminates the learning advantage conferred by statistical stability compared to volatility. Thus, we propose that anxiety disrupts behavioural adaptation to environmental statistics, and that multiple subcortical and limbic regions are implicated in this process.

neuroscience↗

Reversing chemorefraction in colorectal cancer cells by controlling mucin secretion

15% of colorectal cancers (CRC) cells exhibit a mucin hypersecretory phenotype, which is suggested to provide resistance to immune surveillance and chemotherapy. We now formally show that colorectal cancer cells build a barrier to chemotherapeutics by increasing mucins secretion. We show that low levels of KChIP3, a negative regulator of mucin secretion (Cantero-Recasens et al., 2018), is a risk factor for CRC patients relapse in subset of untreated tumours. Our results also reveal that cells depleted of KChIP3 are four times more resistant (measured as cell viability and DNA damage) to chemotherapeutics 5-Fluorouracil plus Irinotecan (5-FU+iri.) compared to control cells, whereas KChIP3 overexpressing cells are 10 times more sensitive to killing by chemotherapeutics. Similar increase in tumour cell death is observed upon chemical inhibition of mucin secretion by the sodium/calcium exchanger (NCX) blockers (Mitrovic et al., 2013). Finally, sensitivity of CRC patient-derived organoids to 5-FU+iri increases 40-fold upon mucin secretion inhibition. Reducing mucin secretion thus provides a means to control chemoresistance of mucinous colorectal cancer cells and other mucinous tumours.

cell biology↗

Neural and computational processes of accelerated perceptual awareness and decisions: A 7T fMRI Study

Rapidly detecting salient information in our environments is critical for survival. Visual processing in subcortical areas like the pulvinar and amygdala have been shown to facilitate unconscious processing of salient stimuli. It is unknown, however, if and how these areas might interact with cortical networks to facilitate faster conscious perception of salient stimuli. Here we investigated these neural processes using 7T functional Magnetic Resonance Imaging (fMRI) in concert with computational modelling while participants (n = 32) engaged in a breaking continuous flash suppression paradigm (bCFS) in which fearful and neutral faces are initially suppressed from conscious perception but then eventually "breakthrough" into awareness. We found that participants reported faster breakthrough times for fearful faces compared to neutral faces. Drift-diffusion modelling suggested that perceptual evidence was accumulated at a faster rate for fearful faces compared to neutral faces. For both neutral and fearful faces, faster response times coincided with greater activity in the amygdala (specifically within its subregions, including superficial, basolateral and amygdalo-striatal transition area) and the insula. Faster rates of evidence accumulation coincided with greater activity in frontoparietal regions and the occipital lobe, as well as the amygdala. Overall, our findings suggest that hastened perceptual awareness of salient stimuli recruits the amygdala and, more specifically, is driven by accelerated evidence accumulation in fronto-parietal and visual areas. In sum, we have uncovered and mapped distinct neural computations that accelerate perceptual awareness of visually suppressed faces.

neuroscience↗

Chemotherapy induces a YAP1-dependent fetal conversion to human Colorectal Cancer cells that is predictive of poor patient outcome

Current therapy against colorectal cancer is based on DNA-damaging agents that eradicate highly proliferative malignant cells. Whether sublethal chemotherapy affects tumor cell behavior and impacts on patient outcome is primarily unstudied. We now show that sublethal chemotherapy imposes a quiescent-like state to p53 wildtype human colorectal cancer (CRC) cells that is linked to the acquisition of a fetal phenotype downstream of YAP1, similar to that observed after intestinal damage. CRC cells displaying this fetal phenotype exhibit tumor- initiating activity comparable to untreated cells but superior metastatic capacity. Notably, nuclear YAP1 accumulation, or detection of the fetal signature in tumors predict poor prognosis in CRC patients carrying p53 wildtype tumors. Collectively, our results uncover a potential adverse response of tumor cells to suboptimal chemotherapy, and identify nuclear YAP1 and fetal conversion of colorectal tumors as biomarkers for prognosis and therapy prescription. Statement of significanceChemotherapy induces a quiescent-like phenotype to colorectal cancer cells that is linked to the acquisition of a YAP1-dependent fetal signature. Notably, this signature is predictive of patient outcome in different cohorts of human colorectal cancer.

cancer biology↗

Aberrant connectivity in auditory precision encoding in schizophrenia spectrum disorder and across the continuum of psychotic-like experiences

BackgroundThe ability to generate a precise internal model of statistical regularities is impaired in schizophrenia. Predictive coding accounts of schizophrenia suggest that psychotic symptoms may be explained by a failure to build precise beliefs or a model of the world. The precision of this model may vary with context. For example, in a noisy environment the model will be more imprecise compared to a model built in an environment with lower noise. However compelling, this idea has not yet been empirically studied in schizophrenia. Methods: In this study, 62 participants engaged in a stochastic mismatch negativity paradigm with high and low precision. We included inpatients with a schizophrenia spectrum disorder (N=20), inpatients with a psychiatric disorder but without psychosis (N=20), and healthy controls (N=22), with comparable sex ratio and age distribution. Bayesian mapping and dynamic causal modelling were employed to investigate the underlying microcircuitry of precision encoding of auditory stimuli. Results: We found strong evidence (exceedance p > 0.99) for differences in the underlying connectivity associated with precision encoding between the three groups as well as on the continuum of psychotic-like experiences assessed across all participants. Critically, we show changes in interhemispheric connectivity between the two inpatient groups, with some connections further aligning on the continuum of psychotic-like experiences. Conclusions: While our results suggest continuity in backward connectivity alterations with psychotic-like experiences regardless of diagnosis, they also point to specificity for the schizophrenia spectrum disorder group in interhemispheric connectivity alterations.

neuroscience↗

Bayesian hierarchical models for disease mapping applied to contagious pathologies

Disease mapping aims to determine the underlying disease risk from scattered epidemiological data and to represent it on a smoothed colored map. This methodology is based on Bayesian inference and is classically dedicated to non-infectious diseases whose incidence is low and whose cases distribution is spatially (and eventually temporally) structured. Over the last decades, disease mapping has received many major improvements to extend its scope of application: integrating the temporal dimension, dealing with missing data, taking into account various a prioris (environmental and population covariates, assumptions concerning the repartition and the evolution of the risk), dealing with overdispersion, etc. We aim to adapt this approach to rare infectious diseases. In the context of a contagious disease, the outcome of a primary case can in addition generate secondary occurrences of the pathology in a close spatial and temporal neighborhood; this can result in local overdispersion and in higher spatial and temporal dependencies due to direct and/or indirect transmission. We have proposed and tested 60 Bayesian hierarchical models on 400 simulated datasets and bovine tuberculosis real data. This analysis shows the relevance of the CAR (Conditional AutoRegressive) processes to deal with the structure of the risk. We can also conclude that the negative binomial models outperform the Poisson models with a Gaussian noise to handle overdispersion. In addition our study provided relevant maps which are congruent with the real risk (simulated data) and with the knowledge concerning bovine tuberculosis (real data).\n\nAuthor summaryDisease mapping is dedicated to non-infectious diseases whose incidence is low and whose distribution is spatially (and eventually temporally) structured. In this paper, we aim to adapt this approach to rare infectious pathologies. In the context of a contagious disease, the outcome of a primary case can in addition generate secondary occurrences of the pathology in a close spatial and temporal neighborhood, resulting in local overdispersion and in high spatial and temporal dependencies. We thus explored different adapted spatial, temporal and spatiotemporal links and highlight the most adapted to likely risk structures for infectious diseases. We also conclude that the negative binomial models outperform the Poisson models with a Gaussian noise to handle overdispersion. Our study also provided relevant maps which are congruent with the real risk (in case of simulated data) and with the knowledge concerning bovine tuberculosis (when applying to real data). Thus disease mapping appears as a promising way to investigate rare infectious diseases.

scientific communication and education↗

Auditory prediction errors and auditory white matter microstructure as predictors of psychotic experiences in healthy individuals

Our sensory systems actively predict sensory information based on previously learnt patterns. An inability to accurately predict forthcoming information results in prediction errors. Individuals with schizophrenia consistently show reduced auditory prediction errors as well as reduced microstructure in auditory white matter pathways. However, it is not clear if also healthy individuals with psychotic experiences demonstrate such deficits. Participants underwent electroencephalography (EEG) recordings while listening to a simple two-tone duration deviant oddball paradigm (N=103) and a stochastic oddball paradigm (N=89). A subset of participants (N=89) also underwent diffusion-weighted magnetic resonance imaging (MRI), from which fractional anisotropy (FA), a measure of overall white matter microstructure, was obtained for auditory pathways namely the auditory interhemispheric pathway, as well as the left and right arcuate fasciculi. We investigated both structural and functional predictors of positive psychotic experiences in healthy participants as measured by the Community Assessment for Psychic Experiences positive dimension (CAPE+) scores. Prediction errors evoked by the classical oddball paradigm failed to reveal significant effects, whereas the stochastic oddball paradigm revealed significant clusters at typical mismatch negativity periods predictive of CAPE+ scores. Furthermore, we show that white matter microstructure from auditory pathways in addition to mismatches significantly predict CAPE+ scores. We suggest that structural and functional prediction error measures together may have potential in predicting psychotic experiences in the healthy population.

neuroscience↗

White matter connectivity disruptions in the pre-clinical continuum of psychosis: A connectome study

BackgroundWidespread white matter disruptions in schizophrenia have been commonly reported, but it remains unanswered whether these abnormalities are associated with schizophrenia specifically or whether they range along a psychotic continuum into the healthy population. Investigating the extent of white matter connectivity disruptions specific to psychotic-like experiences in healthy individuals is insofar important as it is a necessary first step towards the development of prodromal psychosis biomarkers.\n\nMethodsHigh resolution, multi-shell diffusion-weighted magnetic resonance images were acquired from 89 healthy individuals. Whole-brain white matter fiber tracking was performed to quantify the strength of white matter connections. Network-based statistics were applied to white matter connections in a regression model in order to test for a linear relationship between streamline count and psychotic-like experiences.\n\nResultsA significant subnetwork was identified whereby streamline count declined with increasing quantity of psychotic-like experiences. This network of significant connectivity reductions affected all cortical lobes, subcortical structures and the cerebellum.\n\nConclusionA widespread network of linearly declining connectivity strength with increasing number of psychotic-like experiences was identified in healthy individuals. This finding is in line with white matter connectivity reductions reported from early to chronic stages of schizophrenia. We suggest that these white matter changes might be a potential biomarker for the identification of individuals at high risk for transitioning to psychosis.

neuroscience↗

Structural connectivity facilitates functional connectivity of auditory prediction error generation within a fronto-temporal network

Auditory prediction errors, i.e. the mismatch between predicted and actual auditory input, are generated by a hierarchical functional network of cortical sources. This network is also interconnected by auditory white matter pathways. Hence it would be reasonable to assume that these structural and functional networks are quantitatively related, which is what the present study set out to investigate. Specifically, whether structural connectivity of auditory white matter pathways enables effective connectivity of auditory prediction error generation. Eighty-nine participants underwent diffusion weighted magnetic resonance imaging. Anatomically-constrained tractography was used to extract auditory white matter pathways, namely the bilateral arcuate fasciculus, the inferior occipito-frontal fasciculi (IOFF), and the auditory interhemispheric pathway, from which Apparent Fibre Density (AFD) was calculated. The same participants also underwent a stochastic oddball paradigm, which was used to elicit prediction error responses, while undergoing electroencephalographic recordings. Dynamic causal modelling (DCM) was used to investigate the effective connectivity of auditory prediction error generation in brain regions interconnected by the above mentioned auditory white matter pathways. Brain areas interconnected by all auditory white matter pathways best explained the dynamics of auditory prediction error responses. Furthermore, AFD in the right IOFF and right arcuate fasciculus significantly predicted the effective connectivity parameters underlying auditory prediction error generation. In conclusion, the generation of auditory prediction errors within an effectively connected, fronto-temporal network was found to be facilitated by the structural connectivity of auditory white matter pathways. These findings build upon the notion that structural connectivity facilitates dynamic interactions within brain regions that are effectively connected.\n\nSignificance statementThe brain continuously generates and updates hypotheses that predict forthcoming sensory input. Within the auditory domain, it has repeatedly been reported that these predictions about the auditory environment are facilitated by specific functional cortical connections. These functionally connected brain regions are also structurally connected via auditory white matter pathways. For the first time, this study provides quantitative evidence for a structural basis along which this functional network of auditory prediction error generation operates. This finding provides evidence for the notion that the functional connectivity of dynamically interacting brain areas is facilitated by structural connectivity amongst these brain areas.

neuroscience↗