Cerebral Cortex Communications

Time perception difficulties are frequently reported in Autism Spectrum Disorder, yet empirical findings remain inconsistent. A key methodological limitation is the failure to separate perceptual sensitivity from decision-making strategies. We applied Signal Detection Theory (SDT) to a subsecond duration discrimination task (100 and 500 ms) in 65 non-clinical adults varying in autistic traits, assessed via the Autism-Spectrum Quotient (AQ) and a Principal Component Analysis (PCA) of its subscales. Autistic traits did not predict reduced perceptual sensitivity (d'): temporal discrimination remained intact across the full autism-trait continuum, with Bayesian analyses providing converging evidence against a perceptual deficit. Instead, a PCA-derived cognitive component -- combining heightened Attention to Detail with reduced Imagination -- was systematically associated with a shift in decision bias (c). Individuals with this profile showed a graded attenuation of standard-based anchoring, with ordinal position progressively filling the gap. This shift operated consistently across both temporal scales, as confirmed by trial-level generalized linear mixed modelling, and reflects a quantitative redistribution of anchoring weight rather than a categorical switch in strategy. These findings reframe temporal "rigidity" in ASD not as a perceptual deficit, but as a suboptimal yet internally consistent decision-making style favouring within-trial information over accumulated representational knowledge. Lay AbstractMany autistic people report difficulties with time in daily life, but scientists have long disagreed on whether this reflects a genuine perceptual problem. This study found that autistic traits do not impair the basic ability to judge duration. Instead, people with more autistic traits tend to rely on which event came first, rather than accumulating experience across trials to refine their judgments -- a less effective but internally consistent strategy.

Background: Persistent neurological and cognitive symptoms following SARS-CoV-2 infection point to long-term alterations in brain structure and function. The thalamus, orbitofrontal cortex, and limbic networks are particularly susceptible to inflammatory and neurovascular stressors. However, the relationship between cortical, white-matter, and thalamocortical alterations in post-COVID syndrome remains unclear. Methods: 76 COVID-19 recovered participants (CRPs) and 51 healthy controls (HCs) underwent multimodal MRI comprising T1-weighted structural, diffusion, and resting-state functional acquisitions. Grey-matter morphology was assessed using voxel-based morphometry (VBM), white-matter microstructure using tract-based spatial statistics (TBSS), and thalamocortical functional connectivity (TC-FC) using seed-based analyses from major thalamic nuclei. Results were evaluated both across the groups (HC vs. CRP) and after stratifying CRPs by hospitalisation status (HC vs. Non-hospitalized patients (NHPs) vs. Hospitalized patients (HPs)). Results: No group-level grey-matter differences were observed between HCs and CRPs; however, HPs showed localized volume loss in the orbitofrontal and frontal-pole cortices (pFWE < 0.05). TBSS revealed widespread microstructural abnormalities, including reduced fractional anisotropy and mean diffusivity across association and commissural tracts (pcorr < 0.05), with regional increases in mode of anisotropy indicating selective loss of crossing fibres (pcorr < 0.05). Resting-state analyses revealed increased TC-FC from the mediodorsal thalamic nucleus to anterior cingulate, parietal, and occipital cortices (pcorr < 0.05), while differences in pulvinar and ventrolateral nuclei were not significant (pcorr > 0.05). Conclusions: Our findings indicate that COVID-19 recovery is associated with enduring alterations in fronto-limbic and thalamo-cortical circuits, most prominently in individuals with severe infection. Convergent structural and functional changes involving the orbitofrontal cortex and mediodorsal thalamus suggest network-specific reorganisation that may underpin persistent cognitive and affective symptoms of post-COVID syndrome.

Humans possess an astounding ability to acquire complex movement sequences with limited practice. Motor sequence learning engages a distributed network of brain regions that show distinct learning-related changes: the prefrontal cortex (PFC) is predominantly involved early in learning, whereas the primary motor cortex (M1) becomes increasingly engaged later in learning. Because motor regions mature relatively earlier than the PFC during development, we examined how children and adults differ in the time course of neural changes underlying motor sequence learning. Using functional magnetic resonance imaging (fMRI), we compared brain activation in children (7-10 years, N = 39, 17 female) and adults (20-32 years, N = 39, 19 female) during an associative visuomotor learning task. In both age groups, response times decreased with sequence repetition, with greater reductions in adults than in children. Across age groups, early learning was associated with heightened PFC activation, whereas later learning was characterized by increased activation in left M1 and bilateral supplementary motor area. Children and adults showed comparable decreases in PFC activation and PFC-M1 connectivity with sequence repetition. In contrast, adults exhibited larger learning-related increases in activation and stability of multivariate patterns in left M1. Together, these findings indicate that although both age groups engage the PFC similarly to support increased control demands in early learning, children show less pronounced modulation of M1 activation and representational similarity, suggesting that M1s capacity to form stable, sequence-related representations may still be developing in middle childhood. Significance StatementAlthough motor sequence learning has been widely studied in adults, less is known about how brain activation changes as learning progresses during childhood. This question is particularly relevant because prefrontal cortex (PFC) and primary motor cortex (M1) both support motor learning, but mature at different rates, with PFC developing relatively later than M1. Here, we used functional MRI to compare children (7-10 years) and adults performing a motor sequence learning task. We found no age-related differences in PFC engagement early in learning; instead children showed less refinement of M1 activation and neural representations over the course of learning than adults. These findings provide new insight into how the brain supports motor learning throughout development.

Verbal fluency is a behavioral task that requires the generation of words from a semantic category (category fluency) or words beginning with a specific letter (letter fluency). Although word production engages a frontal-temporal-parietal network, no studies have tested how lesions to temporal and parietal lobe areas that represent semantic and phonological knowledge dampen neural responses in the left pars triangularis and the left pars opercularis, two adjacent regions in the left inferior frontal gyrus implicated in word search and retrieval. Here, 52 patients with temporal lobe lesions underwent clinical functional MRI while performing the category and letter fluency tasks. We investigated where lesion presence was inversely related to the magnitude of task-specific neural responses in pars triangularis and pars opercularis using a technique referred to as voxel-based lesion activity mapping (VLAM). We found that lesions to the left anterior superior temporal gyrus, left temporal pole, left hippocampus, left insula, and underlying inferior fronto-occipital fasciculus were associated with reduced neural responses in the left pars triangularis during the category fluency task. Lesion damage to the right hippocampus was associated with reduced neural responses in the left pars opercularis during category fluency. By contrast, lesions to the left posterior superior temporal gyrus, left supramarginal gyrus, left parietal operculum, and the inferior fronto-occipital fasciculus and left arcuate fasciculus were associated with reduced neural responses in the left pars triangularis and the left pars opercularis during the letter fluency task. These results suggest that anatomically dissociable brain networks interact with the left inferior frontal gyrus when different search strategies constrain the retrieval of word representations.

The thalamus is essential for learning, dynamically engaging with other subcortical and cerebral cortex regions throughout the learning process. Here, the thalamus serves as a critical connector hub and synchroniser within the thalamocortical system of the brain. However, whilst higher order thalamic nuclei are known to be particularly important for this process, the exact contributions of individual higher order and first order thalamic nuclei, alongside their individual involvement with cortical networks and subcortical regions, remains unexplored within the initial phase of learning. In light of this, we analysed fMRI data obtained within a paradigm which is designed to examine initial learning processes within feedback-driven stimulus-response learning, in order to explore thalamic contributions. We investigated dynamic learning-related functional connectivity alterations between various thalamic nuclei with other subcortical regions and cortical networks. Our results show that the initial phase of learning was associated with: (1) decreasing functional connectivity between thalamic nuclei and frontoparietal and cingulo-opercular networks, (2) increasing functional connectivity between thalamic nuclei with default mode and salience networks, (3) decreasing functional connectivity between thalamic nuclei and the putamen, and (4) decreasing functional connectivity amongst higher order thalamic nuclei. Furthermore (5) these dynamic alterations were associated primarily by mediodorsal thalamus. Altogether, these results indicate that higher order thalamic nuclei play a crucial role within initial learning and in the generation of novel goal-directed behaviour. This was demonstrated through enhanced functional connectivity with selected cortical networks which drive goal-directed behaviour, alongside decreased functional connectivity with striatal regions which drive motor selectivity.

Infant environments are rich in rhythms, many of which are social in nature. These rhythms are proposed to play an important role in early communication and interpersonal synchrony. In this cross-sectional electroencephalography (EEG) study with 3- and 6-month-olds (n=31 and n=30, respectively), we examined whether the infant brain tracks the rhythmicity of locomotion-related biological motion in the visual domain and which experiential factors relate to this ability. We found robust neural tracking of biological motion rhythms at both ages, with no effects of age or orientation (upright or inverted). Additionally, we found that caregiver-reported practice of infant carrying/babywearing and caregiver attitudes toward social touch were linked to infant neural tracking of biological motion rhythms, particularly in the inverted condition. Finally, exploratory analyses revealed a lateralisation effect, whereby the left hemisphere processed rightward (vs. leftward) biological motion rhythms more strongly. Our findings suggest that from early on, the infant brain tracks the rhythmicity of whole-body biological motion. Furthermore, caregiver touch-related practices, particularly infant carrying/babywearing, may play a role in infant neural tracking of socially-relevant rhythms.

BackgroundNon-suicidal self-injury (NSSI) represents a growing public health concern, particularly in adolescents. Emotion dysregulation is central to prevailing NSSI models, yet it remains unclear whether acceptance-based emotion regulation (ER) and its underlying neural processes are disrupted in naturalistic, dynamic contexts. MethodsPre-registered neuroimaging trial in recently diagnosed and treatment-naive adolescents with NSSI (n=25) and healthy controls (n=25) using an ER paradigm with dynamic video clips and concomitant functional magnetic resonance imaging. Behavioral, neural activity, and connectivity indices during emotion reactivity and acceptance-based regulation were compared between groups. ResultsAdolescents with NSSI experienced elevated negative feelings during neutral clips, reflecting heightened baseline negativity. In comparison to controls, they displayed reduced temporal and ventrolateral prefrontal engagement during emotional reactivity, but increased engagement of regions implicated in both emotion reactivity (right amygdala, insula) and ER (right dlPFC, dmPFC, vlPFC) when utilizing acceptance. Higher activation in the right dlPFC was positively associated with difficulties in accessing ER strategies in everyday life. Adolescents with NSSI showed reduced functional connectivity between the right amygdala and left dlPFC. ConclusionsAdolescents with NSSI exhibited a baseline negativity bias and altered neural engagement during both negative emotional reactivity and acceptance-based regulation, characterized by increased activation and reduced amygdala-dlPFC connectivity. These findings highlight atypical emotion processing in real-life contexts in individuals with NSSI. Targeting acceptance-based regulation and prefrontal-limbic circuitry may represent a promising intervention approach for adolescents with NSSI.

A hallmark of human intelligence is the ability to use tools. Yet the cognitive processes supporting this ability remain debated. One contemporary view holds that mechanical reasoning is central for tool use, especially in the case of tools with which we have no prior experience. However, previous support for the role of mechanical reasoning often relies on circular logic, wherein poor performance on novel tool-use tasks is taken as evidence that impaired mechanical reasoning causes tool-use deficits in limb apraxia. To address this limitation, we independently assessed mechanical reasoning and novel tool use in separate tasks in individuals with limb apraxia, and compared their performance to individuals without apraxia. We also examined whether these two abilities are similarly associated with other cognitive abilities including motor imagery, mental rotation of non-body objects, general reasoning, and spatial working memory. Finally, we explored brain-behavior relationships using support vector regression lesion-symptom mapping. Our behavioral and imaging data together showed that mechanical reasoning does not underlie novel tool-use deficits in apraxia. Graphical analysis further revealed that novel tool use and mechanical reasoning loaded onto distinct latent clusters: novel tool use was strongly associated with other praxis abilities yet separable from cognitive abilities that require reasoning and mental simulation, whereas mechanical reasoning was primarily linked to other high-level reasoning abilities but not tool use. These findings challenge the notion that mechanical reasoning is central to tool-use ability, and instead suggest that tool use is more likely to be an intuitive or automatic process.

When experiencing music, humans readily perceive and move along with a periodic beat. This ability has been proposed to rely on an enhanced representation of the beat periodicity in brain activity. However, whether this beat representation is achieved in sensory areas or whether it involves associative brain regions remains debated. Here, we addressed this question using intracerebral depth electrodes implanted in 13 human individuals to record local field potentials directly inside the brain. Participants were presented with an acoustic rhythm known to induce perception of a consistent beat across Western adults. The rhythmic stimulus elicited significant responses in a number of areas, especially superior temporal, parietal and frontal cortices located along the dorsal auditory pathway. Notably, these regions, including the primary auditory cortex but also frontal motor regions, showed significantly enhanced beat periodicity as compared to a biomimetic model of subcortical auditory processing. This beat representation was further sharpened in the inferior parietal lobe, indicating that this associative region may play a key role in the mapping between rhythmic inputs and perceptual templates of beat, in line with its posited function as a sensory-motor interface. Together, these findings provide direct evidence for a gradual transformation of rhythmic sensory input into an abstract representation of beat periodicity. This process appears to rely on the dorsal auditory pathway as a functional network supporting the categorization of rhythmic stimuli into behaviorally relevant timing templates that may be experienced as the beat.

Impaired reading, i.e., alexia, is common after left hemisphere stroke. The most common deficit in alexia is a difficulty reading aloud pronounceable novel words, also called pseudowords. While semantic and phonological processes both subserve reading real words, pseudoword reading deficits in alexia are typically ascribed to phonological deficits alone. Some theories, however, suggest that pseudoword reading relies in part on lexical-semantic knowledge, such that semantic deficits could also contribute to poor pseudoword reading in alexia. Leveraging a large sample of left-hemisphere stroke survivors, we examine the cognitive and neural substrates of pseudoword reading accuracy and two error types: lexicalization errors, where a pseudoword is incorrectly read as a real word, and nonword errors, where a pseudoword is read as an incorrect nonword. 76 left-hemisphere stroke survivors read 60 pseudowords aloud, and performed two pseudoword repetition tasks to assess phonological processing and two picture naming tasks to assess mappings between lexical semantics and phonology. Regression models assessed how pseudoword repetition and naming related to overall accuracy and rates of lexicalization and nonword errors in pseudoword reading. Voxel-based and connectome lesion-symptom mapping localized the neural territory responsible for these errors. Both pseudoword repetition and naming independently related to pseudoword reading accuracy. Pseudoword repetition but not naming deficits predicted higher rates of lexicalization errors, while naming but not pseudoword repetition deficits predicted higher rates of nonword errors. Greater nonword error rate also predicted smaller imageability effects in real word reading (t(71)=-3.2, p=0.002). Lexicalization errors were associated with lesions to and disconnections of the left putamen and basal ganglia. Nonword errors were associated with lesions to the superior and middle temporal gyri, as well as broad temporo-parietal disconnections, overlapping with previous lesion-mapping results implicating these regions in semantic contributions to word reading. These results suggest that lexicalization errors result from impaired planning and execution of novel motor plans, causing a reliance on the well-learned motor plans associated with lexical items. In contrast, greater rates of nonword errors, relative to lexicalization errors, occur when semantic contributions to reading are impaired. Overall, these findings demonstrate that semantic processes are involved in reading pseudowords, at least in stroke alexia. These findings support connectionist accounts of reading in which damage in the direct orthography to phonology route for reading leads to reliance on semantic representations, even for pseudowords, suggesting a reinterpretation of pseudoword reading as a pure measure of phonological reading deficits.

Prior studies in bilinguals have reported relationships between brain structure and the dimensions of (i) language proficiency or (ii) language balance (the discrepancy between a bilinguals two proficiencies), but rarely both, even though they are highly related. These studies were often conducted in late bilinguals and the analyses limited to regions of interest. Here, we tested for relationships between brain structure and these two dimensions in 46 early cultural Spanish-English bilinguals (mean age = 16.7 years) at the level of the whole brain for gray matter volume (GMV) and cortical thickness (CT). Results revealed a positive association between GMV and proficiency in the weaker language in the right angular gyrus (AG; BA 39) extending into the superior temporal gyrus (BA 22). More balanced bilingualism was also associated with more GMV in the AG (BA 39), in addition to less GMV in left postcentral gyrus (BA 1), right cerebellum lobule IX and right superior occipital gyrus (BA 18). However, these relationships between GMV and balance disappeared after controlling for language proficiency. No significant associations were observed for CT and these two dimensions of language. Our findings suggest that relationships between GMV and balance are driven by language proficiency, and that the relationship between GMV and language proficiency likely does not involve language-specific mechanisms, given the location of the association is in the right inferior parietal cortex. Together, this study separates the neuroanatomical bases of these two language dimensions and places them in brain regions outside those usually targeted in prior studies. HighlightsO_LINeuroanatomy was correlated with proficiencies in early Spanish-English bilinguals C_LIO_LIRight angular gyrus gray matter volume (GMV) was positively related to proficiency C_LIO_LIGMV was positively related to balance, but not after controlling for proficiency C_LIO_LIRelations with these language dimensions are located outside of language cortex C_LIO_LINo significant associations were observed for cortical thickness C_LI

The prefrontal cortex (PFC) plays a critical role in maintaining working memory (WM) representations while filtering irrelevant distractors. In macaques, PFC neurons exhibit persistent delay period activity that is robust to distractor interference. The common marmoset has emerged recently as a complementary primate model for investigating the neural basis of cognitive processes including WM, in part because the relatively lissencephalic cortex of this species enables laminar recordings which could provide substantial insight into the microcircuit basis of these functions. It remains unknown however, whether marmoset WM performance is robust to distractors presented during delay periods of WM tasks, and how such distractor filtering may be implemented in PFC circuits. Here, we addressed this gap by conducting wireless recordings of PFC in freely moving marmosets performing a touchscreen-based delayed-match-to-location (DML) task in which a salient visual distractor was presented during the delay period on a subset of trials. Marmosets maintained WM performance on distractor trials, showing a decrease in accuracy of only 5%. Consistent with prior observations in both the macaque and marmoset models, we found that many PFC neurons exhibited activity related to the stimulus sample, during the delay period, and around the time of the behavioural response. In a subset of neurons, we observed distractor-mediated modulations of persistent delay period activity which were associated with a greater incidence of performance errors on the DML task. These findings reveal that marmoset WM is robust to distractor interference, and that the PFC mechanisms instantiating WM and distractor filtering are conserved in this primate species. Taken together, they support the common marmoset as a complementary model for investigating the contribution of PFC circuits to mnemonic and attentional processes.

Voluntary contraction in one limb can facilitate motor output in a distant limb, a phenomenon commonly referred to as the remote effect. However, the neural mechanisms underlying this remote interlimb facilitation remain unclear. This study investigated cortical and spinal contributions to the remote effect in able-bodied participants. Transcranial magnetic stimulation (TMS) was applied over the hand area of the primary motor cortex using posterior-anterior (PA) and anterior-posterior (AP) current directions, which are sensitive to different cortical inputs. Cortical excitability was assessed using single- and paired-pulse paradigms to measure short-interval intracortical inhibition (SICI), short-interval intracortical facilitation (SICF), and short-latency afferent inhibition (SAI). Spinal motoneuron excitability was assessed from F-waves elicited by peripheral nerve stimulation. During voluntary lower-limb contractions, single-pulse TMS elicited larger motor evoked potentials in hand muscles across current directions, indicating a broad increase in net corticospinal output. However, only AP-sensitive paired-pulse measures showed reduced SICI and enhanced SICF during contraction, whereas PA-sensitive SICI and SICF were not significantly altered, suggesting that cortical modulation during the remote effect is expressed more clearly in AP-sensitive measures. SAI with PA stimulation was less consistently expressed during contraction, suggesting that afferent-related inhibitory modulation may also be influenced during the remote effect. In parallel, F-wave amplitude and persistence increased, consistent with enhanced spinal motoneuron excitability. Together, these results provide converging evidence that the remote effect in humans involves broad corticospinal and spinal facilitation, accompanied by current direction-dependent modulation of cortical excitability measures. KEY POINTS SUMMARYO_LIVoluntary contraction in one limb can facilitate motor output in a distant limb, but the mechanisms underlying this remote interlimb facilitation remain unclear. C_LIO_LIWe tested whether remote lower-limb contraction modulates corticospinal output, intracortical excitability, and spinal motoneuron excitability in a resting hand muscle. C_LIO_LISingle-pulse transcranial magnetic stimulation showed that motor evoked potentials in the hand were facilitated during remote lower-limb contraction across multiple current directions, indicating a broad increase in net corticospinal output. C_LIO_LIPaired-pulse measures were modulated preferentially with anterior-posterior stimulation, with reduced short-interval intracortical inhibition and increased short-interval intracortical facilitation, suggesting current direction-dependent modulation of cortical excitability measures. C_LIO_LIF-wave amplitude and persistence were also enhanced during remote lower-limb contraction, indicating increased spinal motoneuron excitability. These findings provide converging evidence that the remote effect involves both cortical and spinal contributions. C_LI

People frequently gesture while speaking, even when listeners cannot see them--for instance, during phone calls or behind barriers. Congenitally blind individuals also gesture, indicating that gestures serve functions beyond visual communication. Previous models of gesture production (e.g., Kita & Ozyurek, 2003; Rauscher et al., 1996) suggest that gestures facilitate speech, but they rely heavily on behavioural data and provide limited insight into temporal dynamics. This study used magnetoencephalography (MEG), a neuroimaging technique with high temporal resolution, to investigate when gestures influence speech. Twenty-three native Japanese speakers took part in a storytelling task under two conditions: Gesture-Required (gesture use instructed) and Gesture-Prohibited (hands kept still). Participants described cartoon clips across multiple sessions (30 trials x 3 sessions per condition). Using speech onset as the reference point, we compared root mean square (RMS) values within a -0.25 to 0 second window. RMS values were higher in the Gesture-Prohibited condition, with increased activity in the bilateral anterior temporal lobes (Left ATL: p = .049; Right ATL: p = .027), but not in motor regions (p = .29). These findings suggest that gestures reduce neural load in language-related regions before articulation. Co-speech gestures may support speech planning by facilitating lexical retrieval or semantic structuring. The lack of motor region effects indicates that this influence is linguistic rather than motoric. This study provides direct direct neurophysiological evidence of the timing of gesture-speech interaction, supporting models that view gestures as an integral part of speech production.

The lateral prefrontal cortex (LPFC) actively contributes to the adaptive control of goal-directed behavior. Evidence suggests that the LPFC encodes the behavioral relevance of stimuli, distinguishing action targets from irrelevant objects; however, how this selectivity emerges over time and integrates within large-scale cortical dynamics underlying action preparation remains unclear. We recorded stereo-electroencephalography (sEEG) activity from 43 patients affected by drug-resistant epilepsy while they prepared to grasp an object and compared it with passive observation of the same object. Gamma-band responses were used to characterize cortical responsiveness and to track the spatiotemporal propagation of activity during action preparation. Neural activity first emerged in the occipitotemporal cortex in both experimental conditions and then progressed along two parallel pathways: an intraparietal and a prefrontal one. The intraparietal pathway showed highly similar dynamics during both action preparation and passive observation, suggesting largely intention-independent visuospatial processing. In contrast, the prefrontal pathway exhibited progressively stronger selectivity for behaviorally relevant objects as activity advanced rostrally. Within this pathway, area 46 exhibited sustained responses selectively associated with action-relevant objects, preceding the similarly selective engagement of premotor and motor regions. Overall, our findings identify area 46 as a key node in whole-brain dynamics that orchestrates action preparation by integrating object relevance into executive control signals guiding premotor and motor engagement. NEW & NOTEWORTHYFilling a critical gap in system-level accounts of LPFC function, whole-brain recordings reveal that area 46 selectively codes object-related information relevant for action and gates motor region activity only when the object represents a true action target.

Abstract: BACKGROUND: Perivascular spaces (PVS), visible on brain MRI, contribute to the brain clearance system and are associated with age and neurodegenerative disorders. While lower volumes of PVS in the forebrains white matter and basal ganglia have been also demonstrated in preterm-born neonates, the long-term trajectory of PVS after premature birth remains unclear. This study tests for altered PVS volumes in very preterm/very low birthweight-born (VP/VLBW) adults compared to full-term controls and explores potential associations with cognitive performance. METHODS: PVS were assessed on T2-weighted MRI from 97 VP/VLBW and 89 full-term (FT) subjects at 26 years from the prospective, population-based Bavarian Longitudinal Study. PVS volume and count was based on automated nnU-Net-based segmentation. Regional PVS volumes were normalized by corresponding regional parenchyma volumes. Cognitive performance was assessed by the Wechsler Adult Intelligence Scale. MANCOVA was used for PVS group comparisons, Spearman rank correlations for testing PVS relationships with birth variables and cognitive scores. RESULTS: VP/VLBW-born adults showed significantly higher normalized PVS volumes in bilateral basal ganglia (p < 0.001, partial eta-squared = 0.096) and insula-related white matter (p = 0.001, partial eta-squared = 0.057). In the basal ganglia, higher PVS volumes were negatively correlated with gestational age (rho = -0.223, p = 0.030) and positively correlated with the Intensity of Neonatal Treatment Index (rho = 0.222, p = 0.030) in the VP/VLBW group. PVS volume was not associated with IQ scores. CONCLUSION: We demonstrate region-specific alterations of perivascular spaces in VP/VLBW-born adults. Data suggest that prematurity has lasting impact on the PVS.

Iconicity refers to systematic links between word form and meaning. Although evidence for iconicity in natural language continues to grow, its neural basis remains unclear. Using functional magnetic resonance imaging (fMRI) and multivariate pattern analysis (MVPA), we examined iconic shape associations of auditory real words and pseudowords. The pseudowords were matched to the real words in phonemic and phonotactic properties, while differing primarily in the absence of learned semantic representations. Participants listened to each item and judged whether it sounded rounded or pointed. Searchlight MVPA revealed significant decoding for both stimulus types. For real words, iconic shape associations were decoded above chance in regions associated with visual and haptic shape processing (left lateral occipital complex and left anterior intraparietal sulcus), visual imagery (bilateral precuneus), phonological processing (bilateral supramarginal gyri), and semantic processing (left middle frontal and right superior frontal gyri). For pseudowords, significant decoding was found in regions associated with multisensory feature organization (right posterior intraparietal sulcus) and language processing (left angular and inferior frontal gyri). Together, these findings provide evidence for neural mechanisms mediating iconic associations, with language-related areas involved for both real words and pseudowords, and visual processing for real words.

The heartbeat-evoked potential (HEP) reflects the cortical processing of cardiac afferent signals. However, it remains unclear whether trial-level interoceptive prediction errors can be quantified directly from spontaneous resting cardiac fluctuations and whether these model-derived errors are associated with HEP amplitude. Here, we applied a Kalman filter, implemented as a sequential Bayesian estimation procedure, to resting-state EEG and ECG recordings from 21 healthy adults to estimate trial-by-trial signed prediction errors in RR-intervals. Positive prediction errors reflected unexpected cardiac deceleration, whereas negative prediction errors reflected unexpected cardiac acceleration. Cluster-based permutation tests showed that unexpected cardiac acceleration was associated with greater fronto-centro-parietal HEP amplitude than unexpected deceleration in an early post-R-peak window, spanning FC1, CP1, Pz, CP2, Cz, C4 and FC2 from 215 to 250 ms. A Bayesian linear mixed-effects model further indicated a credible negative association between signed prediction error and HEP amplitude after controlling for respiratory phase and preceding RR interval. In a secondary connectivity analysis, unexpected acceleration was associated with stronger Cz-to-frontal beta-band phase synchrony during a later post-R-peak window from 250 to 500 ms. Exploratory individual-difference analyses suggested that neuroticism was negatively correlated with late frontal HEP amplitude during unexpected acceleration, but not during unexpected deceleration or when trials were pooled across conditions. These findings demonstrate that spontaneous cardiac fluctuations can be used to derive trial-level computational estimates of interoceptive prediction error and that these estimates are reflected in early HEP amplitude. They further suggest that the cortical processing of unexpected cardiac acceleration may be related to individual differences in affective personality traits.

The enteric nervous system (ENS) is the main branch of the peripheral nervous system that innervates the gastrointestinal tract controlling vital functions. It arises during embryogenesis via migration and differentiation of neural crest-derived ENS progenitors. Perturbation of these processes, caused by mutations in key signalling pathway components and transcription factors, prevents progenitor colonisation of the distal gut causing aganglionic phenotypes and enteric neuropathies such as Hirschsprung (HSCR) disease. While animal models implicate Notch signalling in ENS specification, its role in human ENS progenitor cell fate decisions remains unclear. Here, we employ a human pluripotent stem cell-based model to show that Notch signalling regulates the tempo of ENS progenitor differentiation. Quantitative modelling of our in vitro data supports a branching lineage model marked by an early pro-neurogenic bias; Notch signalling attenuation accelerates differentiation coincident with a shift toward increased gliogenesis. Furthermore, we establish that Notch signalling influences human ENS progenitor migration. Together, these findings provide mechanistic insights into how Notch signalling disruption may contribute to the pathogenesis of human intestinal aganglionosis. SUMMARY STATEMENTIn vitro generation of human enteric nervous system (ENS) cells and quantitative modelling reveal that Notch signalling regulates ENS progenitor differentiation rates and migration.

Flow, as defined by Mihalyi Csikszentmihalyi (1975), is a holistic sensation experienced when individuals are fully immersed in an activity, resulting in a mental state characterized by a diminished sense of self and altered perception of time. To investigate the global neural dynamics underlying flow, we employed EEG microstate analysis to capture the spatial and temporal properties of dominant transient global brain states (Lehmann et al., 1998). In a study involving 43 participants playing the video game Thumper for 25 minutes, we extracted three four-minute EEG segments from each session corresponding to reported experiences of flow, boredom, and frustration, as determined by self-reports and performance metrics. Across conditions, six distinct microstate topographies (A-F) accounted for most of the global variance. Given that reduced self-referential processing is a key feature of flow, we hypothesized that flow would modulate the properties of microstates C and E, which have been associated with brain regions resembling the default mode network (DMN). Compared to boredom and frustration, the flow condition showed significantly decreased global explained variance, mean duration, time coverage, and occurrence frequency of microstate E, as well as reduced mean duration and time coverage of microstate C. These findings suggest that microstates associated with self-referential processing are shorter and less frequent during flow than during boredom and frustration. This supports the notion that the flow experience modulates global brain dynamics, particularly within the DMN. Furthermore, our results align with previous research reporting reduced DMN activity during meditative and psychedelic states, reinforcing the idea of diminished self-awareness in such conditions.