Cerebral Cortex

Some participants are consistently easier to decode than others. We asked whether this difference belongs to the person or to the conditions under which the brain is measured. We compared visual decoding in EEG, MEG, intracranial EEG, and fMRI, testing classifiers on runs and stimulus identities excluded from training. Within-instrument decoding was reproducible. Attention, behavior, and peripheral signals affected recording quality but did not explain most of the stable differences between participants. Anatomy provided one explanation. Source-to-sensor distance strongly predicted modeled signal gain, and its effect was steepest in planar gradiometers. Intracranial recordings provided another: participants with sharper local category selectivity were easier to decode. This association chiefly reflected a smaller response to the nonpreferred category relative to overall visual responsivity. Cross-site prediction was uneven. EEG and MEG expressed the preferred and nonpreferred responses differently. MEG category separation and task-aligned variance described the information available to the decoder. Simultaneous EEG-MEG recordings contained a shared participant component, but external paired cohorts did not yield a common ordering across instruments. Correspondence depended on the measure, the instrument pair and, in one cohort, participant-linked stimulus sets. Repeated observations improved performance in participants with weak single-observation decoding. Stable decoding differences therefore reflect the relation between the individual, the represented distinction, and the instrument. They chiefly determine how much information a recording supplies per observation.

The neural substrates of tactile long-term memory (LTM) in humans remain poorly understood, as relatively few neuroimaging studies have addressed this question. Here, we asked whether retrieval of tactile stimulation engages modality-specific representations in the primary and secondary somatosensory cortices (S1 and S2), alongside domain-general retrieval networks. Participants learned 16 tactile trajectories, each presented for 1.2 s on the left thumb through sequential activation of 10 vibrating dots on a Braille-like display. Three learning sessions within one week were followed by a recognition test during functional magnetic resonance imaging (fMRI). In the final sample (n = 26), we contrasted BOLD responses during successful recognition of learned stimuli with those during correct rejection of novel stimuli. Successful recognition was associated with increased activity in contralateral S1 and S2, alongside activation in the hippocampus as well as frontal and parietal regions implicated in memory retrieval. A psychophysiological interaction analysis (PPI) further revealed increased task-dependent connectivity between the hippocampus and contralateral S1 and S2 during successful recognition. Together, these findings suggest that tactile long-term memory retrieval relies on coordinated hippocampal-somatosensory interactions and may engage long-term memory representations in somatosensory cortex.

For more than a century we have pictured the dendritic spine as the postsynaptic point where a single presynaptic bouton delivers its message. That picture is correct but incomplete, since it overlooks other neuronal elements surrounding each spine. Here we characterize that neighborhood for the first time by counting and measuring the proximity of the elements encircling each postsynaptic spine. We call this neighborhood the vicinome: the full set of neuronal and glial elements surrounding a dendritic spine. We used ground-truth three-dimensional meshes from the H01 petavoxel dataset, a reconstruction of the human cerebral cortex. We analyzed 4550 neighboring elements across 322 spines from 17 pyramidal neurons in cortical layers 2 through 5, with each spine classified as apical or basal. Neighbor number followed a depth gradient, falling from 17.2 {+/-} 4.2 elements per spine in layer 2 apical spines to 12.5 {+/-} 3.1 in layer 5 basal spines. A linear mixed model with a random intercept per neuron confirmed a strong effect of layer (p = 4.3 x 10-5) with large effect sizes (Cohen's d up to 1.45) and no effect of polarity. The minimum spine-to-neighbor distance stayed uniform, near 30 nm in every group, and although some depth-related contrasts were significant, all effect sizes were negligible (Cohen's d below 0.21). We conclude that cortical depth, and not pyramidal neuron polarity, was related to the number of neuronal elements neighboring the spine. We suggest that vicinome crowding could offer a measurable observable for comparison across regions, ages, species, and disease.

Working memory (WM) and decision-making (DM) are closely linked cognitive processes that rely on frontoparietal regions, yet their distinct and shared neural dynamics remain unclear. Using intracranial EEG recordings from 24 human subjects performing a delayed match-to-sample task, we examined high-frequency broadband (HFB) activity to dissociate WM- and DM-related processes with high spatiotemporal resolution. Principal component analysis of frontoparietal HFB activity revealed multiple temporally distinct patterns spanning stimulus presentation and delay phases. The most dominant component reflected sustained WM-related activity across task phases, consistent with persistent maintenance of internal representations. Additional components captured transient WM encoding across trial phases, as well as both stimulus-linked and ramping DM-related activity suggesting dual early and late stages of evaluative processing. These processes were distributed across frontoparietal regions but showed systematic differences in anatomical focus, with WM-related activity concentrated in dorsolateral prefrontal cortex (PFC) and DM-related activity concentrated in ventrolateral PFC, while inferior parietal cortex preferentially tracked the behavioral significance of incoming stimuli and superior parietal cortex tracked the appearance of new information that may require updating ongoing processing. Together, these findings demonstrate that WM and DM processes are separable yet interleaved over time within distributed cortical networks, revealing coordinated but functionally distinct contributions to goal-directed behavior.

Face familiarity elicits reliable neural signatures during perception, yet how it is represented when faces are recalled from memory by using visual imagery and how these signals relate to perceptual representations, remains unclear. We combined perceptual and imagery conditions with electroencephalography and multivariate pattern analysis. In a perceptual session we presented of four famous individuals, while in the imagery session we used a cued recall paradigm and presented abstract symbols, associated to them. By using time-resolved multivariate decoding we tested if familiarity information is shared across stimulus categories, and if perceptual face familiarity representations overlap with processing during cued recall, related to imagery. The face perception condition showed typical and robust familiarity information over occipito-temporal electrodes. The symbolic cues also carried similar familiarity information, demonstrating cross-category familiarity processing between symbols and faces. During cued recall, familiarity information emerged over posterior regions and evolved into a prolonged and late information component over right anterior electrodes. Importantly, cross-domain temporal generalization analysis revealed an overlap between perceptual face familiarity patterns and recall/imagery related processing: perceptual face familiarity information mapped onto later processing during cued recall, with a pronounced and prolonged right anterior dominance and a shorter overlap over left posterior channels. Together, these results suggest that familiarity processing, similarly to category representations, is supported by overlapping neural patterns across perception and recall/imagery, transitioning from dynamic posterior representations, consistent with perceptual analysis, to a stable and prolonged representation over right anterior sites, that is compatible with a sustained processing, related to recall and/or imagery.

Social isolation and loneliness are major determinants of well-being in older adults. Shrinking social networks and age-related shifts in social behavior and decision-making may increase vulnerability to loneliness. These changes in social decision-making strategies can be conceptualized within an exploration-exploitation tradeoff framework, in which social options with known outcomes are prioritized over uncertain ones. Yet, no study has characterized how complementary decision-making strategies, undirected novelty seeking and goal-directed exploration, relate to social network constructs or are supported by distinct neural systems. These strategies capture distinct forms of decision-making: undirected novelty seeking is driven by the intrinsic salience of novel options independent of expected informational gain, whereas goal-directed exploration involves deliberately sampling uncertain options to reduce uncertainty and optimize future choices. Here, we used fMRI and a novel social bandit reinforcement task to identify dissociable social constructs and brain systems linked to undirected novelty seeking and goal-directed exploration in older adults. Undirected novelty seeking was associated with social network size and with activity of temporoparietal and mid-cingulate brain areas. Goal-directed exploration predicted subjective feelings of social connectedness and was associated with activity of anterior cingulate and prefrontal brain areas. Crucially, choice probabilities from a non-social version of the three-arm bandit task were not associated with social decision-making nor with social constructs. Our findings suggest that, in later life, dissociable social decision-making strategies, when faced with unknown options, rely on distinct neural systems supporting social network size as well as subjective feelings of social connectedness.

Episodic memory critically depends on the hippocampal-entorhinal system. Despite a rapid developmental change in human episodic memory during the first two years of life, little is known about the developmental trajectory of the hippocampal-entorhinal circuitry during this critical time period. In the current study, we collected high-quality precision fMRI data from five typically developing infants over the time period between 1 and 2 years of life and examined the cortical networks associated with subregions of the hippocampal-entorhinal system. We show that already at around 1 year of age, subdivisions of the canonical default network (DN) are dissociated at the neocortex but are differently associated with the hippocampal-entorhinal system, with tentatively differential developmental trajectories. While the DN-A, associated with episodic simulation, coupled with the anterior hippocampus and the medial part of the entorhinal cortex, the DN-B, associated with social cognition, showed weaker connectivity with the hippocampal-entorhinal system. The parietal memory network, in turn, coupled with the posterior hippocampus and the lateral part of the entorhinal cortex. Exploratory longitudinal results suggest that associations of the DN-B with the hippocampus and the intermediate part of the entorhinal cortex increase towards the end of the second postnatal year, and the associations of the parietal memory network become more topographically restricted to the posterior hippocampus. These networks and their differential maturation may provide the basis for important developments in episodic memory and social cognition in the second postnatal year and suggest that potentially unique properties of human hippocampal-entorhinal circuitry may emerge latest in development.

Humans effortlessly shift their attention between objects and events in the environment. These attentional shifts modulate the representation of information in many regions of the cerebral cortex, including those that represent visual-semantic information. Based on recent evidence that the cerebellum also represents semantic information, we hypothesized that attention would also shift semantic representations in the cerebellum. To test this hypothesis, we used fMRI to measure brain activity while participants watched naturalistic movie clips and were instructed to attend to either people or vehicles. We used a voxelwise encoding model framework to recover visual-semantic representations in the cerebral cortex and cerebellum under the two conditions, and quantified the direction and magnitude of visual-semantic tuning shifts between conditions. Attention to different semantic categories had a large effect on visual-semantic tuning in the cerebellum. Representations in some regions shifted toward the attended category, and representations in other regions shifted away from the attended category. Within cerebellar regions that best represent visual-semantic information, the tuning shifts were most pronounced in Crus I and II and in lobule VI. Further, the magnitude of attentional tuning shifts was greater in the cerebellum than in the cerebral cortex, particularly for tuning shifts towards the attended category. These differences suggest that attentional modulation in the cerebellum is different than in the cerebral cortex and may not solely be driven by cerebral inputs.

Preterm birth is associated with an increased risk of later language difficulties, yet whether and how prematurity alters the brain's ability to track the rhythmic structure of speech has remained understudied. Using EEG, we tracked neural entrainment to delta- and theta-rate syllable sequences produced by the infant's mother or an unfamiliar speaker in term and preterm 6-month-old infants, modeling how oscillatory responses evolved over the course of a testing session. Term infants progressively strengthened frequency-matched delta tuning over bilateral frontal regions; preterm infants did not. This divergence took two distinct forms: a change in frequency selectivity over left frontal channels, where term infants sharpened and preterm infants blurred, and a shift in band weighting in other regions. The frontal delta difference emerged only for the unfamiliar speaker. Preterm birth thus alters how frequency-specific tuning is refined during exposure, identifying a candidate neural pathway with implications for early language learning.

The posterior parietal cortex integrates somatosensory information with signals supporting action, spatial cognition, and multisensory processing, yet the fine-scale topographic relationship between the intraparietal sulcus (IPS) and primary somatosensory cortex (S1) remains poorly understood. Here, we used resting-state fMRI in 10 awake rhesus macaques to characterize functional connectivity between four S1 subregions (areas 3a, 3b, 1, and 2) and 223 single-voxel seeds densely sampling an IPS-centered parietal territory. Across S1 subregions and hemispheres, IPS-S1 connectivity exhibited a highly structured spatial organization characterized by systematic anteroposterior and mediolateral gradients and a prominent semi-oval topology following the geometry of the intraparietal sulcus. Connectivity was generally stronger toward the cortical banks and convexities and weaker near the sulcal fundus, a pattern that could not be explained by reduced local temporal signal-to-noise ratio. Unsupervised hierarchical clustering independently recovered this spatial organization and identified connectivity-defined subdivisions that only partially corresponded to classical cytoarchitectonic boundaries. Along the S1 mediolateral axis, prominent troughs in cluster-averaged connectivity profiles corresponded to several previously described somatotopic transitions, allowing to consistently map putative boundaries between tongue and face representations and between hand and trunk-leg representations. Based on these boundaries, individual IPS clusters exhibited connectivity with multiple S1 body-part sectors, with the pattern of connectivity across these sectors varying across IPS clusters and S1 subregions. Together, our findings reveal that IPS-S1 functional connectivity is organized by a large-scale sulcal topology while preserving fine-grained features of S1 somatotopic organization. These findings suggest that the functional organization of the IPS is shaped by multiple spatial dimensions, including large-scale sulcal topology and the organization of S1 subregions and body-part representations, which may together contribute to the functional specialization of individual IPS regions.

The development of speech in human children is a protracted process that depends on social experience. From early life, young children produce vocalizations in the presence of others, which affords unique opportunities for feedback about how to communicate successfully. However, for feedback to happen, young childrens speech needs to effect change in the brains of their caregivers. Using dual-brain functional near-infrared spectroscopy (fNIRS) to measure real-time communication between caregivers and their 2- to 3-year-old children (n = 56), we found that children's vocalizations selectively modulated caregivers' brain activity. Parents' brains showed a rapid response to children's production of speech that was communicatively advanced (multiword utterances) vs. less advanced (babble). The findings imply that if part of learning to talk is figuring out how to get your communication partner to listen, then early conversations likely present continuous opportunities for feedback that guide children toward advances in spoken language.

Attention is a fundamental brain function supporting perception, decision-making, and social behavior, and its dysfunction profoundly impairs daily life. It is both dynamic and stable, varying across observations and individuals, changing across the lifespan, and being shaped by social and environmental experience. Yet capturing this complexity remains a central challenge in neuroscience. Here, we integrated longitudinal behavioral assessments of semi-free-ranging macaques living in naturalistic social groups with resting-state fMRI. We quantified performance across days, ages, and social hierarchies and related it to intrinsic brain organization. Distinct attentional phenotypes emerged, including individuals with reduced attentional control. Performance followed an inverted-U lifespan trajectory, improving from childhood to adulthood before declining. Social status modulated attentional performance. Critically, nonlinear lifespan trajectories and associations with individual attentional differences were most clearly expressed in frontoparietal connectivity. Together, these findings reveal how sustained attention is organized across scales, providing a biological framework for its individual diversity, social modulation, and neural basis.

Neuroimaging studies identify the superior temporal sulcus (STS) as an anatomical and functional target in autism spectrum disorder (ASD). Yet, the STS is a heterogeneous structure containing unique subregions, such as the superior temporal asymmetrical pit (STAP), which is a recently identified human-specific landmark. To date, no study has compared the STAP between ASD individuals and neurotypical controls (NTs) in a large sample. Here, we analyzed the mean intra-hemispheric sulcal depth and inter-hemispheric laterality of the STAP, as well as the anterior and posterior portions of the STS (aSTS, pSTS), in 100 NTs and 100 ASD male individuals (ages 5-18) using a discovery-replication design. Across samples, the STAP and pSTS showed rightward asymmetry, while the aSTS showed leftward asymmetry within groups. All features of the STAP, aSTS, or pSTS did not differ significantly between groups. However, pSTS laterality related to individual differences in social cognition, which was further supported by a meta-analysis across over 200 studies showing that neurocognitive functional differences associated with social cognition and ASD are restricted to portions of the STS outside of the STAP. Together, these findings provide fine-grained insight into prior studies showing coarse morphological differences of the STS between individuals with ASD and NTs, as well as open up new questions and new neuroanatomical targets of the heterogeneous STS in future studies of brain structure, brain function, and cognition in ASD, as well as other neurodevelopmental disorders targeting the superior temporal cortex.

Early brain development is intrinsically dynamic, yet most neonatal resting-state functional magnetic resonance imaging (rs-fMRI) studies rely on static and symmetric measures of functional connectivity. Here, we investigated whether response-based metrics can capture latent dynamical organization of the neonatal brain. We analysed rs-fMRI data from the Developing Human Connectome Project (n = 714). Using a statistical-physics framework grounded in the fluctuation dissipation theorem, we estimated intrinsic pairwise response functions between 46 cortical and subcortical grey matter regions, enabling quantification of regional responsiveness and response duration. Response-based measures differed markedly from conventional functional connectivity and predicted gestational age at birth from a single scan. Preterm infants showed reduced responsiveness and shorter response persistence compared with term born neonates. Importantly, directed analyses revealed a developmental reorganization of driver listener roles across the brain, with preterm infants preserving the regional ordering of the term hierarchy but expressing it at approximately half amplitude. These findings reveal that intrinsic responsiveness captures a previously underappreciated dynamical dimension of neonatal brain organization and provides sensitive markers of neurodevelopmental maturity. Response-based metrics may offer a principled framework for detecting early network dysmaturation following preterm birth. They further indicate that prematurity does not reorganize the directed hierarchy of the neonatal connectome so much as arrest its expansion.

Language processing does not occur in a vacuum. Language comprehension and production have its own temporal organization, and it unfolds against ongoing neural. We examined whether the base organization persists from rest into sentence processing, and we further examined how it relates to evoked responses and semantic decisions. Sentences crossed linguistic argument versus adjunct completions with semantic plausibility. Anomalies elicited a centroparietal late positivity from 600 to 900 ms (+0.628 microvolt, 95% CI 0.349-0.907). Channel-wise autocorrelation timescales formed person-specific topographies: own-person rest-task similarity exceeded mismatched-person similarity (Fisher-z advantage = 0.463, permutation P = 5.00 x 10^-6), identifying 78.6% of participants against 7.1% chance. The advantage survived Cz re-referencing and surface-Laplacian transformation. In separate ERP predictor tests, longer absolute task timescales accompanied a smaller anomaly effect (cross-fitted Spearman rho = -0.486, Holm-adjusted P = 0.030). Stronger topographic continuity also accompanied greater anomaly-related decision slowing, although the behavioral association fell short of correction across six endpoints (rho = 0.547, familywise P = 0.054). Supporting analyses evaluated larger eligible samples and an eyes-closed subset. The findings place persistent, person-specific temporal organization within sentence processing and link absolute task timescale to the neural response to semantic anomaly.

Purpose: Electrical stimulation of the occipital cortex evokes visual percepts known as phosphenes. To date, most human studies have examined phosphenes elicited by large surface or depth electrodes. These differ considerably from the small penetrating intracortical microelectrodes capable of stimulating highly localized cortical populations that are the basis of current next-generation devices. Here, we provide a detailed characterization of phosphenes evoked by such intracortical microelectrodes. Methods: As part of the CORTIVIS clinical trial, a Utah Electrode Array with 100 penetrating electrodes was implanted in the early visual cortex of four blind volunteers. Participants completed drawing and description tasks in response to single-electrode stimulation. Two participants also performed forced-choice tasks to determine whether phosphenes elicited by different electrodes could be reliably discriminated. Results: Single-electrode stimulation reliably evoked phosphenes in all participants. Most percepts appeared in the contralateral visual field, although two participants reported near-midline ipsilateral percepts. Phosphenes ranged from simple dots to elongated, textured, circular, or otherwise idiosyncratic forms. One participant reported distinguishable phosphene colors, which depended on electrode and amplitude structure and varied across sessions. The two participants tested on forced-choice discrimination could successfully identify electrode-specific phosphenes across multiple sessions. Conclusions: Intracortical microstimulation of the human visual cortex produces phosphenes with diverse, electrode-specific appearances that are recognizable across repeated trials. These findings indicate that penetrating microelectrodes often evoke more structured percepts than simple points or blobs, providing foundational evidence that electrode-specific encoding strategies will be necessary in future visual prosthetic devices.

Neuroimaging studies have shown close overlap between neural representations of nociceptive stimuli and non-nociceptive, salient stimuli (such as low-probability sounds), leading to the proposal that nociception and salience share a common neural substrate in the human brain. Here we use high-resolution intracranial recordings from 13 neurosurgical patients (2,018 total electrodes) to show that neural representations of nociception and salience are anatomically and functionally distinct in the human brain. 77% of 107 electrodes that encoded nociceptive stimuli did not encode low-probability sounds ("nociceptive representations"), whereas 23% encoded both nociceptive and low-probability sounds ("salience representations"). Nociceptive representations were distinct from salience representations in terms of anatomical prevalence (posterior insula, inferior parietal, and perirolandic cortex vs. anterior insula, thalamus, and inferior frontal gyrus), timing (nociception preceded salience by 120 ms on a trial-by-trial basis), and function (intracranial electrical stimulation was more likely to cause sensory experience when applied near nociceptive representations, as compared to salience representations). These results provide strong evidence that nociception and salience have distinct neural substrates in the human brain, and that selective measurement of these distinct processes may help understand patient-to-patient variability in chronic pain and develop personalized brain stimulation treatments.

Voluntary cognitive regulation can increase or decrease pain, but direction-sensitive neural correlates may emerge at different analytical levels. We reanalyzed 3,201 thermal-stimulation trials from 33 participants, integrating 0-200 warmth/pain ratings, regional fMRI activity, and trial-wise lagged coupling. Both instructions shifted ratings in the intended direction, with no reliable difference in mean success. Down-regulation was associated with lower bilateral S2/opercular and insular activity and higher left dlPFC/IFJ activity after FDR correction across 32 regions; run-matched comparisons were weaker and none survived the corresponding correction. Contrast-map Neurologic Pain Signature attenuation did not replicate in a rating-adjusted FWL-LSS trial-wise analysis despite strong temperature sensitivity. Up-regulation success covaried with an exploratory, post selection lagged dlPFC/IFJ-valuation composite (r = -0.546, 95% CI [-0.764, -0.270]). The association exceeded matched reverse-direction, zero-lag, and time-reversed controls, lay outside permutation and circular-shift nulls, and persisted after AR(1) prewhitening. A transition-level analysis across 297 up-regulation transitions preserved a negative success-by-source interaction (adjusted three-target mean beta = -0.163, cluster-bootstrap 95% CI [-0.290, -0.054], Freedman-Lane p = 0.010). Six session-wise DCM variants showed no consistent regulation-versus-passive effective-connectivity effect and did not independently validate an up-specific directed mechanism. These analyses identify a down-regulation-associated regional pattern and a candidate prefrontal-valuation coupling association requiring independent confirmation.

The electrophysiological events underlying the conscious perception of touch in humans remain elusive. Scalp-EEG studies have identified a negative deflection peaking 120-200 ms after stimulus onset, known as the N140. This component, recently reinterpreted as the somatosensory awareness negativity (N140/SAN), has been proposed as a putative marker of tactile awareness, but its underlying neuronal dynamics are still unknown. Intracranial studies have shown that responses to median nerve stimulation include, after an initial phasic activation mainly localized to primary somatosensory cortices, a predominantly insulo-opercular tonic broadband high-frequency activity (BHA; 50-150 Hz) that has been linked to tactile awareness. Yet these scalp and intracranial signatures have never been directly linked. Using simultaneous high-density scalp EEG and intracranial EEG recordings, we show that the N140/SAN is the scalp manifestation of the insulo-opercular local field potential that follows the BHA response to stimulation. By bridging invasive and non-invasive recordings our results identify the neural origins of the N140/SAN and connect scalp and intracranial correlates of somatosensory awareness.

Robust sex differences in brain morphology and function exist from birth onwards. While traditionally conceptualized as categorical, they were recently shown to be best described along a female-to-male continuum. Here, we probed the under-explored implications of this proposal for understanding early life vulnerability to psychiatric conditions with sex-biased prevalence. We analyzed environmental, clinical and resting state functional neuroimaging data from 411 participants in Developing Human Connectome Project (dHCP) and 214 children from the Oregon ADHD 1000 study. In the dHCP, we identified complementary patterns of neonatal alignment with sex-typical young adult architecture, which overlapped areas rich in nicotinic cholinergic receptors and predicted the same psychiatric symptoms across sexes in toddlerhood. Specifically, for association (compared to sensorimotor) areas, greater alignment with female-typical functional connectivity (FC) patterns foreshadowed higher anxiety, whereas greater alignment with male-typical FC patterns forecasted autism-related problems. The latter effect was weaker among toddlers with an older epigenetic age at birth and exposure to fewer maternal health problems, but greater environmental enrichment. In the independent child sample, patterns of alignment with sex-typical FC, overlapping those observed in neonates, distinguished a history of depression and generalized anxiety (greater alignment with female-typical FC) from a history of separation anxiety, behavioral problems and current ADHD (greater alignment with male-typical FC). Our study speaks to the psychiatric relevance of sex-related functional brain architecture from birth onwards, its value in identifying vulnerable youths and its promise in monitoring the success of environmental interventions.