CEREBRAL CORTEX

Effects of parental socioeconomic status on offspring's fetal neurodevelopment
Mathan J, Maximino-Pinheiro M, He Q, Rezende G, Menu I, Tissier C, Salvia E, Mevel K, Le Stanc L, Vidal J, Moyon M, Delalande L, Orliac F, Poirel N, Oppenheim C, Houdé O, Chaumette B, Borst G and Cachia A
Emerging evidence underscores the prenatal period's critical role in shaping later cognition and health, influenced by an intricate interplay of parental genetic and environmental factors. Birth weight is commonly used as a retrospective indicator of fetal development, but recent focus has shifted to more specific proxies of neurodevelopment, like cortical sulcal patterns, which are established in utero and remain stable after birth. This study aimed to elucidate the interrelated effects of parental socioeconomic status, brain volume, birth weight, and sulcal patterns in the anterior cingulate cortex. Utilizing structural Magnetic Resonance Imaging (MRI), parental educational attainment, and related polygenic risk scores, the study analyzed 203 healthy right-handed participants aged 9 to 18. Structural equation modeling demonstrated that the anterior cingulate cortex sulcal pattern is influenced by parental socioeconomic status and global brain volume, with socioeconomic status correlating with a polygenic risk score. These findings suggest that prenatal neurodevelopmental processes may mediate the intergenerational transmission of inequalities.
Neuronal fate resulting from indirect neurogenesis in the mouse neocortex
Hatanaka Y, Yamada K, Eritate T, Kawaguchi Y and Hirata T
Excitatory cortical neurons originate from cortical radial glial cells (RGCs). Initially, these neurons were thought to derive directly from RGCs (direct neurogenesis) and be distributed in an inside-out fashion. However, the discovery of indirect neurogenesis, whereby intermediate neuronal progenitors (INPs) generate neurons, challenged this view. To investigate the integration of neurons via these two modes, we developed a method to identify INP progeny and analyze their fate using transgenic mice expressing tamoxifen-inducible Cre recombinase under the neurogenin-2 promoter, alongside thymidine analog incorporation. Their fate was further analyzed using mosaic analysis with double markers in mice. Indirect neurogenesis was prominent during early neurogenesis, generating neuron types that would emerge slightly later than those produced via direct neurogenesis. Despite the timing difference, both neurogenic modes produced fundamentally similar neuron types, as evidenced by marker expression and cortical-depth location. Furthermore, INPs generated pairs of similar phenotype neurons. These findings suggest that indirect neurogenesis, like direct neurogenesis, generates neuron types in a temporally ordered sequence and increases the number of similar neuron types, particularly in deep layers. Thus, both neurogenic modes cooperatively generate a diverse array of neuron types in a similar order, and their progeny populate together to form a coherent cortical structure.
Neural signatures of visual awareness independent of postperceptual processing
Cohen MA, Dembski C, Ortego K, Steinhibler C and Pitts M
What are the neural processes associated with perceptual awareness that are distinct from preconscious sensory encoding and postperceptual processes such as reporting an experience? Using electroencephalography and a no-report visual masking paradigm, we manipulated stimulus visibility by varying the time between stimuli and masks in linear steps (17, 33, 50, 67, and 83 ms). Awareness increased nonlinearly, with stimuli never seen at the two shortest intervals, always seen at the two longest, and 50% seen at the intermediate interval. Separate report and no-report conditions were used to isolate awareness from task performance. Our results revealed a neural signal closely linked to perceptual awareness, independent of the task: a fronto-central event-related potential that we refer to as the N2 (~250 to 300 ms). Earlier event-related potential signals reflected the linear manipulation of stimulus strength, while later signals like P3b and temporal generalization of decoding were tied to task performance, appearing only in the report condition. Taken together, these findings inform current debates regarding theories of consciousness and offer new avenues for exploring the neural mechanisms supporting conscious processing.
Convolutional neural networks uncover the dynamics of human visual memory representations over time
Zohar E, Kozak S, Abeles D, Shahar M and Censor N
The ability to accurately retrieve visual details of past events is a fundamental cognitive function relevant for daily life. While a visual stimulus contains an abundance of information, only some of it is later encoded into long-term memory representations. However, an ongoing challenge has been to isolate memory representations that integrate various visual features and uncover their dynamics over time. To address this question, we leveraged a novel combination of empirical and computational frameworks based on the hierarchal structure of convolutional neural networks and their correspondence to human visual processing. This enabled to reveal the contribution of different levels of visual representations to memory strength and their dynamics over time. Visual memory strength was measured with distractors selected based on their shared similarity to the target memory along low or high layers of the convolutional neural network hierarchy. The results show that visual working memory relies similarly on low and high-level visual representations. However, already after a few minutes and on to the next day, visual memory relies more strongly on high-level visual representations. These findings suggest that visual representations transform from a distributed to a stronger high-level conceptual representation, providing novel insights into the dynamics of visual memory over time.
Neuroanatomical correlates of subjective tinnitus: insights from advanced cortical morphology analysis
Pandey HR, Keshri A, Sinha N and Kumar U
Subjective tinnitus, characterized by the perception of phantom sounds in the absence of external stimuli, presents significant challenges in both audiology and neurology. Once thought to primarily involve aberrant neural activity within auditory pathways, it is now understood to engage a broader array of neuroanatomical structures. This study investigated the connections between auditory, cognitive, and sensory processing regions, which are crucial for unraveling the complex neurobiological basis of tinnitus. Using high-resolution T1-weighted magnetic resonance imaging, we compared 52 individuals with subjective tinnitus with 52 age-matched healthy controls, focusing on cerebral cortex features, including fractal dimensionality, gyrification, and sulcal depth. Covariate analyses were conducted to explore the relationships between tinnitus duration, Tinnitus Handicap Inventory scores, anxiety score, and neuroanatomical changes. We found significant alterations in key brain regions involved in sensory processing, cognition, and emotional regulation, including the insula, lateral occipital cortex, middle frontal gyrus, and superior parietal lobule. These neuroanatomical changes were strongly correlated with the severity and chronicity of tinnitus symptoms. Our findings reveal profound structural changes in the brain associated with subjective tinnitus, offering valuable insights into the condition's underlying mechanisms and providing a potential framework for guiding future research and therapeutic interventions.
When emotion and time meet from human and rodent perspectives: a central role for the amygdala?
Doyère V and Droit-Volet S
Initiated by a long stay of Valérie Doyère in the laboratory of Joseph LeDoux, a Franco-American collaborative group was formed around the topic of emotion and time perception in a comparative perspective between humans and non-human animals. Here, we discuss results from our studies on the mechanisms underlying time distortion under 2 conditions, timing of a threatening stimulus and timing of a neutral stimulus in the context of fear, with insights from neurodevelopment. Although the type of temporal distortion depends on the experimental situations, in both humans and rodents a high-arousal emotion automatically triggers acceleration of an "internal clock" system, an effect that may rely on the early maturing amygdala. Our studies, particularly in humans, also point to the role of attention and self-awareness in regulating the effect of fear on timing, relying on the prefrontal cortex, a late maturing structure. Thus, in line with LeDoux, while the amygdala may process all characteristics of events (including time) necessary to quickly trigger appropriate survival behaviors, some type of time distortions may rely on higher-order processing, some specific to humans. The extent of the network underlying threat-related time distortions remains to be explored, with species comparisons being a promising means of investigation.
Examining threat responses through a developmental lens
Casey BJ, Lin YC and Meyer HC
Adolescence has been characterized by risk taking and fearlessness. Yet, the emergence of anxiety disorders that are associated with fear peaks during this developmental period. Moreover, adolescents show heightened sensitivity to stress relative to children and adults. To address inconsistencies between the common characterization of adolescents as fearless and the evidence of heightened anxiety and stress during this time, we build upon foundational discoveries of threat-related circuitry and behavior in adult rodents by Joseph LeDoux and colleagues. Specifically, the conservation of this circuitry across species has provided opportunities for identifying mechanisms underlying threat responses that we have extended to developing humans and rodents. We elucidate situations in which adolescents show heightened threat responses and others where they appear fearless and link them to developmental changes of threat circuitry during this period. We discuss the potential adaptiveness of these threat responses for survival of the individual and species but also the potential risks for anxiety and stress. We end by offering potential new ways in which behavioral treatments for youth with anxiety and stress-related disorders may be optimized to target the developing vs developed brain.
Global changes in the pattern of connectivity in developmental prosopagnosia
Epihova G, Cook R and Andrews TJ
Developmental prosopagnosia is a neurodevelopmental condition characterized by difficulties in recognizing the identity of a person from their face. While current theories of the neural basis of developmental prosopagnosia focus on the face processing network, successful recognition of face identities requires broader integration of neural signals across the whole brain. Here, we asked whether disruptions in global functional and structural connectivity contribute to the face recognition difficulties observed in developmental prosopagnosia. We found that the left temporal pole was less functionally connected to the rest of the brain in developmental prosopagnosia. This was driven by weaker contralateral connections to the middle and inferior temporal gyri, as well as to the medial prefrontal cortex. The pattern of global connectivity in the left temporal pole was also disrupted in developmental prosopagnosia. Critically, these changes in global functional connectivity were only evident when participants viewed faces. Structural connectivity analysis revealed localized reductions in connectivity between the left temporal pole and a number of regions, including the fusiform gyrus, inferior temporal gyrus, and orbitofrontal cortex. Our findings underscore the importance of whole-brain integration in supporting typical face recognition and provide evidence that disruptions in connectivity involving the left temporal pole may underlie the characteristic difficulties of developmental prosopagnosia.
Repetition of critical search features modulates EEG lateralized potentials in visual search
Oxner M, Mazza V and Müller MM
In visual search, the repetition of target and distractor colors enables both successful search and effective distractor handling. Nevertheless, the specific consequences of trial-to-trial feature repetition in different search contexts are poorly understood. Here, we investigated how feature repetition shapes the electrophysiological and behavioral correlates of target processing and distractor handling, testing theoretically informed predictions with single-trial mixed-effects modeling. In two experiments, the colors of a fixed-shape target and singleton distractor changed unpredictably across trials. Targets were color singletons in Experiment 1, allowing efficient search among pop-out items, but were not uniquely colored in Experiment 2, encouraging slower shape-feature search. Interference by the distractor occurred only in pop-out search but was reduced by repetition. This was paralleled by the contralateral electroencephalography (EEG) response: Following a search color change, the target-related N2pc was greatly reduced, and salient distractors elicited an N2pc followed by an enhanced PD. This biphasic response was absent in Experiment 2, where color was less useful to search. Overall, distractor positivities were not sensitive to feature repetition, suggesting that they are unrelated to preparatory suppression. Attention-related lateralization components are not universally elicited by target or distractor feature values but are driven specifically by expected features important to the search task.
Monitoring of nonspatial information within working memory in the common marmoset (Callithrix jacchus)
Zlatkina V, Frey S and Petrides M
The mid-dorsolateral prefrontal cortical region (areas 46 and 9/46) is critical for the monitoring of information in working memory both in the macaque monkey brain and the human brain. The presence of this cytoarchitectonic region in the New World marmoset brain was in debate, but recent anatomical evidence demonstrated a limited area 46. This finding raised the question of the extent to which the marmoset brain can support the cognitive control process of monitoring information within working memory. This cognitive control process was assessed in adult marmosets and was shown to be limited to the monitoring of only two items in contrast to macaque monkeys, who can monitor as many as five items in working memory. The results are consistent with the limited development of the relevant prefrontal region in the marmoset and contribute to understanding the evolution of higher cognitive control processes in the primate brain.
Correction to: Partisans process policy-based and identity-based messages using dissociable neural systems
Introspective psychophysics for the study of subjective experience
Peters MAK
Studying subjective experience is hard. We believe that pain is not identical to nociception, nor pleasure a computational reward signal, nor fear the activation of "threat circuitry". Unfortunately, introspective self-reports offer our best bet for accessing subjective experience, but many still believe that introspection is "unreliable" and "unverifiable". But which of introspection's faults do we find most damning? Is it that introspection provides imperfect access to brain processes (e.g. perception, memory)? That subjective experience is not objectively verifiable? That it is hard to isolate from non-subjective processing capacity? Here, I argue none of these prevents us from building a meaningful, impactful psychophysical research program that treats subjective experience as a valid empirical target through precisely characterizing relationships among environmental variables, brain processes and behavior, and self-reported phenomenology. Following recent similar calls by Peters (Towards characterizing the canonical computations generating phenomenal experience. 2022. Neurosci Biobehav Rev: 142, 104903), Kammerer and Frankish (What forms could introspective systems take? A research programme. 2023. J Conscious Stud 30:13-48), and Fleming (Metacognitive psychophysics in humans, animals, and AI. 2023. J Conscious Stud 30:113-128), "introspective psychophysics" thus treats introspection's apparent faults as features, not bugs-just as the noise and distortions linking environment to behavior inspired Fechner's psychophysics over 150 years ago. This next generation of psychophysics will establish a powerful tool for building and testing precise explanatory models of phenomenology across many dimensions-urgency, emotion, clarity, vividness, confidence, and more.
Brain functional gradients are related to cortical folding gradient
He Z, Zhang T, Wang Q, Zhang S, Cao G, Liu T, Zhao S, Jiang X, Guo L, Yuan Y and Han J
Cortical folding is closely linked to brain functions, with gyri acting more like local functional "hubs" to integrate information than sulci do. However, understanding how anatomical constraints relate to complex functions remains fragmented. One possible reason is that the relationship is estimated on brain mosaics divided by brain functions and cortical folding patterns. The boundaries of these hypothetical hard-segmented mosaics could be subject to the selection of functional/morphological features and as well as the thresholds. In contrast, functional gradient and folding gradient could provide a more feasible and unitless platform to mitigate the uncertainty introduced by boundary definition. Based on the MRI datasets, we used cortical surface curvature as the folding gradient and related it to the functional connectivity transition gradient. We found that, at the local scale, the functional gradient exhibits different function transition patterns between convex/concave cortices, with positive/negative curvatures, respectively. At the global scale, a cortex with more positive curvature could provide more function transition efficiency and play a more dominant role in more abstractive functional networks. These results reveal a novel relation between cortical morphology and brain functions, providing new clues to how anatomical constraint is related to the rise of an efficient brain function architecture.
Specific inhibition and disinhibition in the higher-order structure of a cortical connectome
Reimann MW, Egas Santander D, Ecker A and Muller EB
Neurons are thought to act as parts of assemblies with strong internal excitatory connectivity. Conversely, inhibition is often reduced to blanket inhibition with no targeting specificity. We analyzed the structure of excitation and inhibition in the MICrONS $mm^{3}$ dataset, an electron microscopic reconstruction of a piece of cortical tissue. We found that excitation was structured around a feed-forward flow in large non-random neuron motifs with a structure of information flow from a small number of sources to a larger number of potential targets. Inhibitory neurons connected with neurons in specific sequential positions of these motifs, implementing targeted and symmetrical competition between them. None of these trends are detectable in only pairwise connectivity, demonstrating that inhibition is structured by these large motifs. While descriptions of inhibition in cortical circuits range from non-specific blanket-inhibition to targeted, our results describe a form of targeting specificity existing in the higher-order structure of the connectome. These findings have important implications for the role of inhibition in learning and synaptic plasticity.
Synesthesia is linked to large and extensive differences in brain structure and function as determined by whole-brain biomarkers derived from the HCP (Human Connectome Project) cortical parcellation approach
Ward J, Simner J, Simpson I, Rae C, Del Rio M, Eccles JA and Racey C
There is considerable interest in understanding the developmental origins and health implications of individual differences in brain structure and function. In this pre-registered study we demonstrate that a hidden subgroup within the general population-people with synesthesia (e.g. who "hear" colors)-show a distinctive behavioral phenotype and wide-ranging differences in brain structure and function. We assess the performance of 13 different brain-based biomarkers (structural and functional MRI) for classifying synesthetes against general population samples, using machine learning models. The features in these models were derived from subject-specific parcellations of the cortex using the Human Connectome Project approach. All biomarkers performed above chance with intracortical myelin being a particularly strong predictor that has not been implicated in synesthesia before. Resting state data show widespread changes in the functional connectome (including less hub-based connectivity). These brain-based individual differences within the neurotypical population can be as large as those that differentiate neurotypical from clinical brain states.
Oculomotor functional connectivity associated with motor sequence learning
Rubino C, Andrushko JW, Rinat S, Harrison AT and Boyd LA
Acquisition of learned motor sequences involves saccades directed toward the goal to gather visual information prior to reaching. While goal-directed actions involve both eye and hand movements, the role of brain areas controlling saccades during motor sequence learning is still unclear. This study aimed to determine whether resting-state functional connectivity of oculomotor regions is associated with behavioral changes resulting from motor sequence learning. We investigated connectivity between oculomotor control regions and candidate regions involved in oculomotor control and motor sequence learning. Twenty adults had brain scans before 3 days of motor task practice and after a 24-hour retention test, which was used to assess sequence-specific learning. During testing, both saccades and reaches were tracked. Stronger connectivity in multiple oculomotor regions prior to motor task practice correlated with greater sequence-specific learning for both saccades and reaches. A more negative connectivity change involving oculomotor regions from pre- to post-training correlated with greater sequence-specific learning for both saccades and reaches. Overall, oculomotor functional connectivity was associated with the magnitude of behavioral change resulting from motor sequence learning, providing insight into the function of the oculomotor system during motor sequence learning.
Neural representations of phonological information in bilingual language production
Liu X, Wu X, Feng Y, Yang J, Gu N and Mei L
Previous research has explored the neural mechanisms of bilinguals' language production, but most studies focused on neural mechanisms of cognitive control during language production. Therefore, it is unclear which brain regions represent lexical information (especially phonological information) during production and how they are affected by language context. To address those questions, we used representational similarity analysis to explore neural representations of phonological information in native (L1) and second languages (L2) in the single- and mixed-language contexts, respectively. Results showed that Chinese-English bilinguals behaviorally performed worse and exhibited more activations in brain regions associated with language processing and cognitive control in the mixed-language context relative to the single-language context. Further representational similarity analysis revealed that phonological representations of L1 were detected in the left pars opercularis, middle frontal gyrus, and anterior supramarginal gyrus, while phonological representations of L2 were detected in the bilateral occipitotemporal cortex regardless of the target language. More interestingly, robust phonological representations of L1 were observed in brain areas related to phonological processing during L2 production regardless of language context. These results provide direct neuroimaging evidence for the nonselective processing hypothesis and highlight the superiority of phonological representations in the dominant language during bilingual language production.
The aging of emotional words processing in implicit and explicit emotion task: an ERP study
Bao L and Zhang Q
This study examined how cognitive aging affects emotional word processing using event-related potential technique. Young and older adults completed both implicit lexical decision and explicit emotion categorization tasks involving positive, negative, and neutral words. Behaviorally, older adults displayed a negative emotion effect in the implicit task, which was absent in young adults. While both age groups exhibited both positive and negative emotion effects in the explicit task, older adults demonstrated a greater positivity bias compared to young adults. Event-related potential technique data revealed that young adults exhibited an early negative emotion effect on the P2 and a late emotion effect on the late positivity potentials in the implicit task. In contrast, older adults exhibited an early negativity bias effect on the P2, as well as both negative and positive emotion effects on the N400, and positive emotion effects on the late positivity potentials. In the explicit task, young adults showed both early and late negative emotion effects on the P2 and late positivity potentials, while older adults showed both negative and positive emotion effects on the late positivity potentials. The results suggest distinct processing mechanisms for emotion words in young and older adults, involving both bottom-up and top-down mechanisms, which support the socioemotional selectivity theory.
Local and interareal alpha and low-beta band oscillation dynamics underlie the bilateral field advantage in visual working memory
Sattelberger J, Haque H, Juvonen JJ, Siebenhühner F, Palva JM and Palva S
Visual working memory has a limited maximum capacity, which can be larger if stimuli are presented bilaterally vs. unilaterally. However, the neuronal mechanisms underlying this bilateral field advantage are not known. Visual working memory capacity is predicted by oscillatory delay-period activity, specifically, by a decrease in alpha (8 to 12 Hz) band amplitudes in posterior brain regions reflecting attentional deployment and related shifts in excitation, as well as a concurrent increase of prefrontal oscillation amplitudes and interareal synchronization in multiple frequencies reflecting active maintenance of information. Here, we asked whether posterior alpha suppression or prefrontal oscillation enhancement explains the bilateral field advantage. We recorded brain activity with high-density electroencephalography, while subjects (n = 26, 14 males) performed a visual working memory task with uni- and bilateral visual stimuli. The bilateral field advantage was associated with early suppression of low-alpha (6 to 10 Hz) and alpha-beta (10 to 17 Hz) band amplitudes, and a subsequent alpha-beta amplitude increase, which, along with a concurrent load-dependent interareal synchronization in the high-alpha band (10 to 15 Hz), correlated with hit rates and reaction times and thus predicted higher maximum capacities in bilateral than unilateral visual working memory. These results demonstrate that the electrophysiological basis of the bilateral field advantage in visual working memory is both in the changes in attentional deployment and enhanced interareal integration.
Neurophysiological characteristics of reward processing in individuals at different levels of gaming
Peng Y, Wu D, Tian M, Zhou Y, Peng X, Peng Z, Gong K, Liu K, Chen J and Lei W
Altered reward processing has been repeatedly reported in Internet gaming disorder (IGD). However, it remains unclear whether these changes are linked to the severity of addictive symptoms or the extent of gaming experience. This study examined the neurophysiological responses regarding reward anticipation and consummation in individuals at different levels of gaming (including 22 casual gamers, 31 regular gamers, and 27 individuals with IGD) through a monetary incentive delay task. Three event-related potential components during reward anticipation-cue-related P300 (Cue-P3), contingent negative variation, and stimulus-preceding negativity (SPN)-and two during reward consummation-feedback-related negativity and feedback-related P300 (FB-P3)-were measured. We found that IGD individuals exhibited greater Cue-P3 but lower SPN amplitude compared to casual gamers, while regular gamers fell between the two without significant differences. Regressions indicated that more extensive gaming experience, rather than the severity of the symptoms, primarily contributed to the increased Cue-P3 in IGD. No group differences were found during reward consummation. Our results highlight disrupted reward anticipation processing in IGD, characterized by increased attention bias toward reward cues (Cue-P3) but diminished cognitive resources for reward anticipation (SPN) and emphasize the role of gaming experience in increased attention bias in IGD.
Individual differences in functional connectivity during suppression of imagined threat
Westhoff M, Vogelbacher C, Schuster V and Hofmann SG
Functional magnetic resonance imaging studies typically rely on between-person analyses. To examine individual differences in functional connectivity, we used Group Iterative Multiple Model Estimation and its subgrouping function to analyze functional magnetic resonance imaging data of 54 participants who were suppressing imagined future threat. A two-stage random-effects meta-analytic approach was employed to examine individual differences. In addition to generalizable connections between brain regions, we identified individual differences in personalized models suggesting different pathways through which individuals suppress future threat. Two subgroups with distinct connectivity patterns emerged: One subgroup (n = 29; 53.70%), characterized by an additional lagged connection from the right to the left posterior cingulate cortex, exhibited comparatively higher anxiety and less brain connectivity, whereas the other subgroup (n = 25; 46.30%), showing an additional connection from the left posterior cingulate cortex to the ventromedial prefrontal cortex, was associated with lower anxiety levels and greater connectivity. This study points to individual differences in functional connectivity during emotion regulation.