Cerebral Cortex

Early sensory deprivation drives large-scale reconfiguration of cortical networks, yet we still lack a clear understanding of the relative contributions of early visual experience versus spontaneous prenatal retinal waves on the establishment of the cortical network. We compared two mouse models of congenital blindness: neonatal enucleation and congenital anophthalmia, across two genetic strains (C57Bl/6J and ZRDBA) using mesoscopic calcium imaging of spontaneous activity and graph-theoretical analysis. Spectral analyses revealed localized strain-specific increases in infraslow and low delta power following visual deprivation, with C57Bl/6J enucleated and ZRDBA anophthalmic mice exhibiting a more generalized nodal increase. Concomitantly, the functional network organization was redirected toward medial higher-order visual areas, the associative retrosplenial cortex, and somatosensory regions, while the primary and lateral visual cortices exhibited reduced influence and integration within the modular architecture. Notably, ZRDBA groups showed limited global changes to their cortical network. However, anophthalmic ZRDBA mice, lacking prenatal retinal waves, exhibited connectivity patterns more akin to enucleated C57Bl/6J than to their enucleated littermates, highlighting the instructive role of spontaneous prenatal retinal activity. These findings support a connectivity-constrained, experience-dependent model in which preexisting structural pathways guide diffuse, resilient reorganization following sensory loss.

Neocortical layer 6 plays a crucial role in sensorimotor coordination and integration through functionally segregated circuits linking intracortical and subcortical areas. However, because of the high neuronal heterogeneity and sparse intralaminar connectivity data on the cell-type specific synaptic microcircuits in layer 6 remain few and far between. To address this issue, whole-cell recordings combined with morphological reconstructions have been used to identify morpho-electric types of layer 6A pyramidal cells (PCs) in rat barrel cortex. Cortico-thalamic (CT), cortico-cortical (CC) and cortico-claustral (CCla) pyramidal cells have been distinguished based on to their distinct dendritic and axonal morphologies as well as their different electrophysiological properties. Here we demonstrate that these three types of layer 6A pyramidal cells innervate neighboring excitatory neurons with distinct synaptic properties: CT PCs establish weak facilitating synapses to other L6A PCs; CC PCs form synapses of moderate efficacy; while synapses made by putative CCla PCs display the highest release probability and a marked short-term depression. Furthermore, for excitatory-inhibitory synaptic connections in layer 6 we were able to show that both the presynaptic PC type and the postsynaptic interneuron type govern the dynamic properties of the of the respective synaptic connections. We have identified a functional division of local layer 6A excitatory microcircuits which may be responsible of the differential temporal engagement of layer 6 feed-forward and feedback networks. Our results provides a basis for further investigations on the long-range cortico-cortical, cortico-thalamic and cortico-claustral pathways.

The superior colliculus (SC) receives inputs from various brain regions in a layer- and radial location-specific manner, but whether the SC exhibits location-specific dynamics remains unclear. To address this issue, we recorded the spiking activity of single SC neurons while photoactivating cortical areas in awake head-fixed Thy1-ChR2 rats. We classified 309 neurons that responded significantly into 8 clusters according to the response dynamics. Among them, neurons with monophasic excitatory responses (7-12 ms latency) that returned to baseline within 20 ms were commonly observed in the optic and intermediate gray layers of centromedial and centrolateral SC. In contrast, neurons with complex polyphasic responses were commonly observed in the deep layers of the anterolateral SC. Cross-correlation analysis suggested that the complex pattern could be only partly explained by an internal circuit of the deep gray layer. Our results indicate that medial to centrolateral SC neurons simply relay cortical activity, whereas neurons in the deep layers of the anterolateral SC dynamically integrate inputs from the cortex, SNr, CN, and local circuits. These findings suggest a spatial gradient in SC integration, with a division of labor between simple relay circuits and those integrating complex dynamics.

Primate brain evolution has involved prominent expansions of the cerebral cortex, with largest effects observed in the human lineage. Such expansions were accompanied by fine-grained anatomical alterations, including increased cortical folding. However, the molecular bases of evolutionary alterations in human sulcal organisation are not yet well understood. Here, we integrated data from recently completed large-scale neuroimaging genetic analyses with annotations of the human genome relevant to various periods and events in our evolutionary history. These analyses identified single-nucleotide polymorphism (SNP) heritability enrichments in foetal brain human-gained enhancer elements for a number of sulcal structures, including the central sulcus, which is implicated in human hand dexterity. We zeroed-in on a genomic region which harbours DNA variants associated with left central sulcus shape, a human-gained enhancer element, and genetic loci involved in neurogenesis including ZIC4, to illustrate the value of this approach for probing the complex factors contributing to human sulcal evolution.

Congenital blindness is associated with atypical morphology, and functional connectivity within and from, visual cortical regions; changes that are hypothesized to originate from a life-long absence of visual input and could be regarded as a general (re)organization principle of sensory cortices. Challenging this is the fact that individuals with congenital anosmia (life-long olfactory sensory loss) display little to no morphological changes in primary olfactory cortex. To determine whether olfactory input from birth is essential to establish and maintain normal functional connectivity in olfactory processing regions, akin to the visual system, we assessed differences in functional connectivity within olfactory cortex between individuals with congenital anosmia (n=33) and matched controls (n=34). Specifically, we assessed differences in connectivity between core olfactory processing regions as well as differences in regional homogeneity and homotopic connectivity within primary olfactory cortex. In contrast to congenital blindness, none of the analyses indicated atypical connectivity in individuals with congenital anosmia. In fact, post-hoc Bayesian analysis provided support for an absence of group differences. These results suggest that a lifelong absence of olfactory experience has limited impact on the functional connectivity in olfactory cortex, a finding that indicates a clear difference between sensory modalities in how sensory cortical regions develop.

Early deafness leads to the reorganization of large-scale brain networks, involving and extending beyond the auditory system. Body-centered visuomotor transformation is impaired after early auditory deprivation, associated with a hyper-crosstalk between the task-critical frontoparietal network (FPN) and the default-mode network (DMN). It remains to be elucidated, how the reorganized functional connectivity between the auditory system, the FPN, and the DMN contributes to the impaired visuomotor transformation after early deafness. In this fMRI study, we asked early deaf participants and hearing controls to judge the spatial location of a visual target, either about the middle-sagittal line of their own body (the egocentric task) or another background object (the allocentric task). The bilateral superior temporal gyrus (STG) in the deaf group exhibited cross-modal reorganization, with generally enhanced neural activity during the visual tasks, compared to hearing controls. Moreover, the STG showed significantly increased functional connectivity with both the FPN and the DMN in the deaf group compared to hearing controls, specifically during the egocentric task. The increased STG-FPN and STG-DMN coupling, however, showed antagonistic effects on the egocentric performance of the deaf participants. The increased STG-FPN connectivity was associated with improved (i.e., a beneficial role) while the increased STG-DMN with deteriorated (i.e., a detrimental role) egocentric performance in the deaf participants. No such effect was observed in hearing controls. Therefore, the auditory cortex is reorganized to functionally resemble the FPN in the deaf brain, representing compensatory neuroplasticity to mitigate the impaired visuomotor transformation after early deafness. Significance StatementOur brain constantly plans vision-guided actions, transforming visuospatial representations of external visual targets into visuomotor representations. The frontoparietal network (FPN) critically supports this visuomotor transformation process, which is impaired after early deafness. To mitigate the impaired visuomotor transformation, the deaf auditory cortex in the bilateral superior temporal gyrus (STG) shows compensatory cross-modal reorganization that functionally resembles the FPN regions. Specifically, the deaf auditory cortex becomes functionally coupled with the dorsal FPN regions. The stronger the STG-FPN coupling, the more improved the deaf adults visuomotor transformation performance, indicating the reorganized STG as a critical node of the task-critical network. Correspondingly, increased coupling between the task-critical deaf STG and the default-mode network impairs the visuomotor transformation.

Episodic memories are thought to be stabilized through the coordination of cortico-hippocampal activity during sleep. However, the timing and mechanism of this coordination remain unknown. To investigate this, we studied the relationship between hippocampal reactivation and slow-wave sleep UP and Down states of the retrosplenial cortex (RTC) and prefrontal cortex (PFC). We found that hippocampal reactivation are strongly correlated with specific cortical states. Reactivation occurred during sustained cortical UP states or during the transition from UP to Down state. Interestingly, sustained UP states from the PFC were more coordinated with memory reactivation in the hippocampus, whereas hippocampal reactivation was biased to occur during the cortical UP to Down state transition of the RTC. Reactivation usually occurred within 150-200 ms of a cortical UP-state onset, indicating that a build-up of excitation during cortical UP state activity influences the probability of memory reactivation in CA1. Conversely, CA1 reactivation occurred 30-50 ms before the onset of a cortical Down state, suggesting that memory reactivation affects Down state initiation in RTC and PFC, but the effect in RTC was more robust. Our findings provide evidence that supports and highlights the complexity of bidirectional communication between cortical regions and the hippocampus during sleep.

Plasticity in the brain is differentially affected by age of blindness onset. One possible, but not yet identified mechanism is that the cholinergic signals originating from the nucleus basalis of Meynert may underlie differential extent of plasticity in early and late blind individuals. This prospect is based on the fact that the nucleus basalis of Meynert modulates cortical processes such as plasticity and sensory encoding and that the degree of cross-modal plasticity varies depending on the age of blindness onset. However, this question yet remains largely unclear. Here, we tested whether the early and late blind individuals develop dissociable plasticity in the nucleus basalis of Meynert using multi-parametric magnetic resonance imaging. We found the relatively preserved volumetric size and cerebrovascular reactivity, but significant disruption in the white matter integrity of the nucleus basalis of Meynert in both early and late blind individuals. Critically, despite its reduction in the white matter integrity, the nucleus basalis of Meynert of early blind individuals presented greater global and network functional connectivity including visual, language, and default-mode networks. Such changes in the functional connectivity were not observed in the late-blind individuals. Further, less duration of the visual experience was associated with greater global and network functional connectivity. These results indicate that the nucleus basalis of Meynert is differentially involved in the plasticity of early and late blind individuals - a similar amount of reduction in microstructural integrity in early and late blind individuals, but stronger and more widespread functional connectivity of the NBM in the early blind individuals. Our findings suggest that the nucleus basalis of Meynert may develop greater cholinergic influence on the cortex of early blind individuals. Such change may explain why early blind individuals present stronger and more widespread cross-modal plasticity during non-visual tasks compared to late blind individuals.

Children with neurodevelopmental disorders have a high rate of listening difficulties, but despite decades of research, the relation between these conditions remains unclear. Using resting state fMRI to image the childs brain noninvasively, we investigate the distribution of speech, non-speech sound, and visual processing networks in the forebrain, and examine a cross-section of age differences within these networks in children (6-14 years old) with normal hearing, including typically developing children, children with listening difficulties (LiD), and children with attention-deficit/hyperactivity disorder (ADHD). Relative to typically developing children, a reduction in functional connectivity of the speech network was found in children with LiD. No reduction was found in connections processing non-speech sounds or visual stimuli in the children with LiD, suggesting a specific deficit in speech processing. A second group of children diagnosed with ADHD showed reduced connectivity in both speech and sound networks, but not in the visual network, suggesting a common underlying cause for auditory and speech difficulties in the auditory system of children with ADHD. We conclude that listening difficulties in children are mediated by speech-specific neural mechanisms. The findings strengthen research calls for obligatory speech intelligibility testing under challenging listening conditions (noise, reverberation) as a component of clinical pediatric audiological assessment.

Early sensory deprivation profoundly alters cortical organization, yet the cell-type-specific mechanisms driving large-scale functional reconfiguration remain poorly understood. Here, we combined wide-field mesoscale calcium imaging with cell-type-specific promoters (hSyn, Thy1, mDLX) to quantify resting-state functional connectivity across pan-neuronal, excitatory, and inhibitory networks in sighted and neonatal enucleated mice. Using graph-theoretic analyses of spontaneous cortical activity, we found that early visual deprivation induced a convergent pattern across neuronal populations in which medial higher visual and associative cortices strengthened connectivity with somatosensory and motor regions, while V1 and lateral higher visual areas lost network influence. However, reorganizations differed between neuronal population. Excitatory networks exhibited a reduced global efficiency and connection strength, revealing a selective vulnerability to sensory loss and a redistribution of hub architecture toward associative cortices. Global efficiency was preserved in the inhibitory network, but extensive hub reassignments and an increased cross-modular coupling were observed in this network, reflecting a reconfiguration of long-range inhibitory coordination. Pan-neuronal networks showed large-scale redistribution without global integration loss, suggesting a stabilized mesoscale balance between excitation and inhibition. Community detection revealed enhanced intermodular communication and population-specific reallocation of connectors, provincial, and bridging hubs. These results demonstrate that early blindness evokes a coordinated yet cell-type-specific reorganization of cortical mesoscale networks, in which excitatory and inhibitory populations contribute distinctively to cortical integration and plasticity. This population-resolved approach bridges mesoscale dynamics in mice with human evidence of occipital recruitment following sensory deprivation, offering mechanistic insight into the cellular foundations of cortical resilience and cross-modal plasticity.

Experience-dependent cortical plasticity is a pivotal process of human brain development and essential for the formation of most cognitive functions. Although studies found that early visual experience could influence the endogenous development of visual cortex in animals, little is known about such impact on human infants. Using the multi-modal MRI data from developing human connectome project, we revealed the early structural and functional maps in the ventral visual cortex and their development across the first month of age. Particularly, we found the postnatal experience could modulate both the cortical morphology in ventral visual cortex and the functional circuit between bilateral primary visual cortices. But the cortical myelination and overall functional circuits of ventral cortex, particularly that of the high-order visual cortex, developed without significant influence of postnatal experience in such early period. These experience-dependent cortical properties were further validated in the preterm-born infants who have longer postnatal time but immature cortical development at birth. The results confirmed that the development of cortical thickness was dominated by the postnatal experience but the functional circuit might be determined by the overall maturity of visual cortex. These data suggest in human newborns that early postnatal experience shapes the structural and functional development of the visual cortex in selective and organized pattern.

Comparisons of visual cortex function across blind and sighted adults reveals effects of experience on human brain function. Since almost all research has been done with adults, little is known about the developmental origins of plasticity. We compared resting state functional connectivity of visual cortices of blind adults (n = 30), blindfolded sighted adults (n = 50) to a large cohort of infants (Developing Human Connectome Project, n = 475). Visual cortices of sighted adults show stronger coupling with non-visual sensory-motor networks (auditory, somatosensory/motor), than with higher-cognitive prefrontal cortices (PFC). In contrast, visual cortices of blind adults show stronger coupling with higher-cognitive PFC than with nonvisual sensory-motor networks. Are infant visual cortices functionally like those of sighted adults, with blindness leading to functional change? We find that, on the contrary that secondary visual cortices of infants are functionally more like those of blind adults: stronger coupling with PFC than with nonvisual sensory-motor networks, suggesting that visual experience modifies elements of the sighted-adult long-range functional connectivity profile. Infant primary visual cortices are in-between blind and sighted adults i.e., more balanced PFC and sensory-motor connectivity than either adult group. The lateralization of occipital-to-frontal connectivity in infants resembles the sighted adults, consistent with the idea that blindness leads to functional change. These results suggest that both vision and blindness modify functional connectivity through experience-driven (i.e., activity-dependent) plasticity.

Histology studies revealed that the macaque insular cortex was characterized by the gradual organizations containing agranular, dysgranular and granular insula. However, no consensus has been reached on the elaborate subdivisions of macaque insula. Until now, no neuroimaging study to our knowledge combining connectivity-based gradients and parcellation has been performed to investigate the topographic organization of the macaque insular cortex. In this study, we used high-resolution ex vivo diffusion-weighted imaging data to explore the macaque insular cortexs global gradient organization and subdivisions. We found a rostrocaudal organization of the dominant gradient in the macaque insula using a diffusion map embedding. Meanwhile, extracting the 25% top and bottom components from the dominant and second gradient, which explained variance over 60% in total within ten gradients, the connectivity-based parcellation method was performed to subdivide each component into two subregions confirmed by the cross-validation analysis. Furthermore, permutations tests identified that two subregions from each component showed significant differences between their connectivity fingerprints. Finally, we found that the dominant and second gradients were significantly correlated with the T1w/T2w and cortical thickness maps in the macaque insula. Taken together, the global gradients combining the subdivisions examined the topographic organization of the macaque insular cortex based on the structural connectivity, which may contribute to a better understanding of the intricate insular cortex anatomy.

Attentional distribution depends on both endogenous and exogenous processes, but how they interact in attention allocation remains unclear. The attentional priority map, jointly determined by stimulus saliency and task relevance, provides a framework for investigating their interplay. We propose that the human posterior inferotemporal cortex (hPIT), located near object-processing cortical areas, serves as an attentional priority map. Using fMRI with behavioral tasks, we show that hPIT shows stronger attentional modulation than classical attention regions across motion, color, and shape tasks. hPIT shows lateralized attentional enhancement even in the absence of visual input, with further elevated modulation in the presence of stimuli, indicating its integrated role in priority control. Furthermore, its modulation is invariant to stimulus category but sensitive to attentional demands, and the region is functionally connected to both dorsal and ventral attentional networks. These findings highlight the hPIT as an integrator in attentional control and provide critical insights into the brains strategy for optimizing responses to the environment.

Understanding the synaptic characteristics of each cortical layer is essential for elucidating the functional architecture of each brain region. In the current study, we made a detailed quantitative comparison of the synaptic structure in the predominantly input layers of primate primary visual cortex (layer 4C) and in the predominant output layer (layer 3B) using focused ion beam scanning electron microscopy (FIB/SEM). We quantified the synaptic density in each layer, classified synaptic boutons according to their number of synapses and mitochondrial content, and quantified key morphometric parameters, including bouton volume, postsynaptic density (PSD) area and morphology, volume occupied by mitochondria, and postsynaptic targets. Our results revealed that for all the layers there is a higher proportion of single-synapse boutons without mitochondria. Multisynaptic boutons containing mitochondria (MSBm+)-- which likely correspond to TC terminals --were significantly more abundant in the thalamocortical recipient layers 4C and 4C{beta}. These MSBm+ boutons were also larger, more likely to contact dendritic spines, and contained more mitochondria than other bouton categories. In contrast, layer 3B, displayed a lower prevalence of MSBm+ boutons, these boutons were smaller than those in layer 4C and made fewer synapses. These findings highlight laminar differences in bouton architecture and support the idea that TC synapses are structurally adapted to support high synaptic efficacy. Together, our data provide a detailed quantitative framework for understanding the synaptic organization of primate V1, with implications for sensory processing and cortical circuit function.

Abstract/SummaryAs the tools to simultaneously record electrophysiological signals from large numbers of neurons within and across brain regions become increasingly available, this opens up for the first time the possibility of establishing the details of causal relationships between monosynaptically connected neurons and the patterns of neural activation that underlie perception and behavior. Although recorded activity across synaptically connected neurons has served as the cornerstone for much of what we know about synaptic transmission and plasticity, this has largely been relegated to ex-vivo preparations that enable precise targeting under relatively well-controlled conditions. Analogous studies in-vivo, where image-guided targeting is often not yet possible, rely on indirect, data-driven measures, and as a result such studies have been sparse and the dependence upon important experimental parameters has not been well studied. Here, using in-vivo extracellular single unit recordings in the topographically aligned rodent thalamocortical pathway, we sought to establish a general experimental and computational framework for inferring synaptic connectivity. Specifically, attacking this problem within a statistical signal-detection framework utilizing experimentally recorded data in the ventral-posterior medial (VPm) region of the thalamus and the homologous region in layer 4 of primary somatosensory cortex (S1) revealed a trade-off between network activity levels needed for the data-driven inference and synchronization of nearby neurons within the population that result in masking of synaptic relationships. Taken together, we provide a framework for establishing connectivity in multi-site, multi-electrode recordings based on statistical inference, setting the stage for large-scale assessment of synaptic connectivity within and across brain structures. New & NoteworthyDespite the fact that all brain function relies on the long-range transfer of information across different regions, the tools enabling us to measure connectivity across brain structures are lacking. Here, we provide a statistical framework for identifying and assessing potential monosynaptic connectivity across neuronal circuits from population spiking activity that generalizes to large-scale recording technologies that will help us to better understand the signaling within networks that underlies perception and behavior.

Response inhibition and sustained attention are critical for higher-order cognition and rely upon specific patterns of functional brain network organization. This study investigated how functional brain networks reconfigure to execute these cognitive processes during a go/no-go task with and without the presence of rewards in 26 children between the ages of 8 and 12 years. First, we compared task performance between standard and rewarded versions of a go/no-go task. We found that the presence of rewards reduced commission error rate, a measure considered to indicate improved response inhibition. Tau, thought to index sustained attention, did not change across task conditions. Next, changes in functional brain network organization were assessed between the resting state, the standard go/no-go task, and the rewarded go/no-go task. Relative to the resting state, integration decreased and segregation increased during the standard go/no-go task. A further decrease in integration and increase in segregation was observed when rewards were introduced. These patterns of reconfiguration were present globally and across several key brain networks of interest, as well as in individual regions implicated in the processes of response inhibition, attention, and reward processing. These findings align with patterns of brain network organization found to support the cognitive strategy of sustained attention, rather than response inhibition, during go/no-go task performance and suggest that rewards enhance this organization. Overall, this study used large-scale brain network organization and a within-subjects multi-task design to examine different cognitive strategies and the influence of rewards on response inhibition and sustained attention in late childhood.

An essential aspect of human cognition is the ability to explicitly think about semantic relations between concepts. Neuroimaging studies have found that individual concepts are encoded by distributed patterns of cortical activity, but relatively little is known about how semantic relations between concepts are encoded in the brain. Some theoretical models suggest that relation representations are embedded within concept representations, while others suggest that relation representations are independent of any specific concept pair. We designed a study to compare how semantic relations and concepts are encoded across the cerebral cortex. To characterize how relations are encoded across cortex, fMRI was used to record brain activity while six participants each answered over one thousand questions about different semantic relations. We find that relations are encoded independently of the specific concepts that are connected in any particular instance of the relation. Our results further suggest that relations and concepts are represented in the same set of cortical regions, and that, within these regions, each location is preferentially selective for specific relations. Overall, these results suggest that in the human cerebral cortex, relations and concepts may have the same type of functional representation.

Spontaneous and sensory-evoked neuronal activity plays a decisive role in network formation during postnatal development. The thalamus is a major gateway for sensory outputs to the cortex, so that thalamic neuronal activity in newborn animals might be crucial for maturation of the thalamocortical network. The sensory-evoked intracellular thalamic activity and signal propagation in newborn animals remain largely unknown. Here we performed local field potential (LFP), juxtacellular, and patch clamp recordings in the somatosensory thalamus of urethane anesthetized rats at postnatal days 6-7 (P6-7, both sexes) with one whisker stimulation. To reach the thalamus with the electrodes the majority of the overlying cortex and hippocampus were removed. Deflection of only one (the principal) whisker induced spikes in a particular thalamic cell. Sensory stimulation evoked excitatory and inhibitory postsynaptic events in thalamocortical cells. Up to 5-10 sensory-evoked large-amplitude excitatory events followed with 100-200 ms inter-event intervals, while multiple inhibitory events tended to form 20-40 ms inter-event intervals. Large-amplitude excitatory events produced spike bursts with an intraburst frequency of 50-100 Hz and/or short plateau potentials in thalamocortical cells. Inhibitory events could down-modulate evoked spiking or prevented a depolarization block. Juxtacellular recordings confirmed the partial inactivation of spikes during short plateau potentials. Excitatory events evoked low-threshold spikes (LTS) in thalamocortical cells, but, in agreement with previously reported results, hyperpolarizing current pulses generated weak LTS without spike bursts. We conclude that thalamic neuronal activity in rat pups is determined by relatively weak and slow intrinsic membrane currents and relatively strong synapses that might underlay immature forms of thalamocortical synchrony and signal propagation.

AO_SCPLOWBSTRACTC_SCPLOWMemory retrieval reactivates previously encoded representations, allowing for their modification and strengthening. However, the neural processes that follow reactivation and contribute to long-term retention remain poorly understood. Here, we examined the post-retrieval resting period to identify neural markers of memory reactivation and their relation to subsequent memory performance. Participants learned pairs of nonsense syllables in multisensory contexts and, on the following day, received either a cue-syllable reminder (context + cue syllable; RX) or a context-only reminder (RCTX) while EEG activity was recorded before and after the reminder presentation. Both reminders elicited significant reductions in beta power (25-40 Hz) during the post-reminder rest, consistent with memory reactivation. The magnitude of beta decrement correlated with better long-term performance. Graph-theoretical analyses of phase synchronization networks in the beta band revealed that the RCTX reminder produced higher bilateral frontal betweenness centrality, suggesting greater engagement of frontal regions in mediating global information flow when retrieving only contextual cues. Moreover, frontal centrality and network density were predictive of subsequent memory accuracy. These findings demonstrate that memory reactivation extends beyond cue presentation into post-retrieval rest, leaving identifiable oscillatory and topological signatures that influence memory persistence. Our results underscore the crucial role of frontal network dynamics and beta-band activity in facilitating long-term memory.