Large-scale Cortical Networks Research Articles

Altered long-range functional connectivity in PTSD: Role of the infraslow oscillations of cortical activity amplitude envelopes

ObjectiveCoupling between the amplitude envelopes (AEs) of regional cortical activity reflects mechanisms that coordinate the excitability of large-scale cortical networks. We used resting-state MEG recordings to investigate the association between alterations in the coupling of cortical AEs and symptoms of post-traumatic stress disorder (PTSD). MethodsParticipants (n = 96) were service members with combat exposure and various levels of post-traumatic stress severity (PTSS). We assessed the correlation between PTSS and (1) coupling of broadband cortical AEs of beta band activity, (2) coupling of the low- (<0.5 Hz) and high-frequency (>0.5 Hz) components of the AEs, and (3) their time-varying patterns. ResultsPTSS was associated with widespread hypoconnectivity assessed from the broadband AE fluctuations, which correlated with subscores for the negative thoughts and feelings/emotional numbing (NTF/EN) and hyperarousal clusters of symptoms. Higher NTF/EN scores were also associated with smaller increases in resting-state functional connectivity (rsFC) with time during the recordings. The distinct patterns of rsFC in PTSD were primarily due to differences in the coupling of low-frequency (infraslow) fluctuations of the AEs of beta band activity. ConclusionsOur findings implicate the mechanisms underlying the regulation/coupling of infraslow oscillations in the alterations of rsFC assessed from broadband AEs and in PTSD symptomatology. SignificanceAltered coordination of infraslow amplitude fluctuations across large-scale cortical networks can contribute to network dysfunction and may provide a target for treatment in PTSD.

Distinct neural signatures of pulvinar in C9orf72 amyotrophic lateral sclerosis mutation carriers and noncarriers.

Thalamic alterations have been reported as a major feature in presymptomatic and symptomatic patients carrying the C9orf72 mutation across the frontotemporal dementia-amyotrophic lateral sclerosis (ALS) spectrum. Specifically, the pulvinar, a high-order thalamic nucleus and timekeeper for large-scale cortical networks, has been hypothesized to be involved in C9orf72-related neurodegenerative diseases. We investigated whether pulvinar volume can be useful for differential diagnosis in ALS C9orf72 mutation carriers and noncarriers and how underlying functional connectivity changes affect this region. We studied 19 ALS C9orf72 mutation carriers (ALSC9+) accurately matched with wild-type ALS (ALSC9-) and ALS mimic (ALSmimic) patients using structural and resting-state functional magnetic resonance imaging data. Pulvinar volume was computed using automatic segmentation. Seed-to-voxel functional connectivity analyses were performed using seeds from a pulvinar functional parcellation. Pulvinar structural integrity had high discriminative values for ALSC9+ patients compared to ALSmimic (area under the curve [AUC] = 0.86) and ALSC9- (AUC = 0.77) patients, yielding a volume cutpoint of approximately 0.23%. Compared to ALSmimic, ALSC9- showed increased anterior, inferior, and lateral pulvinar connections with bilateral occipital-temporal-parietal regions, whereas ALSC9+ showed no differences. ALSC9+ patients when compared to ALSC9- patients showed reduced pulvinar-occipital connectivity for anterior and inferior pulvinar seeds. Pulvinar volume could be a differential biomarker closely related to the C9orf72 mutation. A pulvinar-cortical circuit dysfunction might play a critical role in disease progression and development, in both the genetic phenotype and ALS wild-type patients.

Cortical cell assemblies and their underlying connectivity: An in silico study.

Recent developments in experimental techniques have enabled simultaneous recordings from thousands of neurons, enabling the study of functional cell assemblies. However, determining the patterns of synaptic connectivity giving rise to these assemblies remains challenging. To address this, we developed a complementary, simulation-based approach, using a detailed, large-scale cortical network model. Using a combination of established methods we detected functional cell assemblies from the stimulus-evoked spiking activity of 186,665 neurons. We studied how the structure of synaptic connectivity underlies assembly composition, quantifying the effects of thalamic innervation, recurrent connectivity, and the spatial arrangement of synapses on dendrites. We determined that these features reduce up to 30%, 22%, and 10% of the uncertainty of a neuron belonging to an assembly. The detected assemblies were activated in a stimulus-specific sequence and were grouped based on their position in the sequence. We found that the different groups were affected to different degrees by the structural features we considered. Additionally, connectivity was more predictive of assembly membership if its direction aligned with the temporal order of assembly activation, if it originated from strongly interconnected populations, and if synapses clustered on dendritic branches. In summary, reversing Hebb's postulate, we showed how cells that are wired together, fire together, quantifying how connectivity patterns interact to shape the emergence of assemblies. This includes a qualitative aspect of connectivity: not just the amount, but also the local structure matters; from the subcellular level in the form of dendritic clustering to the presence of specific network motifs.

An interpretable mechanism for grating-induced cross-inhibition and gamma oscillation based on a visual cortical neuronal network model

&lt;abstract&gt;&lt;p&gt;Biological experiments targeting the mammalian primary visual cortex have shown that neuronal response to a preferred orientation grating is cross-inhibited by an orthogonal orientation mask grating. The plaid formed by the overlap of the two gratings not only causes a decrease in the neuronal firing rate but also shifts the gamma oscillation to a weaker oscillation at a higher frequency. The mechanism for the above phenomena is unclarified. In this paper, a large-scale cortical neuronal network model with biological details is constructed. In this model, two modes of connectivity that may contribute to cross-inhibition are considered: the thalamo-cortical feedforward pathway and the push-pull organization of cortical layer 4. Based on this model, the modulation of firing rate and gamma oscillation by a plaid stimulation are successfully reproduced, which is consistent with biological experiments and suggests that it is the thalamo-cortical feedforward pathway that leads to cross-inhibition. Furthermore, our analysis of the neuronal spike clusters and current fluctuations suggests that the push-pull organization leads to an increase in gamma frequency during the transition of visual stimuli from grating to plaid by modulating the source of synaptic inhibition in local neuronal populations. Such results will help to understand the visual processing under multi-input integration.&lt;/p&gt;&lt;/abstract&gt;

Resting-state EEG dynamics help explain differences in response control in ADHD: Insight into electrophysiological mechanisms and sex differences.

Reductions in response control (greater reaction time variability and commission error rate) are consistently observed in those diagnosed with attention-deficit/hyperactivity disorder (ADHD). Previous research suggests these reductions arise from a dysregulation of large-scale cortical networks. Here, we extended our understanding of this cortical-network/response-control pathway important to the neurobiology of ADHD. First, we assessed how dynamic changes in three resting-state EEG network properties thought to be relevant to ADHD (phase-synchronization, modularity, oscillatory power) related with response control during a simple perceptual decision-making task in 112 children/adolescents (aged 8-16) with and without ADHD. Second, we tested whether these associations differed in males and females who were matched in age, ADHD-status and ADHD- subtype. We found that changes in oscillatory power (as opposed to phase-synchrony and modularity) are most related with response control, and that this relationship is stronger in ADHD compared to controls. Specifically, a tendency to dwell in an electrophysiological state characterized by high alpha/beta power (8-12/13-30Hz) and low delta/theta power (1-3/4-7Hz) supported response control, particularly in those with ADHD. Time in this state might reflect an increased initiation of alpha-suppression mechanisms, recruited by those with ADHD to suppress processing unfavourable to response control. We also found marginally significant evidence that this relationship is stronger in males compared to females, suggesting a distinct etiology for response control in the female presentation of ADHD.

Acquisition and processing methods of whole-brain layer-fMRI VASO and BOLD: The Kenshu dataset

Cortical depth-dependent functional magnetic resonance image (fMRI), also known as layer-fMRI, has the potential to capture directional neural information flow of brain computations within and across large-scale cortical brain networks. For example, layer-fMRI can differentiate feedforward and feedback cortical input in hierarchically organized brain networks. Recent advancements in 3D-echo-planar imaging (EPI) sampling approaches and MR-contrast generation strategies have allowed proof-of-principle studies showing that layer-fMRI can provide sufficient data quality for capturing laminar changes in functional connectivity. These studies have, however, not shown how reliable the signal is and how repeatable the respective results are. It is especially unclear whether whole-brain layer-fMRI functional connectivity protocols are widely applicable across common neuroscience-driven analysis approaches. Moreover, there are no established preprocessing fMRI methods that are optimized to work for whole-brain layer-fMRI datasets. In this work, we aimed to serve the field of layer-fMRI and build tools for future routine whole-brain layer-fMRI in application-based neuroscience research. We have developed publicly available sequences, acquisition protocols, and processing pipelines for whole-brain layer-fMRI. These protocols are validated across 60 hours of scanning in nine participants. Specifically, we identified and exploited methodological advancements for maximizing tSNR efficiency and test-retest reliability. We are sharing an extensive multi-modal whole-brain layer-fMRI dataset (20 scan hours of movie watching in a single participant) for benchmarking future method developments: The Kenshu dataset. With this dataset, we are also exemplifying the usefulness of whole-brain layer-fMRI in conjunction with commonly applied analysis approaches in modern cognitive neuroscience fMRI studies. This includes connectivity analyses, representational similarity matrix estimations, general linear model analyses, principal component analysis clustering, and so on. We believe that this work paves the road for future routine measurements of directional functional connectivity across the entire brain.

Atrophy in behavioural variant frontotemporal dementia spans multiple large-scale prefrontal and temporal networks.

The identification of a neurodegenerative disorder's distributed pattern of atrophy-or atrophy "signature"- can lend insights into the cortical networks that degenerate in individuals with specific constellations of symptoms. In addition, this signature can be used as a biomarker to support early diagnoses and to potentially reveal pathological changes associated with said disorder. Here, we characterized the cortical atrophy signature of Behavioral Variant Frontotemporal Dementia (bvFTD). We used a data-driven approach to estimate cortical thickness using surface-based analyses in two independent, sporadic bvFTD samples (n=30 and n=71, total n=101), using age- and gender-matched cognitively and behaviorally normal individuals. We found highly similar patterns of cortical atrophy across the two independent samples, supporting the reliability of our bvFTD signature. Next, we investigated whether our bvFTD signature targets specific large-scale cortical networks, as is the case for other neurodegenerative disorders. We specifically asked whether the bvFTD signature topographically overlaps with the salience network, as previous reports have suggested. We hypothesized that because phenotypic presentations of bvFTD are diverse, this would not be the case, and that the signature would cross canonical network boundaries. Consistent with our hypothesis, the bvFTD signature spanned rostral portions of multiple networks, including the default-mode, limbic, frontoparietal control, and salience networks. We then tested whether the signature comprised multiple anatomical subtypes which themselves overlapped with specific networks. To explore this, we performed a hierarchical clustering analysis. This yielded three clusters, only one of which extensively overlapped with a canonical network (the limbic network). Taken together, these findings argue against the hypothesis that the salience network is preferentially affected in bvFTD, but rather suggest that-at least in patients who meet diagnostic criteria for the full-blown syndrome-neurodegeneration in bvFTD encompasses a distributed set of prefrontal, insular, and anterior temporal nodes of multiple large-scale brain networks, in keeping with the phenotypic diversity of this disorder.

Evaluating methods for measuring background connectivity in slow event-related functional magnetic resonance imaging designs.

Resting-state functional magnetic resonance imaging (fMRI) is widely used for measuring functional interactions between brain regions, significantly contributing to our understanding of large-scale brain networks and brain-behavior relationships. Furthermore, idiosyncratic patterns of resting-state connections can be leveraged to identify individuals and predict individual differences in clinical symptoms, cognitive abilities, and other individual factors. Idiosyncratic connectivity patterns are thought to persist across task states, suggesting task-based fMRI can be similarly leveraged for individual differences analyses. Here, we tested the degree to which functional interactions occurring in the background of a task during slow event-related fMRI parallel or differ from those captured during resting-state fMRI. We compared two approaches for removing task-evoked activity from task-based fMRI: (1) applying a low-pass filter to remove task-related frequencies in the signal, or (2) extracting residuals from a general linear model (GLM) that accounts for task-evoked responses. We found that the organization of large-scale cortical networks and individual's idiosyncratic connectivity patterns are preserved during task-based fMRI. In contrast, individual differences in connection strength can vary more substantially between rest and task. Compared to low-pass filtering, background connectivity obtained from GLM residuals produced idiosyncratic connectivity patterns and individual differences in connection strength that more resembled rest. However, all background connectivity measures were highly similar when derived from the low-pass-filtered signal or GLM residuals, indicating that both methods are suitable for measuring background connectivity. Together, our results highlight new avenues for the analysis of task-based fMRI datasets and the utility of each background connectivity method.

Functional re-organization of hippocampal-cortical gradients during naturalistic memory processes

The functional organization of the hippocampus mirrors that of the cortex, changing smoothly along connectivity gradients and abruptly at inter-areal boundaries. Hippocampal-dependent cognitive processes require flexible integration of these hippocampal gradients into functionally related cortical networks. To understand the cognitive relevance of this functional embedding, we acquired fMRI data while participants viewed brief news clips, either containing or lacking recently familiarized cues. Participants were 188 healthy mid-life adults and 31 adults with mild cognitive impairment (MCI) or Alzheimer's disease (AD). We employed a recently developed technique - connectivity gradientography - to study gradually changing patterns of voxel to whole brain functional connectivity and their sudden transitions. We observed that functional connectivity gradients of the anterior hippocampus map onto connectivity gradients across the default mode network during these naturalistic stimuli. The presence of familiar cues in the news clips accentuates a stepwise transition across the boundary from the anterior to the posterior hippocampus. This functional transition is shifted in the posterior direction in the left hippocampus of individuals with MCI or AD. These findings shed new light on the functional integration of hippocampal connectivity gradients into large-scale cortical networks, how these adapt with memory context and how these change in the presence of neurodegenerative disease.

Modulation of pulvinar connectivity with cortical areas in the control of selective visual attention

Selective attention mechanisms operate across large-scale cortical networks by amplifying behaviorally relevant sensory information while suppressing interference from distractors. Although it is known that fronto-parietal regions convey information about attentional priorities, it is unclear how such cortical communication is orchestrated. Based on its unique connectivity pattern with the cortex, we hypothesized that the pulvinar, a nucleus of the thalamus, may play a key role in coordinating and modulating remote cortical activity during selective attention. By using a visual task that orthogonally manipulated top-down selection and bottom-up competition during functional MRI, we investigated the modulations induced by task-relevant (spatial cue) and task-irrelevant but salient (distractor) stimuli on functional interactions between the pulvinar, occipito-temporal cortex, and frontoparietal areas involved in selective attention. Pulvinar activity and connectivity were distinctively modulated during the co-occurrence of the cue and salient distractor stimuli, as opposed to the presence of one of these factors alone. Causal modelling analysis further indicated that the pulvinar acted by weighting excitatory signals to cortical areas, predominantly in the presence of both the cue and the distractor. These results converge to support a pivotal role of the pulvinar in integrating top-down and bottom-up signals among distributed networks when confronted with conflicting visual stimuli, and thus contributing to shape priority maps for the guidance of attention.

A Novel Method for Constructing EEG Large-Scale Cortical Dynamical Functional Network Connectivity (dFNC): WTCS.

As a kind of biological network, the brain network conduces to understanding the mystery of high-efficiency information processing in the brain, which will provide instructions to develop efficient brain-like neural networks. Large-scale dynamical functional network connectivity (dFNC) provides a more context-sensitive, dynamical, and straightforward sight at a higher network level. Nevertheless, dFNC analysis needs good enough resolution in both temporal and spatial domains, and the construction of dFNC needs to capture the time-varying correlations between two multivariate time series with unmatched spatial dimensions. Effective methods still lack. With well-developed source imaging techniques, electroencephalogram (EEG) has the potential to possess both high temporal and spatial resolutions. Therefore, we proposed to construct the EEG large-scale cortical dFNC based on brain atlas to probe the subtle dynamic activities in the brain and developed a novel method, that is, wavelet coherence-S estimator (WTCS), to assess the dynamic couplings among functional subnetworks with different spatial dimensions. The simulation study demonstrated its robustness and availability of applying to dFNC. The application in real EEG data revealed the appealing "Primary peak" and "P3-like peak" in dFNC network properties and meaningful evolutions in dFNC network topology for P300. Our study brings new insights for probing brain activities at a more dynamical and higher hierarchical level and pushing forward the development of brain-inspired artificial neural networks. The proposed WTCS not only benefits the dFNC studies but also gives a new solution to capture the time-varying couplings between the multivariate time series that is often encountered in signal processing disciplines.

Human visual consciousness involves large scale cortical and subcortical networks independent of task report and eye movement activity

The full neural circuits of conscious perception remain unknown. Using a visual perception task, we directly recorded a subcortical thalamic awareness potential (TAP). We also developed a unique paradigm to classify perceived versus not perceived stimuli using eye measurements to remove confounding signals related to reporting on conscious experiences. Using fMRI, we discovered three major brain networks driving conscious visual perception independent of report: first, increases in signal detection regions in visual, fusiform cortex, and frontal eye fields; and in arousal/salience networks involving midbrain, thalamus, nucleus accumbens, anterior cingulate, and anterior insula; second, increases in frontoparietal attention and executive control networks and in the cerebellum; finally, decreases in the default mode network. These results were largely maintained after excluding eye movement-based fMRI changes. Our findings provide evidence that the neurophysiology of consciousness is complex even without overt report, involving multiple cortical and subcortical networks overlapping in space and time.

Relay and higher-order thalamic nuclei show an intertwined functional association with cortical-networks

Almost all functional processing in the cortex strongly depends on thalamic interactions. However, in terms of functional interactions with the cerebral cortex, the human thalamus nuclei still partly constitute a terra incognita. Hence, for a deeper understanding of thalamic-cortical cooperation, it is essential to know how the different thalamic nuclei are associated with cortical networks. The present work examines network-specific connectivity and task-related topical mapping of cortical areas with the thalamus. The study finds that the relay and higher-order thalamic nuclei show an intertwined functional association with different cortical networks. In addition, the study indicates that relay-specific thalamic nuclei are not only involved with relay-specific behavior but also in higher-order functions. The study enriches our understanding of interactions between large-scale cortical networks and the thalamus, which may interest a broader audience in neuroscience and clinical research.

Functional connector hubs in the cerebellum

Accumulating evidence from anatomical and neuroimaging studies suggests that the cerebellum is engaged in a variety of motor and cognitive tasks. Given its various functions, a key question is whether the cerebellum also plays an important role in the brain's integrative functions. Here, we hypothesize the existence of connector regions, also known as connector hubs, where multiple resting state networks converged in the cerebellum. To verify this, we employed a recently developed voxel-level network measure called functional connectivity overlap ratio (FCOR), which could be used to quantify the spatial extent of a region's connection to several large-scale cortical networks. Using resting state functional MRI data from 101 healthy participants, cerebellar FCOR maps were constructed and used to identify the locations of connector hubs in the cerebellum. Results showed that a number of cerebellar regions exhibited strong connectivity with multiple functional networks, verifying our hypothesis. These highly connected regions were located in the posterior cerebellum, especially in lobules VI, VII, and IX, and mainly connected to the core neurocognitive networks such as default mode and executive control networks. Regions associated with the sensorimotor network were also localized in lobule V, VI, and VIII, albeit in small clusters. These cerebellar connector hubs may play an essential role in the processing of information across the core neurocognitive networks.

Disruption of large-scale electrophysiological networks in stroke patients with visuospatial neglect.

Stroke frequently produces attentional dysfunctions including symptoms of hemispatial neglect, which is characterized by a breakdown of awareness for the contralesional hemispace. Recent studies with functional MRI (fMRI) suggest that hemineglect patients display abnormal intra- and interhemispheric functional connectivity. However, since stroke is a vascular disorder and fMRI signals remain sensitive to nonneuronal (i.e., vascular) coupling, more direct demonstrations of neural network dysfunction in hemispatial neglect are warranted. Here, we utilize electroencephalogram (EEG) source imaging to uncover differences in resting-state network organization between patients with right hemispheric stroke (N = 15) and age-matched, healthy controls (N = 27), and determine the relationship between hemineglect symptoms and brain network organization. We estimated intra- and interregional differences in cortical communication by calculating the spectral power and amplitude envelope correlations of narrow-band EEG oscillations. We first observed focal frequency-slowing within the right posterior cortical regions, reflected in relative delta/theta power increases and alpha/beta/gamma decreases. Secondly, nodes within the right temporal and parietal cortex consistently displayed anomalous intra- and interhemispheric coupling, stronger in delta and gamma bands, and weaker in theta, alpha, and beta bands. Finally, a significant association was observed between the severity of left-hemispace search deficits (e.g., cancellation test omissions) and reduced functional connectivity within the alpha and beta bands. In sum, our novel results validate the hypothesis of large-scale cortical network disruption following stroke and reinforce the proposal that abnormal brain oscillations may be intimately involved in the pathophysiology of visuospatial neglect.

Cortical traveling waves reflect state-dependent hierarchical sequencing of local regions in the human connectome network

Recent human studies using electrocorticography have demonstrated that alpha and theta band oscillations form traveling waves on the cortical surface. According to neural synchronization theories, the cortical traveling waves may group local cortical regions and sequence them by phase synchronization; however these contributions have not yet been assessed. This study aimed to evaluate the functional contributions of traveling waves using connectome-based network modeling. In the simulation, we observed stable traveling waves on the entire cortical surface wherein the topographical pattern of these phases was substantially correlated with the empirically obtained resting-state networks, and local radial waves also appeared within the size of the empirical networks (< 50 mm). Importantly, individual regions in the entire network were instantaneously sequenced by their internal frequencies, and regions with higher intrinsic frequency were seen in the earlier phases of the traveling waves. Based on the communication-through-coherence theory, this phase configuration produced a hierarchical organization of each region by unidirectional communication between the arbitrarily paired regions. In conclusion, cortical traveling waves reflect the intrinsic frequency-dependent hierarchical sequencing of local regions, global traveling waves sequence the set of large-scale cortical networks, and local traveling waves sequence local regions within individual cortical networks.

Chapter 24 - Frontotemporal dementia: A unique window on the functional role of the temporal lobes

Frontotemporal dementia (FTD) is an umbrella term covering a plethora of progressive changes in executive functions, motor abilities, behavior, and/or language. Different clinical syndromes have been described in relation to localized atrophy, informing on the functional networks that underlie these specific cognitive, emotional, and behavioral processes. These functional declines are linked with the underlying neurodegeneration of frontal and/or temporal lobes due to diverse molecular pathologies. Initially, the accumulation of misfolded proteins targets specifically susceptible cell assemblies, leading to relatively focal neurodegeneration that later spreads throughout large-scale cortical networks. Here, we discuss the most recent clinical, neuropathological, imaging, and genetics findings in FTD-spectrum syndromes affecting the temporal lobe. We focus on the semantic variant of primary progressive aphasia and its mirror image, the right temporal variant of FTD. Incipient focal atrophy of the left anterior temporal lobe (ATL) manifests with predominant naming, word comprehension, reading, and object semantic deficits, while cases of predominantly right ATL atrophy present with impairments of socioemotional, nonverbal semantic, and person-specific knowledge. Overall, the observations in FTD allow for crucial clinical-anatomic inferences, shedding light on the role of the temporal lobes in both cognition and complex behaviors. The concerted activity of both ATLs is critical to ensure that percepts are translated into concepts, yet important hemispheric differences should be acknowledged. On one hand, the left ATL attributes meaning to linguistic, external stimuli, thus supporting goal-oriented, action-related behaviors (e.g., integrating sounds and letters into words). On the other hand, the right ATL assigns meaning to emotional, visceral stimuli, thus guiding socially relevant behaviors (e.g., integrating body sensations into feelings of familiarity).

Attention network modulation via tRNS correlates with attention gain.

Transcranial random noise stimulation (tRNS) can enhance vision in the healthy and diseased brain. Yet, the impact of multi-day tRNS on large-scale cortical networks is still unknown. We investigated the impact of tRNS coupled with behavioral training on resting-state functional connectivity and attention. We trained human subjects for 4 consecutive days on two attention tasks, while receiving tRNS over the intraparietal sulci, the middle temporal areas, or Sham stimulation. We measured resting-state functional connectivity of nodes of the dorsal and ventral attention network (DVAN) before and after training. We found a strong behavioral improvement and increased connectivity within the DVAN after parietal stimulation only. Crucially, behavioral improvement positively correlated with connectivity measures. We conclude changes in connectivity are a marker for the enduring effect of tRNS upon behavior. Our results suggest that tRNS has strong potential to augment cognitive capacity in healthy individuals and promote recovery in the neurological population.

An altered balance of integrated and segregated brain activity is a marker of cognitive deficits following sleep deprivation.

Sleep deprivation (SD) leads to impairments in cognitive function. Here, we tested the hypothesis that cognitive changes in the sleep-deprived brain can be explained by information processing within and between large-scale cortical networks. We acquired functional magnetic resonance imaging (fMRI) scans of 20 healthy volunteers during attention and executive tasks following a regular night of sleep, a night of SD, and a recovery nap containing nonrapid eye movement (NREM) sleep. Overall, SD was associated with increased cortex-wide functional integration, driven by a rise of integration within cortical networks. The ratio of within versus between network integration in the cortex increased further in the recovery nap, suggesting that prolonged wakefulness drives the cortex towards a state resembling sleep. This balance of integration and segregation in the sleep-deprived state was tightly associated with deficits in cognitive performance. This was a distinct and better marker of cognitive impairment than conventional indicators of homeostatic sleep pressure, as well as the pronounced thalamocortical connectivity changes that occurs towards falling asleep. Importantly, restoration of the balance between segregation and integration of cortical activity was also related to performance recovery after the nap, demonstrating a bidirectional effect. These results demonstrate that intra- and interindividual differences in cortical network integration and segregation during task performance may play a critical role in vulnerability to cognitive impairment in the sleep-deprived state.

A tale of two gradients: differences between the left and right hemispheres predict semantic cognition

Decomposition of whole-brain functional connectivity patterns reveals a principal gradient that captures the separation of sensorimotor cortex from heteromodal regions in the default mode network (DMN). Functional homotopy is strongest in sensorimotor areas, and weakest in heteromodal cortices, suggesting there may be differences between the left and right hemispheres (LH/RH) in the principal gradient, especially towards its apex. This study characterised hemispheric differences in the position of large-scale cortical networks along the principal gradient, and their functional significance. We collected resting-state fMRI and semantic, working memory and non-verbal reasoning performance in 175 + healthy volunteers. We then extracted the principal gradient of connectivity for each participant, tested which networks showed significant hemispheric differences on the gradient, and regressed participants’ behavioural efficiency in tasks outside the scanner against interhemispheric gradient differences for each network. LH showed a higher overall principal gradient value, consistent with its role in heteromodal semantic cognition. One frontotemporal control subnetwork was linked to individual differences in semantic cognition: when it was nearer heteromodal DMN on the principal gradient in LH, participants showed more efficient semantic retrieval—and this network also showed a strong hemispheric difference in response to semantic demands but not working memory load in a separate study. In contrast, when a dorsal attention subnetwork was closer to the heteromodal end of the principal gradient in RH, participants showed better visual reasoning. Lateralization of function may reflect differences in connectivity between control and heteromodal regions in LH, and attention and visual regions in RH.