Biology subjects

Kawasaki, H.

Publications and source records attributed to Kawasaki, H..

At least 37 records · Page 2Linked to original sources

bioRxiv2023

A single-cell atlas of transcribed cis-regulatory elements in the human genome

Transcribed cis-regulatory elements (tCREs), such as promoters and enhancers, are fundamental to modulate gene expression and define cell identity. The detailed mapping of tCREs at single-cell resolution is essential for understanding the regulatory mechanisms that govern cellular functions. Prior tCRE catalogs, limited by bulk analysis, have often overlooked cellular heterogeneity. We have constructed a tCRE atlas using single-cell 5-RNA-seq, capturing over 340,000 single-cells from 23 human tissues and annotating more than 175,000 tCREs, substantially enhancing the scope and granularity of existing cis-regulatory element annotations in the human genome. This atlas unveils patterns of gene regulation, revealing connections between broadly expressed promoters and cell type-specific distal tCREs. Assessing trait heritability at single-cell resolution with a novel tCRE module-based approach, we uncovered the nuanced trait-gene regulatory relationships across a continuum of cell populations, offering insights beyond traditional gene-level and bulk-sample analyses. Our study bridges the gap between gene regulation and trait heritability, underscoring the potential of single-cell analysis to elucidate the genetic foundations of complex traits. These insights set the stage for future research to investigate the impact of genetic variations on diseases at the individual level, advancing the understanding of cellular and molecular basis of trait heritability.

genomics↗

bioRxiv2023

Activity-induced gene expression in the human brain

Direct electrical stimulation (eSTIM) is widely used clinically, from neurosurgical mapping to therapeutic interventions for neurological and neuropsychiatric disorders1-10. Despite over a century of application, its molecular and cellular underpinnings remain unknown. Here, using state-of-the-art single-nuclei multiomic profiling, we map changes in cell-type-specific gene expression and chromatin accessibility in vivo in the human cortex following eSTIM of neurosurgery patients. eSTIM impacts a network of cells that extends beyond excitatory neurons to include inhibitory neurons, astrocytes, oligodendrocytes and microglia. We observed an upregulation of canonical immediate-early genes (IEGs: FOS, NPAS4, EGR4) in excitatory and inhibitory neurons and induction of cytokine-related genes CCL3 and CCL4 in microglia. The cross-species conservation of this gene signature, together with our examination of a cohort of both epilepsy and cancer patients, underscores the fundamental role of these changes in stimulation-driven plasticity while controlling for disease and environmental confounds. Our study of changes in chromatin accessibility reveals a common code that involves a cell-type specific signature of transcription factor binding motifs for members of the EGR family. By addressing these previously unexplored questions about activity-induced gene expression in vivo in the human brain, our findings challenge the long-standing neuron-centric view of eSTIM, highlighting the broader role of non-neuronal cells, including microglia, in mediating the impact of brain stimulation.

neuroscience↗

bioRxiv2023

Exercise modulates human hippocampal-cortical ripple dynamics

Physical exercise acutely improves hippocampus-dependent memory. Whereas animal studies have offered cellular- and synaptic-level accounts of these effects, human neuroimaging studies show that exercise improves hippocampal-cortical connectivity at the macroscale level. However, the neurophysiological basis of exercise-induced effects on hippocampal-cortical circuits remains unknown. Experimental evidence supports that hippocampal sharp wave-ripples (SWR) play a critical role in learning and memory. Coupling between SWRs in the hippocampus and neocortex may reflect modulations in inter-regional connectivity required by mnemonic processes. Here, we examine the hypothesis that exercise modulates hippocampal-cortical ripple dynamics in the human brain. We performed intracranial recordings in epilepsy patients undergoing pre-surgical evaluation, during awake resting state, before and after an exercise session. Exercise increased ripple rate in the hippocampus. Exercise also enhanced the coupling and phase-synchrony between cortical ripples in the limbic and the default mode (DM) cortical networks and hippocampal SWRs. Further, higher heart rate during exercise, reflecting exercise intensity, was related to a subsequent increase in resting state ripples across specific cortical networks including the DMN. These results offer the first direct evidence that a single exercise session elicits changes in ripple events, a well-established neurophysiological marker of mnemonic processing. The characterization and anatomical distribution of the described modulation points to hippocampal ripples as a potential mechanism by which exercise elicits its reported short-term effects in cognition.

neuroscience↗

bioRxiv2023

Temporally organized representations of reward and risk in the human brain

AO_SCPLOWBSTRACTC_SCPLOWThe value and uncertainty associated with choice alternatives constitute critical features along which decisions are made. While the neural substrates supporting reward and risk processing have been investigated, the temporal organization by which these computations are encoded remains elusive. Here we leverage the high spatiotemporal precision of intracranial electroencephalography (iEEG) to uncover how representations of decision-related computations unfold in time. We present evidence of locally distributed representations of reward and risk variables that are temporally organized across multiple regions of interest. Reward outcome representations across wide-spread regions follow a temporally cascading order along the anteroposterior axis of the brain. In contrast, expected value can be decoded from multiple regions at the same time, and error signals in both reward and risk domains reflect a mixture of sequential and parallel encoding. We highlight the role of the anterior insula in generalizing between reward prediction error (RePE) and risk prediction error (RiPE), within which the encoding of RePE in the distributed iEEG signal predicts RiPE. Together our results emphasize the utility of uncovering temporal dynamics in the human brain for understanding how computational processes critical for value-based decisions under uncertainty unfold.

neuroscience↗

bioRxiv2022

Consciousness is indexed by analogous cortical reorganization during sleep and anesthesia

Although sleep and anesthesia are predicted to share common neural signatures of transitions into and out of unconsciousness, supportive evidence has been elusive. We identified these signatures using intracranial electroencephalography in neurosurgical patients. We applied diffusion map embedding to map cortical location into a space where proximity indicates functional similarity using a normalized connectivity ( diffusion) matrix, itself a rich source of information about network properties. During reduced consciousness, diffusion matrices exhibited decreased effective dimensionality, reflecting reduced network entropy. Furthermore, functional brain regions exhibited tighter clustering in embedding space with greater distances between regions, corresponding to decreased differentiation and functional integration. These changes were not region-specific, suggesting global network reorganization. These results strongly suggest common neural substrates for loss and recovery of consciousness during anesthesia and sleep, providing a systems-level mechanistic understanding within an intuitive geometric context and laying the foundation for evaluation of cortical state transitions in clinical settings.

neuroscience↗

bioRxiv2022

Epigenetics of post-operative delirium: A genome-wide DNA methylation study of neurosurgery patients

AimsThere is no previous study demonstrating the differences of genome-wide DNA methylation (DNAm) profiles between patients with and without postoperative delirium (POD). We aimed to discover epigenetic (DNAm) markers that are associated with POD in blood obtained from patients before and after neurosurgery. MethodsPre- and post-surgical blood DNA samples from 37 patients, including 10 POD cases, were analyzed using the Illumina EPIC array genome-wide platform. We examined DNAm differences in blood from patients with and without POD. Enrichment analysis with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes terms were also conducted. ResultsWhen POD cases were tested for DNAm change before and after surgery, enrichment analyses showed many relevant signals with statistical significance in immune response related-pathways and inflammatory cytokine related-pathways such as "cellular response to cytokine stimulus", "regulation of immune system process", "regulation of cell activation", and "regulation of cytokine production". Furthermore, after excluding the potential effect of common factors related to surgery and anesthesia between POD cases and non-POD controls, the enrichment analyses showed significant signals such as "immune response" and "T cell activation", which are same pathways previously identified from an independent non-surgical inpatient cohort. Conclusions: Our first genome-wide DNAm investigation of POD showed promising signals related to immune response, inflammatory response and other relevant signals considered to be associated with delirium pathophysiology. Our data supports the hypothesis that epigenetics are playing an important role in pathophysiological mechanism of delirium and suggest the potential usefulness of epigenetics based biomarker of POD.

neuroscience↗

bioRxiv2022

Immediate neural network impact after the loss of a semantic hub

The human brain extracts meaning from the world using an extensive neural system for semantic knowledge. Whether such broadly distributed systems1-3 crucially depend on or can compensate for the loss of one of their highly interconnected hubs4-6 is controversial4. The strongest level of causal evidence for the role of a brain hub is to evaluate its acute network-level impact following disconnection and any rapid functional compensation that ensues. We report rare neurophysiological data from two patients who underwent awake intracranial recordings during a speech prediction task immediately before and after neurosurgical treatment that required disconnection of the left anterior temporal lobe (ATL), a crucial hub for semantic knowledge4-6. Informed by a predictive coding framework, we tested three sets of hypotheses including diaschisis causing disruption in interconnected sites7 and incomplete or complete compensation by other language-critical and speech processing sites8-10. Immediately after ATL disconnection, we observed highly specific neurophysiological alterations in the recorded fronto-temporal network, including abnormally magnified high gamma responses to the speech sounds in auditory cortex. We also observed evidence for rapid compensation, seen as focal increases in effective connectivity involving language-critical sites in the inferior frontal gyrus and speech processing sites in auditory cortex. However, compensation was incomplete, in part because after ATL disconnection speech prediction signals were depleted in auditory cortex. This study provides direct causal evidence for a semantic hub in the human brain and shows striking neural impact and a rapid attempt at compensation in a neural network after the loss of one of its hubs.

neuroscience↗

bioRxiv2022

Functional geometry of auditory cortical resting state networks derived from intracranial electrophysiology

Understanding central auditory processing critically depends on defining underlying auditory cortical networks and their relationship to the rest of the brain. We addressed these questions using resting state functional connectivity derived from human intracranial electroencephalography. Mapping recording sites into a low-dimensional space where proximity represents functional similarity revealed a hierarchical organization. At fine scale, a group of auditory cortical regions excluded several higher order auditory areas and segregated maximally from prefrontal cortex. On mesoscale, the proximity of limbic structures to auditory cortex suggested a limbic stream that parallels the classically described ventral and dorsal auditory processing streams. Identities of global hubs in anterior temporal and cingulate cortex depended on frequency band, consistent with diverse roles in semantic and cognitive processing. On a macro scale, observed hemispheric asymmetries were not specific for speech and language networks. This approach can be applied to multivariate brain data with respect to development, behavior, and disorders. BlurbWe describe the organization of human neocortex on multiple spatial scalesbased on resting state intracranial electrophysiology. We focus on cortical regions involved in auditory processing and examine inter-regional hierarchical relationships, network topology, and hemispheric lateralization. This work introduces a powerful analytical tool to examine mechanisms of altered arousal states, brain development, and neuropsychiatric disorders.

neuroscience↗

bioRxiv2021

Distribution of multi-unit pitch responses recorded intracranially from human auditory cortex

The perception of pitch requires the abstraction of stimulus properties related to the spectrotemporal structure of sound. Previous studies utilizing both animal electrophysiology and human imaging have indicated the presence of a center for pitch representation in the auditory cortex. Recent data from our own group - examining local field potentials (LFPs) in humans - indicate more widely distributed pitch-associated responses within the auditory cortex (Gander et al., 2019). To probe this with greater spatial resolution, we examined multi-unit activity related to three different auditory stimuli, in seven epilepsy patients who were implanted with high-impedance electrodes in auditory cortex for the clinical purpose of localizing seizures. The stimuli were regular-interval noise (RIN) with a pitch strength that is related to the temporal regularity, and pitch value determined by repetition rate, and harmonic complexes with missing fundamentals. We demonstrated increases in spiking activity in 69 of 104 (66%) responsive multiunit activity in auditory cortex due to pitch-associated stimuli. Importantly, these responses were distributed across the entire extent of Heschls gyrus (HG), in both primary and non-primary areas, rather than isolated to a specific region, and this finding was evident regardless of the stimulus presented. These findings are the first multi-unit pitch responses recorded from humans, and align with a recent study in macaques (Kikuchi et al., 2019) demonstrating that both local field potential and unit responses to pitch-inducing stimuli are distributed throughout auditory cortex. Significance StatementThe perception of pitch is a fundamental acoustic attribute that is mediated by the auditory system. Despite its importance, there is still debate as to the precise areas responsible for its encoding, which may be due to differences in the recording measures and choices of stimuli used in previous studies. Here, we present the first study to measure multi-unit pitch responses in the auditory cortices of intracranially-implanted humans. Importantly, we demonstrate reliable responses to three different pitch-inducing paradigms that are distributed throughout Heschls gyrus, rather than being localized to a particular region. These data provide a bridge across animal and human studies, and aid in our understanding of the processing of a critical attribute of acoustic stimuli.

neuroscience↗

bioRxiv2021

A role of cryptochrome for magnetic field-dependent improvement of sleep quality, lifespan and motor function in Drosophila

Understanding the molecular genetic basis of animal magnet reception has been one of the big challenges in biology. Recently it was discovered that the magnetic sense of Drosophila melanogaster is mediated by the ultraviolet (UV)-A/blue light photoreceptor cryptochrome (Cry). Here, using the fruit fly as a magnet receptive model organism, we show that exposure to a specific AC magnetic field during night time affected the health of the fly. AC magnetic field exposure showed lifespan extension under starvation, sleep improvement and prevention of decreased motor function. In contrast, all the health improvement effect was not observed in cryptochrome mutant flies (cryb). We showed that AC magnetic field exposure prevented motor dysfunction in Gauchers disease model Drosophila. The data suggests that magnetic field-dependent improvement of sleep quality, lifespan and motor function is mediated through a cry-dependent pathway in animals.

animal behavior and cognition↗

bioRxiv2020

Protective effects of saffron and its constituent crocetin to motor symptoms, short life span and rough-eyed phenotypes in the fly models of Parkinson's disease in vivo

Parkinsons disease (PD) is a common neurodegenerative disorder with motor symptoms linked to the loss of dopaminergic neurons in the brain. -Synuclein is an aggregation-prone neural protein that plays a role in the pathogenesis of PD. In our previous paper, we found that saffron; the stigma of Crocus sativus Linne (Iridaceae), and its constituents (crocin and crocetin) suppressed aggregation of -synuclein and promoted the dissociation of -synuclein fibrils in vitro. In this study, we investigated the effect of dietary saffron and its constituent, crocetin, in vivo on a fly PD model overexpressing several mutant -synuclein in a tissue-specific manner. Saffron and crocetin significantly suppressed the decrease of climbing ability in the Drosophila overexpressing A30P (A30P fly PD model) or G51D (G51D fly PD model) mutated -synuclein in neurons. Saffron and crocetin extended the life span in the G51D fly PD model. Saffron suppressed the rough-eyed phenotype and the dispersion of the size histogram of the ocular long axis in A30P fly PD model in eye. Saffron had a cytoprotective effect on a human neuronal cell line with -synuclein fibrils. These data showed that saffron and its constituent crocetin have protective effects on the progression of PD disease in animals in vivo and suggest that saffron and crocetin can be used to treat PD.

pharmacology and toxicology↗

bioRxiv2020

Effects of a 50-Hz electric field on sleep quality and life span mediated by ultraviolet (UV)-A/blue light photoreceptor CRYPTOCHROME in Drosophila melanogaster

Although electric fields (EF) exert beneficial effects on animal wound healing and differentiation, the molecular mechanisms of these effects have remained unclear for years. Therefore, we aimed to elucidate the molecular mechanisms underlying these effects in Drosophila melanogaster as a genetic animal model. The sleep quality of wild-type (WT) flies was improved by exposure to a 50-Hz (35 kv/m) constant electric field during the daytime, but not during the night. This effect was undetectable in Cryptochrome mutant (Cryb) flies. Exposure to a 50-Hz electric field under low nutrient conditions elongated the lifespan of male and female WT flies by ~18%, but not of three diferrent Cry mutants and Cry RNAi strains. Metabolome analysis indicated that the adenosine triphosphate (ATP) content was 5-fold higher in intact WT than Cry gene mutant strains exposed to an electric field. A putative magnetoreceptor protein and UV-A/blue light photoreceptor, CRYPTOCHROME (CRY) is involved in electric field receptors in animals. The present findings constitute hitherto unknown genetic evidence of a CRY-based system that is electric-field sensitive in animals.

physiology↗

bioRxiv2020

Oscillatory correlates of auditory working memory examined with human electrocorticography

This work examines how sounds are held in auditory working memory (AWM) in humans by examining oscillatory local field potentials (LFPs) in candidate brain regions. Previous fMRI studies by our group demonstrated blood oxygenation level-dependent (BOLD) response increases during maintenance in auditory cortex, inferior frontal cortex and the hippocampus using a paradigm with a delay period greater than 10s. The relationship between such BOLD changes and ensemble activity in different frequency bands is complex, and the long delay period raised the possibility that long-term memory mechanisms were engaged. Here we assessed LFPs in different frequency bands in six subjects with recordings from all candidate brain regions using a paradigm with a short delay period of 3 s. Sustained delay activity was demonstrated in all areas, with different patterns in the different areas. Enhancement in low frequency (delta) power and suppression across higher frequencies (beta/gamma) were demonstrated in primary auditory cortex in medial Heschls gyrus (HG) whilst non-primary cortex showed patterns of enhancement and suppression that altered at different levels of the auditory hierarchy from lateral HG to superior- and middle-temporal gyrus. Inferior frontal cortex showed increasing suppression with increasing frequency. The hippocampus and parahippocampal gyrus showed low frequency increases and high frequency decreases in oscillatory activity. The work demonstrates sustained activity patterns that can only be explained by AWM maintenance, with prominent low-frequency increases in medial temporal lobe regions.

neuroscience↗

bioRxiv2020

Differential causal involvement of human auditory and frontal cortices in vocal motor control

Speech motor control requires integration of sensory and motor information. Bidirectional communication between frontal and auditory cortices is crucial for speech production, self-monitoring and motor control. We used cortical direct electrical stimulation (DES) to functionally dissect audio-motor interactions underlying speech production and motor control. Eleven neurosurgical patients performed a visually cued vocal task in which a short auditory feedback perturbation was introduced during vocalization. We evaluated the effect of DES on vocal initiation, voice fundamental frequency (F0) and feedback-dependent motor control. DES of frontal sites modulated vocal onset latencies. Stimulation of different inferior frontal gyrus sites elicited either shortening or prolongation of vocal latencies. DES distinctly modulated voice F0 at different vocalization stages. Frontal and temporal areas played an important role in setting voice F0 in the first 250 ms of an utterance, while Heschls gyrus was involved later when auditory input is available for self-monitoring. Vocal responses to pitch-shifted auditory feedback were mostly reduced by DES of non-core auditory cortices. Overall, we demonstrate that vocal planning and initiation are driven by frontal cortices, while feedback-dependent control relies predominantly on non-core auditory cortices. Our findings represent direct evidence of the role played by different auditory and frontal regions in vocal motor control.

neuroscience↗

bioRxiv2020

Focal cortical surface cooling is a novel and safe method for intraoperative functional brain mapping

ObjectiveElectrical cortical stimulation (ECS) has been the gold standard for intraoperative functional mapping in neurosurgery, yet it carries the risk of induced seizures. Here we assess the safety of focal cortical cooling (CC) as a potential alternative to ECS for functional brain mapping. MethodsWe retrospectively reviewed 40 consecutive subjects (n=13 tumor, 27 mesial temporal lobe epilepsy (MTLE) resection) who underwent intraoperative CC during craniotomy at the University of Iowa Hospital and Clinics from 2007 through 2019 (CC group). Thirty-eight of the 40 subjects had ECS performed along with CC during the same procedure. To assess the safety of CC, intra- and post-operative seizure incidence and post-operative neurological deficits were collected together with new post-operative radiographic findings not related to the surgical procedure itself (i.e. non-mapping portions). As a control cohort, we collected 55 consecutive subjects (n=21 MTLE, 34 tumor/vascular pathology) who underwent awake ECS mapping without CC between 2006 and 2019 (ECS-alone group). To evaluate potential long term effects of mapping techniques (CC and/or ECS), we separately collected another 25 consecutive subjects who underwent anterior temporal lobectomy(ATL) without CC nor ECS between 2007 and 2019 (No ECS/No CC-ATL group). ResultsA total of 79 brain sites were cooled in the 40 CC subjects, including inferior frontal gyrus (44%), precentral gyrus (39%), postcentral gyrus (6%), subcentral gyrus (4%) and superior temporal gyrus (6%). No intraoperative seizures were reported in the CC group, whereas 3.6% of ECS-alone group had intraoperative seizures. The incidence of seizure(s) within the first post-operative week did not significantly differ amongst CC (7.9%), ECS-alone (9.0%) and No ECS/No CC-ATL groups (12%). There was no significante difference in the incidence of postoperative radiographic change between CC (7.5%) and ECS-alone groups (5.5 %). The long term seizure outcome for MTLE subjects did not statistically differ regarding good outcomes (Engel I+II): CC group (80%), ECS-alone (83.3%) and No ECS/No CC-ATL group (83.3%). ConclusionsCortical cooling when used as an intraoperative mapping technique is safe, and may complement traditional electrical cortical stimulation.

neuroscience↗

bioRxiv2020

Common Fronto-temporal Effective Connectivity in Humans and Monkeys

Cognitive pathways supporting human language and declarative memory are thought to have uniquely evolutionarily differentiated in our species. However, cross-species comparisons are missing on site-specific effective connectivity between regions important for cognition. We harnessed a new approach using functional imaging to visualize the impact of direct electrical brain stimulation in human neurosurgery patients. Applying the same approach with macaque monkeys, we found remarkably comparable patterns of effective connectivity between auditory cortex and ventro-lateral prefrontal cortex (vlPFC) and parahippocampal cortex in both species. Moreover, in humans electrical tractography revealed rapid evoked potentials in vlPFC from stimulating auditory cortex and speech sounds drove vlPFC, consistent with prior evidence in monkeys of direct projections from auditory cortex to vocalization responsive regions in vlPFC. The results identify a common effective connectivity signature that from auditory cortex is equally direct to vlPFC and indirect to the hippocampus (via parahippocampal cortex) in human and nonhuman primates. HighlightsO_LIPrivileged human auditory to inferior frontal connectivity, linked to monkeys C_LIO_LICommon auditory to parahippocampal effective connectivity in both species C_LIO_LIGreater lateralization in human effective connectivity, more symmetrical in monkeys C_LIO_LIHuman fronto-temporal network function rooted in evolutionarily conserved signature C_LI eTOC short summaryFunctional connectivity between regions crucial for language and declarative memory is thought to have substantially differentiated in humans. Using a new technique to similarly visualize directional effective connectivity in humans and monkeys, we found remarkably comparable connectivity patterns in both species between fronto-temporal regions crucial for cognition.

neuroscience↗

bioRxiv2020

Inositol synthesis gene is required for circadian rhythm of Drosophila melanogaster mating behavior.

Accumulating evidence indicates that the molecular circadian clock underlies the mating behavior of Drosophila melanogaster. However, information about which gene affects circadian mating behavior is poorly understood in animals. The present study found that feeding Myo-inositol enhanced the close-proximity (CP) rhythm of D. melanogaster mating behavior and lengthened the period of the CP rhythm. Then, to understand a role for inositol synthesis to fly mating behavior, we established the Inos (Myo-inositol 1-phosphate synthase) gene knock down fly strains with RNAi. Interestingly, the CP behavior of this three-different driver knock down strains was arrhythmic, but the locomotor rhythm was rhythmic. The data of three-different Inos knock down strains suggests that Inos gene expression of upper LNd, l-LNV, 5ths-LNv in brain is necessary for proper CP rhythm generation in D. melanogaster. The data indicated that the Inos gene is involved in the role for the circadian rhythm of D. melanogaster mating behavior.

animal behavior and cognition↗

bioRxiv2019

Cortical functional connectivity indexes arousal state during sleep and anesthesia

Disruption of cortical connectivity likely contributes to loss of consciousness (LOC) during both sleep and general anesthesia, but the degree of overlap in the underlying mechanisms is unclear. Both sleep and anesthesia comprise states of varying levels of arousal and consciousness, including states of largely maintained consciousness (sleep: N1, REM; anesthesia: sedated but responsive) as well as states of substantially reduced consciousness (sleep: N2/N3; anesthesia: unresponsive). Here, we tested the hypotheses that (1) cortical connectivity will reflect clear changes when transitioning into states of reduced consciousness, and (2) these changes are similar for arousal states of comparable levels of consciousness during sleep and anesthesia. Using intracranial recordings from five neurosurgical patients, we compared resting state cortical functional connectivity (as measured by weighted phase lag index) in the same subjects across arousal states during natural sleep [wake (WS), N1, N2, N3, REM] and propofol anesthesia [pre-drug wake (WA), sedated/responsive (S) and unresponsive (U)]. In wake states WS and WA, alpha-band connectivity within and between temporal, parietal and occipital regions was dominant. This pattern was largely unchanged in N1, REM and S. Transitions into states of reduced consciousness N2, N3 and U were characterized by dramatic and strikingly similar changes in connectivity, with dominant connections shifting to frontal cortex. We suggest that shifts from temporo-parieto-occipital to frontal cortical connectivity may reflect impaired sensory processing in states of reduced consciousness. The data indicate that functional connectivity can serve as a biomarker of arousal state and suggest common mechanisms of LOC in sleep and anesthesia.

neuroscience↗