Biology subjects

Hudetz, A. G.

Publications and source records attributed to Hudetz, A. G..

At least 19 recordsLinked to original sources

bioRxiv2026

Low-intensity focused ultrasound pulsation along the anterior-posterior thalamic axis differentially modulates the latency of reporting conscious visual experience

Background: Transcranial low-intensity focused ultrasound (LIFU) neuromodulation can alter human task performance depending on target and acoustic configurations. However, single behavioral endpoints cannot locate effects within multistep tasks, and predefined target labels ignore acoustic variations. Objective: To determine whether thalamic LIFU affects visual categorization or subsequent subjective report latency and whether the effects vary with target, acoustic parameter, and beam location. Methods: Sixty healthy adults were randomized to 70% or 5% duty cycle (DC70 or DC5) and received sonication on four left thalamic targets with matched pulse repetition frequency (10 Hz) and temporal-average intensity (0.72 W/cm2). Behavioral models tested target-by-DC interactions in categorization (RT1) and subjective report (RT2) latencies. Spatial analyses correlated focal spot coordinates and voxel-wise intensity from 179 acoustic simulations to baseline-adjusted RT2. Results: The target-by-DC interaction was detected for RT2 but not RT1. At the ventroposterior thalamic target, adjusted RT2 was 55.9 ms longer under DC70 than DC5. More anterior focal spots shortened RT2 under DC70 but increased RT2 under DC5. Correlation between intensity and adjusted RT2 significantly differed between DC70 and DC5 in 18.8% of thalamic voxels. These voxels formed an anterior mediodorsal-motor set and a posterior pulvinar-dominant set. Conclusions: The latency of reporting conscious visual experience, but not categorization latency, was affected by thalamic LIFU. This effect varied jointly with anterior-posterior target engagement and acoustic configuration. Analyzing sequential reaction times separately and treating field variation as an anatomical variable revealed associations not fully captured by a single endpoint or predefined target labels.

neuroscience↗

bioRxiv2026

State-dependent, frequency-specific modulation of electrocortical traveling waves by anesthesia

Emerging evidence suggests that cortical activity is organized in traveling waves that coordinate neural activity across space and time. How anesthesia alters these waves remains underexplored. We recently showed that cortical activity undergoes spontaneous state transitions at steady-state anesthetic concentrations including a paradoxical state exhibiting awake-like spectral properties during deep anesthesia. Here, we investigated traveling wave dynamics across spontaneous cortical states using hemispheric electrocorticography in rats anesthetized with desflurane at inhaled concentrations of 6, 4, 2, and 0%. Compared with the awake state, delta-band traveling waves in cortical states predominantly associated with 4-6% desflurane were more frequent and exhibited more stereotyped propagation patterns, characterized by a greater prevalence of planar waves and a corresponding reduction in source/sink wave patterns. The occurrence rate and pattern complexity of theta- and gamma-band waves remained largely unchanged, whereas the propagation direction of planar waves became more variable. Feedforward-feedback organization was also altered: compared with the awake state, the feedback-dominance of theta-band diminished, and the feed-forward dominance of gamma-band was attenuated. Despite occurring predominantly in deep anesthesia associated with behavioral unresponsiveness, traveling-wave dynamics of the paradoxical state exhibited partial, frequency-dependent shifts toward those observed in the awake state. These findings demonstrate that spontaneous cortical states under anesthesia are associated with frequency-dependent reorganization of cortical traveling waves and identify the paradoxical state as a distinct dynamical regime of deep anesthesia. Significance StatementAnesthesia is commonly thought to alter cortical dynamics progressively with increasing anesthetic depth, yet cortical activity can transition spontaneously between distinct states even at constant anesthetic concentrations. Here, we show that cortical states spectrally derived from the electrocorticogram of rats are associated with distinct frequency-specific organization of cortical traveling waves, revealing spatiotemporal dynamics beyond conventional spectral measures. Notably, a paradoxical state, occurred predominantly in deep anesthesia associated with behavioral unresponsiveness, exhibited traveling-wave dynamics that approached those observed during wakefulness. These findings demonstrate that cortical traveling-wave organization changes dynamically with brain state rather than anesthetic concentration alone. They suggest that structured cortical dynamics can emerge during deep anesthesia, providing new insights into large-scale cortical dynamics associated with anesthetic modulation of consciousness.

neuroscience↗

bioRxiv2026

Reorganization of Human Brain Waves Across Diverse States of Consciousness

Brain waves are ubiquitous phenomena of human brain activity. As they propagate, they coordinate neural communication, shaping conscious perception. Understanding how brain waves unfold across space and time is thus critical for uncovering the neural mechanisms that support and suppress consciousness. Here, we analyzed data from the Human Connectome Project alongside multiple independent human datasets of various states of consciousness collected during non-rapid eye movement sleep, propofol anesthesia, and psychedelic states produced by lysergic acid diethylamide, N,N-dimethyltryptamine, psilocybin, nitrous oxide, and ketamine. We then applied complex principal component analysis to map spatiotemporal propagation patterns of blood oxygen level-dependent activity across the human brain, under these diverse states of consciousness. We identified four dominant motifs of wave propagation: a global synchronized wave supporting unimodal-transmodal propagation, an anti-correlated unimodal-transmodal wave, an anti-correlated task-positive/task-negative wave, and an anti-correlated visual-somatomotor wave. Among them, the global wave exhibited the most pronounced state-dependent reconfiguration: in diminished states (sleep and anesthesia), the time needed for the wave to propagate across brain regions consistently increased and the distribution of regional contributions to the waves power became more spatially concentrated and heterogeneous across individuals, indicating slower, more fragmented, and less stereotyped dynamics. In contrast, propagation duration decreased under psychedelic states, reflecting accelerated global wave dynamics alongside a trend towards more spatially distributed and uniform regional contributions, consistent with a more integrated global wave propagation pattern. Beyond this global mode, diminished states slowed propagation primarily along the unimodal-transmodal axis, whereas psychedelic states selectively accelerated propagation along the task-positive/task-negative axis. Together, our findings reveal that diminished (sleep and anesthesia) and psychedelic states alter the spatiotemporal structure of wave propagation across the brain in opposite and distinct ways, providing a unifying account of how macroscale brain dynamics are dynamically reshaped under pharmacological and endogenous perturbations of consciousness.

neuroscience↗

bioRxiv2026

Opposing Network Patterns of Integration-Segregation in Psychedelic and Sedated States of Consciousness

Understanding the relationship of conscious states to large-scale brain dynamics remains a central challenge in neuroscience. Here, diverse pharmacological and physiological perturbations--including psychedelic states, sleep, and propofol sedation--were used to examine integration-segregation organization of brain networks across altered states of consciousness in humans using functional MRI. Across analyses, psychedelic and sedative states exhibited a robust "mirror-image" pattern of integration and segregation. Psychedelics were characterized by increased large-scale integration and reduced segregation of brain network interactions, whereas sleep and propofol sedation showed the opposite configuration. These opposing integration-segregation patterns were consistently indexed by complementary measures of functional connectivity, network topology, and interaction complexity, capturing non-redundant dimensions of large-scale brain organization. Importantly, this mirror-image organization generalized across multiple spatial levels and reliably differentiated conscious states in an unbiased, data-driven manner. Together, these findings demonstrate that psychedelic and sedated states are characterized by systematic and opposing shifts in large-scale integration and segregation, with implications for mechanisms of consciousness.

neuroscience↗

bioRxiv2025

A Mesoscale Framework for Psychedelic Drug Action in the Human Brain

The mechanism of psychedelic drug action is a dynamic area of neuroscience, with two major lines of investigation: (1) laboratory studies at the molecular and cellular level, and (2) human neuroimaging studies of functional brain networks. Despite considerable progress, there remains insufficient understanding of the link between molecular/cellular substrates of psychedelics and the whole-brain network effects that result. Here we report a study of psychedelic action that focuses on the intermediate spatial scale of local brain regions (<1cm3). We analyzed the effects of classical psychedelics (dimethyltryptamine [DMT], lysergic acid diethylamide [LSD], psilocybin) and non-classical psychedelics (nitrous oxide, ketamine) in humans using functional magnetic resonance imaging. We found that all five drugs reduced regional homogeneity, that is, they disrupted local synchrony, in small-scale brain regions; this disruption occurred extensively in cortical regions and sparsely in subcortical regions. Dynamic analysis of both regional homogeneity and global functional connectivity showed an inverse pattern, with large-scale functional connectivity being enhanced as local synchrony declined. We then conducted dominance analysis to assess the contribution of various neurotransmitter receptors to changes in regional homogeneity. DMT, LSD, and psilocybin showed the 5-HT receptors as the most dominant association; by contrast, regional homogeneity changes attributable to both nitrous oxide and ketamine were most strongly associated with the NMDA receptor. Both neuronal (including interneurons) and non-neuronal cell types were linked to psychedelic-induced changes in synchrony at the level of local brain regions. These data, across five drugs from two drug classes, provide evidence that a diverse set of molecular and cellular events lead to a common outcome of disrupted synchrony in local brain regions, which in turn mediate drug-specific changes in global functional connectivity.

neuroscience↗

bioRxiv2025

Intravenous Administration of Serotonergic Psychedelics Produce Short-lasting Changes in Sleep-Wake Behavior and High Gamma Functional Connectivity in Rats

Background and PurposeGiven the increase in recreational psychedelic use and ongoing efforts to explore psychedelics as therapeutic agents for mental health disorders, there is an urgent need to understand the effect of psychedelics such as psilocybin and N,N-dimethyltryptamine (DMT) on sleep-wake states, which share a bidirectional relationship with mental health. Here, we investigated the effects of intravenous psilocybin and DMT on sleep-wake states and EEG spectral power and functional connectivity in rats. Experimental ApproachSprague Dawley rats (n=25, 13 male) were surgically instrumented to record high-density EEG (27 electrodes) and EMG during 12-h light and 12-h dark cycle after intravenous psilocybin (2.5 mg/kg, 10 mg/kg), DMT (3.75 mg/kg, 7.5 mg/kg) or 0.9% saline. The EEG/EMG data were scored in 4-second epochs into wake, slow-wave sleep (SWS), and rapid eye movement (REM) sleep. EEG spectral power and corticocortical coherence, a surrogate for functional connectivity, were computed in 12-second epochs. Key ResultsPsilocybin and DMT delayed the onset of SWS and REM sleep, and caused a short-lasting increase in wakefulness and decrease in SWS. Psilocybin also produced a 1) decrease in REM sleep, 2) decrease in theta power and coherence and increase in high gamma power and coherence during wake and SWS, and 3) increase in high gamma coherence during REM sleep. DMT increased gamma coherence only during wakefulness. Conclusions and ImplicationsSerotonergic psychedelics have minimal effects on sleep-wake states. The enhanced high gamma functional connectivity suggests that the psychedelic-induced changes in EEG/neural dynamics can occur independent of the arousal states.

neuroscience↗

bioRxiv2025

Dynamic electrocortical states and paradoxical complexity during desflurane anesthesia

BackgroundHow general anesthesia alters the dynamics of electrocortical activity is crucial to understand the neural mechanisms of unconsciousness. Local cortical activity undergoes spontaneous transitions at constant anesthetic concentration. The spatial organization and temporal dynamics of state transitions in large-scale electrocortical activity is incompletely understood. MethodsEpidural electrocorticogram was recorded from the right hemisphere in 8 rats (14 experiments) using chronically implanted 32-channel flexible electrode arrays during desflurane anesthesia at 6%, 4%, 2%, 0% inhaled concentrations, each maintained for 1 hour. Cortical states were identified by principal component analysis of power spectrograms followed by density-based clustering simultaneously across all anesthetic conditions. State-specific spatiotemporal complexity was quantified by the normalized Lempel-Ziv algorithm to capture signal variability beyond spectral effects. Temporal dynamics were assessed by state occurrence, dwell times, and transition probabilities. ResultsSeven cortical states were identified. Six states generally tracked anesthetic depth with an increase in delta power and decrease in complexity, but their occurrence was not tied to any anesthetic level (p<0.001). The 7th state was a paradoxical, activated state that mostly occurred during deep anesthesia and was marked by reduced delta (p<0.001) and elevated complexity (p<0.001). Cortical activity was more likely to remain in a given state than to switch (mean dwell time of 136.55 s, persistence likelihood of 99.36%). When transitions occurred, they followed structured, non-random dynamics, primarily within light- or deep-anesthesia states (FDR-corrected p<0.05), with a mild tendency to exit deep states and enter light states (p=0.0039), consistent with anesthetic emergence. ConclusionsElectrocortical activity is not a unitary function of anesthetic concentration but involves spontaneous dynamics and paradoxically activated states with increased global complexity during deep anesthesia. The results suggest ongoing spontaneous reorganization of cortical activity during prolonged anesthetic challenge and provide new insight into anesthesia-induced brain dynamics that may inform future strategies for monitoring and manipulating the state of consciousness and facilitating recovery from general anesthesia.

neuroscience↗

bioRxiv2024

Neural Correlates of Psychedelic, Sleep, and Sedated States Support Global Theories of Consciousness

Understanding neural mechanisms of consciousness remains a challenging question in neuroscience. A central debate in the field concerns whether consciousness arises from global interactions that involve multiple brain regions or focal neural activity, such as in sensory cortex. Additionally, global theories diverge between the Global Neuronal Workspace (GNW) hypothesis, which emphasizes frontal and parietal areas, and the Integrated Information Theory (IIT), which focuses on information integration within posterior cortical regions. To disentangle the global vs. local and frontoparietal vs. posterior dilemmas, we measured global functional connectivity and local neural synchrony with functional magnetic resonance imaging (fMRI) data across a spectrum of conscious states in humans induced by psychedelics, sleep, and deep sedation. We found that psychedelic states are associated with increased global functional connectivity and decreased local neural synchrony. In contrast, non-REM sleep and deep sedation displayed the opposite pattern, suggesting that consciousness arises from global brain network interactions rather than localized activity. This mirror-image pattern between enhanced and diminished states was observed in both anterior-posterior (A-P) and posterior-posterior (P-P) brain regions but not within the anterior part of the brain alone. Moreover, anterior transmodal regions played a key role in A-P connectivity, while both posterior transmodal and posterior unimodal regions were critical for P-P connectivity. Overall, these findings provide empirical evidence supporting global theories of consciousness in relation to varying states of consciousness. They also bridge the gap between two prominent theories, GNW and IIT, by demonstrating how different theories can converge on shared neuronal mechanisms.

neuroscience↗

bioRxiv2024

Thalamic Roles in Conscious Perception Revealed by Low-Intensity Focused Ultrasound Neuromodulation

The neural basis of consciousness remains incompletely understood. While cortical mechanisms of conscious perception have been extensively investigated in humans, the role of subcortical structures, including the thalamus, remains less explored. Here, we elucidate the causal contributions of different thalamic regions to conscious perception using transcranial low-intensity focused ultrasound (LIFU) neuromodulation. We hypothesize that modulating distinct thalamic regions alters perceptual outcomes derived from Signal Detection Theory. We apply LIFU to healthy human anterior (transmodal-dominant) and posterior (unimodal-dominant) thalamic regions, further subdivided into ventral and dorsal regions, during a near-threshold visual perception task. We show that high duty cycle modulation of the ventral anterior (VA) part of thalamus enhances object recognition sensitivity. Sensitivity enhancement magnitude correlates with the core-matrix cell compositions of the stimulated thalamic region. Connectivity analysis of a large-scale functional magnetic resonance imaging dataset confirms strong transmodal connectivity of VA thalamus with frontoparietal and default-mode networks. We also demonstrate target-invariant effects of high duty cycle LIFU disrupting object categorization accuracy. These findings provide causal insight into the cytoarchitectural and functional organization of the thalamus that shapes human visual experience, especially the role of matrix cell-rich, transmodal-dominant VA thalamus.

neuroscience↗

bioRxiv2024

Microstimulation reveals anesthetic state-dependent effective connectivity of neurons in cerebral cortex

Complex neuronal interactions underlie cortical information processing that can be compromised in altered states of consciousness. Here intracortical microstimulation was applied to investigate the state-dependent effective connectivity of neurons in rat visual cortex in vivo. Extracellular activity was recorded at 32 sites in layers 5/6 while stimulating with charge-balanced discrete pulses at each electrode in random order. The same stimulation pattern was applied at three levels of anesthesia with desflurane and in wakefulness. Spikes were sorted and classified by their waveform features as putative excitatory and inhibitory neurons. Microstimulation caused early (<10ms) increase followed by prolonged (11-100ms) decrease in spiking of all neurons throughout the electrode array. The early response of excitatory but not inhibitory neurons decayed rapidly with distance from the stimulation site over 1mm. Effective connectivity of neurons with significant stimulus response was dense in wakefulness and sparse under anesthesia. Network motifs were identified in graphs of effective connectivity constructed from monosynaptic cross-correlograms. The number of motifs, especially those of higher order, increased rapidly as the anesthesia was withdrawn indicating a substantial increase in network connectivity as the animals woke up. The results illuminate the impact of anesthesia on functional integrity of local circuits affecting the state of consciousness.

neuroscience↗

bioRxiv2024

Measuring the dynamic balance of integration and segregation underlying consciousness, anesthesia, and sleep

Consciousness requires a dynamic balance of integration and segregation in functional brain networks. An optimal integration-segregation balance depends on two key aspects of functional connectivity: global efficiency (i.e., integration) and clustering (i.e., segregation). We developed a new fMRI-based measure, termed the integration-segregation difference (ISD), which captures both aspects. We used this metric to quantify changes in brain state from conscious wakefulness to loss of responsiveness induced by the anesthetic propofol. The observed changes in ISD suggest a profound shift to segregation in both whole brain and all brain subnetworks during anesthesia. Moreover, brain networks displayed similar sequences of disintegration and subsequent reintegration during, respectively, loss and return of responsiveness. Random forest machine learning models, trained with the integration and segregation of brain networks, identified the awake vs. unresponsive states and their transitions with accuracy up to 93%. We found that metastability (i.e., the dynamic recurrence of non-equilibrium transient states) is more effectively explained by integration, while complexity (i.e., diversity and intricacy of neural activity) is more closely linked with segregation. The analysis of a sleep dataset revealed similar findings. Our results demonstrate that the integration-segregation balance is a useful index that can differentiate among various conscious and unconscious states.

neuroscience↗

bioRxiv2024

Propofol Disrupts the Functional Core-Matrix Architecture of the Thalamus in Humans

Research into the role of thalamocortical circuits in anesthesia-induced unconsciousness is difficult due to anatomical and functional complexity. Prior neuroimaging studies have examined either the thalamus as a whole or focused on specific subregions, overlooking the distinct neuronal subtypes like core and matrix cells. We conducted a study of heathy volunteers and functional magnetic resonance imaging during conscious baseline, deep sedation, and recovery. We advanced the functional gradient mapping technique to delineate the functional geometry of thalamocortical circuits, within a framework of the unimodal-transmodal functional axis of the cortex. We observed a significant shift in this geometry during unconsciousness, marked by the dominance of unimodal over transmodal geometry. This alteration was closely linked to the spatial variations in the density of matrix cells within the thalamus. This research bridges cellular and systems-level understanding, highlighting the crucial role of thalamic core-matrix functional architecture in understanding the neural mechanisms of states of consciousness.

neuroscience↗

bioRxiv2023

Psychedelic Concentrations of Nitrous Oxide Reduce Functional Differentiation in Frontoparietal and Somatomotor Cortical Networks

AO_SCPLOWBSTRACTC_SCPLOWDespite the longstanding use of nitrous oxide and descriptions of its psychological effects more than a century ago, there is a paucity of neurobiological investigation of associated psychedelic experiences. Identifying the impact of nitrous oxide on functional brain networks would advance understanding and contribute to the growing body of research in psychedelic neuroscience. Based on human resting-state fMRI data acquired before and during the administration of 35% nitrous oxide, we measured the brains functional geometry (through analysis of cortical gradients) and temporal dynamics (through analysis of co-activation patterns). Both analyses show that nitrous oxide reduces functional differentiation in frontoparietal and somatomotor networks. Importantly, the subjective psychedelic experience induced by nitrous oxide is inversely correlated with the degree of functional differentiation. Thus, like classical psychedelics acting on 5-HT2 receptors, nitrous oxide flattens the functional geometry of the cortex and disrupts temporal dynamics in association with psychoactive effects.

neuroscience↗

bioRxiv2022

Anesthesia alters cortical spike sequences in rodent visual cortex

Recurring spike sequences are thought to underlie cortical computations and may be essential for information processing in the conscious state. How anesthesia at graded levels may influence spontaneous and stimulus-related spike sequences in visual cortex has not been systematically examined. We recorded extracellular single-unit activity in the rat primary visual cortex in vivo during wakefulness and three levels of anesthesia produced by desflurane. The latencies of spike sequences within 0~200ms from the onset of spontaneous UP states and visual flash-evoked responses were compared. During wakefulness, spike latency patterns linked to the local field potential theta cycle were similar to stimulus-evoked patterns. Under anesthesia, spontaneous UP state sequences differed from flash-evoked sequences due to the recruitment of low-firing excitatory neurons to the UP state. Flash-evoked spike sequences showed higher reliability and longer latency when stimuli were applied during DOWN states compared to UP states. At deeper levels, anesthesia altered both UP state and flash-evoked spike sequences by selectively suppressing inhibitory neuron firing. The results reveal anesthesia-induced complex changes in cortical firing sequences that may influence visual information processing.

neuroscience↗

bioRxiv2022

The Neural Correlates of Arousal: The Ventral Posterolateral Nucleus-Global Transient Co-Activation

Arousal and awareness are two components of consciousness whose the neural mechanisms remain unclear. Spontaneous increases of global (brain-wide) blood-oxygenation-level-dependent (BOLD) signal has been found to be sensitive to changes in arousal. By contrasting BOLD datasets with altered arousal levels, we found that the activation of ventral posterolateral nucleus (VPL) decreased during transient increase in the global signal (top 17% data) in low arousal and awareness states (non-rapid eye movement sleep and anesthesia) as compared to wakefulness, and even in eye-closed (compared with eyes-open) in healthy awake-states, while this activation remained unchanged in patients with unresponsive wakefulness syndrome characterized by high arousal without awareness. These results demonstrate that co-activation of the VPL and global activity is critical to arousal, but not to awareness. One-Sentence SummaryThe VPL nucleus-global brain transient co-activation is related to physiological arousal but not to perceptual awareness.

neuroscience↗

bioRxiv2022

Canonical and Non-Canonical Psychedelic Drugs Induce Common Network Changes in Human Cortex

AO_SCPLOWBSTRACTC_SCPLOWThe neurobiology of the psychedelic experience is not fully elucidated. Identifying common brain network changes induced by both canonical (i.e., acting at the 5-HT2 receptor) and non-canonical psychedelics would provide mechanistic insight into state-specific characteristics. We analyzed whole-brain functional connectivity based on resting-state fMRI data in humans, acquired before and during the administration of nitrous oxide, ketamine, and lysergic acid diethylamide. We report that, despite distinct molecular mechanisms and modes of delivery, all three psychedelics reduced within-network functional connectivity and enhanced between-network functional connectivity. More specifically, all drugs tested increased connectivity between right temporoparietal junction and bilateral intraparietal sulcus as well as between precuneus and left intraparietal sulcus. These regions fall within the posterior cortical "hot zone," posited to mediate the content of consciousness. Thus, both canonical and non-canonical psychedelics modulate networks within an area of known relevance for conscious experience, identifying a biologically plausible candidate for their subjective effects.

neuroscience↗

bioRxiv2021

Modeling Synaptic Effects of Anesthesia and its Cortical Cholinergic Reversal

General anesthetics work through a variety of molecular mechanisms while resulting in the common end point of sedation and loss of consciousness. Generally, the administration of common inhalation anesthetics induces decreases in synaptic excitation while promoting synaptic inhibition. Animal studies have shown that, during anesthesia, exogenously induced increases in acetylcholine-mediated effects in the brain can elicit wakeful-like behavior despite the continued presence of the anesthetic. Less investigated, however, is the question of whether the brains electrophysiological activity is also restored to pre-anesthetic levels and quality by such interventions. Here we apply a computational model of a network composed of excitatory and inhibitory neurons to simulate the network effects of changes in synaptic inhibition and excitation due to anesthesia and its reversal by muscarinic receptor-mediated cholinergic effects. We use a differential evolution algorithm to fit model parameters to match measures of spiking activity, neuronal connectivity, and network dynamics recorded in the visual cortex of rodents during anesthesia with desflurane in vivo. We find that facilitating muscarinic receptor effects of acetylcholine on top of anesthetic-induced synaptic changes predicts reversal of the neurons spiking activity, functional connectivity, as well as pairwise and population interactions. Thus, our model results predict a possible neuronal mechanism for the induced reversal of the effects of anesthesia on post synaptic potentials, consistent with experimental behavioral observations. Author SummaryHere, we apply a computational model of a network composed of excitatory and inhibitory neurons to simulate the network effects of changes in synaptic inhibition and excitation due to anesthesia and we investigate the possibility of its reversal by muscarinic receptor-mediated cholinergic effects. Specifically, we use a differential evolution algorithm to fit model parameters to match dynamics recorded in the visual cortex of rodents during anesthesia with desflurane in vivo. We find that changes of the fitted synaptic parameters in response to the increasing desflurane concentration matched those established by neurophysiology. Further, our results demonstrate that the cellular effects induced by anesthesia can be mitigated by the changes in cellular excitability due to acetylcholine.

neuroscience↗

bioRxiv2021

The cortical hubs related to recovery of consciousness

Background and ObjectivesThe neural mechanism that enables the recovery of consciousness in patients with unresponsive wakefulness syndrome (UWS) remains unclear. The aim of the current study is to characterize the cortical hub regions related to the recovery of consciousness in patients with UWS. MethodsVoxel-wise degree centrality analysis was adopted to identify the cortical hubs related to the recovery of consciousness, for which a total of 27 UWS patients were used, including 13 patients who emerged from UWS (UWS-E), and 14 patients who remained in UWS (UWS-R) at least three months after the experiment performance. Furthermore, other recoverable unconscious states including three independent deep sleep datasets (n = 12, 9, 9 respectively) and three independent anesthesia datasets (n = 27, 14, 6 respectively) were adopted as validation groups. Spatial similarity of the hub characteristic with the validation groups between the UWS-E and UWS-R was compared using the dice coefficient. Finally, with the cortical regions persistently shown as hubs across UWS-E and validation states, functional connectivity analysis was further performed to explore the connectivity patterns underlying the recovery of consciousness. ResultsFour cortical hubs were identified with significantly higher degree centrality for UWS-E than UWS-R, including the anterior precuneus, left inferior parietal lobule, left inferior frontal gyrus, and left middle frontal gyrus, of which the degree centrality value also positively correlated with the patients Glasgow Outcome Scale (GOS) score. Furthermore, the anterior precuneus was found to show significantly higher similarity of hub characteristics as well as functional connectivity pattern between UWS-E and validation groups, compared with UWS-R. DiscussionThe results suggest that the recovery of consciousness may be relevant to the integrity of cortical hubs, especially the anterior precuneus. The identified cortical hub regions could serve as potential targets for noninvasive stimulation aimed at promoting the patients consciousness recovery.

neuroscience↗