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 a fine scale, a group of auditory cortical regions excluded several higher-order auditory areas and segregated maximally from the prefrontal cortex. On mesoscale, the proximity of limbic structures to the 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 macroscale, 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.

Analogous cortical reorganization accompanies entry into states of reduced consciousness during anesthesia and sleep.

Theories of consciousness suggest that brain mechanisms underlying transitions into and out of unconsciousness are conserved no matter the context or precipitating conditions. We compared signatures of these mechanisms using intracranial electroencephalography in neurosurgical patients during propofol anesthesia and overnight sleep and found strikingly similar reorganization of human cortical networks. We computed the "effective dimensionality" of the normalized resting state functional connectivity matrix to quantify network complexity. Effective dimensionality decreased during stages of reduced consciousness (anesthesia unresponsiveness, N2 and N3 sleep). These changes were not region-specific, suggesting global network reorganization. When connectivity data were embedded into a low-dimensional space in which proximity represents functional similarity, we observed greater distances between brain regions during stages of reduced consciousness, and individual recording sites became closer to their nearest neighbors. These changes corresponded to decreased differentiation and functional integration and correlated with decreases in effective dimensionality. This network reorganization constitutes a neural signature of states of reduced consciousness that is common to anesthesia and sleep. These results establish a framework for understanding the neural correlates of consciousness and for practical evaluation of loss and recovery of consciousness.

Differential Utilization of Parental Presence and Premedication for Induction of Anesthesia in Pediatric Patients.

PURPOSE: Known disparities exist in pain treatment between African American, Latino, and White children. A recent study described 'adultification' of Black children, with Black children being less likely to have a parent present at induction of anesthesia and less likely to receive an anxiolytic premedication before proceeding to the operating room. The aim of this study is to identify differences based on race and socioeconomic status when treating children and their families for anesthetic induction. We hypothesize that differences exist such that certain populations are less likely to receive sedative premedication and less likely to have parents present at induction of anesthesia. DESIGN: This was a retrospective cohort study. METHODS: Demographic data were obtained along with type of surgical procedure, type of anesthesia induction, use of premedication, and involvement of child life services (including the plan for parental presence at induction) for all pediatric patients presenting for anesthetics from February 2019 to March 2020. Statistical analysis consisted of fitting logistic mixed effects models for caregiver presence or for midazolam use during induction, with fixed effects for sex, race, ethnicity, language, public/private insurance, and anesthetic risk, and with the provider as a random effect. FINDINGS: A total of 7,753 patients were included in our statistical analyses, and parental presence focused on 4,102 patients with documentation from child life specialists. Females were less likely than males to have parents present at induction (odds ratio [OR] 0.77, confidence interval [CI] [0.67, 0.89]). When looking at race, American Indian/Alaskan Native patients (OR 0.23 [CI 0.093, 0.47]) and Black/African American patients OR 0.64 [CI 0.47, 0.89]) were less likely to have a parent present induction than White patients. Patients with private insurance were more likely to have parents present than patients with public insurance (OR 0.63 CI [0.5, 0.78]). These findings held true in age-separated sensitivity analysis. Asian patients were less likely to receive midazolam premedication (OR 0.65 CI [0.49, 0.86]). CONCLUSIONS: This study supports previous work showing differential use of parental presence at induction based on race. Additionally, it also shows different treatment based on sex and public insurance status, a surrogate for socioeconomic status.

High-dimensional multivariate autoregressive model estimation of human electrophysiological data using fMRI priors.

Multivariate autoregressive (MVAR) model estimation enables assessment of causal interactions in brain networks. However, accurately estimating MVAR models for high-dimensional electrophysiological recordings is challenging due to the extensive data requirements. Hence, the applicability of MVAR models for study of brain behavior over hundreds of recording sites has been very limited. Prior work has focused on different strategies for selecting a subset of important MVAR coefficients in the model to reduce the data requirements of conventional least-squares estimation algorithms. Here we propose incorporating prior information, such as resting state functional connectivity derived from functional magnetic resonance imaging, into MVAR model estimation using a weighted group least absolute shrinkage and selection operator (LASSO) regularization strategy. The proposed approach is shown to reduce data requirements by a factor of two relative to the recently proposed group LASSO method of Endemann et al (Neuroimage 254:119057, 2022) while resulting in models that are both more parsimonious and more accurate. The effectiveness of the method is demonstrated using simulation studies of physiologically realistic MVAR models derived from intracranial electroencephalography (iEEG) data. The robustness of the approach to deviations between the conditions under which the prior information and iEEG data is obtained is illustrated using models from data collected in different sleep stages. This approach allows accurate effective connectivity analyses over short time scales, facilitating investigations of causal interactions in the brain underlying perception and cognition during rapid transitions in behavioral state.

Multivariate autoregressive model estimation for high-dimensional intracranial electrophysiological data.

Fundamental to elucidating the functional organization of the brain is the assessment of causal interactions between different brain regions. Multivariate autoregressive (MVAR) modeling techniques applied to multisite electrophysiological recordings are a promising avenue for identifying such causal links. They estimate the degree to which past activity in one or more brain regions is predictive of another region's present activity, while simultaneously accounting for the mediating effects of other regions. Including as many mediating variables as possible in the model has the benefit of drastically reducing the odds of detecting spurious causal connectivity. However, effective bounds on the number of MVAR model coefficients that can be estimated reliably from limited data make exploiting the potential of MVAR models challenging for even modest numbers of recording sites. Here, we utilize well-established dimensionality-reduction techniques to fit MVAR models to human intracranial data from ∼100 - 200 recording sites spanning dozens of anatomically and functionally distinct cortical regions. First, we show that high-dimensional MVAR models can be successfully estimated from long segments of data and yield plausible connectivity profiles. Next, we use these models to generate synthetic data with known ground-truth connectivity to explore the utility of applying principal component analysis and group least absolute shrinkage and selection operator (gLASSO) to reduce the number of parameters (connections) during model fitting to shorter data segments. We show that gLASSO is highly effective for recovering ground-truth connectivity in the limited data regime, capturing important features of connectivity for high-dimensional models with as little as 10 seconds of data. The methods presented here have broad applicability to the analysis of high-dimensional time series data in neuroscience, facilitating the elucidation of the neural basis of sensation, cognition, and arousal.

Cortical Responses to Vowel Sequences in Awake and Anesthetized States: A Human Intracranial Electrophysiology Study.

Elucidating neural signatures of sensory processing across consciousness states is a major focus in neuroscience. Noninvasive human studies using the general anesthetic propofol reveal differential effects on auditory cortical activity, with a greater impact on nonprimary and auditory-related areas than primary auditory cortex. This study used intracranial electroencephalography to examine cortical responses to vowel sequences during induction of general anesthesia with propofol. Subjects were adult neurosurgical patients with intracranial electrodes placed to identify epileptic foci. Data were collected before electrode removal surgery. Stimuli were vowel sequences presented in a target detection task during awake, sedated, and unresponsive states. Averaged evoked potentials (AEPs) and high gamma (70-150 Hz) power were measured in auditory, auditory-related, and prefrontal cortex. In the awake state, AEPs were found throughout studied brain areas; high gamma activity was limited to canonical auditory cortex. Sedation led to a decrease in AEP magnitude. Upon LOC, there was a decrease in the superior temporal gyrus and adjacent auditory-related cortex and a further decrease in AEP magnitude in core auditory cortex, changes in the temporal structure and increased trial-to-trial variability of responses. The findings identify putative biomarkers of LOC and serve as a foundation for future investigations of altered sensory processing.

Electrophysiology of the Human Superior Temporal Sulcus during Speech Processing.

The superior temporal sulcus (STS) is a crucial hub for speech perception and can be studied with high spatiotemporal resolution using electrodes targeting mesial temporal structures in epilepsy patients. Goals of the current study were to clarify functional distinctions between the upper (STSU) and the lower (STSL) bank, hemispheric asymmetries, and activity during self-initiated speech. Electrophysiologic properties were characterized using semantic categorization and dialog-based tasks. Gamma-band activity and alpha-band suppression were used as complementary measures of STS activation. Gamma responses to auditory stimuli were weaker in STSL compared with STSU and had longer onset latencies. Activity in anterior STS was larger during speaking than listening; the opposite pattern was observed more posteriorly. Opposite hemispheric asymmetries were found for alpha suppression in STSU and STSL. Alpha suppression in the STS emerged earlier than in core auditory cortex, suggesting feedback signaling within the auditory cortical hierarchy. STSL was the only region where gamma responses to words presented in the semantic categorization tasks were larger in subjects with superior task performance. More pronounced alpha suppression was associated with better task performance in Heschl's gyrus, superior temporal gyrus, and STS. Functional differences between STSU and STSL warrant their separate assessment in future studies.

Scheduled methadone reduces overall opioid requirements after pediatric posterior spinal fusion: A single center retrospective case series.

BACKGROUND: Posterior spinal fusion to correct adolescent idiopathic scoliosis is associated with significant postoperative pain. Different modalities have been reported as part of a multimodal analgesic plan. Intravenous methadone acts as a mu-opioid agonist and N-Methyl-D-aspartate (NMDA) antagonist and has been shown to have opioid-sparing effects. Our multimodal approach has included hydromorphone patient-controlled analgesia (PCA) with and without preincisional methadone, and recently postoperative methadone without a PCA. AIMS: We hypothesized that a protocol including scheduled postoperative methadone doses would reduce opioid usage compared to PCA-based strategy. METHODS: A retrospective chart review of patients undergoing posterior spinal fusion for adolescent idiopathic scoliosis between 2015 and 2020 was performed. There were three patient groups: Group PCA received a hydromorphone PCA without methadone; Group PCA + Methadone received preincisional methadone and a hydromorphone PCA; Group Methadone received preincisional methadone, scheduled postoperative methadone, and no PCA. The primary outcome was postoperative opioid use over 72 h. Secondary outcomes included pain scores, sedation scores, and length of stay. RESULTS: Group PCA (n = 26) consumed 0.33 mg/kg (95% CI [0.28, 0.38]) total hydromorphone equivalents, Group PCA + methadone (n = 39) 0.30 mg/kg (95% CI [0.25, 0.36]) total hydromorphone equivalents, and Group methadone (n = 22) 0.18 mg/kg (95% CI [0.15, 0.21]) total hydromorphone equivalents (p = .00096). There were no statistically significant differences between the groups for secondary outcomes. CONCLUSION: A protocol with intraoperative and scheduled postoperative methadone doses resulted in a 45% reduction in opioid usage compared to a PCA-based protocol with similar analgesia after pediatric posterior spinal fusion.

Electrophysiological signatures of acute systemic lipopolysaccharide-induced inflammation: potential implications for delirium science.

BACKGROUND: Novel preventive therapies are needed for postoperative delirium, which especially affects older patients. A mouse model is presented that captures inflammation-associated cortical slow wave activity (SWA) observed in patients, allowing exploration of the mechanistic role of prostaglandin-adenosine signalling. METHODS: EEG and cortical cytokine measurements (interleukin 6, monocyte chemoattractant protein-1) were obtained from adult and aged mice. Behaviour, SWA, and functional connectivity were assayed before and after systemic administration of lipopolysaccharide (LPS)+piroxicam (cyclooxygenase inhibitor) or LPS+caffeine (adenosine receptor antagonist). To avoid the confounder of inflammation-driven changes in movement which alter SWA and connectivity, electrophysiological recordings were classified as occurring during quiescence or movement, and propensity score matching was used to match distributions of movement magnitude between baseline and post-LPS administration. RESULTS: LPS produces increases in cortical cytokines and behavioural quiescence. In movement-matched data, LPS produces increases in SWA (likelihood-ratio test: χ2(4)=21.51, P<0.001), but not connectivity (χ2(4)=6.39, P=0.17). Increases in SWA associate with interleukin 6 (P<0.001) and monocyte chemoattractant protein-1 (P=0.001) and are suppressed by piroxicam (P<0.001) and caffeine (P=0.046). Aged animals compared with adult animals show similar LPS-induced SWA during movement, but exaggerated cytokine response and increased SWA during quiescence. CONCLUSIONS: Cytokine-SWA correlations during wakefulness are consistent with observations in patients with delirium. Absence of connectivity effects after accounting for movement changes suggests decreased connectivity in patients is a biomarker of hypoactivity. Exaggerated effects in quiescent aged animals are consistent with increased hypoactive delirium in older patients. Prostaglandin-adenosine signalling may link inflammation to neural changes and hence delirium.

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 conscious experience (sleep: N1, REM; anesthesia: sedated but responsive) as well as states of substantially reduced conscious experience (sleep: N2/N3; anesthesia: unresponsive). Here, we tested the hypotheses that (1) cortical connectivity will exhibit clear changes when transitioning into states of reduced consciousness, and (2) these changes will be similar for arousal states of comparable levels of consciousness during sleep and anesthesia. Using intracranial recordings from five adult neurosurgical patients, we compared resting state cortical functional connectivity (as measured by weighted phase lag index, wPLI) 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)]. Analysis of alpha-band connectivity indicated a transition boundary distinguishing states of maintained and reduced conscious experience in both sleep and anesthesia. In wake states WS and WA, alpha-band wPLI within the temporal lobe 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 changes in connectivity, with dominant connections shifting to prefrontal cortex. Secondary analyses indicated similarities in reorganization of cortical connectivity in sleep and anesthesia. Shifts from temporal 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.

PV+ Cells Enhance Temporal Population Codes but not Stimulus-Related Timing in Auditory Cortex.

Spatio-temporal cortical activity patterns relative to both peripheral input and local network activity carry information about stimulus identity and context. GABAergic interneurons are reported to regulate spiking at millisecond precision in response to sensory stimulation and during gamma oscillations; their role in regulating spike timing during induced network bursts is unclear. We investigated this issue in murine auditory thalamo-cortical (TC) brain slices, in which TC afferents induced network bursts similar to previous reports in vivo. Spike timing relative to TC afferent stimulation during bursts was poor in pyramidal cells and SOM+ interneurons. It was more precise in PV+ interneurons, consistent with their reported contribution to spiking precision in pyramidal cells. Optogenetic suppression of PV+ cells unexpectedly improved afferent-locked spike timing in pyramidal cells. In contrast, our evidence suggests that PV+ cells do regulate the spatio-temporal spike pattern of pyramidal cells during network bursts, whose organization is suited to ensemble coding of stimulus information. Simulations showed that suppressing PV+ cells reduces the capacity of pyramidal cell networks to produce discriminable spike patterns. By dissociating temporal precision with respect to a stimulus versus internal cortical activity, we identified a novel role for GABAergic cells in regulating information processing in cortical networks.

Pregnancy-Associated Plasma Protein-aa Regulates Photoreceptor Synaptic Development to Mediate Visually Guided Behavior.

To guide behavior, sensory systems detect the onset and offset of stimuli and process these distinct inputs via parallel pathways. In the retina, this strategy is implemented by splitting neural signals for light onset and offset via synapses connecting photoreceptors to ON and OFF bipolar cells, respectively. It remains poorly understood which molecular cues establish the architecture of this synaptic configuration to split light-onset and light-offset signals. A mutant with reduced synapses between photoreceptors and one bipolar cell type, but not the other, could reveal a critical cue. From this approach, we report a novel synaptic role for pregnancy-associated plasma protein aa (pappaa) in promoting the structure and function of cone synapses that transmit light-offset information. Electrophysiological and behavioral analyses indicated pappaa mutant zebrafish have dysfunctional cone-to-OFF bipolar cell synapses and impaired responses to light offset, but intact cone-to-ON bipolar cell synapses and light-onset responses. Ultrastructural analyses of pappaa mutant cones showed a lack of presynaptic domains at synapses with OFF bipolar cells. pappaa is expressed postsynaptically to the cones during retinal synaptogenesis and encodes a secreted metalloprotease known to stimulate insulin-like growth factor 1 (IGF1) signaling. Induction of dominant-negative IGF1 receptor expression during synaptogenesis reduced light-offset responses. Conversely, stimulating IGF1 signaling at this time improved pappaa mutants' light-offset responses and cone presynaptic structures. Together, our results indicate Pappaa-regulated IGF1 signaling as a novel pathway that establishes how cone synapses convey light-offset signals to guide behavior.SIGNIFICANCE STATEMENT Distinct sensory inputs, like stimulus onset and offset, are often split at distinct synapses into parallel circuits for processing. In the retina, photoreceptors and ON and OFF bipolar cells form discrete synapses to split neural signals coding light onset and offset, respectively. The molecular cues that establish this synaptic configuration to specifically convey light onset or offset remain unclear. Our work reveals a novel cue: pregnancy-associated plasma protein aa (pappaa), which regulates photoreceptor synaptic structure and function to specifically transmit light-offset information. Pappaa is a metalloprotease that stimulates local insulin-like growth factor 1 (IGF1) signaling. IGF1 promotes various aspects of synaptic development and function and is broadly expressed, thus requiring local regulators, like Pappaa, to govern its specificity.

Micropools of reliable area MT neurons explain rapid motion detection.

Many models of perceptually based decisions postulate that actions are initiated when accumulated sensory signals reach a threshold level of activity. These models have received considerable neurophysiological support from recordings of individual neurons while animals are engaged in motion discrimination tasks. These experiments have found that the activity of neurons in a particular visual area strongly associated with motion processing (MT), when pooled over hundreds of milliseconds, is sufficient to explain behavioral timing and performance. However, this level of pooling may be problematic for urgent perceptual decisions in which rapid detection dictates temporally precise integration. In this paper, we explore the physiological basis of one such task in which macaques detected brief (~70 ms) transients of coherent motion within ~240 ms. We find that a simple linear summation model based on realistic stimulus responses of as few as 40 correlated neurons can predict the reliability and timing of rapid motion detection. The model naturally reproduces a distinctive physiological relationship observed in rapid detection tasks in which the individual neurons with the most reliable stimulus responses are also the most predictive of impending behavioral choices. Remarkably, we observed this relationship across our simulated neuronal populations even when all neurons within the pool were weighted equally with respect to readout. These results demonstrate that small numbers of reliable sensory neurons can dominate perceptual judgments without any explicit reliability based weighting and are sufficient to explain the accuracy, latency, and temporal precision of rapid detection. NEW & NOTEWORTHY Computational and psychophysical models suggest that performance in many perceptual tasks may be based on the preferential sampling of reliable neurons. Recent studies of MT neurons during rapid motion detection, in which only those neurons with the most reliable sensory responses were strongly predictive of the animals' decisions, seemingly support this notion. Here we show that a simple threshold model without explicit reliability biases can explain both the behavioral accuracy and precision of these detections and the distribution of sensory- and choice-related signals across neurons.

Analysis of stimulus-related activity in rat auditory cortex using complex spectral coefficients.

The neural mechanisms of sensory responses recorded from the scalp or cortical surface remain controversial. Evoked vs. induced response components (i.e., changes in mean vs. variance) are associated with bottom-up vs. top-down processing, but trial-by-trial response variability can confound this interpretation. Phase reset of ongoing oscillations has also been postulated to contribute to sensory responses. In this article, we present evidence that responses under passive listening conditions are dominated by variable evoked response components. We measured the mean, variance, and phase of complex time-frequency coefficients of epidurally recorded responses to acoustic stimuli in rats. During the stimulus, changes in mean, variance, and phase tended to co-occur. After the stimulus, there was a small, low-frequency offset response in the mean and modest, prolonged desynchronization in the alpha band. Simulations showed that trial-by-trial variability in the mean can account for most of the variance and phase changes observed during the stimulus. This variability was state dependent, with smallest variability during periods of greatest arousal. Our data suggest that cortical responses to auditory stimuli reflect variable inputs to the cortical network. These analyses suggest that caution should be exercised when interpreting variance and phase changes in terms of top-down cortical processing.

Control of contextual memory through interneuronal α5-GABAA receptors.

γ-Aminobutyric acid type A receptors that incorporate α5 subunits (α5-GABAARs) are highly enriched in the hippocampus and are strongly implicated in control of learning and memory. Receptors located on pyramidal neuron dendrites have long been considered responsible, but here we report that mice in which α5-GABAARs have been eliminated from pyramidal neurons (α5-pyr-KO) continue to form strong spatial engrams and that they remain as sensitive as their pseudo-wild-type (p-WT) littermates to etomidate-induced suppression of place cells and spatial engrams. By contrast, mice with selective knockout in interneurons (α5-i-KO) no longer exhibit etomidate-induced suppression of place cells. In addition, the strength of spatial engrams is lower in α5-i-KO mice than p-WT littermates under control conditions. Consistent with the established role of the hippocampus in contextual fear conditioning, α5-i-KO mice resisted etomidate's suppression of freezing to context, but so too did α5-pyr-KO mice, supporting a role for extra-hippocampal regions in the development of contextual fear memory. Overall, our results indicate that interneuronal α5-GABAARs serve a physiological role in promoting spatial learning and that they mediate suppression of hippocampus-dependent contextual memory by etomidate.

Descending projections from extrastriate visual cortex modulate responses of cells in primary auditory cortex.

Primary sensory cortical responses are modulated by the presence or expectation of related sensory information in other modalities, but the sources of multimodal information and the cellular locus of this integration are unclear. We investigated the modulation of neural responses in the murine primary auditory cortical area Au1 by extrastriate visual cortex (V2). Projections from V2 to Au1 terminated in a classical descending/modulatory pattern, with highest density in layers 1, 2, 5, and 6. In brain slices, whole-cell recordings revealed long latency responses to stimulation in V2L that could modulate responses to subsequent white matter (WM) stimuli at latencies of 5-20 ms. Calcium responses imaged in Au1 cell populations showed that preceding WM with V2L stimulation modulated WM responses, with both summation and suppression observed. Modulation of WM responses was most evident for near-threshold WM stimuli. These data indicate that corticocortical projections from V2 contribute to multimodal integration in primary auditory cortex.

Cortical responses to auditory novelty across task conditions: An intracranial electrophysiology study.

Elucidating changes in sensory processing across attentional and arousal states is a major focus in neuroscience. The local/global deviant (LGD) stimulus paradigm engages auditory predictive coding over short (local deviance, LD) and long (global deviance, GD) time scales, and has been used to assay disruption of auditory predictive coding upon loss of consciousness. Our previous work (Nourski et al., 2018, J Neurosci 38:8441-52) examined effects of general anesthesia on short- and long-term novelty detection. GD effects were suppressed at subhypnotic doses of propofol, suggesting that they may be more related to task engagement than consciousness per se. The present study addressed this hypothesis by comparing cortical responses to auditory novelty during passive versus active listening conditions in awake listeners. Subjects were seven adult neurosurgical patients undergoing chronic invasive monitoring for medically intractable epilepsy. LGD stimuli were sequences of four identical vowels followed by a fifth identical or different vowel. In the passive condition, the stimuli were presented to subjects as they watched a silent TV program and were instructed to attend to its content. In the active condition, stimuli were presented in the absence of a TV program, and subjects were instructed to press a button in response to GD target stimuli. Intracranial recordings were made from multiple brain regions, including core and non-core auditory, auditory-related, prefrontal and sensorimotor cortex. Metrics of task performance included hit rate, sensitivity index, and reaction times. Cortical activity was measured as averaged auditory evoked potentials (AEPs) and event-related band power in high gamma (70-150 Hz) and alpha (8-14 Hz) frequency bands. The vowel stimuli and LD elicited robust AEPs in all studied brain areas in both passive and active conditions. High gamma responses to stimulus onset and LD were localized predominantly to the auditory cortex in the superior temporal plane and had a comparable prevalence and spatial extent between the two conditions. In contrast, GD effects (AEPs, high gamma and alpha suppression) were greatly enhanced during the active condition in all studied brain areas. The prevalence of high gamma GD effects was positively correlated with individual subjects' task performance. The data demonstrate distinct task engagement-related effects on responses to auditory novelty across the auditory cortical processing hierarchy. The results motivate a closer examination of effective connectivity underlying attentional modulation of cortical sensory responses, and serve as a foundation for examining changes in sensory processing associated with general anesthesia, sleep and disorders of consciousness.

Association between major surgical admissions and the cognitive trajectory: 19 year follow-up of Whitehall II cohort study.

OBJECTIVE: To quantify the association between major surgery and the age related cognitive trajectory. DESIGN: Prospective longitudinal cohort study. SETTING: United Kingdom. PARTICIPANTS: 7532 adults with as many as five cognitive assessments between 1997 and 2016 in the Whitehall II study, with linkage to hospital episode statistics. Exposures of interest included any major hospital admission, defined as requiring more than one overnight stay during follow-up. MAIN OUTCOMES MEASURES: The primary outcome was the global cognitive score established from a battery of cognitive tests encompassing reasoning, memory, and phonemic and semantic fluency. Bayesian linear mixed effects models were used to calculate the change in the age related cognitive trajectory after hospital admission. The odds of substantial cognitive decline induced by surgery defined as more than 1.96 standard deviations from a predicted trajectory (based on the first three cognitive waves of data) was also calculated. RESULTS: After accounting for the age related cognitive trajectory, major surgery was associated with a small additional cognitive decline, equivalent on average to less than five months of aging (95% credible interval 0.01 to 0.73 years). In comparison, admissions for medical conditions and stroke were associated with 1.4 (1.0 to 1.8) and 13 (9.6 to 16) years of aging, respectively. Substantial cognitive decline occurred in 2.5% of participants with no admissions, 5.5% of surgical admissions, and 12.7% of medical admissions. Compared with participants with no major hospital admissions, those with surgical or medical events were more likely to have substantial decline from their predicted trajectory (surgical admissions odds ratio 2.3, 95% credible interval 1.4 to 3.9; medical admissions 6.2, 3.4 to 11.0). CONCLUSIONS: Major surgery is associated with a small, long term change in the average cognitive trajectory that is less profound than for major medical admissions. The odds of substantial cognitive decline after surgery was about doubled, though lower than for medical admissions. During informed consent, this information should be weighed against the potential health benefits of surgery.

Respiratory neuron characterization reveals intrinsic bursting properties in isolated adult turtle brainstems (Trachemys scripta).

It is not known whether respiratory neurons with intrinsic bursting properties exist within ectothermic vertebrate respiratory control systems. Thus, isolated adult turtle brainstems spontaneously producing respiratory motor output were used to identify and classify respiratory neurons based on their firing pattern relative to hypoglossal (XII) nerve activity. Most respiratory neurons (183/212) had peak activity during the expiratory phase, while inspiratory, post-inspiratory, and novel pre-expiratory neurons were less common. During synaptic blockade conditions, ∼10% of respiratory neurons fired bursts of action potentials, with post-inspiratory cells (6/9) having the highest percentage of intrinsic burst properties. Most intrinsically bursting respiratory neurons were clustered at the level of the vagus (X) nerve root. Synaptic inhibition blockade caused seizure-like activity throughout the turtle brainstem, which shows that the turtle respiratory control system is not transformed into a network driven by intrinsically bursting respiratory neurons. We hypothesize that intrinsically bursting respiratory neurons are evolutionarily conserved and represent a potential rhythmogenic mechanism contributing to respiration in adult turtles.