Electroencephalographic effects of ketamine on power, cross-frequency coupling, and connectivity in the alpha bandwidth

Blain-Moraes, Stefanie; Lee, UnCheol; Ku, Seung-Woo; Noh, Gyu Jeong; Mashour, George A.

doi:10.3389/fnsys.2014.00114

Cited by 115 publications

(124 citation statements)

References 41 publications

Supporting

Mentioning

110

Contrasting

Order By: Relevance

“…1). 13,14,18,19,21 The results of these studies are in line with earlier electrophysiological work in animals 22 and humans, 23 which demonstrated a loss of neural synchronization, under general anesthesia, between anterior and posterior parts of the brain. The work of John et al 23 is particularly noteworthy in this regard because they analyzed electroencephalography data from a total of 176 surgical patients anesthetized with a wide variety of pharmacological agents (induction of anesthesia with propofol, thiopental, or etomidate; maintenance of anesthesia with propofol, isoflurane, desflurane, or sevoflurane).…”

Section: " H Ow Do General Anesthetics Work?" In 2005supporting

confidence: 87%

“…1). 13,14,18,19,21 The results of these studies are in line with earlier electrophysiological work in animals 22 …”

supporting

confidence: 88%

“…Several recent studies-carried out in both humans and animals, and using a variety of different anesthetic agents-have investigated differences in directional corticocortical connectivity between the awake state and anesthesia-induced unconsciousness. [12][13][14][15][16][17][18][19][20][21] Intriguingly, the vast majority of these studies [12][13][14]16,[18][19][20][21] (two exceptions 15,17 shall be discussed later in this section) indicate that connectivity along the sensory pathways, under general anesthesia, is reduced primarily in the top-down direction. In other words, unconsciousness, which is the anesthetic endpoint this article is exclusively concerned with, appears to be correlated with reduced signaling from higher-order association cortices to early sensory cortices (table 1 and fig.…”

Section: " H Ow Do General Anesthetics Work?" In 2005mentioning

confidence: 99%

“…Note that in two cases (in the studies by Barrett et al 15 and Boly et al, 16 on the one hand, and in the studies by Lee et al 19 and Blain-Moraes et al, 21 on the other) research groups analyzed overlapping data sets using different methods of connectivity analysis. V1 = primary visual cortex.…”

Section: " H Ow Do General Anesthetics Work?" In 2005mentioning

confidence: 99%

“…1B). 13,14,18,19,21 Recall that this asymmetry disappears when consciousness is lost due to a selective anesthetic suppression of top-down information flow. Thus, in terms of hierarchical predictive coding, anesthesia-induced unconsciousness would be caused by a breakdown of the top-down predictive process.…”

Section: Prediction As the Central Element Of Conscious Perceptionmentioning

confidence: 99%

See 4 more Smart Citations

The Role of Dendritic Signaling in the Anesthetic Suppression of Consciousness

Meyer

2015

Anesthesiology

View full text Add to dashboard Cite

Despite considerable progress in the identification of the molecular targets of general anesthetics, it remains unclear how these drugs affect the brain at the systems level to suppress consciousness. According to recent proposals, anesthetics may achieve this feat by interfering with corticocortical topdown processes, that is, by interrupting information flow from association to early sensory cortices. Such a view entails two immediate questions. First, at which anatomical site, and by virtue of which physiological mechanism, do anesthetics interfere with top-down signals? Second, why does a breakdown of top-down signaling cause unconsciousness? While an answer to the first question can be gleaned from emerging neurophysiological evidence on dendritic signaling in cortical pyramidal neurons, a response to the second is offered by increasingly popular theoretical frameworks that place the element of prediction at the heart of conscious perception. Science magazine posed this question in a special section titled "What don't we know?," dedicated to the greatest challenges of contemporary science. 1 "Scientists are chipping away at the drugs' effects on individual neurons," the article reads, "but understanding how they render us unconscious will be a tougher nut to crack." This prediction proved correct: a decade later, we have expanded considerably our knowledge of the molecular targets of general anesthetics, but it remains enigmatic how these drugs affect the brain at the systems level. Why does the potentiation of γ-aminobutyric acid (GABA) receptors caused by propofol or desflurane cause unconsciousness? How are the brain's computational processes affected by this and other molecular mechanisms of anesthetics, so that patients undergoing surgery cease to experience their surrounds in terms of sight, sound, and touch? Anesthesiologists and cognitive neuroscientists alike have been captivated by these questions and have proposed a number of models in an attempt to answer them, such as Flohr's "information processing theory of anesthesia," 2 Alkire's "thalamic consciousness switch hypothesis," 3-6 Mashour's "cognitive unbinding paradigm," 7,8 John and Prichep's "anesthetic cascade," 9 or Hudetz's "forgotten present." 10,11 We shall return to some of these frameworks in a later section of the article.One recent development is particularly intriguing. Given that the most striking feature of general anesthesia is an interruption of the patient's ability to perceive the environment, it would appear intuitive for anesthetics to interfere primarily with bottom-up information flow along the sensory pathways, that is, with the signals that carry perceptual information from the thalamus to the primary sensory cortices and on to unimodal and multimodal association cortices. However, the very opposite appears to be the case. Several recent studies-carried out in both humans and animals, and using a variety of different anesthetic agents-have investigated differences in directional corticocortical connectivity bet...

show abstract

Section: " H Ow Do General Anesthetics Work?" In 2005supporting

confidence: 87%

“…1). 13,14,18,19,21 The results of these studies are in line with earlier electrophysiological work in animals 22 …”

supporting

confidence: 88%

Section: " H Ow Do General Anesthetics Work?" In 2005mentioning

confidence: 99%

Section: " H Ow Do General Anesthetics Work?" In 2005mentioning

confidence: 99%

Section: Prediction As the Central Element Of Conscious Perceptionmentioning

confidence: 99%

See 3 more Smart Citations

The Role of Dendritic Signaling in the Anesthetic Suppression of Consciousness

Meyer

2015

Anesthesiology

View full text Add to dashboard Cite

show abstract

Effects of ketamine and midazolam on resting state connectivity and comparison with ENIGMA connectivity deficit patterns in schizophrenia

Adhikari

Dukart

Hipp

et al. 2019

Human Brain Mapping

View full text Add to dashboard Cite

Subanesthetic administration of ketamine is a pharmacological model to elicit positive and negative symptoms of psychosis in healthy volunteers. We used resting-state pharmacological functional MRI (rsPhfMRI) to identify cerebral networks affected by ketamine and compared them to the functional connectivity (FC) in schizophrenia.Ketamine can produce sedation and we contrasted its effects with the effects of the anxiolytic drug midazolam. Thirty healthy male volunteers (age = 19-37 years) underwent a randomized, three-way, cross-over study consisting of three imaging sessions, with 48 hr between sessions. A session consisted of a control period followed by infusion of placebo or ketamine or midazolam. The ENIGMA rsfMRI pipeline was used to derive two long-distance (seed-based and dual-regression) and one local (regional homogeneity, ReHo) FC measures. Ketamine induced significant reductions in the connectivity of the salience network (Cohen's d: 1.13 ± 0.28, p = 4.0 × 10 −3 ), auditory network (d: 0.67 ± 0.26, p = .04) and default mode network (DMN, d: 0.63 ± 0.26, p = .05).Midazolam significantly reduced connectivity in the DMN (d: 0.77 ± 0.27, p = .03). The effect sizes for ketamine for resting networks showed a positive correlation (r = .59, p = .07) with the effect sizes for schizophrenia-related deficits derived from ENIGMA's study of 261 patients and 327 controls. Effect sizes for midazolam were not correlated with the schizophrenia pattern (r = −.17, p = .65). The subtraction of ketamine and Bhim M. Adhikari and Juergen Dukart contributed equally to this study.

show abstract

Modulation of simultaneously collected hemodynamic and electrophysiological functional connectivity by ketamine and midazolam

Forsyth

McMillan

Campbell

et al. 2019

Human Brain Mapping

View full text Add to dashboard Cite

The pharmacological modulation of functional connectivity in the brain may underlie therapeutic efficacy for several neurological and psychiatric disorders. Functional magnetic resonance imaging (fMRI) provides a noninvasive method of assessing this modulation, however, the indirect nature of the blood‐oxygen level dependent signal restricts the discrimination of neural from physiological contributions. Here we followed two approaches to assess the validity of fMRI functional connectivity in developing drug biomarkers, using simultaneous electroencephalography (EEG)/fMRI in a placebo‐controlled, three‐way crossover design with ketamine and midazolam. First, we compared seven different preprocessing pipelines to determine their impact on the connectivity of common resting‐state networks. Independent components analysis (ICA)‐denoising resulted in stronger reductions in connectivity after ketamine, and weaker increases after midazolam, than pipelines employing physiological noise modelling or averaged signals from cerebrospinal fluid or white matter. This suggests that pipeline decisions should reflect a drug's unique noise structure, and if this is unknown then accepting possible signal loss when choosing extensive ICA denoising pipelines could engender more confidence in the remaining results. We then compared the temporal correlation structure of fMRI to that derived from two connectivity metrics of EEG, which provides a direct measure of neural activity. While electrophysiological estimates based on the power envelope were more closely aligned to BOLD signal connectivity than those based on phase consistency, no significant relationship between the change in electrophysiological and hemodynamic correlation structures was found, implying caution should be used when making cross‐modal comparisons of pharmacologically‐modulated functional connectivity.

show abstract

Electroencephalographic effects of ketamine on power, cross-frequency coupling, and connectivity in the alpha bandwidth

Cited by 115 publications

References 41 publications

The Role of Dendritic Signaling in the Anesthetic Suppression of Consciousness

The Role of Dendritic Signaling in the Anesthetic Suppression of Consciousness

Effects of ketamine and midazolam on resting state connectivity and comparison with ENIGMA connectivity deficit patterns in schizophrenia

Modulation of simultaneously collected hemodynamic and electrophysiological functional connectivity by ketamine and midazolam

Contact Info

Product

Resources

About