Topological analysis of differential effects of ketamine and propofol anaesthesia on brain dynamics.
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ABSTRACT:
SUBMITTER: Varley TF
PROVIDER: S-EPMC8220281 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Whether the brain operates at a critical "tipping" point is a long standing scientific question, with evidence from both cellular and systems-scale studies suggesting that the brain does sit in, or near, a critical regime. Neuroimaging studies of humans in altered states of consciousness have prompted the suggestion that maintenance of critical dynamics is necessary for the emergence of consciousness and complex cognition, and that reduced or disorganized consciousness may be associated with deviations from criticality. Unfortunately, many of the cellular-level studies reporting signs of criticality were performed in non-conscious systems (in vitro neuronal cultures) or unconscious animals (e.g. anaesthetized rats). Here we attempted to address this knowledge gap by exploring critical brain dynamics in invasive ECoG recordings from multiple sessions with a single macaque as the animal transitioned from consciousness to unconsciousness under different anaesthetics (ketamine and propofol). We use a previously-validated test of criticality: avalanche dynamics to assess the differences in brain dynamics between normal consciousness and both drug-states. Propofol and ketamine were selected due to their differential effects on consciousness (ketamine, but not propofol, is known to induce an unusual state known as "dissociative anaesthesia"). Our analyses indicate that propofol dramatically restricted the size and duration of avalanches, while ketamine allowed for more awake-like dynamics to persist. In addition, propofol, but not ketamine, triggered a large reduction in the complexity of brain dynamics. All states, however, showed some signs of persistent criticality when testing for exponent relations and universal shape-collapse. Further, maintenance of critical brain dynamics may be important for regulation and control of conscious awareness.
| S-EPMC7785236 | biostudies-literature
Project description:The brain is possibly the most complex system known to mankind, and its complexity has been called upon to explain the emergence of consciousness. However, complexity has been defined in many ways by multiple different fields: here, we investigate measures of algorithmic and process complexity in both the temporal and topological domains, testing them on functional MRI BOLD signal data obtained from individuals undergoing various levels of sedation with the anaesthetic agent propofol, replicating our results in two separate datasets. We demonstrate that the various measures are differently able to discriminate between levels of sedation, with temporal measures showing higher sensitivity. Further, we show that all measures are strongly related to a single underlying construct explaining most of the variance, as assessed by Principal Component Analysis, which we interpret as a measure of "overall complexity" of our data. This overall complexity was also able to discriminate between levels of sedation and serum concentrations of propofol, supporting the hypothesis that consciousness is related to complexity - independent of how the latter is measured.
| S-EPMC6978464 | biostudies-literature
Project description:AIMS: Pharmacological-challenge magnetic resonance imaging (phMRI) is powerful new tool enabling researchers to map the central effects of neuroactive drugs in vivo. To employ this technique pre-clinically, head movements and the stress of restraint are usually reduced by maintaining animals under general anaesthesia. However, interactions between the drug of interest and the anaesthetic employed may potentially confound data interpretation. NMDA receptor (NMDAR) antagonists used widely to mimic schizophrenia have recently been shown to interact with the anaesthetic halothane. It may be the case that neural and cerebrovascular responses to NMDAR antagonists are dependent on the types of anaesthetic used. METHODOLOGY: We compared the phMRI response to NMDAR antagonist ketamine in rats maintained under ?-chloralose to those under isoflurane anaesthesia. A randomized placebo/vehicle controlled design was used in each of the anaesthetic groups. RESULTS: Changes in the anaesthetic agent resulted in two very different profiles of activity. In the case of ?-chloralose, positive activations in cortical and sub-cortical structures reflected a response which was similar to patterns seen in healthy human volunteers and metabolic maps of conscious rats. However, the use of isoflurane completely reversed such effects, causing widespread deactivations in the cortex and hippocampus. CONCLUSION: This study provides initial evidence for a drug-anesthetic interaction between ketamine and isoflurane that is very different from responses to ?-chloralose-ketamine.
| S-EPMC3378209 | biostudies-other
Project description:Background and Aims:Using remifentanil-propofol target-controlled infusion (TCI) in open gynaecological surgeries could be associated with opioid-induced hyperalgesia postoperatively. This study's aim was to investigate the effect of low-dose S-ketamine compared with control on cumulative morphine consumption 24 h postoperatively in women undergoing open abdominal hysterectomy with remifentanil-propofol TCI technique. Methods:Ninety female patients above 21 years old who underwent elective open abdominal hysterectomy under general anaesthesia with remifentanil-propofol TCI were recruited. They were randomised to receive either normal saline as control (n = 44) or 0.25 mg/kg intravenous boluses of S-ketamine before skin incision and after complete removal of uterus (n = 45). The primary outcome measure was cumulative morphine consumption measured over 24 h postoperatively. The secondary outcome measures were incidences of opioid-related and psychotomimetic side effects, pain and level of sedation scores. Results:The cumulative 24-h morphine consumption postoperatively (P = 0.0547) did not differ between both the groups. S-ketamine group had slower emergence from general anaesthesia (P = 0.0308) and lower pain scores (P = 0.0359) 15 min postoperatively. Sedation level, common opioid-related side effects (nausea, vomiting, pruritus), respiratory depression and psychotomimetic side effects were similar between both the study groups. Conclusion:Low-dose S-ketamine did not reduce the total cumulative morphine consumption in patients undergoing major open gynaecological surgeries with remifentanil-propofol TCI.
| S-EPMC6383487 | biostudies-literature
Project description:BackgroundAnaesthetic drugs act at sites within the brain that undergo profound changes during typical ageing. We postulated that anaesthesia-induced brain dynamics observed in the EEG change with age.MethodsWe analysed the EEG in 155 patients aged 18-90 yr who received propofol (n=60) or sevoflurane (n=95) as the primary anaesthetic. The EEG spectrum and coherence were estimated throughout a 2 min period of stable anaesthetic maintenance. Age-related effects were characterized by analysing power and coherence as a function of age using linear regression and by comparing the power spectrum and coherence in young (18- to 38-yr-old) and elderly (70- to 90-yr-old) patients.ResultsPower across all frequency bands decreased significantly with age for both propofol and sevoflurane; elderly patients showed EEG oscillations ∼2- to 3-fold smaller in amplitude than younger adults. The qualitative form of the EEG appeared similar regardless of age, showing prominent alpha (8-12 Hz) and slow (0.1-1 Hz) oscillations. However, alpha band dynamics showed specific age-related changes. In elderly compared with young patients, alpha power decreased more than slow power, and alpha coherence and peak frequency were significantly lower. Older patients were more likely to experience burst suppression.ConclusionsThese profound age-related changes in the EEG are consistent with known neurobiological and neuroanatomical changes that occur during typical ageing. Commercial EEG-based depth-of-anaesthesia indices do not account for age and are therefore likely to be inaccurate in elderly patients. In contrast, monitoring the unprocessed EEG and its spectrogram can account for age and individual patient characteristics.
| S-EPMC4501918 | biostudies-literature
Project description:BackgroundPostoperative cognitive dysfunction (POCD) is a very common event in elderly noncardiac surgical patients. The effects of inhalational anaesthetics and propofol on the incidence of POCD and postoperative cognitive status at different time points after surgery are currently unclear.MethodsWe searched the Embase, Medline, Cochrane Library, and Web of Science databases for randomized controlled trials (RCTs), in which inhalation anaesthesia and propofol anaesthesia were compared. The incidence of POCD or postoperative cognitive status was assessed in elderly patients undergoing noncardiac surgery.ResultsFifteen RCTs with 1854 patients were included in this meta-analysis. The incidence of POCD on postoperative Days 2-6 after propofol anaesthesia was markedly lower than that after inhalation anaesthesia (risk ratio (RR): 0.37, 95% confidence interval (CI): 0.15-0.88, P = .025), and Mini-Mental State Examination (MMSE) scores after propofol anaesthesia were substantially higher than those after inhalation anaesthesia (standard mean difference (SMD): 0.59, 95% CI: 0.07-1.11, P = .026). The levels of interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) were much lower after propofol anaesthesia than after inhalation anaesthesia (SMD: -2.027, 95% CI: -3.748- -0.307, P = .021; SMD: -0.68, 95% CI: -0.93- -0.43, P < .001).ConclusionsThe moderate evidence from this meta-analysis shows that, in elderly noncardiac surgical patients, propofol anaesthesia is superior to inhalation anaesthesia for attenuating of early POCD incidence, and low-level evidence shows that cognitive status is higher and systemic inflammation is less severe after propofol anaesthesia in the early days after surgery.LimitationsThe sample size was not sufficiently large for systemic inflammation, and the tools to identify POCD were not uniform in the included studies.
| S-EPMC8556046 | biostudies-literature
Project description:There is an ongoing debate as to whether ketamine anesthesia suppresses neurophysiologic complexity at doses sufficient for surgical anesthesia, with previous human studies reporting surrogates of both suppressed and preserved levels of cortical complexity. However, these studies have not assessed cortical dynamics in higher gamma frequencies, which have previously been demonstrated to correlate with the level of consciousness during anesthesia. In this study, we used Lempel-Ziv complexity (LZc) to characterize frontal and parietal electroencephalographic complexity (0.5-175 Hz, 0.5-55 Hz, 65-175 Hz) before, during, and after ketamine or propofol anesthesia in the rat. To control for the potential influence of spectral changes in complexity estimation, LZc was normalized with phase-shuffled surrogate data. We demonstrate that ketamine and propofol anesthesia were characterized by a significant reduction in broadband (0.5-175 Hz) LZc. Further analysis showed that while the reduction of LZc during ketamine anesthesia was significant in 65-175 Hz range, during propofol anesthesia, a significant decrease was observed in 0.5-55 Hz bandwidth. LZc in broadband and 0.5-55 Hz range showed a significant increase during emergence from ketamine anesthesia. Phase-shuffled normalized LZc revealed that (1) decrease in complexity during ketamine and propofol anesthesia-not increase in complexity during emergence-were dissociable from the influence of spectral changes, and (2) reduced LZc during ketamine anesthesia was present across all three bandwidths. Ketamine anesthesia was characterized by reduced complexity in high gamma bandwidth, as reflected in both raw and phase-shuffled normalized LZc, which suggests that reduced high gamma complexity is a neurophysiological feature of ketamine anesthesia.
| S-EPMC7431468 | biostudies-literature
Project description:INTRODUCTION:The aim of this study was to measure the haemodynamic responses to a etomidate-propofol combination used for anaesthesia induction and to compare the haemodynamic responses with the separate use of each drug. METHODS:The patients were randomly divided into three groups as group P (n = 30, propofol 2.5 mg kg(-1)), group E (n = 30, etomidate 0.3 mg kg(-1)) and group PE (n = 30, propofol 1.25 mg kg(-1) + etomidate 0.15 mg kg(-1)). For each patient, the times of measurement of the heart rate (HR) and mean arterial pressure values were defined as baseline, after the induction, before the intubation, immediately after the intubation and 1, 2, 3, 4, 5 and 10 minutes after the intubation. RESULTS:In all 3 groups, a significant decrease in MAP values were seen at T2 and T3 compared to the baseline values, and this decrease was greater in group P compared to that in group E and PE (P < 0.001, P < 0.01). A significant increase was seen in all 3 groups in the mean arterial pressure (MAP) value at T4 after the intubation. When the groups were compared with each other, this increase was greater in group E than in the other two groups (with group P, P < 0.001; with group PE, P < 0.01). CONCLUSION:Etomidate-propofol combination may be a valuable alternative when extremes of hypotensive and hypertensive responses due to propofol and etomidate are best to be avoided.
| S-EPMC4685278 | biostudies-literature
Project description:BackgroundIn the search for novel treatments for depression, ketamine has emerged as a unique agent with rapid antidepressant effects. Experimental tasks involving emotional processing can be used during functional magnetic resonance imaging scanning to investigate ketamine's effects on brain function in major depressive disorder (MDD). This study examined ketamine's effects on functional magnetic resonance imaging activity during an emotional processing task.MethodsA total of 33 individuals with treatment-resistant MDD and 24 healthy control participants (HCs) took part in this double-blind, placebo-controlled crossover study. Participants received ketamine and placebo infusions 2 weeks apart, and functional magnetic resonance imaging scans were conducted at baseline and 2 days after each infusion. Blood oxygen level-dependent signal was measured during an emotional processing task, and a linear mixed-effects model was used to analyze differences in activation among group, drug, and task-specific factors.ResultsA group-by-drug interaction was observed in several brain regions, including a right frontal cluster extending into the anterior cingulate cortex and insula. Participants with MDD had greater activity than HCs after placebo infusion but showed lower activity after ketamine infusion, which was similar to the activity in HCs after placebo. A group-by-drug-by-task condition interaction was also found, which showed further differences that varied between implicit and explicit emotional conditions.ConclusionsThe main results indicate that ketamine had differential effects on brain activity in participants with MDD versus HCs. The pattern of activation in participants with MDD after ketamine infusion resembled the activation in HCs after placebo infusion, suggesting a normalization of function during emotional processing. The findings contribute to a better understanding of ketamine's actions in the brain.
| S-EPMC6612456 | biostudies-literature
Project description:While brain imaging tools like functional magnetic resonance imaging (fMRI) afford measurements of whole-brain activity, it remains unclear how best to interpret patterns found amid the data's apparent self-organization. To clarify how patterns of brain activity support brain function, one might identify metric spaces that optimally distinguish brain states across experimentally defined conditions. Therefore, the present study considers the relative capacities of several metric spaces to disambiguate experimentally defined brain states. One fundamental metric space interprets fMRI data topographically, that is, as the vector of amplitudes of a multivariate signal, changing with time. Another perspective compares the brain's functional connectivity, that is, the similarity matrix computed between signals from different brain regions. More recently, metric spaces that consider the data's topology have become available. Such methods treat data as a sample drawn from an abstract geometric object. To recover the structure of that object, topological data analysis detects features that are invariant under continuous deformations (such as coordinate rotation and nodal misalignment). Moreover, the methods explicitly consider features that persist across multiple geometric scales. While, certainly, there are strengths and weaknesses of each brain dynamics metric space, wefind that those that track topological features optimally distinguish experimentally defined brain states.
| S-EPMC8233107 | biostudies-literature