Dependence of rhythmic activity and oddball effects in the rat cortex on the depth of sedation during dissociative anesthesia.

The reactions to novelty manifesting in mismatch negativity in the rat brain were studied. During dissociative anesthesia, mismatch negativity-like waves were recorded from the somatosensory cortex using an epidural 32-electrode array. Experimental animals: 7 wild-type Wistar rats and 3 transgenic rats. During high-dose anesthesia, deviant 1,500 Hz tones were presented randomly among many standard 1,000 Hz tones in the oddball paradigm. "Deviant minus standard_before_deviant" difference waves were calculated using both the classical method of Naatanen and method of cross-correlation of sub-averages. Both methods gave consistent results: an early phasic component of the N40 and later N100 to 200 (mismatch negativity itself) tonic component. The gamma and delta rhythms power and the frequency of down-states (suppressed activity periods) were assessed. In all rats, the amplitude of tonic component grew with increasing sedation depth. At the same time, a decrease in gamma power with a simultaneous increase in delta power and the frequency of down-states. The earlier phasic frontocentral component is associated with deviance detection, while the later tonic one over the auditory cortex reflects the orienting reaction. Under anesthesia, this slow mismatch negativity-like wave most likely reflects the tendency of the system to respond to any influences with delta waves, K-complexes and down-states, or produce them spontaneously.

Relationship between preinduction electroencephalogram patterns and propofol sensitivity in adult patients.

PURPOSE: To determine the precise induction dose, an objective assessment of individual propofol sensitivity is necessary. This study aimed to investigate whether preinduction electroencephalogram (EEG) data are useful in determining the optimal propofol dose for the induction of general anesthesia in healthy adult patients. METHODS: Seventy healthy adult patients underwent total intravenous anesthesia (TIVA), and the effect-site target concentration of propofol was observed to measure each individual's propofol requirements for loss of responsiveness. We analyzed preinduction EEG data to assess its relationship with propofol requirements and conducted multiple regression analyses considering various patient-related factors. RESULTS: Patients with higher relative delta power (ρ = 0.47, p < 0.01) and higher absolute delta power (ρ = 0.34, p = 0.01) required a greater amount of propofol for anesthesia induction. In contrast, patients with higher relative beta power (ρ = -0.33, p < 0.01) required less propofol to achieve unresponsiveness. Multiple regression analysis revealed an independent association between relative delta power and propofol requirements. CONCLUSION: Preinduction EEG, particularly relative delta power, is associated with propofol requirements during the induction of general anesthesia. The utilization of preinduction EEG data may improve the precision of induction dose selection for individuals.

Excitation of Putative Glutamatergic Neurons in the Rat Parabrachial Nucleus Region Reduces Delta Power during Dexmedetomidine but not Ketamine Anesthesia.

BACKGROUND: Parabrachial nucleus excitation reduces cortical delta oscillation (0.5 to 4 Hz) power and recovery time associated with anesthetics that enhance γ-aminobutyric acid type A receptor action. The effects of parabrachial nucleus excitation on anesthetics with other molecular targets, such as dexmedetomidine and ketamine, remain unknown. The hypothesis was that parabrachial nucleus excitation would cause arousal during dexmedetomidine and ketamine anesthesia. METHODS: Designer Receptors Exclusively Activated by Designer Drugs were used to excite calcium/calmodulin-dependent protein kinase 2α-positive neurons in the parabrachial nucleus region of adult male rats without anesthesia (nine rats), with dexmedetomidine (low dose: 0.3 µg · kg-1 · min-1 for 45 min, eight rats; high dose: 4.5 µg · kg-1 · min-1 for 10 min, seven rats), or with ketamine (low dose: 2 mg · kg-1 · min-1 for 30 min, seven rats; high dose: 4 mg · kg-1 · min-1 for 15 min, eight rats). For control experiments (same rats and treatments), the Designer Receptors Exclusively Activated by Designer Drugs were not excited. The electroencephalogram and anesthesia recovery times were recorded and analyzed. RESULTS: Parabrachial nucleus excitation reduced delta power in the prefrontal electroencephalogram with low-dose dexmedetomidine for the 150-min analyzed period, excepting two brief periods (peak median bootstrapped difference [clozapine-N-oxide - saline] during dexmedetomidine infusion = -6.06 [99% CI = -12.36 to -1.48] dB, P = 0.007). However, parabrachial nucleus excitation was less effective at reducing delta power with high-dose dexmedetomidine and low- and high-dose ketamine (peak median bootstrapped differences during high-dose [dexmedetomidine, ketamine] infusions = [-1.93, -0.87] dB, 99% CI = [-4.16 to -0.56, -1.62 to -0.18] dB, P = [0.006, 0.019]; low-dose ketamine had no statistically significant decreases during the infusion). Recovery time differences with parabrachial nucleus excitation were not statistically significant for dexmedetomidine (median difference for [low, high] dose = [1.63, 11.01] min, 95% CI = [-20.06 to 14.14, -20.84 to 23.67] min, P = [0.945, 0.297]) nor low-dose ketamine (median difference = 12.82 [95% CI: -3.20 to 39.58] min, P = 0.109) but were significantly longer for high-dose ketamine (median difference = 11.38 [95% CI: 1.81 to 24.67] min, P = 0.016). CONCLUSIONS: These results suggest that the effectiveness of parabrachial nucleus excitation to change the neurophysiologic and behavioral effects of anesthesia depends on the anesthetic's molecular target.

Delta oscillations are a robust biomarker of dopamine depletion severity and motor dysfunction in awake mice.

Delta oscillations (0.5-4 Hz) are a robust feature of basal ganglia pathophysiology in patients with Parkinson's disease (PD) in relationship to tremor, but their relationship to other parkinsonian symptoms has not been investigated. While delta oscillations have been observed in mouse models of PD, they have only been investigated in anesthetized animals, suggesting that the oscillations may be an anesthesia artifact and limiting the ability to relate them to motor symptoms. Here, we establish a novel approach to detect spike oscillations embedded in noise to provide the first study of delta oscillations in awake, dopamine-depleted mice. We find that approximately half of neurons in the substantia nigra pars reticulata (SNr) exhibit delta oscillations in dopamine depletion and that these oscillations are a strong indicator of dopamine loss and akinesia, outperforming measures such as changes in firing rate, irregularity, bursting, and synchrony. These oscillations are typically weakened, but not ablated, during movement. We further establish that these oscillations are caused by the loss of D2-receptor activation and do not originate from motor cortex, contrary to previous findings in anesthetized animals. Instead, SNr oscillations precede those in M1 at a 100- to 300-ms lag, and these neurons' relationship to M1 oscillations can be used as the basis for a novel classification of SNr into two subpopulations. These results give insight into how dopamine loss leads to motor dysfunction and suggest a reappraisal of delta oscillations as a marker of akinetic symptoms in PD.NEW & NOTEWORTHY This work introduces a novel method to detect spike oscillations amidst neural noise. Using this method, we demonstrate that delta oscillations in the basal ganglia are a defining feature of awake, dopamine-depleted mice and are strongly correlated with dopamine loss and parkinsonian motor symptoms. These oscillations arise from a loss of D2-receptor activation and do not require motor cortex. Similar oscillations in human patients may be an underappreciated marker and target for Parkinson's disease (PD) treatment.

Effects of an Orexin-2 Receptor Antagonist on Sleep and Event-Related Oscillations in Female Rats Exposed to Chronic Intermittent Ethanol During Adolescence.

BACKGROUND: Alcohol use is on the rise among women in the United States which is especially concerning since women who drink have a higher risk of alcohol-related problems. Orexin (hypocretin) receptor antagonists may have some therapeutic value for alcohol-induced insomnia; however, the use of this class of drugs following female adolescent binge drinking is limited. The current study will address whether adolescent intermittent ethanol (AIE) in female rats can result in lasting changes in sleep pathology and whether orexin-targeted treatment can alleviate these deficits. METHODS: Following a 5-week AIE vapor model, young adult rats were evaluated on waking event-related oscillations (EROs) and EEG sleep. Subsequently, AIE rats were treated with orexin receptor 2 (OX2 R) antagonist (MK-1064; 10, 20mg/kg) to test for modifications in sleep pathology and waking ERO. RESULTS: Female AIE rats exhibited lasting changes in sleep compared to controls. This was demonstrated by increased fragmentation of slow wave sleep (SWS) and rapid eye movement sleep, as well as reductions in delta and theta power during SWS. There was no impact of AIE on waking EROs. Acute MK-1064 hastened SWS onset and increased the number of SWS episodes, without increasing sleep fragmentation in AIE and controls. While treatment with MK-1064 did not impact sleep EEG spectra, waking ERO energy was increased in delta, theta, and beta frequency bands. CONCLUSIONS: These results demonstrate that AIE can produce lasting changes in sleep in female rats, highly similar to what we previously found in males. Additionally, while the OX2 R antagonist promoted sleep in both alcohol-exposed and unexposed rats, it did not reverse most of the alcohol-induced disruptions in sleep. Thus, OX2 R antagonism may serve as a potential therapeutic strategy for the treatment of insomnia, but not the specific signs of alcohol-induced insomnia.

δ-Oscillation Correlates of Anesthesia-induced Unconsciousness in Large-scale Brain Networks of Human Infants.

BACKGROUND: Functional brain connectivity studies can provide important information about changes in brain-state dynamics during general anesthesia. In adults, γ-aminobutyric acid-mediated agents disrupt integration of information from local to the whole-brain scale. Beginning around 3 to 4 months postnatal age, γ-aminobutyric acid-mediated anesthetics such as sevoflurane generate α-electroencephalography oscillations. In previous studies of sevoflurane-anesthetized infants 0 to 3.9 months of age, α-oscillations were absent, and power spectra did not distinguish between anesthetized and emergence from anesthesia conditions. Few studies detailing functional connectivity during general anesthesia in infants exist. This study's aim was to identify changes in functional connectivity of the infant brain during anesthesia. METHODS: A retrospective cohort study was performed using multichannel electroencephalograph recordings of 20 infants aged 0 to 3.9 months old who underwent sevoflurane anesthesia for elective surgery. Whole-brain functional connectivity was evaluated during maintenance of a surgical state of anesthesia and during emergence from anesthesia. Functional connectivity was represented as networks, and network efficiency indices (including complexity and modularity) were computed at the sensor and source levels. RESULTS: Sevoflurane decreased functional connectivity at the δ-frequency (1 to 4 Hz) in infants 0 to 3.9 months old when comparing anesthesia with emergence. At the sensor level, complexity decreased during anesthesia, showing less whole-brain integration with prominent alterations in the connectivity of frontal and parietal sensors (median difference, 0.0293; 95% CI, -0.0016 to 0.0397). At the source level, similar results were observed (median difference, 0.0201; 95% CI, -0.0025 to 0.0482) with prominent alterations in the connectivity between default-mode and frontoparietal regions. Anesthesia resulted in fragmented modules as modularity increased at the sensor (median difference, 0.0562; 95% CI, 0.0048 to 0.1298) and source (median difference, 0.0548; 95% CI, -0.0040 to 0.1074) levels. CONCLUSIONS: Sevoflurane is associated with decreased capacity for efficient information transfer in the infant brain. Such findings strengthen the hypothesis that conscious processing relies on an efficient system of integrated information transfer across the whole brain.

Co-existence of Rolandic and 3 Hz Spike-Wave Discharges on EEG in Children with Epilepsy.

OBJECTIVE: Benign epilepsy of childhood with central temporal spikes (BECTS) and absence epilepsy are common epilepsy syndromes in children with similar age of onset and favorable prognosis. However, the co-existence of the electrocardiogram (EEG) findings of rolandic spike and 3 Hz generalized spike-wave (GSW) discharges is extremely rare, with few cases reported in the literature. Our objective was to characterize the EEG findings of these syndromes in children in our center and review the electro-clinical features. METHODS: All EEGs at BC Children's Hospital are entered in a database, which include EEG findings and clinical data. Patients with both centro-temporal spikes and 3 Hz GSW discharges were identified from the database and clinical data were reviewed. RESULTS: Among the 43,061 patients in the database from 1992 to 2017, 1426 with isolated rolandic discharges and 528 patients with isolated 3 Hz GSW discharges were identified, and 20 (0.05%) patients had both findings: 3/20 had BECTS, and subsequently developed childhood absence epilepsy and 17/20 had no seizures characteristic for BECTS. At follow-up, 17 (85%) were seizure-free, 1 (5%) had rare, and 2 (10%) had frequent seizures. CONCLUSIONS: This is the largest reported group of patients to our knowledge with the co-existence of rolandic and 3 Hz GSW discharges on EEGs in one institution, not drug-induced. As the presence of both findings is extremely rare, distinct pathophysiological mechanisms are likely. The majority had excellent seizure control at follow-up, similar to what would be expected for each type of epilepsy alone.

OBJECTIF: L'épilepsie bénigne de l'enfance à pointes centro-temporales (ou épilepsie rolandique bénigne [ERB]) et l'absence épileptique sont des syndromes épileptiques communs chez des enfants dont le pronostic est favorable et dont l'apparition des premiers symptômes s'est produite à un âge similaire. Cependant, la coexistence, lors d'EEG, de résultats montrant des décharges rolandiques et des décharges à pointes-ondes continues de 3 Hz demeure extrêmement rare, peu de cas ayant été signalés dans la littérature scientifique. Notre objectif a donc consisté à décrire les résultats d'EEG liés à ces syndromes dans le cas d'enfants fréquentant notre établissement et à examiner leurs caractéristiques électro-cliniques. MÉTHODES: En plus de certaines données cliniques, tous les résultats d'EEG réalisés au BC Children's Hospital sont saisis dans une base de données. Tant les jeunes patients donnant à voir des décharges à pointes centro-temporales que ceux atteints de décharges à pointes-ondes continues de 3 Hz ont été identifiés à partir de cette base de données. Leurs données cliniques ont été ensuite passées en revue. RÉSULTATS: Sur un total de 43 061 jeunes patients présents dans la base de données de 1992 à 2017, nous en avons identifié 1426 avec des décharges rolandiques isolées et 528 avec des décharges isolées à pointes-ondes de 3 Hz. À noter que seulement vingt d'entre eux, soit 0,05 %, étaient concernés par ces deux types de décharge. À cet égard, 3 sur 20 étaient atteints d'ERB et ont développé ultérieurement un syndrome d'absence épileptique; chez les 17 autres, aucune convulsion caractéristique de l'ERB n'a été observée. Lors d'un suivi, 17 (85 %) d'entre eux n'avaient plus de crises convulsives tandis que 1 (5 %) avait exceptionnellement des crises et 2 (10 %), des crises fréquentes. CONCLUSIONS: À notre connaissance, il s'agit là du plus vaste groupe déclaré de patients donnant à voir, lors d'EGG menés au sein d'un seul établissement, une coexistence entre des décharges rolandiques et des décharges à pointes-ondes de 3 Hz, et ce, sans qu'elles n'aient été causées par des médicaments. Considérant que la présence de ces deux phénomènes est particulièrement inhabituelle, le rôle de divers mécanismes pathophysiologiques est fort probable. Fait à souligner, la majorité de ces patients ont pu montrer, au moment de leur suivi, une excellente maîtrise de leurs crises convulsives, maîtrise semblable à celle à laquelle on pourrait s'attendre pour chaque type d'épilepsie pris individuellement.

Alterations in spontaneous delta and gamma activity might provide clues to detect changes induced by amyloid-ß administration.

Alzheimer's disease (AD) is the most prevalent form of dementia and has an increasing incidence. The neuropathogenesis of AD is suggested to be a result of the accumulation of amyloid-ß (Aß) peptides in the brain. To date, Aß-induced cognitive and neurophysiologic impairments have not been illuminated sufficiently. Therefore, we aimed to examine how spontaneous brain activities of rats changed by injection of increasing Aß doses into the brain hemispheres, and whether these changes could be used as a new biomarker for the early diagnosis of the AD. Rats were randomized into following groups: sham (Sham) and seven Aß-treated (i.c.v.) groups in increasing concentrations (from Aß-1 to Aß-7). After recovery, EEG recordings were obtained from implanted electrodes from eight electrode locations, and then, spectral and statistical analyses were performed. A significant decrement in gamma activity was observed in all Aß groups compared with the sham group. In delta activity, we observed significant changes from Aß-4 to Aß-7 group compared with sham group. Delta coherence values were decreased from Aß-4 to Aß-7 and Aß-5 to Aß-7 groups for frontal and temporal electrode pairs, respectively. A gradual increment was observed in Aß1-42 level till Aß-4 group. Positive correlation for global delta power and negative correlation for global gamma power between Aß1-42 peptide levels were detected. Consequently, it is conceivable to suggest gamma oscillation might be used to detect early stages of AD. Moreover, changes in delta activity provide information about the onset of major pathologic changes in the progress of AD.

Inhibition of Cortical Activity and Apoptosis Caused by Ethanol in Neonatal Rats In Vivo.

Alcohol consumption during pregnancy causes fetal alcohol spectrum disorder, which includes neuroapoptosis and neurobehavioral deficits. The neuroapoptotic effects of alcohol have been hypothesized to involve suppression of brain activity. However, in vitro studies suggest that ethanol acts as a potent stimulant of cortical activity. We explored the effects of alcohol (1-6 g/kg) on electrical activity in the rat somatosensory cortex in vivo at postnatal days P1-23 and compared them with its apoptotic actions. At P4-7, when the peak of alcohol-induced apoptosis was observed, alcohol strongly suppressed spontaneous gamma and spindle-bursts and almost completely silenced neurons in a dose-dependent manner. The dose-dependence of suppression of neuronal activity strongly correlated with the alcohol-induced neuroapoptosis. Alcohol also profoundly inhibited sensory-evoked bursts and suppressed motor activity, a physiological trigger of cortical activity bursts in newborns. The suppressive effects of ethanol on neuronal activity waned during the second and third postnatal weeks, when instead of silencing the cortex, alcohol evoked delta-wave electrographic activity. Thus, the effects of alcohol on brain activity are strongly age-dependent, and during the first postnatal week alcohol profoundly inhibits brain activity. Our findings suggest that the adverse effects of alcohol in the developing brain involve suppression of neuronal activity.

Resistance to valproic acid as predictor of treatment resistance in genetic generalized epilepsies.

This study aimed at defining clinical predictors of drug resistance in adults with genetic generalized epilepsy (GGE) who were treated with a broad spectrum of antiepileptic drugs. Of a cohort of 137 unselected adult GGE patients with long-term follow up, clinical and demographic data, putative prognostic factors (e.g., psychiatric comorbidities, electroencephalography [EEG]), treatment response, and data indicative of social status were collected. Fifty-eight patients had seizures within the past year. Thirty-three patients met the definition of "drug-resistant epilepsy" according to the International League Against Epilepsy (ILAE) definition. Psychiatric comorbidities, age at first diagnosis, and absences were associated with worse seizure control, whereas focal changes in EEG remained without prognostic impact. Resistance to valproic acid was the most important prognostic factor for refractory seizures. Resistance to valproic acid had a specificity of 100% to identify patients with drug resistance and correlated strongly with bad social outcome and seizure burden. Conversely, 21.2% of all patients with refractory seizures according to the ILAE definition later became seizure free (mainly with valproic acid). Our data suggest that "drug resistant GGE" must not be declared unless patients were adequately treated with valproic acid, and advocate resistance to valproic acid as a new clinical biomarker for drug-resistant GGE. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

Comparative analysis of background EEG activity in childhood absence epilepsy during valproate treatment: a standardized, low-resolution, brain electromagnetic tomography (sLORETA) study.

Valproate (VPA) is an antiepileptic drug (AED) used for initial monotherapy in treating childhood absence epilepsy (CAE). EEG might be an alternative approach to explore the effects of AEDs on the central nervous system. We performed a comparative analysis of background EEG activity during VPA treatment by using standardized, low-resolution, brain electromagnetic tomography (sLORETA) to explore the effect of VPA in patients with CAE. In 17 children with CAE, non-parametric statistical analyses using sLORETA were performed to compare the current density distribution of four frequency bands (delta, theta, alpha, and beta) between the untreated and treated condition. Maximum differences in current density were found in the left inferior frontal gyrus for the delta frequency band (log-F-ratio = -1.390, P > 0.05), the left medial frontal gyrus for the theta frequency band (log-F-ratio = -0.940, P > 0.05), the left inferior frontal gyrus for the alpha frequency band (log-F-ratio = -0.590, P > 0.05), and the left anterior cingulate for the beta frequency band (log-F-ratio = -1.318, P > 0.05). However, none of these differences were significant (threshold log-F-ratio = ±1.888, P < 0.01; threshold log-F-ratio = ±1.722, P < 0.05). Because EEG background is accepted as normal in CAE, VPA would not be expected to significantly change abnormal thalamocortical oscillations on a normal EEG background. Therefore, our results agree with currently accepted concepts but are not consistent with findings in some previous studies.

The effects of dexamphetamine on the resting-state electroencephalogram and functional connectivity.

The catecholamines-dopamine and noradrenaline-play important roles in directing and guiding behavior. Disorders of these systems, particularly within the dopamine system, are associated with several severe and chronically disabling psychiatric and neurological disorders. We used the recently published group independent components analysis (ICA) procedure outlined by Chen et al. (2013) to present the first pharmaco-EEG ICA analysis of the resting-state EEG in healthy participants administered 0.45 mg/kg dexamphetamine. Twenty-eight healthy participants between 18 and 41 were recruited. Bayesian nested-domain models that explicitly account for spatial and functional relationships were used to contrast placebo and dexamphetamine on component spectral power and several connectivity metrics. Dexamphetamine led to reductions across delta, theta, and alpha spectral power bands that were predominantly localized to Frontal and Central regions. Beta 1 and beta 2 power were reduced by dexamphetamine at Frontal ICs, while beta 2 and gamma power was enhanced by dexamphetamine in posterior regions, including the parietal, occipital-temporal, and occipital regions. Power-power coupling under dexamphetamine was similar for both states, resembling the eyes open condition under placebo. However, orthogonalized measures of power coupling and phase coupling did not show the same effect of dexamphetamine as power-power coupling. We discuss the alterations of low- and high-frequency EEG power in response to dexamphetamine within the context of disorders of dopamine regulation, in particular schizophrenia, as well as in the context of a recently hypothesized association between low-frequency power and aspects of anhedonia. Hum Brain Mapp 37:570-588, 2016. © 2015 Wiley Periodicals, Inc.

Abuse potential and adverse cognitive effects of mitragynine (kratom).

Mitragynine is the major psychoactive alkaloid of the plant kratom/ketum. Kratom is widely used in Southeast Asia as a recreational drug, and increasingly appears as a pure compound or a component of 'herbal high' preparations in the Western world. While mitragynine/kratom may have analgesic, muscle relaxant and anti-inflammatory effects, its addictive properties and effects on cognitive performance are unknown. We isolated mitragynine from the plant and performed a thorough investigation of its behavioural effects in rats and mice. Here we describe an addictive profile and cognitive impairments of acute and chronic mitragynine administration, which closely resembles that of morphine. Acute mitragynine has complex effects on locomotor activity. Repeated administration induces locomotor sensitization, anxiolysis and conditioned place preference, enhances expression of dopamine transporter- and dopamine receptor-regulating factor mRNA in the mesencephalon. While there was no increase in spontaneous locomotor activity during withdrawal, animals showed hypersensitivity towards small challenging doses for up to 14 days. Severe somatic withdrawal signs developed after 12 hours, and increased level of anxiety became evident after 24 hours of withdrawal. Acute mitragynine independently impaired passive avoidance learning, memory consolidation and retrieval, possibly mediated by a disruption of cortical oscillatory activity, including the suppression of low-frequency rhythms (delta and theta) in the electrocorticogram. Chronic mitragynine administration led to impaired passive avoidance and object recognition learning. Altogether, these findings provide evidence for an addiction potential with cognitive impairments for mitragynine, which suggest its classification as a harmful drug.

Prefrontal left--dominant hemisphere--gamma and delta oscillators in general anaesthesia with volatile anaesthetics during open thoracic surgery.

OBJECTIVES: The main objective was to indicate sufficient general anaesthesia (GA) inhibition for negative experience rejection in GA. PATIENTS AND METHODS: We investigated the group of patients (n = 17, mean age 63.59 years, 9 male--65.78 years, 8 female - 61.13 years) during GA in open thorax surgery and analyzed EEG signal by power spectrum (pEEG) delta (DR), and gamma rhythms (GR). EEG was performed: OPO - the day before surgery and in surgery phases OP1-OP5 during GA. Particular GA phases: OP1 = after pre- medication, OP2 = surgery onset, OP3 = surgery with one-side lung ventilation, OP4 = end of surgery, both sides ventilation, OP5 = end of GA. pEEG registering in the left frontal region Fp1-A1 montage in 17 right handed persons. RESULTS: Mean DR power in OP2 phase is significantly higher than in phase OP5 and mean DR power in OP3 is higher than in OP5. One-lung ventilation did not change minimal alveolar concentration and gases should not accelerate decrease in mean DR power. Higher mean value of GR power in OPO than in OP3 was statistically significant. Mean GR power in OP3 is statistically significantly lower than in OP4 correlating with the same gases concentration in OP3 and OP4. CONCLUSION: Our results showed DR power decreased since OP2 till the end of GA it means inhibition represented by power DR fluently decreasing is sufficient for GA depth. GR power decay near the working memory could reduce conscious cognition and unpleasant explicit experience in GA.

Nicotine administration in the wake-promoting basal forebrain attenuates sleep-promoting effects of alcohol.

Nicotine and alcohol co-abuse is highly prevalent, although the underlying causes are unclear. It has been suggested that nicotine enhances pleasurable effects of alcohol while reducing aversive effects. Recently, we reported that nicotine acts via the basal forebrain (BF) to activate nucleus accumbens and increase alcohol consumption. Does nicotine suppress alcohol-induced aversive effects via the BF? We hypothesized that nicotine may act via the BF to suppress sleep-promoting effects of alcohol. To test this hypothesis, adult male Sprague-Dawley rats were implanted with sleep-recording electrodes and bilateral guides targeted toward the BF. Nicotine (75 pmol/500 nL/side) or artificial cerebrospinal fluid (ACSF; 500 nL/side) was microinjected into the BF followed by intragastric alcohol (ACSF + EtOH and NiC + EtOH groups; 3 g/kg) or water (NiC + W and ACSF + W groups; 10 mL/kg) administration. On completion, rats were killed and processed to localize injection sites in the BF. The statistical analysis revealed a significant effect of treatment on sleep-wakefulness. While rats exposed to alcohol (ACSF + EtOH) displayed strong sleep promotion, nicotine pre-treatment in the BF (NiC + EtOH) attenuated alcohol-induced sleep and normalized sleep-wakefulness. These results suggest that nicotine acts via the BF to suppress the aversive, sleep-promoting effects of alcohol, further supporting the role of BF in alcohol-nicotine co-use.

Cholinergic neurons of the basal forebrain mediate biochemical and electrophysiological mechanisms underlying sleep homeostasis.

The tight coordination of biochemical and electrophysiological mechanisms underlies the homeostatic sleep pressure (HSP) produced by sleep deprivation (SD). We have reported that during SD the levels of inducible nitric oxide synthase (iNOS), extracellular nitric oxide (NO), adenosine [AD]ex , lactate [Lac]ex and pyruvate [Pyr]ex increase in the basal forebrain (BF). However, it is not clear whether all of them contribute to HSP leading to increased electroencephalogram (EEG) delta activity during non-rapid eye movement (NREM) recovery sleep (RS) following SD. Previously, we showed that NREM delta increase evident during RS depends on the presence of BF cholinergic (ChBF) neurons. Here, we investigated the role of ChBF cells in coordination of biochemical and EEG changes seen during SD and RS in the rat. Increases in low-theta power (5-7 Hz), but not high-theta (7-9 Hz), during SD correlated with the increase in NREM delta power during RS, and with the changes in nitrate/nitrite [NOx ]ex and [AD]ex . Lesions of ChBF cells using IgG 192-saporin prevented increases in [NOx ]ex , [AD]ex and low-theta activity, during SD, but did not prevent increases in [Lac]ex and [Pyr]ex . Infusion of NO donor DETA NONOate into the saporin-treated BF failed to increase NREM RS and delta power, suggesting ChBF cells are important for mediating NO homeostatic effects. Finally, SD-induced iNOS was mostly expressed in ChBF cells, and the intensity of iNOS induction correlated with the increase in low-theta activity. Together, our data indicate ChBF cells are important in regulating the biochemical and EEG mechanisms that contribute to HSP.

Prediction of rhythmic and periodic EEG patterns and seizures on continuous EEG with early epileptiform discharges.

BACKGROUND: Continuous EEG (cEEG) is necessary to document nonconvulsive seizures (NCS), nonconvulsive status epilepticus (NCSE), as well as rhythmic and periodic EEG patterns of 'ictal-interictal uncertainty' (RPPIIU) including periodic discharges, rhythmic delta activity, and spike-and-wave complexes in neurological intensive care patients. However, cEEG is associated with significant recording and analysis efforts. Therefore, predictors from short-term routine EEG with a reasonably high yield are urgently needed in order to select patients for evaluation with cEEG. OBJECTIVE: The aim of this study was to assess the prognostic significance of early epileptiform discharges (i.e., within the first 30 min of EEG recording) on the following: (1) incidence of ictal EEG patterns and RPPIIU on subsequent cEEG, (2) occurrence of acute convulsive seizures during the ICU stay, and (3) functional outcome after 6 months of follow-up. METHODS: We conducted a separate analysis of the first 30 min and the remaining segments of prospective cEEG recordings according to the ACNS Standardized Critical Care EEG Terminology as well as NCS criteria and review of clinical data of 32 neurological critical care patients. RESULTS: In 17 patients with epileptiform discharges within the first 30 min of EEG (group 1), electrographic seizures were observed in 23.5% (n = 4), rhythmic or periodic EEG patterns of 'ictal-interictal uncertainty' in 64.7% (n = 11), and neither electrographic seizures nor RPPIIU in 11.8% (n = 2). In 15 patients with no epileptiform discharges in the first 30 min of EEG (group 2), no electrographic seizures were recorded on subsequent cEEG, RPPIIU were seen in 26.7% (n = 4), and neither electrographic seizures nor RPPIIU in 73.3% (n = 11). The incidence of EEG patterns on cEEG was significantly different between the two groups (p = 0.008). Patients with early epileptiform discharges developed acute seizures more frequently than patients without early epileptiform discharges (p = 0.009). Finally, functional outcome six months after discharge was significantly worse in patients with early epileptiform discharges (p=0.01). CONCLUSIONS: Epileptiform discharges within the first 30 min of EEG recording are predictive for the occurrence of ictal EEG patterns and for RPPIIU on subsequent cEEG, for acute convulsive seizures during the ICU stay, and for a worse functional outcome after 6 months of follow-up. This article is part of a Special Issue entitled Status Epilepticus.

The effects of L type calcium channels on the electroencephalogram recordings in WAG/RIJ rat model of absence epilepsy.

BACKGROUND: Epilepsy is one of the most important central nervous system disorder and 1% of the total world population suffers from this disorder which require a chronic drug treatment. Most of the researchers suggested that excessive calcium entry into neurons is the main triggering event in the initiation of epileptic discharges but the role of L type calcium channels has not been clarified in absence epilepsy. AIM: In this study, it is aimed to investigate the antiepileptic effects of nifedipine, an L type calcium channel blocker and BAY K8644, an L type calcium channel opener in a genetic model of absence epilepsy in WAG/Rij rats. MATERIALS AND METHODS: Thirty two WAG/Rij rats were allocated into four groups; sham (only saline injected), only nifedipine (an L type calcium channel blocker) injected group (40 µg/2 µl; 60 µg/2 µl; 80 µg/2 µl), only BAY K8644 (1,4 Dihydro-2,6-dimethyl-5-nitro-4-trifluoromethyl- phenyl-3-pyridine carboxylic acid methyl ester) (L-type Ca2+-channel activator) injected group (40 µg/2 µl; 60 µg/2 µl; 80 µg/2 µl) and combination of their most effective doses BAY K8644 (60 µg/2 µl) after nifedipine (60 µg/2 µl) injected group. All agents were given by intracerebroventricular injection. The beta, alpha, theta and delta wave ratios of electroencephalogram recordings and the frequency and duration of SWDs (spike and wave discharges) were analyzed and compared between four groups. RESULTS: Nifedipine increased the number and duration of spike wave discharges whereas BAY K8644 decreased both of them. When BAY K8644 was given after nifedipine, there was no significant difference with control group. CONCLUSIONS: L type calcium channels play an activator role on spike wave discharges and have positive effects on the duration and frequency.

Electrophysiological correlations of morphological restructuring in experimental local ischemia of different severity in the rat sensorimotor cortex.

Local cerebrovascular disorders were modeled by reversible photochemical clotting of hemispheric cortical vessels. Mild ischemia led to reversible edema in the surface layers of the cortex: cytotoxic edema of the neuropile, primarily of the distal dendrites. This status led to an increase in the lower delta rhythm frequency band power. After administration of systemic anesthetic, delta rhythm appeared sooner in the ischemic foci than in intact cortical areas. More severe ischemia led to the appearance of dark and pyknotic neurons and reduction of oscillation power in all EEG spectrum bands. Restructuring of primarily dendrites caused by local moderate ischemia of the surface cortical layers at the early stage of neurodegenerative processes stimulated the inhibitory recovery processes.

NMDAR antagonist action in thalamus imposes δ oscillations on the hippocampus.

Work on schizophrenia demonstrates the involvement of the hippocampus in the disease and points specifically to hyperactivity of CA1. Many symptoms of schizophrenia can be mimicked by N-methyl-d-aspartate receptor (NMDAR) antagonist; notably, delta frequency oscillations in the awake state are enhanced in schizophrenia, an abnormality that can be mimicked by NMDAR antagonist action in the thalamus. Given that CA1 receives input from the nucleus reuniens of the thalamus, we sought to determine whether an NMDAR antagonist in the thalamus can affect hippocampal processes. We found that a systemic NMDAR antagonist (ketamine; 50 mg/kg) increased the firing rate of cells in the reuniens and CA1 in awake rats. Furthermore, ketamine increased the power of delta oscillations in both structures. The thalamic origin of the change in hippocampal properties was demonstrated in three ways: 1) oscillations in the two structures were coherent; 2) the hippocampal changes induced by systematic ketamine were reduced by thalamic injection of muscimol; and 3) the hippocampal changes could be induced by local injection of ketamine into the thalamus. Lower doses of ketamine (20 mg/kg) did not evoke delta oscillations but did increase hippocampal gamma power, an effect not dependent on the thalamus. There are thus at least two mechanisms for ketamine action on the hippocampus: a low-dose mechanism that affects gamma through a nonthalamic mechanism and a high-dose mechanism that increases CA1 activity and delta oscillations as a result of input from the thalamus. Both mechanisms may be important in producing symptoms of schizophrenia.