Subcortical Arousal Research Articles

Cortical network switching: possible role of the lateral septum and cholinergic arousal.

Cortical networks undergo large-scale switching between states of increased or decreased activity in normal sleep and cognition as well as in pathological conditions such as epilepsy. We previously found that focal hippocampal seizures in rats induce increased neuronal firing and cerebral blood flow in subcortical structures including the lateral septal area, along with frontal cortical slow oscillations resembling slow wave sleep. In addition, stimulation of the lateral septum in the absence of a seizure resulted in cortical deactivation with slow oscillations. We hypothesized that lateral septal activation might cause neocortical deactivation indirectly, possibly through impaired subcortical arousal. But how does subcortical stimulation cause slow wave activity in frontal cortex? How do arousal neurotransmitter levels (e.g. acetylcholine) change in cortex during the excitation of inhibitory projection nuclei? In the current study, we used simultaneous electrophysiology and enzyme-based amperometry in a rat model, and found a decrease in choline, along with slow wave activity in orbital frontal cortex during lateral septal stimulation in the absence of seizures. In contrast, the choline signal and local field potential in frontal cortex had no significant changes when stimulating the hippocampus, but showed increased choline and decreased slow wave activity with an arousal stimulus produced by toe pinch. These findings indicate that the activation of subcortical inhibitory structures (such as lateral septum) can depress subcortical cholinergic arousal. This mechanism may play an important role in large-scale transitions of cortical activity in focal seizures, as well as in normal cortical function.

Consciousness as a useful concept in epilepsy classification.

Impaired consciousness has important practical consequences for people living with epilepsy. Recent pathophysiologic studies show that seizures with impaired level of consciousness always affect widespread cortical networks and subcortical arousal systems. In light of these findings and their clinical significance, efforts are underway to revise the International League Against Epilepsy (ILAE) 2010 report to include impaired consciousness in the classification of seizures. Lüders and colleagues have presented one such effort, which we discuss here. We then propose an alternative classification of impaired consciousness in epilepsy based on functional neuroanatomy. Some seizures involve focal cortical regions and cause selective deficits in the content of consciousness but without impaired overall level of consciousness or awareness. These include focal aware conscious seizures (FACS) with lower order cortical deficits such as somatosensory or visual impairment as well as FACS with higher cognitive deficits including ictal aphasia or isolated epileptic amnesia. Another category applies to seizures with impaired level of consciousness leading to deficits in multiple cognitive domains. For this category, we believe the terms "dyscognitive" or "dialeptic" should be avoided because they may create confusion. Instead we propose that seizures with impaired level of consciousness be described based on underlying pathophysiology. Widespread moderately severe deficits in corticothalamic function are seen in absence seizures and in focal impaired consciousness seizures (FICS), including many temporal lobe seizures and other focal seizures with impaired consciousness. Some simple responses or automatisms may be preserved in these seizures. In contrast, generalized tonic-clonic seizures usually produce widespread severe deficits in corticothalamic function causing loss of all meaningful responses. Further work is needed to understand and prevent impaired consciousness in epilepsy, but the first step is to keep this crucial practical and physiologic aspect of seizures front-and-center in our discussions.

Comment: Awareness in partial seizures—Implications for patients and therapies

Consciousness is a complex process, requiring coordination between cortical and deeper subcortical structures to be maintained. Investigations utilizing multiple modalities have led to the “network inhibition hypothesis,” suggesting that partial seizure propagation inhibits deeper subcortical arousal systems.1 In a more practical sense, for a person with epilepsy, losing consciousness during a seizure carries substantial safety and social implications. The unpredictable loss of awareness leaves patients at risk for injury, impairs their ability to drive, and can affect their employment status.

What is a seizure network? Long-range network consequences of focal seizures.

What defines the spatial and temporal boundaries of seizure activity in brain networks? To fully answer this question a precise and quantitative definition of seizures is needed, which unfortunately remains elusive. Nevertheless, it is possible to ask under conditions where clearly divergent patterns of activity occur in large-scale brain networks whether certain activity patterns are part of the seizure while others are not. Here we examine brain network activity during focal limbic seizures, including diverse regions such as the hippocampus, subcortical arousal systems and fronto-parietal association cortex. Based on work from patients and from animal models we describe a characteristic pattern of intense increases in neuronal firing, cerebral blood flow, cerebral blood volume, blood oxygen level dependent functional magnetic resonance imaging (BOLD fMRI) signals and cerebral metabolic rate of oxygen consumption in the hippocampus during focal limbic seizures. Similar increases are seen in certain closely linked subcortical structures such as the lateral septal nuclei and anterior hypothalamus, which contain inhibitory neurons. In marked contrast, decreases in all of these parameters are seen in the subcortical arousal systems of the upper brainstem and intralaminar thalamus, as well as in the fronto-parietal association cortex. We propose that the seizure proper can be defined as regions showing intense increases, while those areas showing opposite changes are inhibited by the seizure network and constitute long-range network consequences beyond the seizure itself. Importantly, the fronto-parietal cortex shows sleep-like slow wave activity and depressed metabolism under these conditions, associated with impaired consciousness. Understanding which brain networks are directly involved in seizures versus which sustain secondary consequences can provide new insights into the mechanisms of brain dysfunction in epilepsy, hopefully leading to innovative treatment approaches.

Startle response and anxiety sensitivity: Subcortical indices of physiologic arousal and fear responding.

There is a well-established and clinically meaningful relation between the cognitive-affective-based construct of anxiety sensitivity (AS) and risk for the development and maintenance of anxiety psychopathology (B. J. Cox, Fuentes, Borger, & Taylor, 2001). Research findings within this area have revealed mixed results; however, there is evidence to suggest that some individuals with anxiety disorder diagnoses may demonstrate enhanced subcortical arousal (e.g., exaggerated startle response to unexpected, aversive stimuli [A. M. Waters et al., 2008], and deficient prepulse inhibition [PPI; S. Ludewig, Ludewig, Geyer, Hell, & Vollenweider, 2002]), it is presently unclear whether these differences are found within the general population. To address this gap in the extant literature, the current investigation examined the impact of AS on acoustic startle response magnitude and PPI. Results indicated that individuals high and low in AS differ with regard to subcortical measures of arousal, with individuals expressing high levels of AS demonstrating enhanced startle response and deficient PPI. Results are discussed in terms of the role of the cognitive-affective-based factor of AS in the context of physiologic markers for vulnerability for anxiety psychopathology.

Sleep disturbance in pre-school children with obstructive sleep apnoea syndrome

Sleep-disordered breathing in children is most prevalent in the pre-school years and has been associated with sleep fragmentation and hypoxia. We aimed to compare the sleep and spontaneous arousal characteristics of 3-5-year-old children with obstructive sleep apnoea (OSA) with that of non-snoring control children, and to further characterise the arousal responses to obstructive respiratory events. A total of 73 children (48 male) underwent overnight polysomnography: 51 for assessment of snoring who were subsequently diagnosed with OSA (obstructive apnoea hypopnoea index (OAHI)>1 event per h) and 22 control children recruited from the community (OAHI ≤ 1 and no history of snoring). The OSA group had poorer sleep efficiency (p<0.05), spent a smaller proportion of their sleep period time in rapid eye movement (REM) (p<0.05), and had significantly fewer spontaneous arousals (p<0.001) compared with controls. One-quarter of the children with OSA had a sleep pressure score above the cut-off point for increased sleep pressure. In children with OSA, 62% of obstructive respiratory events terminated in a cortical arousal and 21% in a sub-cortical arousal. A significantly higher proportion of obstructive respiratory events terminated in a cortical arousal during non-REM (NREM) compared with REM (p<0.001). These findings suggest that in pre-school children OSA has a profound effect on sleep and arousal patterns. Given that these children are at a critical period for brain development, the impact of OSA may have more severe consequences than in older children.

The Default Mode Network and Altered Consciousness in Epilepsy

The default mode network has been hypothesized based on the observation that specific regions of the brain are consistently activated during the resting state and deactivated during engagement with task. The primary nodes of this network, which typically include the precuneus/posterior cingulate, the medial frontal and lateral parietal cortices, are thought to be involved in introspective and social cognitive functions. Interestingly, this same network has been shown to be selectively impaired during epileptic seizures associated with loss of consciousness. Using a wide range of neuroimaging and electrophysiological modalities, decreased activity in the default mode network has been confirmed during complex partial, generalized tonic-clonic, and absence seizures. In this review we will discuss these three seizure types and will focus on possible mechanisms by which decreased default mode network activity occurs. Although the specific mechanisms of onset and propagation differ considerably across these seizure types, we propose that the resulting loss of consciousness in all three types of seizures is due to active inhibition of subcortical arousal systems that normally maintain default mode network activity in the awake state. Further, we suggest that these findings support a general “network inhibition hypothesis”, by which active inhibition of arousal systems by seizures in certain cortical regions leads to cortical deactivation in other cortical areas. This may represent a push-pull mechanism similar to that seen operating between cortical networks under normal conditions.

The default mode network and altered consciousness in epilepsy.

The default mode network has been hypothesized based on the observation that specific regions of the brain are consistently activated during the resting state and deactivated during engagement with task. The primary nodes of this network, which typically include the precuneus/posterior cingulate, the medial frontal and lateral parietal cortices, are thought to be involved in introspective and social cognitive functions. Interestingly, this same network has been shown to be selectively impaired during epileptic seizures associated with loss of consciousness. Using a wide range of neuroimaging and electrophysiological modalities, decreased activity in the default mode network has been confirmed during complex partial, generalized tonic-clonic, and absence seizures. In this review we will discuss these three seizure types and will focus on possible mechanisms by which decreased default mode network activity occurs. Although the specific mechanisms of onset and propagation differ considerably across these seizure types, we propose that the resulting loss of consciousness in all three types of seizures is due to active inhibition of subcortical arousal systems that normally maintain default mode network activity in the awake state. Further, we suggest that these findings support a general “network inhibition hypothesis”, by which active inhibition of arousal systems by seizures in certain cortical regions leads to cortical deactivation in other cortical areas. This may represent a push-pull mechanism similar to that seen operating between cortical networks under normal conditions.

Epilepsy, consciousness and neurostimulation.

Consciousness is often disrupted in epilepsy. This may involve altered responsiveness or changes in awareness of self and subjective experiences. Subcortical arousal systems and paralimbic fronto-parietal association cortices are thought to underpin current concepts of consciousness. The Network Inhibition Hypothesis proposes a common neuroanatomical substrate for impaired consciousness during absence, complex partial and tonic-clonic seizures.Neurostimulation in epilepsy remains in its infancy with vagal nerve stimulation (VNS) as the only firmly established technique and a series of other methods under investigation including deep brain stimulation (DBS), intracranial cortical stimulation and repetitive transcranial magnetic stimulation (rTMS). Many of these systems impact on the neural systems thought to be involved in consciousness as a continuous duty cycle although some adaptive (seizure triggered) techniques have been developed.Theoretically, fixed duty cycle neurostimulation could have profound effects on responsiveness, awareness of self and subjective experience. Animal studies suggest vagal nerve stimulation positively influences hippocampal long term potentiation. In humans, a chronic effect of increased alertness in VNS implanted subjects and acute effect on memory consolidation have been reported but convincing data on either improvements or deterioration in attention and memory is lacking. Thalamic deep brain stimulation (DBS) is perhaps the most interesting neurostimulation technique in the context of consciousness. Neither bilateral anterior or centromedian thalamic nucleus DBS seem to affect cognition. Unilateral globus pallidus internus DBS caused transient wakefulness in an anaesthetised individual.As intracranial neurostimulation, particularly thalamic DBS, becomes more established as a clinical intervention, the effects on consciousness and cognition with variations in stimulus parameters will need to be studied to understand whether these secondary effects of neurostimulation make a significant positive (or adverse) contribution to quality of life.

Impaired consciousness in temporal lobe seizures: role of cortical slow activity

Impaired consciousness requires altered cortical function. This can occur either directly from disorders that impair widespread bilateral regions of the cortex or indirectly through effects on subcortical arousal systems. It has therefore long been puzzling why focal temporal lobe seizures so often impair consciousness. Early work suggested that altered consciousness may occur with bilateral or dominant temporal lobe seizure involvement. However, other bilateral temporal lobe disorders do not impair consciousness. More recent work supports a 'network inhibition hypothesis' in which temporal lobe seizures disrupt brainstem-diencephalic arousal systems, leading indirectly to depressed cortical function and impaired consciousness. Indeed, prior studies show subcortical involvement in temporal lobe seizures and bilateral frontoparietal slow wave activity on intracranial electroencephalography. However, the relationships between frontoparietal slow waves and impaired consciousness and between cortical slowing and fast seizure activity have not been directly investigated. We analysed intracranial electroencephalography recordings during 63 partial seizures in 26 patients with surgically confirmed mesial temporal lobe epilepsy. Behavioural responsiveness was determined based on blinded review of video during seizures and classified as impaired (complex-partial seizures) or unimpaired (simple-partial seizures). We observed significantly increased delta-range 1-2 Hz slow wave activity in the bilateral frontal and parietal neocortices during complex-partial compared with simple-partial seizures. In addition, we confirmed prior work suggesting that propagation of unilateral mesial temporal fast seizure activity to the bilateral temporal lobes was significantly greater in complex-partial than in simple-partial seizures. Interestingly, we found that the signal power of frontoparietal slow wave activity was significantly correlated with the temporal lobe fast seizure activity in each hemisphere. Finally, we observed that complex-partial seizures were somewhat more common with onset in the language-dominant temporal lobe. These findings provide direct evidence for cortical dysfunction in the form of bilateral frontoparietal slow waves associated with impaired consciousness in temporal lobe seizures. We hypothesize that bilateral temporal lobe seizures may exert a powerful inhibitory effect on subcortical arousal systems. Further investigations will be needed to fully determine the role of cortical-subcortical networks in ictal neocortical dysfunction and may reveal treatments to prevent this important negative consequence of temporal lobe epilepsy.

Pulse transit time for scoring subcortical arousal in infants with obstructive sleep apnea

An altered autonomic control and response to respiratory events during sleep have been reported in infants with obstructive sleep apnea but appropriate methods are not established. We assessed the feasibility of pulse transit time (PTT) in detecting subcortical arousals in eight infants (median age 7 days) suffering from the Pierre Robin sequence and obstructive sleep apnea. Sleep studies including recordings of PTT performed before and after successful orthodontic treatment for their OSA were analyzed. PTT arousals (i.e., fall in PTT by > or =15 ms lasting for > or =3 s) were visually scored using specific analysis software. Apnea-related PTT arousals and spontaneous PTT arousals were distinguished and predicting factors for the occurrence of uninterpretable PTT signal and PTT arousals were analyzed. Six-hundred and seven apneas were analyzed. Uninterpretable PTT signal appeared in 394 (65%) apneas and were due to a disturbed pulse waveform in 63%. Predictors for the occurrence of uninterpretable PTT signal were type of apnea (odds ratio, 95% confidence interval for obstructive apnea = 0.5, 0.4-0.9) and duration of apnea (odds ratio, 95% confidence interval per second duration = 1.4, 1.3-1.5). Of 213 apneas with interpretable PTT signal, 43 (7% of all apneas) were followed by a PTT arousal. Predictor for their occurrence was treatment status (odds ratio, 95% confidence interval for pre-treatment status = 3.4, 1.3-8.8). Spontaneous PTT arousals during control periods appeared more frequently pre-treatment compared to post-treatment (41% vs. 16%; p-value = 0.001). There were only weak correlations between changes in PTT, heart rate, and arterial oxygen saturation (correlation coefficient <0.3). The feasibility of PTT in scoring apnea-related subcortical arousals in infants may be questionable. However, scoring spontaneous PTT arousals may be an approach for assessing sleep disruption in infants with obstructive sleep apnea.

Distinguishing specific sexual and general emotional effects in fMRI—Subcortical and cortical arousal during erotic picture viewing

Sexual activity involves excitement with high arousal and pleasure as typical features of emotions. Brain activations specifically related to erotic feelings and those related to general emotional processing are therefore hard to disentangle. Using fMRI in 21 healthy subjects (11 males and 10 females), we investigated regions that show activations specifically related to the viewing of sexually intense pictures while controlling for general emotional arousal (GEA) or pleasure. Activations in the ventral striatum and hypothalamus were found to be modulated by the stimulus' specific sexual intensity (SSI) while activations in the anterior cingulate cortex were associated with an interaction between sexual intensity and emotional valence. In contrast, activation in other regions like the dorsomedial prefrontal cortex, the mediodorsal thalamus and the amygdala was associated only with a general emotional component during sexual arousal. No differences were found in these effects when comparing females and males. Our findings demonstrate for the first time neural differentiation between emotional and sexual components in the neural network underlying sexual arousal.

Pulse Transit Time and Blood Pressure Changes Following Auditory-Evoked Subcortical Arousal and Waking of Infants

To establish a normal range of data in 3-month-old infants in relation to changes in cardiovascular measurements, with particular reference to pulse transit time (PTT), following subcortical arousals and awakenings from sleep. Prospective study. Sleep laboratory, Dunedin Hospital Twenty healthy infants aged 9-12 weeks. Nap studies were performed using a standard polysomnographic setup with the addition of a Portapres blood pressure (BP) cuff (wrist application) and a piezoelectric sensor on the foot. PTT was measured from the ECG-R waveform to the arrival of the pulse peripherally. Infants were exposed to white noise from 50 to 100 dB at 10 dB intervals within REM and NREM sleep. Awakening thresholds were higher (P = 0.01) in NREM (>90 dB) than REM sleep (mean +/- SD; 74.3 +/- 9.4dB). Subcortical thresholds were always 10 dB below waking thresholds. Following awakening, there was an immediate increase in HR, SBP, and DBP of 21%, 14%, and 17%, respectively, and a 13% decrease in PTT returning to baseline within 25-30 seconds. PTT at baseline measured 140 +/- 11 and 139 +/- 9 msec in NREM and REM sleep, respectively, and decreased approximately 20 msec with waking. PTT changes were negatively correlated with heart rate (HR) but not BP, although a trend was evident. At 3 months of age, infants provoked to arouse from sleep showed PTT changes that inversely mimicked BP trends, suggesting that PTT could be useful in infant studies as a marker for autonomic perturbations that occur during sleep in both clinical and research settings.

The role of cingulate cortex in the detection of errors with and without awareness: a high‐density electrical mapping study

Error-processing research has demonstrated that the brain uses a specialized neural network to detect errors during task performance but the brain regions necessary for conscious awareness of an error are poorly understood. In the present study we show that two well-known error-related event-related potential (ERP) components, the error-related negativity (ERN) and error positivity (Pe) have a differential relationship with awareness during performance of a manual response inhibition task optimized to examine error awareness. While the ERN was unaffected by the participants' conscious experience of errors, the Pe was only seen when participants were aware of committing an error. Source localization of these components indicated that the ERN was generated by a caudal region of the anterior cingulate cortex (ACC) while the Pe was associated with contributions from a more anterior ACC region and the posterior cingulate-precuneus. Tonic EEG measures of cortical arousal were correlated with individual rates of error awareness and showed a specific relationship with the amplitude of the Pe. The latter finding is consistent with evidence that the Pe represents a P3-like facilitation of information processing modulated by subcortical arousal systems. Our data suggest that the ACC might participate in both preconscious and conscious error detection and that cortical arousal provides a necessary setting condition for error awareness. These findings may be particularly important in the context of clinical studies in which a proper understanding of self-monitoring deficits requires an explicit measurement of error awareness.

Dissociation in performance of children with ADHD and high-functioning autism on a task of sustained attention

Attention deficit hyperactivity disorder (ADHD) and autism are two neurodevelopmental disorders associated with prominent executive dysfunction, which may be underpinned by disruption within fronto-striatal and fronto-parietal circuits. We probed executive function in these disorders using a sustained attention task with a validated brain-behaviour basis. Twenty-three children with ADHD, 21 children with high-functioning autism (HFA) and 18 control children were tested on the Sustained Attention to Response Task (SART). In a fixed sequence version of the task, children were required to withhold their response to a predictably occurring no-go target (3) in a 1–9 digit sequence; in the random version the sequence was unpredictable. The ADHD group showed clear deficits in response inhibition and sustained attention, through higher errors of commission and omission on both SART versions. The HFA group showed no sustained attention deficits, through a normal number of omission errors on both SART versions. The HFA group showed dissociation in response inhibition performance, as indexed by commission errors. On the Fixed SART, a normal number of errors was made, however when the stimuli were randomised, the HFA group made as many commission errors as the ADHD group. Greater slow-frequency variability in response time and a slowing in mean response time by the ADHD group suggested impaired arousal processes. The ADHD group showed greater fast-frequency variability in response time, indicative of impaired top-down control, relative to the HFA and control groups. These data imply involvement of fronto-parietal attentional networks and sub-cortical arousal systems in the pathology of ADHD and prefrontal cortex dysfunction in children with HFA.

Electroencephalogram characteristics of autonomic arousals during sleep in healthy men

Objective Many sleep disorders involve frequent, brief arousals, not appreciated during conventional sleep stage scoring due to lack of electroencephalogram (EEG) desynchronization. We evaluated the temporal relation between heart rate (HR) changes, an index of autonomic activation, and EEG in seven healthy subjects during sleep. Methods We identified bouts of tachycardia–bradycardia and performed spectral analysis of EEG during these. We also identified cortical arousals by the appearance of EEG alpha activity. This allowed us to dichotomize bouts of tachycardia–bradycardia by presence or absence of cortical arousal. Results During non-rapid eye movement (REM) sleep, bouts with or without cortical arousal occurred with approximately equal frequency. Those with cortical arousals usually preceded onset of EEG changes. Those without cortical arousals were followed by increases in delta but not alpha power. EEG did not change during bouts in REM sleep. Conclusions Capturing bouts of tachycardia–bradycardia is relatively easy via computerized algorithm. Bouts occur with cortical arousal or with slow wave synchronization suggestive of subcortical arousal. Thus, changes in HR may be useful index of arousal. Significance These brief bursts of tachycardia–bradycardia are consistent with autonomic arousal. Such a measure may be among the first in a continuum of arousal ending with frank awakening.

Postsynaptic excitation of prefrontal cortical pyramidal neurons by hypocretin‐1/orexin a through the inhibition of potassium currents

Hypocretins are crucial for the regulation of wakefulness by the excitatory actions on multiple subcortical arousal systems. To date, there is little information about the direct postsynaptic excitatory effects of hypocretins on the neurons in prefrontal cortex (PFC), which is important for higher cognitive functions and is correlated with level of wakefulness. In this study, we tested the excitatory effects of hypocretin-1 on acutely isolated PFC pyramidal neurons of rats and studied the possible ionic mechanisms by using whole-cell patch-clamp techniques. Puff application of hypocretin-1 caused a dose-dependent excitation. Further observations that perfusion of Ca2+-free artificial cerebrospinal fluid did not influence the depolarizing effects of hypocretin-1, in conjunction with the findings that hypocretin-1 could decrease net whole-cell K+ currents, demonstrate that the excitatory effects of hypocretin-1 on PFC neurons are mediated by the inhibition of K+ currents but not Ca2+ influx. Finally, the decrease in K+ currents induced by hypocretin-1 was abolished by a protein kinase C (PKC) inhibitor (BIS II) or a phospholipase C (PLC) inhibitor (D609), suggesting that PKC and PLC appear to be involved in mediating the inhibitory effects of hypocretin-1 on K+ currents. These results indicate that hypocretin-1 exerts a postsynaptic excitatory action on PFC neurons through the inhibition of K+ currents, which probably results from activation of PKC and PLC signaling pathways.

Neocortex is the major target of sedative concentrations of volatile anaesthetics: strong depression of firing rates and increase of GABAA receptor‐mediated inhibition

General anaesthetics cause sedation, amnesia and hypnosis. Although these clinically desired actions are indicative of an impairment of neocortical information processing, it is widely held that they are to a large part mediated by subcortical neural networks. Anaesthetic action on brain stem, basal forebrain and thalamus, all of which are known to modulate cortical excitability, would thus ultimately converge on neocortex, perturbing and reducing action potential activity therein. However, as neocortex harbours molecular targets of anaesthetics in high densities, notably GABA(A) receptors, neocortex itself should be very sensitive to anaesthetics. Here, we performed experiments to reveal the extent to which neocortex proper is a relevant target of the low concentrations of volatile anaesthetics causing sedation and hypnosis. We compared the effects of isoflurane, enflurane and halothane on spontaneous action potential activity of rat neocortical neurons in vivo and in isolated cortical networks in vitro, i.e. in the presence and absence of subcortical arousal systems. We observed that the anaesthetics decreased spontaneous firing of neurons via intracortical mechanisms; concentrations inducing hypnosis in humans reduced discharge rates both in vivo and in vitro to the same extent, approximately 50%. This decrease in neuronal activity was paralleled by a significant enhancement of neocortical GABA(A) receptor-mediated inhibition. These findings challenge the notion of predominantly subcortical effects of volatile anaesthetics and suggest that intracortical targets, among them neocortical GABA(A) receptors, mediate the sedative and hypnotic properties of volatile anaesthetics.

Subcortical arousal response in child patients with obstructive sleep apnea

Objective: The objective of this study is to assess subcortical arousal response (SCA) in child patients with obstructive sleep apnea syndrome (OSAS). Methods: A new index termed SCA was defined as a sigh associated with elevated chin muscle activity. According to the duration, SCAs were divided into three types; SCA short (1 s or more and less than 3 s), SCA intermediate (3 s or more and less than 10 s), and SCA long (10 s or more). We scored SCAs in six child OSAS patients, aged 2–5 years, before and after adenotonsillectomy. SCAs were also counted in four age-matched controls. Results: In the pretreatment records, 45.5% of SCAs were associated with electroencephalographic arousals. In all patients, SCA short and SCA intermediate decreased after the treatment to the levels in the controls. SCA long exhibited no consistent changes after treatment. The incidence of SCAs was much higher than arousals previously reported in child OSAS patients as well as in normal children. Conclusions: SCAs, especially SCA short and SCA intermediate, are sensitive and useful indices for assessing subcortical involvement in child OSAS patients.

In vitro networks: cortical mechanisms of anaesthetic action

In vitro networks: cortical mechanisms of anaesthetic action