Brain Arousal Research Articles

Interneurons control brain arousal states

Neuroscience The underlying circuit mechanisms coordinating brain arousal and motor activity are poorly understood. Liu et al. found that glutamic acid decarboxylase 2 (GAD2)–expressing, but not parvalbumin-expressing, interneurons in a part of the brain known as the substantia nigra promote sleep (see the Perspective by Wisden and Franks). Parvalbuminergic neurons fire at higher rates in states of high motor activity, and their activation increases movement termination consistent with the function of the substantia nigra in suppressing unwanted movements during action selection. By contrast, GAD2 neurons are preferentially active in states of low motor activity. In addition to motor suppression, their activation powerfully enhances the transition from quiet wakefulness to sleep, which differ mainly in the arousal level rather than motor behavior. GAD2 interneurons thus provide general suppression of both motor activity and brain arousal to promote states of quiescence. Science , this issue p. [440][1]; see also p. [366][2] [1]: /lookup/doi/10.1126/science.aaz0956 [2]: /lookup/doi/10.1126/science.aba4485

Is brain arousal regulation a predictor of response to psychostimulant therapy in adult ADHD patients?

We investigated whether baseline brain arousal instability during resting state EEG, using the Vigilance Algorithm Leipzig (VIGALL 2.1), can predict response to methylphenidate therapy in adult ADHD patients. An arousal stability score of the EEGs of 28 adult ADHD patients was calculated quantifying the extent of arousal decline. In logistic regression analysis, arousal stability score predicted response to MPH [odds ratio 1.28 (95% CI 1.0-1.65); p = 0.027]. In this pilot study, we demonstrated that arousal stability at baseline predicted methylphenidate treatment response, indicating that less stable arousal regulation during a 15-min EEG at rest increases the chance of treatment response.

Arousal Contributions to Resting-State fMRI Connectivity and Dynamics.

Resting-state functional magnetic resonance imaging (rsfMRI) is being widely used for charting brain connectivity and dynamics in healthy and diseased brains. However, the resting state paradigm allows an unconstrained fluctuation of brain arousal, which may have profound effects on resting-state fMRI signals and associated connectivity/dynamic metrics. Here, we review current understandings of the relationship between resting-state fMRI and brain arousal, in particular the effect of a recently discovered event of arousal modulation on resting-state fMRI. We further discuss potential implications of arousal-related fMRI modulation with a focus on its potential role in mediating spurious correlations between resting-state connectivity/dynamics with physiology and behavior. Multiple hypotheses are formulated based on existing evidence and remain to be tested by future studies.

Electrocortical changes associating sedation and respiratory depression by the opioid analgesic fentanyl

Opioid drugs are the mainstay of pain management but present the side-effect of respiratory depression that can be lethal with overdose. In addition to their respiratory effect, opioids also induce a profound sedative state and produce electrocortical features characteristic of a state of reduced brain arousal, similar to anaesthesia or sleep. In such states, respiratory activity depends more on the integrity of the brainstem respiratory network than it does during wakefulness. Accordingly, we propose that sedation by fentanyl induces specific electrocortical changes consistent with reduced brain arousal, and that the magnitude of respiratory depression is associated with distinct electrocortical changes. To these aims, we determined the effects of systemic injections of fentanyl (dosage 100 µg ·kg) versus control on electrocortical and respiratory activities of freely-behaving rats. We found that fentanyl induced electrocortical changes that differed from those observed in sleep or wakefulness. Fentanyl increased δ (1–3 Hz) frequency power (P < 0.001), but reduced α (7.5–13.5 Hz) and β2 (20–30 Hz) powers (P = 0.012 and P < 0.001, respectively), when compared to wakefulness. Interestingly, respiratory rate depression by fentanyl was significantly correlated with increased θ power (R = 0.61, P < 0.001), therefore showing a clear association between electrocortical activity and the magnitude of respiratory rate depression. Overall, we provide new evidence linking specific electrocortical changes to the severity of respiratory depression by opioids, which highlights the importance of considering the cortical and subcortical effects of opioids in addition to their impacts on breathing when evaluating opioid-induced respiratory depression.

Non-visual effects of diurnal exposure to an artificial skylight, including nocturnal melatonin suppression

BackgroundRecently, more consideration is being given to the beneficial effects of lighting on the maintenance and promotion of the health and well-being of office occupants in built environments. A new lighting technology using Rayleigh scattering has made it possible to simulate a blue sky. However, to date, no studies have examined the possible beneficial effects of such artificial skylights. The aims of this study were to examine the non-visual effects of artificial skylights and conventional fluorescent lights in a simulated office environment and to clarify the feature effects of the artificial skylights.MethodsParticipants were 10 healthy male adults. Non-visual effects were evaluated based on brain arousal levels (α-wave ratio and contingent negative variation [CNV]), autonomic nervous activity (heart rate variability [HRV]), work performance, and subjective responses during daytime exposure to either an artificial skylight or fluorescent lights, as well as nocturnal melatonin secretion.ResultsSubjective evaluations of both room lighting-related “natural” and “attractive” items and the “connected to nature” item were significantly higher with the skylight than with the fluorescent lights. Cortical arousal levels obtained from the early component of the CNV amplitude were significantly lower with the skylight than with the fluorescent lights, whereas α-wave ratio and work performance were similar between the two light sources. The HRV evaluation showed that sympathetic nerve tone was lower and parasympathetic nerve tone was higher, both significantly, for the skylight than for the fluorescent lights during daytime. Nocturnal melatonin secretion was significantly greater before and during light exposure at night under the daytime skylight than under the fluorescent lights.ConclusionsOur results suggest that artificial skylights have some advantages over conventional fluorescent lights in maintaining ordinary work performance during daytime with less psychological and physiological stress. The findings also suggest that the artificial skylights would enable built environments to maintain long-term comfort and productivity.

Brain arousal regulation and depressive symptomatology in adults with attention-deficit/hyperactivity disorder (ADHD)

BackgroundThe aim of the present study was to evaluate the stability of brain arousal in adult attention-deficit/hyperactivity disorder (ADHD) outpatients with and without depressive symptomatology, and its association with depressive symptom severity and absolute electroencephalogram (EEG) power in different frequency bands.MethodsWe included 31 outpatient adults (45.16% females), who were diagnosed according to DSM-IV and received no medication. Their arousal stability score (index of the steepness of arousal decline during a 15-min EEG under resting conditions), the absolute EEG power and self-reports, including depressive and ADHD-related symptoms, were analyzed. Participants were split into an unstable and stable arousal group based on the median (= 6) of the arousal stability score.ResultsADHD patients in the stable group reported more severe depressive symptoms (p = 0.018) and showed reduced absolute EEG power in the delta (0.002 ≤ p ≤ 0.025) and theta (0.011 ≤ p ≤ 0.034) bands compared to those in the unstable group. There was no correlation between the arousal stability score and self-report-scales concerning ADHD-related symptoms (0.214 ≤ p ≤ 0.989), but a positive association with self-reported depressive severity (p = 0.018) and negative association with powers in the EEG delta and theta bands (0.001 ≤ p ≤ 0.033).ConclusionsIn view of high comorbidity of depression and ADHD in adult patients, these findings support the assumption that brain arousal regulation could be considered as a helpful marker for the clinical differentiation between ADHD and depression.

Sleep deprivation and Modafinil affect cortical sources of resting state electroencephalographic rhythms in healthy young adults

ObjectiveIt has been reported that sleep deprivation affects the neurophysiological mechanisms underpinning the vigilance. Here, we tested the following hypotheses in the PharmaCog project (www.pharmacog.org): (i) sleep deprivation may alter posterior cortical delta and alpha sources of resting state eyes-closed electroencephalographic (rsEEG) rhythms in healthy young adults; (ii) after the sleep deprivation, a vigilance enhancer may recover those rsEEG source markers. MethodsrsEEG data were recorded in 36 healthy young adults before (Pre-sleep deprivation) and after (Post-sleep deprivation) one night of sleep deprivation. In the Post-sleep deprivation, these data were collected after a single dose of PLACEBO or MODAFINIL. rsEEG cortical sources were estimated by eLORETA freeware. ResultsIn the PLACEBO condition, the sleep deprivation induced an increase and a decrease in posterior delta (2–4 Hz) and alpha (8–13 Hz) source activities, respectively. In the MODAFINIL condition, the vigilance enhancer partially recovered those source activities. ConclusionsThe present results suggest that posterior delta and alpha source activities may be both related to the regulation of human brain arousal and vigilance in quiet wakefulness. SignificanceFuture research in healthy young adults may use this methodology to preselect new symptomatic drug candidates designed to normalize brain arousal and vigilance in seniors with dementia.

P68-F Abnormalities of cortical neural synchronization mechanisms in patients with Alzheimer’s diseases dementia: An EEG study

Background This retrospective study aimed to check whether the resting state eyes-closed electroencephalographic (rsEEG) rhythms might reflect brain arousal in patients with Alzheimer’s disease dementia (ADD) at the group and the individual level. Methods Our dataset was an international archive of Clinical and rsEEG data of 42 ADD and 40 healthy elderly (Nold) subjects. The delta, theta, alpha 1, alpha 2, and alpha 3 frequency bands were determined by Individual alpha frequency peak (IAF). Fixed beta 1, beta 2, and gamma bands were also considered. rsEEG cortical sources were estimated by means of the exact low-resolution brain electromagnetic source tomography and were then classified across individuals, on the basis of the receiver operating characteristic (ROC) curves. Results Compared to the Nold group, IAF showed slowing in the ADD group. Furthermore, The ADD group showed lower posterior alpha 2 source activities and higher occipital delta source activities. The ratio of occipital delta to alpha 2 allowed good classification accuracy (sensitivity: 88.1%, specificity: 85%, and accuracy: 86.6%) between the Nold and ADD individuals. Conclusion In quiet wakefulness, delta and alpha sources unveiled different spatial and frequency features of the cortical neural synchronization underpinning brain arousal in ADD patients compared with Nold subjects. An ongoing study is testing the enrichment of markers derived from structural magnetic resonance imaging (MRI) in the classification accuracy between Nold and ADD patients for potential clinical applications.

P67-F rsEEG markers in subjects with MCI due to Alzheimer’s disease (ADMCI) and interictal epileptiform discharge

Background It is well-known that compared to normal elderly (Nold) subjects, patients with dementia due to Alzheimer’s disease (ADD) manifest ten times convulsive seizures. The present study tested the different features of the resting state eyes-closed electroencephalographic (rsEEG) rhythms in a group of patients with mild cognitive impairment due to AD and interictal epileptiform discharge (ADMCI IED+), compared to groups of ADMCI patients without interictal epileptiform discharge (ADMCI IED−), ADD patients, and Nold subjects. Methods Clinical, neuropsychological, and rsEEG data, in 30 Nold, 31 ADMCI IED−, 11 ADMCI IED+, and 30 ADD subjects were available in an international archive. Individual alpha frequency peak was used to determine the delta, theta, alpha1, alpha2, and alpha3 frequency band ranges. Fixed beta1, beta2, and gamma bands were considered. eLORETA estimated the rsEEG cortical sources in EEG segments free from artifacts and IED. The analysis of the area under the receiver operating characteristic (AUROC) curve computed the classification rate. Results Compared to the Nold group, the ADMCI IED−, ADMCI IED+ and ADD groups presented higher widespread delta source activities and lower posterior alpha source activities. As novel EEG results, compared to the ADMCI IED- group, the ADMCI IED+ unveiled higher frontal and temporal delta source activities. Furthermore, temporal delta source activity allowed a good classification (AUROC > 0.85) between the ADMCI IED− and ADMCI IED+ individuals. Conclusions In quiet wakefulness, the abnormalities in cortical neural synchronization underpinning brain arousal at delta frequencies are higher in the ADMCI IED+ than the ADMCI IED− subjects.

Electrophysiological and phenomenological effects of short-term immersion in an altered sensory environment.

We examined the spontaneous cerebral electrophysiology and phenomenology during short-term perceptual deprivation consisting of an edgeless visual field combined with monotonous auditory input that eliminated potential grounding cues (multimodal Ganzfeld). Subjects (N = 22) were instructed to self-report perceptual fading using a button press. Relaxed wakefulness with closed eyes and viewing of a time-varying stimulus array served as control conditions. The power of parieto-occipital alpha rhythms during perceptual deprivation was midway between the eyes-closed and eyes-open conditions, with a state-specific frequency acceleration. Oscillatory alpha power remained enhanced in the multimodal Ganzfeld relative to viewing time-varying signals, despite no indication of diminished brain arousal. Subjects experienced a range of perceptual phenomena while in the altered sensory environment and individuals with faster alpha oscillations self-reported a greater number of fading episodes. We suggest that alpha-band electroencephalogram (EEG) dynamics signal internally oriented mentation in response to brief perceptual deprivation.

Gigantocellular Neurons Awaken the Brain from Deep Pharmacologically-Induced Coma

Attempts at neuromodulation using deep brain stimulation (DBS) have targeted a number of loci in brain arousal pathways such as the thalamus, mesencephalon and cervical cord. However, recovery following single location stimulation remains modest, especially in comatose patients. Although some of these pathways can trigger awakening from sleep or light planes of anesthesia upon activation are insufficient to promote arousal from a deeper arousal state like coma. Interpretation of these results suggests that to fully emerge from a deep arousal state, coordination of multiple pathways is required. The mechanism through which this coordination is achieved by the brain is poorly understood. Considering that medullary reticular neurons project to arousal- modulating areas throughout the brain, integrate a broad range of sensory and autonomic inputs, and fire in response to salient stimuli in close association with the initiation of behaviors, we modulated their activity during a pharmacologic induced coma (PIC). Our results showed that pharmacologic or optogenetic activation of an area located at the nucleus gigantocellularis (NGC)- elicited robust cortical, autonomic and motor arousal during a state of PIC. To understand how this small subpopulation of neurons exerts such widespread activational effects on arousal, we analyzed immunolabeling of c-Fos-a well-established marker of neuronal activation-following pharmacologic activation of NGC neurons. C-Fos labeling was sparse and largely limited to structures known to participate in arousal including rhombenchephalon (locus coeruleus and parabrachial nucleus); mesencephalon (periaqueductal gray and ventral tegmental area); diencephalon (intralaminar thalamic nuclei as well as posterior and anterior hypothalamus). These findings suggest that NGC is able to recruit these pathways to trigger arousal from a dense PIC. Results of this study will uncover novel mechanisms leading to new approaches for emerging treatments for patients under coma state.

S.02.04 Neuronal underpinnings of pro-cognitive change in mood disorders

EEG measures of arousal have been suggested as diagnostic and predictive biomarkers for major depression. The aim of the present study was to examine whether self-rated depression severity in SSRI-medicated patients with major depression (MD) is associated with EEG measures of brain arousal. Based on previous studies, we expected that a higher level of brain arousal and a slower arousal decline during a 15-min EEG recording are associated with higher symptom severity as assessed with the Beck Depression Inventory (BDI) at the time of the EEG recording. EEGs of 78 MD patients and 46 healthy controls were analyzed. Brain arousal was assessed using the Vigilance Algorithm Leipzig (VIGALL 2.1). Based on automatically classified 1-s segments (EEG-vigilance Stages 0, A1, A2, A3, B1, B2/3 or C) we computed indices to assess the level (mean EEG-vigilance) and the decline of arousal (slope index) during the 15-min resting state EEG under eyes-closed condition. We found that a higher arousal level and a slower arousal decline corresponded to higher severity of depressive symptoms (rho = 0.238, p = .018; and rho = 0.236; p = .019). Self-rated non-remitters (BDI>12) had a higher arousal level (mean EEG-vigilance: t76 = −2.19, p = .016) and slower arousal decline (slope index: Z = −2.08, p = .019) during the 15-min recording as compared to remitters. Similar results were obtained between non-remitters and healthy controls (mean EEG-vigilance: t102 = −2.75, p = .004; slope index: Z = −1.92, p = .028), but not between remitters and controls (p > .260). The findings support the model that brain arousal regulation plays an important role in the pathophysiology and treatment of MD.

Brain arousal regulation in SSRI-medicated patients with major depression

EEG measures of arousal have been suggested as diagnostic and predictive biomarkers for major depression. The aim of the present study was to examine whether self-rated depression severity in SSRI-medicated patients with major depression (MD) is associated with EEG measures of brain arousal. Based on previous studies, we expected that a higher level of brain arousal and a slower arousal decline during a 15-min EEG recording are associated with higher symptom severity as assessed with the Beck Depression Inventory (BDI) at the time of the EEG recording. EEGs of 78 MD patients and 46 healthy controls were analyzed. Brain arousal was assessed using the Vigilance Algorithm Leipzig (VIGALL 2.1). Based on automatically classified 1-s segments (EEG-vigilance Stages 0, A1, A2, A3, B1, B2/3 or C) we computed indices to assess the level (mean EEG-vigilance) and the decline of arousal (slope index) during the 15-min resting state EEG under eyes-closed condition. We found that a higher arousal level and a slower arousal decline corresponded to higher severity of depressive symptoms (rho = 0.238, p = .018; and rho = 0.236; p = .019). Self-rated non-remitters (BDI>12) had a higher arousal level (mean EEG-vigilance: t76 = −2.19, p = .016) and slower arousal decline (slope index: Z = −2.08, p = .019) during the 15-min recording as compared to remitters. Similar results were obtained between non-remitters and healthy controls (mean EEG-vigilance: t102 = −2.75, p = .004; slope index: Z = −1.92, p = .028), but not between remitters and controls (p > .260). The findings support the model that brain arousal regulation plays an important role in the pathophysiology and treatment of MD.

Combined cognitive, psychomotor and electrophysiological biomarkers in major depressive disorder.

The diagnosis of major depressive disorder (MDD) should be based on multimodal evidence, because MDD not only affects mood, but also psychomotor and cognitive functions. Clinical markers such as executive dysfunctions and a reduction in daily motor activity have been observed in MDD. Neurophysiological biomarkers have also been described. In this study, we investigate the utility of combining biomarkers related to executive dysfunctions, motor activity, neurophysiological patterns (i.e. alpha power asymmetry and EEG-vigilance as indicators of brain arousal), and the interaction of these parameters in the diagnosis of MDD. Twenty (female: 11) patients with MDD (age: 51.05 ± 10.50) and 20 (female: 13) healthy controls (HC; age: 47.15 ± 12.57) underwent a 10-min resting EEG. Executive dysfunctions were assessed using the Trail Making Test B (TMT B). Motor activity was analysed by actigraphy measurements. MDD patients displayed significant impairments in executive functions and reduced daily motor activity. In the EEG, MDD patients showed more right than left frontal activity and lower brain arousal relative to HC. TMT B and asymmetrical frontal alpha power alone discriminated between MDD patients and HC with an accuracy of 78%. The interaction of motor activity and the EEG-vigilance stage alongside TMT B increased the accuracy of the discrimination test to 81%. This improved accuracy suggests that the combination of these biomarkers in a discriminant analysis resulted in a more reliable identification of MDD patients.

Changes in brain arousal (EEG-vigilance) after therapeutic sleep deprivation in depressive patients and healthy controls

Depressed patients frequently exhibit a hyperstable brain arousal regulation. According to the arousal regulation model of affective disorders, the antidepressant effect of therapeutic sleep deprivation could be achieved by counter-acting this dysregulation. We investigated the impact of partial sleep deprivation (PSD) on EEG-vigilance (an indicator of brain arousal regulation) in depressed patients (n = 27) and healthy controls (n = 16). PSD was hypothesized to cause a more prominent destabilisation of brain arousal regulation in depressed patients (reflected by increased occurrence of lower EEG-vigilance stages). Furthermore, it was studied whether responders (n = 17) exhibit a more stable baseline brain arousal regulation and would show a more prominent arousal destabilisation after PSD than non-responders (n = 10). Before PSD, patients showed a more stable EEG-vigilance with less declines to lower vigilance stages compared to controls. Contrary to the hypothesis, a greater destabilisation of brain arousal after PSD was seen in controls. Within the patient sample, responders generally showed a less stable EEG-vigilance, especially after PSD when we found significant differences compared to non-responders. EEG-vigilance in non-responders showed only little change from baseline to after PSD. In summary, PSD had a destabilizing impact on brain arousal regulation in healthy controls whereas depressed patients reacted heterogeneously depending on the outcome of treatment.

Different Abnormalities of Cortical Neural Synchronization Mechanisms in Patients with Mild Cognitive Impairment due to Alzheimer's and Chronic Kidney Diseases: An EEG Study.

This study tested whether resting state alpha rhythms (8-13 Hz) may characterize mild cognitive impairment due to Alzheimer's disease (ADMCI) compared with MCI due to chronic kidney disease (CKDMCI). Clinical and resting state eyes-closed electroencephalographic (rsEEG) rhythms from 40 ADMCI, 29 CKDMCI, and 45 cognitively normal elderly (Nold) subjects were available in a national archive. Age, gender, and education were matched in the three groups, and Mini-Mental State Evaluation (MMSE) score was paired in the ADMCI and CKDMCI groups. Delta (<4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), beta 2 (20-30 Hz), and gamma (30-40 Hz) cortical sources were estimated by eLORETA freeware and classified across individuals by area under the receiver operating characteristic curve (AUROCC). Compared with Nold group, posterior alpha 1 source activities were more reduced in ADMCI than CKDMCI group. In contrast, widespread delta source activities were greater in CKDMCI than ADMCI group. These source activities correlated with the MMSE score and correctly classified between Nold and all MCI individuals (AUROCC = 0.8-0.85) and between ADMCI and CKDMCI subjects (AUROCC = 0.75). These results suggest that early AD affects cortical neural synchronization at alpha frequencies underpinning brain arousal and low vigilance in the quiet wakefulness. In contrast, CKD may principally affect cortical neural synchronization at the delta frequencies. Future prospective cross-validation studies will have to test these candidate rsEEG markers for clinical applications and drug discovery.

Resting EEG Measures of Brain Arousal in a Multisite Study of Major Depression.

Several studies have found upregulated brain arousal during 15-minute EEG recordings at rest in depressed patients. However, studies based on shorter EEG recording intervals are lacking. Here we aimed to compare measures of brain arousal obtained from 2-minute EEGs at rest under eyes-closed condition in depressed patients and healthy controls in a multisite project-Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC). We expected that depressed patients would show stable and elevated brain arousal relative to controls. Eighty-seven depressed patients and 36 healthy controls from four research sites in the United States were included in the analyses. The Vigilance Algorithm Leipzig (VIGALL) was used for the fully automatic classification of EEG-vigilance stages (indicating arousal states) of 1-second EEG segments; VIGALL-derived measures of brain arousal were calculated. We found that depressed patients scored higher on arousal stability ( Z = -2.163, P = .015) and A stages (dominant alpha activity; P = .027) but lower on B1 stages (low-voltage non-alpha activity, P = .008) compared with healthy controls. No significant group differences were observed in Stage B2/3. In summary, we were able to demonstrate stable and elevated brain arousal during brief 2-minute recordings at rest in depressed patients. Results set the stage for examining the value of these measures for predicting clinical response to antidepressants in the entire EMBARC sample and evaluating whether an upregulated brain arousal is particularly characteristic for responders to antidepressants.

P19. Vigilance regulation pattern in children with attention-deficit/hyperactivity disorder (ADHD) and depression measured by electroencephalography (EEG)

Objective Disturbed regulation of vigilance in wake state seems to play a key role in the development of mental disorders. In an actual model by Hegerl et al. (2014) hyperactivity in ADHD is assumed to be an attempt to increase a general low vigilance level via external stimulation. For depression the avoidance of stimulation is interpreted as a reaction to a tonic increased vigilance state. Although ADHD is assumed to start during childhood, this vigilance model has only been tested in a pilot study with children diagnosed for ADHD so far and was not compared to children with diagnosis of depression. Routine or assisted EEGs are not recommended for assessing vigilance (Sander et al., 2015) but the question remains if brain arousal can still be measured with it. If yes, it might be useful for clinical praxis, if relevant diagnostic conclusions can be drawn sufficiently from routine EEG measures. Methods 137 reting state EEG (10 min) measures from two groups of psychiatric patients (age: 13 ± 3.7 years) diagnosed with either ADHD or depression were analyzed. Vigilance classifications are compared between both groups via two-sample t-tests and chi-square tests. We used n-mean cluster analysis to detect EEG-patterns of vigilance regulation. In an ANOVA model, the relation between vigilance regulation and mental health symptoms (child behaviour check list, CBCL/6-18) was analyzed. Results We found more classification of low arousing stage B2/3 in ADHD compared to depression (50–20%) p Conclusion This study revealed that vigilance classification based on MTA assisted routine EEG of children showed results which are in accordance to the assumptions of hypo-aroused brain activity in ADHD and a more hyper-aroused brain state in depression. Therefore similar brain arousal states in children in these diagnostic groups can be assumed as has been showed for adults before. Interestingly, we could assign these different brain arousal states directly to attentional problems in our study sample. In order to analyze the validity of vigilance regulation analysis from a routine EEG in more detail a further direct comparison to EEG assessment according to the VIGALL protocol is still needed.

The Feasibility of Encapsulated Embryonic Medullary Reticular Cells to Grow and Differentiate Into Neurons in Functionalized Gelatin-Based Hydrogels.

The study of the behavior of embryonic neurons in controlled in vitro conditions require methodologies that take advantage of advanced tissue engineering approaches to replicate elements of the developing brain extracellular matrix. We report here a series of experiments that explore the potential of photo-polymerized gelatin hydrogels to culture primary embryonic neurons. We employed large medullary reticular neurons whose activity is essential for brain arousal as well as a library of gelatin hydrogels that span a range of mechanical properties, inclusion of brain-mimetic hyaluronic acid, and adhesion peptides. These hydrogel platforms showed inherent capabilities to sustain neuronal viability and were permissive for neuronal differentiation, resulting in the development of neurite outgrowth under specific conditions. The maturation of embryonic medullary reticular cells took place in the absence of growth factors or other exogenous bioactive molecules. Immunocytochemistry labeling of neuron-specific tubulin confirmed the initiation of neural differentiation. Thus, this methodology provides an important validation for future studies of nerve cell growth and maintenance.

S178. International Federation of Clinical Neurophysiology (IFCN) guidelines for topographic and frequency analysis of resting state electroencephalographic rhythms

Introduction Resting state EEG (rsEEG) rhythms reflect neurophysiological mechanisms and operational functions related to the fluctuation of brain arousal and quiet vigilance in humans and are largely investigated in clinical practice and research in Clinical Neurophysiology. In 1999, the International Federation of Clinical Neurophysiology (IFCN) published the Guidelines entitled “IFCN Guidelines for Topographic and Frequency Analysis of EEGs and EPs” (Nuwer et al., 1999). In 2017, the IFCN Executive Committee committed to a Working Group of 15 field experts of four continents (Prof./Dr. Babiloni C., Barry R., Basar E., Blinowska K., Cichocki A., Drinkenburg W., Klimesch W., Knight R., Jeong J., Lopes da Silva F., Nunez P., Oostenveld R., Pascual-Marqui R., Valdes Sosa P., and Hallett M.) the update of the part of those Guidelines concerning frequency and topographic analyses of rsEEG rhythms. This contribution will report the outcome of the mentioned Working Group (That outcome is expected to be published in Clinical Neurophysiology in 2018 after a regular peer-review process). Methods Recommendations about relevant procedures of recording, storage, visualization, and quantitative frequency and topographic analyses of rsEEG data in Clinical Neurophysiology of vigilance were expressed based on theoretical ground and relevant core literature findings. Those recommendations reflected the consensus in the Working Group. Results Recommendations regarded main controversies in the field such as (1) the optimal experimental conditions ensuring that recordings of rsEEG rhythms fit requirements of a neurophysiological experiment on vigilance; (2) the minimum requirements of scalp electrode montage, reference electrode, and settings for subsequent frequency and topographical analyses; (3) choice of frequency bands; (4) linear/nonlinear synchronization and interdependence of rsEEG rhythms at scalp electrodes and sources; and (5) statistical modeling and neurophysiological inferences in clinical practice and research. Conclusion Linear frequency and topographical source analyses of rsEEG rhythms (e.g., 10–20 electrode montage at minimum and extracephalic reference) are mature for both clinical practice and research applications. Nonlinear frequency and connectivity analyses of those rhythms require more research before their current use in clinical practice.