Brain Arousal Research Articles

EEG measures of brain arousal in relation to symptom improvement in patients with major depressive disorder: Results from a randomized placebo-controlled clinical trial

Hyperstable arousal regulation during a 15-min resting electroencephalogram (EEG) has been linked to a favorable response to antidepressants. The EMBARC study, a multicenter randomized placebo-controlled clinical trial, provides an opportunity to examine arousal stability as putative antidepressant response predictor in short EEG recordings. We tested the hypothesis that high arousal stability during a 2-min resting EEG at baseline is related to better outcome in the sertraline arm and explored the specificity of this effect. Outpatients with chronic/recurrent MDD were recruited from four university hospitals and randomized to treatment with sertraline (n = 100) or placebo (n = 104). The change in the Hamilton Rating Scale for Depression (HRSD-17) was the main outcome. Patients were stratified into high and low arousal stability groups. In mixed-model repeated measures (MMRM) analysis HRSD-17 change differed significantly between arousal groups, with high arousal stability being associated with a better outcome in the sertraline arm, and worse outcome in the placebo arm at week 4, with moderate effect sizes. When considering both treatment arms, a significant arousal group x time x treatment interaction emerged, highlighting specificity to the sertraline arm. Although findings indicate that arousal stability is likely to be a treatment-specific marker of response, further out-of-sample validation is warranted.

A biomarker of brain arousal mediates the intergenerational link between maternal and child post-traumatic stress disorder

This study examined whether there is a biological basis in the child's resting brain activity for the intergenerational link between maternal interpersonal violence-related posttraumatic stress disorder (IPV-PTSD) and child subclinical symptoms. We used high-density EEG recordings to investigate the resting brain activity in a sample of 57 children, 34 from mothers with IPV-PTSD, and 23 from mothers without PTSD. These children were part of a prospective, longitudinal study focusing on the offspring of mothers with and without IPV-PTSD, reporting how the severity of a mother's IPV-PTSD can impact her child's emotional regulation and risk for developing mental illness. However, we had not yet looked into potential EEG biomarkers during resting state that might mediate and/or moderate effects of maternal IPV-PTSD severity on child mental health, and in particular the risk for PTSD. The alpha band spectral power as well as the aperiodic exponent of the power spectrum (PLE; power-law exponent) were examined as mediators of maternal IPV-PTSD and child PTSD.While there was no difference in alpha spectral power between the two groups, PLE was significantly reduced in children of mothers with IPV-PTSD compared to control children, indicating cortical hyper-arousal. Interestingly, child PLE was negatively correlated with the severity of maternal IPV-PTSD, suggesting an intergenerational interaction. This interpretation was reinforced by a negative correlation between child PLE and child PTSD symptoms. Finally, causal analyses using structural equation modelling indicated that child PLE mediated the relationship between maternal PTSD severity and child PTSD. Our observations suggest that maternal IPV-PTSD has an intergenerational impact on the child neurobehavioral development through a correlated abnormal marker of brain arousal (i.e. child PLE). These findings are potentially relevant to psychotherapy research and to the development of more effective psycho-neurobehavioral therapies (i.e. neurofeedback) among affected individuals.

Stochastic resonance is not required for pink noise to have beneficial effects on ADHD-related performance? The moderate brain arousal model challenged

ObjectiveRandom noise, such as white or pink noise, has been shown to have beneficial effects on the performance of individuals with (elevated traits of) ADHD. Both the state regulation deficit (SRD) account and the moderate brain arousal (MBA) model argue that this effect is due to enhanced cognitive arousal. The MBA model specifically attributes this to random noise affecting dopaminergic (DA) transmission via stochastic resonance (SR). However, he requirement of SR and the role of DA have not yet been properly examined. To test this, proper control conditions are needed. MethodTo examine the requirement of SR, 60 neurotypical adults with varying levels of ADHD traits performed a slow two-choice reaction time (S1–S2) task in three auditory conditions: pink (random) noise, a pure 100 Hz tone (non-random noise), and silence. All participants also completed the Attention Network Test (ANT) in two conditions (pink noise and silence) to inspect the effect on executive network efficiency which may serve as a proxy measure of DA. ADHD traits were assessed via self-report. ResultsAuditory stimulation improved performance on the S1–S2 task in participants with elevated ADHD traits, however this was the case for both pink noise and the pure tone. Pink noise did not affect executive network efficiency, irrespective of ADHD traits. ConclusionsOur results suggest that stochastic resonance is not required for pink noise to have a beneficial effect on ADHD-related performance. Pink noise did not affect our DA proxy measure, however this negative finding should be interpreted with caution. Our results cast doubt on the tenets of the MBA model, warranting further research.

Coordination between circadian neural circuit and intracellular molecular clock ensures rhythmic activation of adult neural stem cells

The circadian clock throughout the day organizes the activity of neural stem cells (NSCs) in the dentate gyrus (DG) of adult hippocampus temporally. However, it is still unclear whether and how circadian signals from the niches contribute to daily rhythmic variation of NSC activation. Here, we show that norepinephrinergic (NEergic) projections from the locus coeruleus (LC), a brain arousal system, innervate into adult DG, where daily rhythmic release of norepinephrine (NE) from the LC NEergic neurons controlled circadian variation of NSC activation through β3-adrenoceptors. Disrupted circadian rhythmicity by acute sleep deprivation leads to transient NSC overactivation and NSC pool exhaustion over time, which is effectively ameliorated by the inhibition of the LC NEergic neuronal activity or β3-adrenoceptors-mediated signaling. Finally, we demonstrate that NE/β3-adrenoceptors-mediated signaling regulates NSC activation through molecular clock BMAL1. Therefore, our study unravels that adult NSCs precisely coordinate circadian neural circuit and intrinsic molecular circadian clock to adapt their cellular behavior across the day.

EEG-vigilance regulation is associated with and predicts ketamine response in major depressive disorder

Ketamine offers promising new therapeutic options for difficult-to-treat depression. The efficacy of treatment response, including ketamine, has been intricately linked to EEG measures of vigilance. This research investigated the interplay between intravenous ketamine and alterations in brain arousal, quantified through EEG vigilance assessments in two distinct cohorts of depressed patients (original dataset: n = 24; testing dataset: n = 24). Clinical response was defined as a decrease from baseline of >33% on the Montgomery–Åsberg Depression Rating Scale (MADRS) 24 h after infusion. EEG recordings were obtained pre-, start-, end- and 24 h post- infusion, and the resting EEG was automatically scored using the Vigilance Algorithm Leipzig (VIGALL). Relative to placebo (sodium chloride 0.9%), ketamine increased the amount of low-vigilance stage B1 at end-infusion. This increase in B1 was positively related to serum concentrations of ketamine, but not to norketamine, and was independent of clinical response. In contrast, treatment responders showed a distinct EEG pattern characterized by a decrease in high-vigilance stage A1 and an increase in low-vigilance B2/3, regardless of whether placebo or ketamine had been given. Furthermore, pretreatment EEG differed between responders and non-responders with responders showing a higher percentage of stage A1 (53% vs. 21%). The logistic regression fitted on the percent of A1 stages was able to predict treatment outcomes in the testing dataset with an area under the ROC curve of 0.7. Ketamine affects EEG vigilance in a distinct pattern observed only in responders. Consequently, the percentage of pretreatment stage A1 shows significant potential as a predictive biomarker of treatment response.Clinical Trials Registration:https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-000952-17/CZRegistration number: EudraCT Number: 2013-000952-17.

Arousal dysregulation and executive dysfunction in attention deficit hyperactivity disorder (ADHD).

Attention deficit/hyperactivity disorder (ADHD) is a heterogeneous neurodevelopmental condition, that continues to have an elusive etiological background. A number of extant models and theories have historically intended to explain the many factors contributing to ADHD behaviors. One of the most accepted hypotheses has been the executive dysfunction theory associating reduction in executive control to abnormalities in structure and operational dysfunction of dopaminergic signaling networks. Nevertheless, executive functions are not always impaired in ADHD, and the literature describes other symptoms commonly reported suggesting individuals with ADHD would appear to suffer from a more general deficit. Another existing line of research, that has gained much attention recently, establishes that ADHD would have dysregulated states of brain arousal that would account for its commonly observed cognitive deficits and behavioral symptoms, described as the state regulation theory, which has now included measures of autonomic function. This article describes some important aspects that compose and challenge these two most influential theoretical constructs, executive dysfunction and state-regulation, based on their empirical evidence, implying the need to reevaluate the norms used to classify individuals and establish ADHD diagnosis. Large number of controversial results continue to exist within the study of ADHD biological and/or performance markers, possibly due to such heterogeneity and variability within the same diagnosis. The need to resolve these issues and establish newly revised diagnostic criteria for ADHD is critical, as therapeutic success depends on having accurately identified underlying neurophysiological factors in order to appropriately address them in treatment.

The impact of emotional dysregulation and comorbid depressive symptoms on clinical features, brain arousal, and treatment response in adults with ADHD.

The role of emotional dysregulation (ED) in attention-deficit/hyperactivity disorder (ADHD) has become an important issue. This study, in which we analyzed data from a predictive pharmaco-EEG-trial, aimed to examine whether symptoms of ED in adult ADHD affect ADHD symptom severity, brain arousal regulation as measured by resting EEG, and the response to stimulant medication. ED is defined as having a sex- and age-corrected T-score of >70 on the emotional lability subscale of the German version of Conners' Adult ADHD Rating Scale. A total of 115 participants were included in the study, 56 of whom had ED. Participants with ED were more impaired in terms of the severity of core ADHD symptoms, especially inattentive symptoms, comorbid depressive symptoms, interpersonal relationships, and quality of life. In addition, participants with ED were more likely to report a total score above 13 on the Beck Depression Inventory-II, which was considered to be the cutoff for mild depression. No differences were found between the ED and non-ED groups in response to stimulant medication or in brain arousal regulation. In addition, there was no significant effect of ED with comorbid depressive symptoms on treatment response. There was a trend for subgroups that showed a change in brain arousal regulation associated with symptom improvement. Our findings may support the assumption that ED may be an important feature of ADHD. The use of EEG-based brain arousal regulation as a diagnostic and predictive tool in ADHD in the presence of ED and comorbid depressive symptoms should be further investigated.

Improving SSVEP-BCI Performance Through Repetitive Anodal tDCS-Based Neuromodulation: Insights From Fractal EEG and Brain Functional Connectivity.

This study embarks on a comprehensive investigation of the effectiveness of repetitive transcranial direct current stimulation (tDCS)-based neuromodulation in augmenting steady-state visual evoked potential (SSVEP) brain-computer interfaces (BCIs), alongside exploring pertinent electroencephalography (EEG) biomarkers for assessing brain states and evaluating tDCS efficacy. EEG data were garnered across three distinct task modes (eyes open, eyes closed, and SSVEP stimulation) and two neuromodulation patterns (sham-tDCS and anodal-tDCS). Brain arousal and brain functional connectivity were measured by extracting features of fractal EEG and information flow gain, respectively. Anodal-tDCS led to diminished offsets and enhanced information flow gains, indicating improvements in both brain arousal and brain information transmission capacity. Additionally, anodal-tDCS markedly enhanced SSVEP-BCIs performance as evidenced by increased amplitudes and accuracies, whereas sham-tDCS exhibited lesser efficacy. This study proffers invaluable insights into the application of neuromodulation methods for bolstering BCI performance, and concurrently authenticates two potent electrophysiological markers for multifaceted characterization of brain states.

Effects of auditory white noise stimulation on sustained attention and response time variability.

"The moderate brain arousal model" claims that white noise improves attention by optimizing brain arousal. We analyze Conners' Continuous Performance Test-3 (CCPT-3) performance, expecting to find reduced reaction time variability with noise mediated by decrease under long event-rates and in later parts of the test, indicating that noise reverse fall in phasic and tonic arousal. Sixty-five children with high or lower ADHD-symptoms from a child psychiatric unit, succeeded to complete the CCPT-3 with and without white noise. Noise reduced overall variability, improved performance in later parts of the test, and reduced response variability under the longest event rate particularly in the high symptoms group. No overall change in omissions and commissions, but the high symptoms group made fewer omissions during noise compared the low symptom group. The study indicates an arousal effect of noise but should be replicated with other noise variants and amplitudes to improve effect and compliance.

79 Continuous Theta Burst Stimulation (cTBS) over the Inferior Parietal Cortex Decreases Default Mode Connectivity and Improves Overnight Sleep in People with Insomnia

Objective:Chronic insomnia is a highly prevalent disorder affecting approximately one-in-three Americans. Insomnia is associated with increased cognitive and brain arousal. Compared to healthy individuals, those with insomnia tend to show greater activation/connectivity within the default mode network (DMN) of the brain, consistent with the hyperarousal theory. We investigated whether it would be possible to suppress activation of the DMN to improve sleep using a type of repetitive transcranial magnetic stimulation (rTMS) known as continuous theta burst stimulation (cTBS).Participants and Methods:Participants (n=9, 6 female; age=25.4, SD=5.9 years) meeting criteria for insomnia/sleep disorder on standardized scales completed a counterbalanced sham-controlled crossover design in which they served as their own controls on two separate nights of laboratory monitored sleep on separate weeks. Each session included two resting state functional magnetic resonance imaging (fMRI) sessions separated by a brief rTMS session. Stimulation involved a 40 second cTBS stimulation train applied over an easily accessible cortical surface node of the DMN located at the left inferior parietal lobe. After scanning/stimulation, the participant was escorted to an isolated sleep laboratory bedroom, fitted with polysomnography (PSG) electrodes, and allowed an 8-hour sleep opportunity from 2300 to 0700. PSG was monitored continuously and scored for standard outcomes, including total sleep time (TST), percentage of time various sleep stages, and number of arousals.Results:Consistent with our hypothesis, a single session of active cTBS produced a significant reduction of functional connectivity (p < .05, FDR corrected) within the DMN. In contrast, the sham condition produced no changes in functional connectivity from pre- to post-treatment. Furthermore, after controlling for age, we also found that the active treatment was associated with meaningful trends toward greater overnight improvements in sleep compared to the sham condition. First, the active cTBS condition was associated with significantly greater TST compared to sham (F(1,7)=14.19, p=.007, partial eta-squared=.67). Overall, individuals obtained 26.5 minutes more sleep on the nights that they received the active cTBS compared to the sham condition. Moreover, the active cTBS condition was associated with a significant increase in the percentage of time in rapid eye movement (REM%) sleep compared to the sham condition (F(1,7)=7.05, p=.033, partial eta-squared=.50), which was significant after controlling for age. Overall, active treatment was associated with an increase of 6.76% more of total sleep time in REM compared to sham treatment. Finally, active cTBS was associated with fewer arousals from sleep (t(8) = -1.84, p = .051, d = .61), with an average of 15.1 fewer arousals throughout the night than sham.Conclusions:Overall, these findings suggest that this simple and brief cTBS approach can alter DMN brain functioning in the expected direction and was associated with trends toward improved objectively measured sleep, including increased TST and REM% and fewer arousals during the night following stimulation. These findings emerged after only a single 40-second treatment, and it remains to be seen whether multiple treatments over several days or weeks can sustain or even improve upon these outcomes.

Self-regulating arousal via pupil-based biofeedback

The brain’s arousal state is controlled by several neuromodulatory nuclei known to substantially influence cognition and mental well-being. Here we investigate whether human participants can gain volitional control of their arousal state using a pupil-based biofeedback approach. Our approach inverts a mechanism suggested by previous literature that links activity of the locus coeruleus, one of the key regulators of central arousal and pupil dynamics. We show that pupil-based biofeedback enables participants to acquire volitional control of pupil size. Applying pupil self-regulation systematically modulates activity of the locus coeruleus and other brainstem structures involved in arousal control. Furthermore, it modulates cardiovascular measures such as heart rate, and behavioural and psychophysiological responses during an oddball task. We provide evidence that pupil-based biofeedback makes the brain’s arousal system accessible to volitional control, a finding that has tremendous potential for translation to behavioural and clinical applications across various domains, including stress-related and anxiety disorders.

On illusion of flying dreams. the mechanism of their occurrence

It is shown that there is no need to resort to exoteric hypotheses to explain flying in a dream. From a biophysical point of view, the phenomenon of "flying in a dream" is based on the already studied adaptive mechanisms and daily rhythms of the human body. During sleep, the brain's arousal thresholds are lowered, making it easier to arouse the brain with weak signals. This study considers one of the mechanisms of such excitation with a change in body position, which is perceived by the brain in the rapid eye movement sleep phase as a decrease in body weight, which, under certain conditions, can cause the illusion of flying in the brain.

EEG wakefulness regulation in transdiagnostic patients after a recent suicide attempt

ObjectiveDecades of research have not yet produced statistically reliable predictors of preparatory behavior eventually leading to suicide attempts or deaths by suicide. As the nature of suicidal behavior is complex, it is best investigated in a transdiagnostic approach, while assessing objective markers, as proposed by the Research Domain Criteria (Cuthbert, 2013). MethodsA 15-min resting-state EEG was recorded in 45 healthy controls, and 49 transdiagnostic in-patients with a recent (<6 months) suicide attempt. Brain arousal regulation in eyes-closed condition was assessed with the Vigilance Algorithm Leipzig (VIGALL) (Sander et al., 2015). ResultsA significant incline of median vigilance and vigilance slope was observed in patients within the first 3-min of the EEG recording. Additionally, a significant positive correlation of self-reported suicidal ideation with the vigilance slope over 15-min recording time, as well as a significant negative correlation with EEG vigilance stage A1 during the first 3-min was found. ConclusionsTransdiagnostic patients with a recent suicide attempt show a distinct vigilance regulation pattern. Further studies including a control group consisting of patients without life-time suicide attempts are needed to increase the clinical utility of the findings. SignificanceThese findings might serve as potential objective markers of suicidal behavior.

Emotionally Loaded Visual Stimuli to Alter Brain Arousal: A Flicker Fusion Study

Background: Human brain performance and arousal are still challenging and critical, especially in environments such as power plants. Since different emotions are common in daily work life and have inevitable effects on cognitive performance, it is important to evaluate whether emotional interventions can alter brain arousal. Poor cognitive performance in control room operators (CROs) can lead to mental fatigue and affect their cognitive emotion regulation. To address this issue, flicker fusion frequency (FFF) was employed as a simple and reproducible surrogate index for mental fatigue. Objectives: This study aimed to investigate whether emotionally loaded visual stimuli can alter brain arousal (brain fatigue) or is associated with cognitive emotion regulation (CER) ability. Methods: Flicker fusion frequency was assessed by RT-961, and the International Affective Picture System (IAPS) was adopted as the picture database of stimuli. Additionally, the Cognitive Emotion Regulation Questionnaire (CERQ) was used to determine the participants’ cognitive emotion CER ability. Twenty volunteer CROs from Fars Combined Cycle Power Plant participated in this study. After completing the CERQ, they were assessed at 2 different time points (ie, before and after presenting emotional stimuli). Flicker fusion frequency was assessed 20 times at each round, and the average frequency was recorded. Emotionally loaded images were considered as stimuli. The stimuli sets were classified based on their arousal levels and valences, yet they were presented in random order. Subjects were exposed to each image for 5 seconds (30 minutes in total). Results: The participants’ mean age was 39.55 ± 7.02 years. The first and second FFFs were 42.15 ± 3.90 and 41.96 ± 3.98 in the appropriate group and 42.82 ± 3.59 and 42.26 ± 4.07 in the inappropriate group. Based on the statistical tests, there were no significant relationships between the measurements (P &gt; 0.05). Conclusions: Control room operators may positively maintain their brain arousal during specific emotional stimuli when the intervention lasts less than 30 minutes. Considering the prolonged working hours in such industries (roughly over 8 hours a day) and the importance of cognitive aptitude in preventing work-related errors, we propose this line of research to gain momentum.

Virtual Art Therapy: Application of Michelangelo Effect to Neurorehabilitation of Patients with Stroke.

In neurorehabilitation, some studies reported the effective use of art therapy for reducing psychological disorders and for enhancing physical functions and cognitive abilities. Neuroaesthetical studies showed that seeing an art masterpiece can spontaneously elicit a widespread brain arousal, also involving motor networks. To combine contemplative and performative benefits of art therapy protocols, we have developed an immersive virtual reality system, giving subjects the illusion that they are able to paint a copy of famous artistic paintings. We previously observed that during this virtual task, subjects perceived less fatigue and performed more accurate movements than when they were asked to color the virtual canvas. We named this upshot the Michelangelo effect. The aim of this study was to test the rehabilitative efficacy of our system. Ten patients with stroke in the subacute phase were enrolled and trained for one month with virtual art therapy (VAT) and physiotherapy. Their data were compared with those of ten patients matched for pathology, age and clinical parameters, trained only with conventional therapy for the same amount of time. The VAT group showed a significantly higher improvements in the Barthel Index score, a measure of independency in activities of daily living (66 ± 33% vs. 31 ± 28%, p = 0.021), and in pinching strength (66 ± 39% vs. 18 ± 33%, p = 0.008), with respect to the group treated with conventional rehabilitation.

How uncertain are you? Disentangling expected and unexpected uncertainty in pupil-linked brain arousal during reversal learning.

During decision making, we are continuously faced with two sources of uncertainty regarding the links between stimuli, our actions, and outcomes. On the one hand, our expectations are often probabilistic, that is, stimuli or actions yield the expected outcome only with a certain probability (expected uncertainty). On the other hand, expectations might become invalid due to sudden, unexpected changes in the environment (unexpected uncertainty). Several lines of research show that pupil-linked brain arousal is a sensitive indirect measure of brain mechanisms underlying uncertainty computations. Thus, we investigated whether it is involved in disentangling these two forms of uncertainty. To this aim, we measured pupil size during a probabilistic reversal learning task. In this task, participants had to figure out which of two response options led to reward with higher probability, whereby sometimes the identity of the more advantageous response option was switched. Expected uncertainty was manipulated by varying the reward probability of the advantageous choice option, whereas the level of unexpected uncertainty was assessed by using a Bayesian computational model estimating change probability and resulting uncertainty. We found that both aspects of unexpected uncertainty influenced pupil responses, confirming that pupil-linked brain arousal is involved in model updating after unexpected changes in the environment. Furthermore, high level of expected uncertainty impeded the detection of sudden changes in the environment, both on physiological and behavioral level. These results emphasize the role of pupil-linked brain arousal and underlying neural structures in handling situations in which the previously established contingencies are no longer valid.

Activation of brain arousal networks coincident with eye blinks during resting state.

Eye-blinking has been implicated in arousal and attention. Here we test the hypothesis that blinking-moments represent arousal surges associated with activation of the ascending arousal network (AAN) and its thalamic projections. For this purpose, we explored the temporal relationship between eye-blinks and fMRI BOLD activity in AAN and thalamic nuclei, as well as whole brain cluster corrected activations during eyes-open, resting-state fMRI scanning. We show that BOLD activations in the AAN nuclei peaked prior to the eye blinks and in thalamic nuclei peaked prior to and during the blink, consistent with the role of eye blinking in arousal surges. Additionally, we showed visual cortex peak activation prior to the eye blinks, providing further evidence of the visual cortex's role in arousal, and document cerebellar peak activation post eye blinks, which might reflect downstream engagement from arousal surges.

Transcranial Direct Current Stimulation-based Neuromodulation Improves the Performance of Brain-Computer Interfaces Based on Steady-State Visual Evoked Potential.

The study of brain state estimation and intervention methods is of great significance for the utility of brain-computer interfaces (BCIs). In this paper, a neuromodulation technology using transcranial direct current stimulation (tDCS) is explored to improve the performance of steady-state visual evoked potential (SSVEP)-based BCIs. The effects of pre-stimulation, sham-tDCS and anodal-tDCS are analyzed through a comparison of the EEG oscillations and fractal component characteristics. In addition, in this study, a novel brain state estimation method is introduced to assess neuromodulation-induced changes in brain arousal for SSVEP-BCIs. The results suggest that tDCS, and anodal-tDCS in particular, can be used to increase SSVEP amplitude and further improve the performance of SSVEP-BCIs. Furthermore, evidence from fractal features further validates that tDCS-based neuromodulation induces an increased level of brain state arousal. The findings of this study provide insights into the improvement of BCI performance based on personal state interventions and provide an objective method for quantitative brain state monitoring that may be used for EEG modeling of SSVEP-BCIs.

Effects of remifentanil on brain responses to noxious stimuli during deep propofol sedation

BackgroundThe safety of anaesthesia has improved as a result of better control of anaesthetic depth. However, conventional monitoring does not inform on the nature of nociceptive processes during unconsciousness. A means of inferring the quality of potentially painful experiences could derive from analysis of brain activity using neuroimaging. We have evaluated the dose effects of remifentanil on brain response to noxious stimuli during deep sedation and spontaneous breathing. MethodsOptimal data were obtained in 26 healthy subjects. Pressure stimulation that proved to be moderately painful before the experiment was applied to the thumbnail. Functional MRI was acquired in 4-min periods at low (0.5 ng ml−1), medium (1 ng ml−1), and high (1.5 ng ml−1) target plasma concentrations of remifentanil at a stable background infusion of propofol adjusted to induce a state of light unconsciousness. ResultsAt low remifentanil doses, we observed partial activation in brain areas processing sensory-discriminative and emotional-affective aspects of pain. At medium doses, relevant changes were identified in structures highly sensitive to general brain arousal, including the brainstem, cerebellum, thalamus, auditory and visual cortices, and the frontal lobe. At high doses, no significant activation was observed. ConclusionsThe response to moderately intense focal pressure in pain-related brain networks is effectively eliminated with safe remifentanil doses. However, the safety margin in deep sedation-analgesia would be narrowed in minimising not only nociceptive responses, but also arousal-related biological stress.

Resting state electroencephalographic rhythms are affected by immediately preceding memory demands in cognitively unimpaired elderly and patients with mild cognitive impairment.

Experiments on event-related electroencephalographic oscillations in aged people typically include blocks of cognitive tasks with a few minutes of interval between them. The present exploratory study tested the effect of being engaged on cognitive tasks over the resting state cortical arousal after task completion, and whether it differs according to the level of the participant's cognitive decline. To investigate this issue, we used a local database including data in 30 healthy cognitively unimpaired (CU) persons and 40 matched patients with amnestic mild cognitive impairment (aMCI). They had been involved in 2 memory tasks for about 40 min and underwent resting-state electroencephalographic (rsEEG) recording after 5 min from the task end. eLORETA freeware estimated rsEEG alpha source activity as an index of general cortical arousal. In the CU but not aMCI group, there was a negative correlation between memory tasks performance and posterior rsEEG alpha source activity. The better the memory tasks performance, the lower the posterior alpha activity (i.e., higher cortical arousal). There was also a negative correlation between neuropsychological test scores of global cognitive status and alpha source activity. These results suggest that engagement in memory tasks may perturb background brain arousal for more than 5 min after the tasks end, and that this effect are dependent on participants global cognitive status. Future studies in CU and aMCI groups may cross-validate and extend these results with experiments including (1) rsEEG recordings before memory tasks and (2) post-tasks rsEEG recordings after 5, 15, and 30 min.