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Background Management of high-risk newborns should involve the use of standardized protocols and training, continuous and specialized brain monitoring with electroencephalography (EEG), amplitude integrated EEG, Near Infrared Spectroscopy, and neuroimaging. Brazil is a large country with disparities in health care assessment and some neonatal intensive care units (NICUs) are not well structured with trained personnel able to provide adequate neurocritical care. To reduce this existing gap, an advanced telemedicine model of neurocritical care called Protecting Brains and Saving Futures (PBSF) Guidelines was developed and implemented in a group of Brazilian NICUs. Methods A prospective, multicenter, and observational study will be conducted in all 20 Brazilian NICUs using the PBSF Guidelines as standard-of-care. All infants treated accordingly to the guidelines during Dec 2021 to Nov 2024 will be eligible. Ethical approval was obtained from participating centers. The primary objective is to describe adherence to the PBSF Guidelines and clinical outcomes, by center and over a 3-year period. Adherence will be measured by quantification of neuromonitoring, neuroimaging exams, sub-specialties consultation, and clinical case discussions and videoconference meetings. Clinical outcomes of interest are detection of seizures during hospitalization, use of anticonvulsants, inotropes, and fluid resuscitation, death before hospital discharge, length of hospital stay, and referral of patients to specialized follow-up. Discussion The study will provide evaluation of PBSF Guidelines adherence and its impact on clinical outcomes. Thus, data from this large prospective, multicenter, and observational study will help determine whether neonatal neurocritical care via telemedicine can be effective. Ultimately, it may offer the necessary framework for larger scale implementation and development of research projects using remote neuromonitoring. Trial registration NCT03786497, Registered 26 December 2018, https://www.clinicaltrials.gov/ct2/show/NCT03786497?term=protecting+brains+and+saving+futures&draw=2&rank=1.

Background Mal de Débarquement Syndrome (MdDS) is a medically refractory neurotological disorder characterized by persistent oscillating vertigo that follows a period of entrainment to oscillating motion such as experienced during sea or air travel. Fronto-occipital hypersynchrony may correlate with MdDS symptom severity. Materials and methods Individuals with treatment refractory MdDS lasting at least 6 months received single administrations of three fronto-occipital transcranial alternating current stimulation (tACS) protocols in an “n-of-1” double-blind randomized design: alpha frequency anti-phase, alpha-frequency in-phase, and gamma frequency control. Baseline assessments were made on Day 1. The treatment protocol that led to the most acute reduction in symptoms during a test session on Day 2 was administered for 10–12 stacked sessions given on Days 3 through 5 (20-minutes at 2-4mA). Pre to post symptom changes were assessed on Day 1 and Day 5. Participants who could clearly choose a preferred protocol on Day 2 did better on Day 5 than those who could not make a short-term determination on Day 2 and either chose a protocol based on minimized side effects or were randomized to one of the three protocols. In addition, weekly symptom assessments were made for four baseline and seven post stimulation points for the Dizziness Handicap Inventory (DHI), MdDS Balance Rating Scale (MBRS), and Hospital Anxiety and Depression Scale (HADS). Results Of 24 participants, 13 chose anti-phase, 7 chose in-phase, and 4 chose control stimulation. Compared to baseline, 10/24 completers noted ≥ 25% reduction, 5/24 ≥50% reduction, and 2/24 ≥75% reduction in oscillating vertigo intensity from Day 1 to Day 5. Stimulating at a frequency slightly higher than the individual alpha frequency (IAF) was better than stimulating at exactly the IAF, and slightly better than stimulating with a strategy of standardized stimulation at 10Hz. A one-way repeated measures ANOVA of weekly DHI, MBRS, and HADS measurements showed significant reductions immediately after treatment with improvement increasing through post-treatment week 6. Conclusion Fronto-occipital tACS may be effective in reducing the oscillating vertigo of MdDS and serve as a portable neuromodulation alternative for longer-term treatment. Stimulation frequency relative to the IAF may be important in determining the optimum treatment protocol [ClinicalTrials.gov study NCT02540616. https://clinicaltrials.gov/ct2/show/NCT02540616].

Rhythmic neuronal network activity underlies brain oscillations. To investigate how connected neuronal networks contribute to the emergence of the α-band and to the regulation of Up and Down states, we study a model based on synaptic short-term depression-facilitation with afterhyperpolarization (AHP). We found that the α-band is generated by the network behavior near the attractor of the Up-state. Coupling inhibitory and excitatory networks by reciprocal connections leads to the emergence of a stable α-band during the Up states, as reflected in the spectrogram. To better characterize the emergence and stability of thalamocortical oscillations containing α and δ rhythms during anesthesia, we model the interaction of two excitatory networks with one inhibitory network, showing that this minimal topology underlies the generation of a persistent α-band in the neuronal voltage characterized by dominant Up over Down states. Finally, we show that the emergence of the α-band appears when external inputs are suppressed, while fragmentation occurs at small synaptic noise or with increasing inhibitory inputs. To conclude, α-oscillations could result from the synaptic dynamics of interacting excitatory neuronal networks with and without AHP, a principle that could apply to other rhythms., Author summary Brain oscillations, recorded from electroencephalograms characterize behaviors such as sleep, wakefulness, brain evoked responses, coma or anesthesia. The underlying rhythms for these oscillations are associated at a neuronal population level to fluctuations of the membrane potential between Up (depolarized) and Down (hyperpolarized) states. During anesthesia with propofol, a dominant α-band (8–12Hz) can emerge or disappear, but the underlying mechanism remains unclear. Using modeling, we report that the α-band appears during Up states in neuronal populations driven by short-term synaptic plasticity and synaptic noise. Moreover, we show that three connected neuronal networks representing the thalamocortical loop reproduce the dynamics of the α-band, which emerges following the arrest of excitatory stimulations, but that can disappear by increasing inhibitory inputs. To conclude, short-term plasticity in well connected neuronal networks can explain the emergence and fragmentation of the α-band.

Sleep deprivation (SD) leads to impairments in cognitive function. Here, we tested the hypothesis that cognitive changes in the sleep-deprived brain can be explained by information processing within and between large-scale cortical networks. We acquired functional magnetic resonance imaging (fMRI) scans of 20 healthy volunteers during attention and executive tasks following a regular night of sleep, a night of SD, and a recovery nap containing nonrapid eye movement (NREM) sleep. Overall, SD was associated with increased cortex-wide functional integration, driven by a rise of integration within cortical networks. The ratio of within versus between network integration in the cortex increased further in the recovery nap, suggesting that prolonged wakefulness drives the cortex towards a state resembling sleep. This balance of integration and segregation in the sleep-deprived state was tightly associated with deficits in cognitive performance. This was a distinct and better marker of cognitive impairment than conventional indicators of homeostatic sleep pressure, as well as the pronounced thalamocortical connectivity changes that occurs towards falling asleep. Importantly, restoration of the balance between segregation and integration of cortical activity was also related to performance recovery after the nap, demonstrating a bidirectional effect. These results demonstrate that intra- and interindividual differences in cortical network integration and segregation during task performance may play a critical role in vulnerability to cognitive impairment in the sleep-deprived state., Can the cognitive changes that result from sleep deprivation be explained by information processing within and between large-scale networks in the brain? This study shows that the ratio of within- vs between-network integration is tightly associated with deficits in cognitive performance.

The ability to navigate “cocktail party” situations by focusing on sounds of interest over irrelevant, background sounds is often considered in terms of cortical mechanisms. However, subcortical circuits such as the pathway underlying the medial olivocochlear (MOC) reflex modulate the activity of the inner ear itself, supporting the extraction of salient features from auditory scene prior to any cortical processing. To understand the contribution of auditory subcortical nuclei and the cochlea in complex listening tasks, we made physiological recordings along the auditory pathway while listeners engaged in detecting non(sense) words in lists of words. Both naturally spoken and intrinsically noisy, vocoded speech—filtering that mimics processing by a cochlear implant (CI)—significantly activated the MOC reflex, but this was not the case for speech in background noise, which more engaged midbrain and cortical resources. A model of the initial stages of auditory processing reproduced specific effects of each form of speech degradation, providing a rationale for goal-directed gating of the MOC reflex based on enhancing the representation of the energy envelope of the acoustic waveform. Our data reveal the coexistence of 2 strategies in the auditory system that may facilitate speech understanding in situations where the signal is either intrinsically degraded or masked by extrinsic acoustic energy. Whereas intrinsically degraded streams recruit the MOC reflex to improve representation of speech cues peripherally, extrinsically masked streams rely more on higher auditory centres to denoise signals., Understanding speech in background noise is critical to human communication. This study highlights a critical role for neural feedback circuits that modulate the activity of the inner ear, enabling effective listening to degraded speech.

Accumulating evidence from human-based research has highlighted that the prevalent one-size-fits-all approach for neural and behavioral interventions is inefficient. This approach can benefit one individual, but be ineffective or even detrimental for another. Studying the efficacy of the large range of different parameters for different individuals is costly, time-consuming and requires a large sample size that makes such research impractical and hinders effective interventions. Here an active machine learning technique is presented across participants—personalized Bayesian optimization (pBO)—that searches available parameter combinations to optimize an intervention as a function of an individual’s ability. This novel technique was utilized to identify transcranial alternating current stimulation (tACS) frequency and current strength combinations most likely to improve arithmetic performance, based on a subject’s baseline arithmetic abilities. The pBO was performed across all subjects tested, building a model of subject performance, capable of recommending parameters for future subjects based on their baseline arithmetic ability. pBO successfully searches, learns, and recommends parameters for an effective neurointervention as supported by behavioral, simulation, and neural data. The application of pBO in human-based research opens up new avenues for personalized and more effective interventions, as well as discoveries of protocols for treatment and translation to other clinical and non-clinical domains., Author summary The common one-size-fits-all approach used in biological and behavioral research has shown to be inefficient. This is especially the case in the field of brain stimulation, where many different combinations of stimulation parameters (i.e., frequency and current strength of the applied current) can be used for restorative or enhancement purposes, in clinical and non-clinical populations, respectively. Even intervention protocols that have reported to be effective for certain individuals can be detrimental for others. Here we present an active machine learning method, personalized Bayesian optimization (pBO) that successfully searches, learns, and recommends neurostimulation parameters across individuals. Based on an individual’s baseline cognitive ability, the pBO identifies specific combinations of transcranial alternating current stimulation parameters, which are most likely to improve cognitive performance, in which case arithmetic problem solving. This timely approach provides a possible solution for the pressing need for personalization in different disciplines including medicine, psychology, and education.

A number of neuroimaging techniques have been employed to understand how visual information is transformed along the visual pathway. Although each technique has spatial and temporal limitations, they can each provide important insights into the visual code. While the BOLD signal of fMRI can be quite informative, the visual code is not static and this can be obscured by fMRI’s poor temporal resolution. In this study, we leveraged the high temporal resolution of EEG to develop an encoding technique based on the distribution of responses generated by a population of real-world scenes. This approach maps neural signals to each pixel within a given image and reveals location-specific transformations of the visual code, providing a spatiotemporal signature for the image at each electrode. Our analyses of the mapping results revealed that scenes undergo a series of nonuniform transformations that prioritize different spatial frequencies at different regions of scenes over time. This mapping technique offers a potential avenue for future studies to explore how dynamic feedforward and recurrent processes inform and refine high-level representations of our visual world., Author summary The visual information that we sample from our environment undergoes a series of neural modifications, with each modification state (or visual code) consisting of a unique distribution of responses across neurons along the visual pathway. However, current noninvasive neuroimaging techniques provide an account of that code that is coarse with respect to time or space. Here, we present dynamic electrode-to-image (DETI) mapping, an analysis technique that capitalizes on the high temporal resolution of EEG to map neural signals to each pixel within a given image to reveal location-specific modifications of the visual code. The DETI technique reveals maps of features that are associated with the neural signal at each pixel and at each time point. DETI mapping shows that real-world scenes undergo a series of nonuniform modifications over both space and time. Specifically, we find that the visual code varies in a location-specific manner, likely reflecting that neural processing prioritizes different features at different image locations over time. DETI mapping therefore offers a potential avenue for future studies to explore how each modification state informs and refines the conceptual meaning of our visual world.

Evidence accumulation models provide a dominant account of human decision-making, and have been particularly successful at explaining behavioral and neural data in laboratory paradigms using abstract, stationary stimuli. It has been proposed, but with limited in-depth investigation so far, that similar decision-making mechanisms are involved in tasks of a more embodied nature, such as movement and locomotion, by directly accumulating externally measurable sensory quantities of which the precise, typically continuously time-varying, magnitudes are important for successful behavior. Here, we leverage collision threat detection as a task which is ecologically relevant in this sense, but which can also be rigorously observed and modelled in a laboratory setting. Conventionally, it is assumed that humans are limited in this task by a perceptual threshold on the optical expansion rate–the visual looming–of the obstacle. Using concurrent recordings of EEG and behavioral responses, we disprove this conventional assumption, and instead provide strong evidence that humans detect collision threats by accumulating the continuously time-varying visual looming signal. Generalizing existing accumulator model assumptions from stationary to time-varying sensory evidence, we show that our model accounts for previously unexplained empirical observations and full distributions of detection response. We replicate a pre-response centroparietal positivity (CPP) in scalp potentials, which has previously been found to correlate with accumulated decision evidence. In contrast with these existing findings, we show that our model is capable of predicting the onset of the CPP signature rather than its buildup, suggesting that neural evidence accumulation is implemented differently, possibly in distinct brain regions, in collision detection compared to previously studied paradigms., Author summary Evidence accumulation models of decision-making propose that humans accumulate noisy sensory evidence over time up to a decision threshold. We demonstrate that this type of model can describe human behavior well not only in abstract, semi-static laboratory tasks, but also in a task that is relevant to human movement in the real world. Specifically, we show that a model directly accumulating the continuously time-varying visual looming (optical expansion) of an approaching obstacle explains full probability distributions of when humans can detect this collision threat. Using electroencephalography, we find indications that this type of evidence is accumulated differently in the brain compared to evidence accumulation in previously studied, more abstract tasks. Our experimental paradigm, model, and findings open for wider application of this type of decision-making model to laboratory and real-world tasks with ecologically relevant, time-varying sensory evidence, and further studies into how such decisions are implemented neurally. There are also societal implications: In applied safety research and traffic accident litigation it is conventionally assumed that human collision detection is limited by a fixed perceptual threshold, an assumption that our results show to be highly inaccurate.

Despite the clear importance of language in our life, our vital ability to quickly and effectively learn new words and meanings is neurobiologically poorly understood. Conventional knowledge maintains that language learning—especially in adulthood—is slow and laborious. Furthermore, its structural basis remains unclear. Even though behavioural manifestations of learning are evident near instantly, previous neuroimaging work across a range of semantic categories has largely studied neural changes associated with months or years of practice. Here, we address rapid neuroanatomical plasticity accompanying new lexicon acquisition, specifically focussing on the learning of action-related language, which has been linked to the brain’s motor systems. Our results show that it is possible to measure and to externally modulate (using transcranial magnetic stimulation (TMS) of motor cortex) cortical microanatomic reorganisation after mere minutes of new word learning. Learning-induced microstructural changes, as measured by diffusion kurtosis imaging (DKI) and machine learning-based analysis, were evident in prefrontal, temporal, and parietal neocortical sites, likely reflecting integrative lexico-semantic processing and formation of new memory circuits immediately during the learning tasks. These results suggest a structural basis for the rapid neocortical word encoding mechanism and reveal the causally interactive relationship of modal and associative brain regions in supporting learning and word acquisition., This combined neuroimaging and brain stimulation study reveals rapid and distributed microstructural plasticity after a single immersive language learning session, demonstrating the causal relevance of the motor cortex in encoding the meaning of novel action words.

Short-latency afferent inhibition (SAI) and long-latency afferent inhibition (LAI) occur when the motor evoked potential (MEP) elicited by transcranial magnetic stimulation (TMS) is reduced by the delivery of a preceding peripheral nerve stimulus. The intra-individual variability in SAI and LAI is considerable, and the influence of sample demographics (e.g., age and biological sex) and testing context (e.g., time of day) is not clear. There are also no established normative values for these measures, and their reliability varies from study-to-study. To address these issues and facilitate the interpretation of SAI and LAI research, we pooled data from studies published by our lab between 2014 and 2020 and performed several retrospective analyses. Patterns in the depth of inhibition with respect to age, biological sex and time of testing were investigated, and the relative reliability of measurements from studies with repeated baseline SAI and LAI assessments was examined. Normative SAI and LAI values with respect to the mean and standard deviation were also calculated. Our data show no relationship between the depth of inhibition for SAI and LAI with either time of day or age. Further, there was no significant difference in SAI or LAI between males and females. Intra-class correlation coefficients (ICC) for repeated measurements of SAI and LAI ranged from moderate (ICC = 0.526) to strong (ICC = 0.881). The mean value of SAI was 0.71 ± 0.27 and the mean value of LAI was 0.61 ± 0.34. This retrospective study provides normative values, reliability estimates, and an exploration of demographic and testing influences on these measures as assessed in our lab. To further facilitate the interpretation of SAI and LAI data, similar studies should be performed by other labs that use these measures.

Transcranial magnetic stimulation (TMS) is a non-invasive neurostimulation technique that is increasingly used in the treatment of neuropsychiatric disorders and neuroscience research. Due to the complex structure of the brain and the electrical conductivity variation across subjects, identification of subject-specific brain regions for TMS is important to improve the treatment efficacy and understand the mechanism of treatment response. Numerical computations have been used to estimate the stimulated electric field (E-field) by TMS in brain tissue. But the relative long computation time limits the application of this approach. In this paper, we propose a deep-neural-network based approach to expedite the estimation of whole-brain E-field by using a neural network architecture, named 3D-MSResUnet and multimodal imaging data. The 3D-MSResUnet network integrates the 3D U-net architecture, residual modules and a mechanism to combine multi-scale feature maps. It is trained using a large dataset with finite element method (FEM) based E-field and diffusion magnetic resonance imaging (MRI) based anisotropic volume conductivity or anatomical images. The performance of 3D-MSResUnet is evaluated using several evaluation metrics and different combinations of imaging modalities and coils. The experimental results show that the output E-field of 3D-MSResUnet provides reliable estimation of the E-field estimated by the state-of-the-art FEM method with significant reduction in prediction time to about 0.24 second. Thus, this study demonstrates that neural networks are potentially useful tools to accelerate the prediction of E-field for TMS targeting.

We investigated modality differences in the N2 and P3 components of event-related potentials (ERPs) between somatosensory and auditory Go/No-go paradigms in eighteen healthy prepubescent children (mean age: 125.9±4.2 months). We also evaluated the relationship between behavioral responses (reaction time, reaction time variability, and omission and commission error rates) and amplitudes and latencies of N2 and P3 during somatosensory and auditory Go/No-go paradigms. The peak latency of No-go-N2 was significantly shorter than that of Go-N2 during somatosensory paradigms, but not during auditory paradigms. The peak amplitude of P3 was significantly larger during somatosensory than auditory paradigms, and the peak latency of P3 was significantly shorter during somatosensory than auditory paradigms. Correlations between behavioral responses and the P3 component were not found during somatosensory paradigms. On the other hand, in auditory paradigms, correlations were detected between the reaction time and peak amplitude of No-go-P3, and between the reaction time variability and peak latency of No-go-P3. A correlation was noted between commission error and the peak latency of No-go-N2 during somatosensory paradigms. Compared with previous adult studies using both somatosensory and auditory Go/No-go paradigms, the relationships between behavioral responses and ERP components would be weak in prepubescent children. Our data provide findings to advance understanding of the neural development of motor execution and inhibition processing, that is dependent on or independent of the stimulus modality.

The purpose of current study is to reveal spatiotemporal features of oscillatory EEG activities in response to emotional arousal induced by emotional video stimuli, and to find the characteristics of cortical activities showing significant difference according to arousal levels. The EEGs recorded during watching affective video clips were transformed to cortical current density time-series, and then, cluster-based permutation test was applied to determine the spatiotemporal origins of alpha- and beta-band activities showing significant difference between high and low arousal levels. We found stronger desynchronization of alpha-band activities due to higher arousal in visual areas, which may be due to stronger activation for sensory information processing for the highly arousing video stimuli. In precentral and superior parietal regions, the stronger desynchronization in alpha-and low beta-bands was observed for the high arousal stimuli. This is expected to reflect enhanced mirror neuron system activities, which is involved in understanding the intention of other’s action. Similar changes according to arousal level were found also in inter-regional phase synchronization in alpha- and beta-bands.

Category-specific impairments witnessed in patients with semantic deficits have broadly dissociated into natural and artificial kinds. However, how the category of food (more specifically, fruits and vegetables) fits into this distinction has been difficult to interpret, given a pattern of deficit that has inconsistently mapped onto either kind, despite its intuitive membership to the natural domain. The present study explores the effects of a manipulation of a visual sensory (i.e., color) or functional (i.e., orientation) feature on the consequential semantic processing of fruits and vegetables (and tools, by comparison), first at the behavioral and then at the neural level. The categorization of natural (i.e., fruits/vegetables) and artificial (i.e., utensils) entities was investigated via cross–modal priming. Reaction time analysis indicated a reduction in priming for color-modified natural entities and orientation-modified artificial entities. Standard event-related potentials (ERP) analysis was performed, in addition to linear classification. For natural entities, a N400 effect at central channel sites was observed for the color-modified condition compared relative to normal and orientation conditions, with this difference confirmed by classification analysis. Conversely, there was no significant difference between conditions for the artificial category in either analysis. These findings provide strong evidence that color is an integral property to the categorization of fruits/vegetables, thus substantiating the claim that feature-based processing guides as a function of semantic category.

Background Repetitive Transcranial Magnetic Stimulation [rTMS] is increasingly being used to treat Major Depressive Disorder [MDD]. Given that not all patients respond to rTMS, it would be clinically useful to have reliable biomarkers that predict treatment response. Oxidized phosphatidylcholine [OxPC] and some oxylipins are important plasma biomarkers of oxidative stress and inflammation. Not only is depression associated with oxidative stress, but rTMS has been shown to have anti-oxidative effects. Objectives To investigate whether plasma oxolipidomics profiles could predict treatment response in patients with treatment resistant MDD. Methods Fourty-eight patients undergoing rTMS treatment for MDD were recruited along with nine healthy control subjects. Plasma OxPCs and oxylipins were extracted and analyzed through high performance liquid chromatography coupled with mass spectrometry. Patients with a Hamilton Depression Rating Scale score [Ham-D] ≤7 post-treatment were defined as having entered remission. Results Fifty-seven OxPC and 32 oxylipin species were identified in our subjects. MDD patients who entered remission following rTMS had significantly higher pre-rTMS levels of total and fragmented OxPCs compared to non-remitters and controls [one-way ANOVA, p0.05]. No differences in plasma oxylipins were found between remitters and non-remitters at baseline. Conclusion Certain categories of OxPCs may be useful predictive biomarkers for response to rTMS treatment in MDD. Given that elevated oxidized lipids may indicate higher levels of oxidative stress and inflammation in the brain, patients with this phenotype of depression may be more receptive to rTMS treatment.

Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for idiopathic Parkinson’s disease. Despite recent progress, the mechanisms responsible for the technique’s effectiveness have yet to be fully elucidated. The purpose of the present study was to gain new insights into the interactions between STN-DBS and cortical network activity. We therefore combined high-resolution functional near-infrared spectroscopy with low-resolution electroencephalography in seven Parkinsonian patients on STN-DBS, and measured cortical haemodynamic changes at rest and during hand movement in the presence and absence of stimulation (the ON-stim and OFF-stim conditions, respectively) in the off-drug condition. The relative changes in oxyhaemoglobin [HbO], deoxyhaemoglobin [HbR], and total haemoglobin [HbT] levels were analyzed continuously. At rest, the [HbO], [HbR], and [HbT] over the bilateral sensorimotor (SM), premotor (PM) and dorsolateral prefrontal (DLPF) cortices decreased steadily throughout the duration of stimulation, relative to the OFF-stim condition. During hand movement in the OFF-stim condition, [HbO] increased and [HbR] decreased concomitantly over the contralateral SM cortex (as a result of neurovascular coupling), and [HbO], [HbR], and [HbT] increased concomitantly in the dorsolateral prefrontal cortex (DLPFC)—suggesting an increase in blood volume in this brain area. During hand movement with STN-DBS, the increase in [HbO] was over the contralateral SM and PM cortices was significantly lower than in the OFF-stim condition, as was the decrease in [HbO] and [HbT] in the DLPFC. Our results indicate that STN-DBS is associated with a reduction in blood volume over the SM, PM and DLPF cortices, regardless of whether or not the patient is performing a task. This particular effect on cortical networks might explain not only STN-DBS’s clinical effectiveness but also some of the associated adverse effects.

Although investigation of the brains of criminals began quite early in the history of psychophysiological research, little is known about brain plasticity of offenders with psychopathy. Building on our preliminary study reporting successful brain self-regulation using slow cortical potential (SCP) neurofeedback in offenders with psychopathy, we investigated the central nervous and autonomic peripheral changes occurring after brain self-regulation in a group of severe male offenders with psychopathy. Regarding the central nervous system, an overall suppression of the psychopathic overrepresentation of slow frequency bands was found, such as delta and theta band activity, after EEG neurofeedback. In addition, an increase in alpha band activity could be observed after the SCP self-regulation training. Electrodermal activity adaptively changed according to the regulation task, and this flexibility improved over training time. The results of this study point towards a constructive learning process and plasticity in neural and peripheral measures of offenders with psychopathy.

Background Non-convulsive status epilepticus (NCSE) often goes unnoticed and is not easily detected in patients with a decreased level of consciousness, especially in older patients. In this sense, lack of data in this population is available. Aims The aim of the present study was to examine daily clinical practice and evaluate factors that may influence the prognosis of NCSE in non-epileptic medical inpatients. Methods We conducted a retrospective analysis including patients admitted by any cause in an Internal Medicine ward. All patients with compatible symptoms, exclusion of other causes, clinical suspicion or diagnosis of NCSE, and compatible EEG were included. Patients with a previous diagnosis of epilepsy were excluded. We also conducted a literature review by searching the PubMed/Medline database with the terms: Nonconvulsive Status OR Non-Convulsive Status. Results We included 54 patients, mortality rate reached 37% and the main factors linked to it were hypernatremia (OR = 16.2; 95% CI, 1.6–165.6; P = 0.019) and atrial fibrillation (OR = 6.7; 95% CI, 1.7–26; P = 0.006). There were no differences regarding mortality when comparing different diagnosis approach or treatment regimens. Our literature review showed that the main etiology of NCSE were neurovascular causes (17.8%), followed by antibiotic treatment (17.2%) and metabolic causes (17%). Global mortality in the literature review, excluding our series, reached 20%. Discussion We present the largest series of NCSE cases in medical patients, which showed that this entity is probably misdiagnosed in older patients and is linked to a high mortality. Conclusion The presence of atrial fibrillation and hypernatremia in patients diagnosed with NCSE should advise physicians of a high mortality risk.

In the Simon task, participants perform a decision on non-spatial features (e.g., stimulus color) by responding with a left or right key-press to a stimulus presented on the left or right side of the screen. In the flanker task, they classify the central character while ignoring the flanking characters. In each task, there is a conflict between the response-relevant features and the response-irrelevant features (i.e., the location on the screen for the Simon task, and the flankers for the flanker task). Thus, in both tasks, resolving conflict requires to inhibit irrelevant features and to focus on relevant features. When both tasks were combined within the same trial (e.g., when the row of characters was presented on the left or right side of the screen), most previous research has shown an interaction. In the present study, we investigated whether this interaction is affected by a multiplicative priming of the correct response occurring when both Simon and flanker irrelevant features co-activate the correct response (Exp. 1), a spatial overlap between Simon and flanker features (Exp. 2), and the learning of stimulus-response pairings (Exp. 3). The results only show an impact of multiplicative priming.

Objective Cognitive impairments are a frequent and difficult to treat symptom in patients with schizophrenia and the strongest predictor for a successful reintegration in occupational and everyday life. Recent research suggests transcranial direct current stimulation (tDCS) to enhance cognition in this patient group. However, the question regarding its acute effectiveness on executive functions remains largely unanswered. Here, we examined in a randomized, double blind, sham-controlled repeated-measures design the impact of tDCS on performance in several executive functions in patients with schizophrenia, schizoaffective disorder or acute transient psychotic disorder. Methods Patients (N = 48) were tested twice using standardized, well-constructed and clinically validated neuropsychological tests assessing verbal working memory, response inhibition, mental flexibility and problem solving. In session 1 they solely underwent the neuropsychological assessment, whereas in session 2 they additionally received 2 mA of anodal tDCS stimulation over the left dorsolateral prefrontal cortex (DLPFC), cathode right supraorbital ridge, or sham stimulation for 20 minutes. Results Patients of both groups were not able to correctly discriminate the type of stimulation received confirming the success of the blinding procedure. However, analyzing the whole sample the change in performance from session 1 to session 2 was the same in the verum as in the sham condition (all p >.5). Moreover, a subsequent exploratory analysis showed that performance in the response inhibition task was worse for patients that engaged in the task within 20 minutes after the end of the verum stimulation. Conclusion Hence, 2 mA of anodal tDCS applied over the left DLPFC did not acutely enhance executive functions in patients with schizophrenia or related disorders but impaired performance in the response inhibition task shortly after. Future studies should continue to seek for effective stimulation configurations for this patient group. Clinical trial registration The study is registered in the “Deutsches Register Klinischer Studien DRKS”, German Clinical Trial Register and has been allocated the following number: DRKS00022126.

Funder: CHDI Foundation; funder-id: http://dx.doi.org/10.13039/100005725, Sleep disturbance is a common and disruptive symptom of neurodegenerative diseases such as Alzheimer’s and Huntington’s disease (HD). In HD patients, sleep fragmentation appears at an early stage of disease, although features of the earliest sleep abnormalities in presymptomatic HD are not fully established. Here we used novel automated analysis of quantitative electroencephalography to study transitions between wake and non-rapid eye movement sleep in a sheep model of presymptomatic HD. We found that while the number of transitions between sleep and wake were similar in normal and HD sheep, the dynamics of transitions from sleep-to-wake differed markedly between genotypes. Rather than the gradual changes in EEG power that occurs during transitioning from sleep-to-wake in normal sheep, transition into wake was abrupt in HD sheep. Furthermore, transitions to wake in normal sheep were preceded by a significant reduction in slow wave power, whereas in HD sheep this prior reduction in slow wave power was far less pronounced. This suggests an impaired ability to prepare for waking in HD sheep. The abruptness of awakenings may also have potential to disrupt sleep-dependent processes if they are interrupted in an untimely and disjointed manner. We propose that not only could these abnormal dynamics of sleep transitions be useful as an early biomarker of HD, but also that our novel methodology would be useful for studying transition dynamics in other sleep disorders.

Previous studies have suggested that virtual reality (VR) can elicit emotions in different visual modes using 2D or 3D headsets. However, the effects on emotional arousal by using these two visual modes have not been comprehensively investigated, and the underlying neural mechanisms are not yet clear. This paper presents a cognitive psychological experiment that was conducted to analyze how these two visual modes impact emotional arousal. Forty volunteers were recruited and were randomly assigned to two groups. They were asked to watch a series of positive, neutral and negative short VR videos in 2D and 3D. Multichannel electroencephalograms (EEG) and skin conductance responses (SCR) were recorded simultaneously during their participation. The results indicated that emotional stimulation was more intense in the 3D environment due to the improved perception of the environment; greater emotional arousal was generated; and higher beta (21–30 Hz) EEG power was identified in 3D than in 2D. We also found that both hemispheres were involved in stereo vision processing and that brain lateralization existed in the processing.

Studies investigating the neural mechanisms of time perception often measure brain activity while participants perform a temporal task. However, several of these studies are based exclusively on tasks in which time is relevant, making it hard to dissociate activity related to decisions about time from other task-related patterns. In the present study, human participants performed a temporal or color discrimination task of visual stimuli. Participants were informed which magnitude they would have to judge before or after presenting the two stimuli (S1 and S2) in different blocks. Our behavioral results showed, as expected, that performance was better when participants knew beforehand which magnitude they would judge. Electrophysiological data (EEG) was analyzed using Linear Discriminant Contrasts (LDC) and a Representational Similarity Analysis (RSA) approach to investigate whether and when information about time and color was encoded. During the presentation of S1, we did not find consistent differences in EEG activity as a function of the task. On the other hand, during S2, we found that temporal and color information was encoded in a task-relevant manner. Taken together, our results suggest that task goals strongly modulate decision-related information in EEG activity.

Universal primary education is critical for individual academic growth and overall adult productivity of nations. Estimates indicate that 25% of 59 million primary age out of school children drop out and early grade failure is one of the factors. An objective and feasible screening measure to identify at-risk children in the early grades can help to design appropriate interventions. The objective of this study was to use a Machine Learning algorithm to evaluate the power of Electroencephalogram (EEG) data collected at age 4 in predicting academic achievement at age 8 among rural children in Pakistan. Demographic and EEG data from 96 children of a cohort along with their academic achievement in grade 1–2 measured using an academic achievement test of Math and language at the age of 7–8 years was used to develop the machine learning algorithm. K- Nearest Neighbor (KNN) classifier was used on different model combinations of EEG, sociodemographic and home environment variables. KNN model was evaluated using 5 Stratified Folds based on the sensitivity and specificity. In the current dataset, 55% and 74% failed in the mathematics and language test respectively. On testing data across each fold, the mean sensitivity and specificity was calculated. Sensitivity was similar when EEG variables were combined with sociodemographic, and home environment (Math = 58.7%, Language = 66.3%) variables but specificity improved (Math = 43.4% to 50.6% and Language = 32% to 60%). The model requires further validation for EEG to be used as a screening measure with adequate sensitivity and specificity to identify children in their preschool age who may be at high risk of failure in early grades.

Neural spike sorting is prerequisite to deciphering useful information from electrophysiological data recorded from the brain, in vitro and/or in vivo. Significant advancements in nanotechnology and nanofabrication has enabled neuroscientists and engineers to capture the electrophysiological activities of the brain at very high resolution, data rate and fidelity. However, the evolution in spike sorting algorithms to deal with the aforementioned technological advancement and capability to quantify higher density data sets is somewhat limited. Both supervised and unsupervised clustering algorithms do perform well when the data to quantify is small, however, their efficiency degrades with the increase in the data size in terms of processing time and quality of spike clusters being formed. This makes neural spike sorting an inefficient process to deal with large and dense electrophysiological data recorded from brain. The presented work aims to address this challenge by providing a novel data pre-processing framework, which can enhance the efficiency of the conventional spike sorting algorithms significantly. The proposed framework is validated by applying on ten widely used algorithms and six large feature sets. Feature sets are calculated by employing PCA and Haar wavelet features on three widely adopted large electrophysiological datasets for consistency during the clustering process. A MATLAB software of the proposed mechanism is also developed and provided to assist the researchers, active in this domain.

Introduction The number of elderly patients undergoing major surgery is rapidly increasing. They are particularly at risk of developing postoperative neurocognitive disorders (NCD). Earlier studies suggested that processed electroencephalographic (EEG) monitors may reduce the incidence of postoperative NCD. However, none of these studies controlled for intraoperative nociception levels or personalized blood pressure targets. Their results remain unclear if the reduction in the incidence of postoperative NCD relates to avoidance of any electroencephalographic pattern suggesting excessive anesthesia depth. Objective The objective of this trial is to investigate–in patients ≥ 70 years old undergoing major non-cardiac surgery–the effect of EEG-guided anesthesia on postoperative NCD while controlling for intraoperative nociception, personalized blood pressure targets, and using detailed information provided by the EEG monitor (including burst suppression ratio, density spectral array, and raw EEG waveform). Material and methods This prospective, randomized, controlled trial will be conducted in a single Canadian university hospital. Patients ≥ 70 years old undergoing elective major non-cardiac surgery will be included in the trial. The administration of sevoflurane will be adjusted to maintain a BIS index value between 40 and 60, to keep a Suppression Ratio (SR) at 0%, to keep a direct EEG display without any suppression time and a spectrogram with most of the EEG wave frequency within the alpha, theta, and delta frequencies in the EEG-guided group. In the control group, sevoflurane will be administered to achieve an age-adjusted minimum alveolar concentration of [0.8–1.2]. In both groups, a nociception monitor will guide intraoperative opioid administration, individual blood pressure targets will be used, and cerebral oximetry used to tailor intraoperative hemodynamic management. The primary endpoint will be the incidence of NCD at postoperative day 1, as evaluated by the Montreal Cognitive Assessment (MoCA). Secondary endpoints will include the incidence of postoperative NCD at different time points and the evaluation of cognitive trajectories up to 90 days after surgery among EEG-guided and control groups. Study registration NCT04825847 on ClinicalTrials.gov.

The aim of this study is to compare the effects of neuromuscular blockade (NMB) on phase lag entropy (PLE) and the bispectral index (BIS). We recorded the BIS, electromyograph (EMG) activity on a BIS monitor (EMG_BIS), PLE, and EMG activity on a PLE monitor (EMG_PLE) in 40 patients receiving general anesthesia. During the awake state, we analyzed the changes in parameters before and 2 min after the eyes were closed. During sedation, we compared the changes in the parameters before and at 4 min after injecting rocuronium (group R) or normal saline (group C) between the two groups. During anesthesia, we compared the changes in parameters before and at 4 min after injecting sugammadex (group B) or normal saline (group D) between the two groups. During the awake state, the BIS, EMG_BIS, and EMG_PLE, but not PLE, decreased significantly with closed eyes. An effect of EMG on the BIS was evident, but not on PLE. During sedation, the BIS decreased with the decrease in EMG_BIS regardless of NMB caused by rocuronium, but NMB decreased PLE, although the degree of the decrease in EMG_PLE after NMB was similar to that after placebo. To determine the effect of NMB on electroencephalograms (EEGs) in groups R and C, we plotted the power spectra before and at 4 min after injecting rocuronium or normal saline. Changes in slow and delta frequency bands were observed at 4 min after injecting rocuronium relative to before injecting rocuronium. There was no effect of EMG on either the BIS or PLE during anesthesia. In conclusion, the effect of electromyograph activity and/or neuromuscular blockade on BIS or PLE depends on the level of consciousness.

Using event-related potentials (ERPs), we investigated the effects of passive heat stress and recovery on the human cognitive function with Flanker tasks, involving congruent and incongruent stimuli. We hypothesized that modulation of the peak amplitude and latency of the P300 component in ERP waveforms would differ with task difficulty during passive heat stress and recovery. Subjects performed the Flanker tasks before (Pre), at the end of whole body heating (Heat: internal temperature increase of ~1.2°C from the pre-heat baseline), and after the internal temperature had returned to the pre-heat baseline (Recovery). The internal temperature was regulated by a tube-lined suit by perfusing 50°C water for heat stress and 25°C water for recovery immediately after the heat stress. Regardless of task difficulty, the reaction time (RT) was shortened during Heat rather than Pre and Recovery, and standard deviations of RT (i.e., response variability) were significantly smaller during Heat than Pre. However, the peak amplitudes of the P300 component in ERPs, which involved selective attention, expectancy, and memory updating, were significantly smaller during Heat than during Pre, suggesting the impairment of neural activity in cognitive function. Notably, the peak amplitudes of the P300 component were higher during Recovery than during Heat, indicating that the impaired neural activity had recovered after sufficient whole-body cooling. An indicator of the stimulus classification/evaluation time (peak latency of P300) and the RT were shortened during Heat stress, but such shortening was not noted after whole-body cooling. These results suggest that hyperthermia affects the human cognitive function, reflected by the peak amplitude and latency of the P300 component in ERPs during the Flanker tasks, but sufficient treatment such as whole-body cooling performed in this study can recover those functions.

Despite remarkable academic efforts, why Enterprise Resource Planning (ERP) post-implementation success occurs still remains elusive. A reason for this shortage may be the insufficient addressing of an ERP-specific interior boundary condition, i.e., the multi-stakeholder perspective, in explaining this phenomenon. This issue may entail a gap between how ERP success is supposed to occur and how ERP success may actually occur, leading to theoretical inconsistency when investigating its causal roots. Through a case-based, inductive approach, this manuscript presents an ERP success causal network that embeds the overlooked boundary condition and offers a theoretical explanation of why the most relevant observed causal relationships may occur. The results provide a deeper understanding of the ERP success causal mechanisms and informative managerial suggestions to steer ERP initiatives towards long-haul success.

Video games have become a ubiquitous part of demographically diverse cultures. Numerous studies have focused on analyzing the cognitive aspects involved in game playing that could help provide an optimal gaming experience level by improving video game design. To this end, we present a framework for classifying the game player’s expertise level using wearable electroencephalography (EEG) headset. We hypothesize that expert/novice players’ brain activity is different, which can be classified using the frequency domain features extracted from EEG signals of the game player. A systematic channel reduction approach is presented using a correlation-based attribute evaluation method. This approach identifies two significant EEG channels, i.e., AF3 and P7, from the Emotiv EPOC headset’s fourteen channels. The features extracted from these EEG channels contribute the most to the video game player’s expertise level classification. This finding is validated by performing statistical analysis (t-test) over the extracted features. Moreover, among multiple classifiers used, K-nearest neighbor is the best classifier in classifying the game player’s expertise level with up to 98.04% classification accuracy.Author summaryTehmina Hafeez ROLES Investigation, Writing – original draft * E-mail: tehminamalik.52@gmail.com AFFILIATION Department of Computer Engineering, University of Engineering and Technology, Taxila, 47050, Pakistan.Sanay Muhammad Umar Saeed (Corresponding author) ROLES Conceptualization, Writing – review editing * E-mail: sanay.muhammad@uettaxila.edu.pk AFFILIATION Department of Computer Engineering, University of Engineering and Technology, Taxila, 47050, Pakistan.Aamir Arsalan ROLES Methodology, Writing – review editing * E-mail: aamir.arsalan@uettaxila.edu.pk AFFILIATION Department of Computer Engineering, University of Engineering and Technology, Taxila, 47050, Pakistan.Syed Muhammad Anwar ROLES Validation, Writing – review editing * E-mail: s.anwar@uettaxila.edu.pk AFFILIATION Department of Software Engineering, University of Engineering and Technology, Taxila, 47050, Pakistan.Muhammad Usman Ashraf (Corresponding author) ROLES Validation, Writing – review editing * E-mail: usman.ashraf@skt.umt.edu.pk AFFILIATION Department of Computer Science, University of management and Technology, Lahore (Sialkot), 51040, Pakistan.Khalid Alsubhi ROLES Conceptualization, Writing – review editing AFFILIATION Department of Computer Science, King Abdul Aziz University, Jeddah, Saudi Arabia.

Electrical stimulation involving visual areas of the brain produces artificial light percepts called phosphenes. These visual percepts have been extensively investigated in previous studies involving intracortical microsimulation (ICMS) and serve as the basis for developing a visual prosthesis for the blind. Although advances have been achieved, many challenges still remain with implementing a functional ICMS for visual rehabilitation purposes. Transcranial magnetic stimulation (TMS) over the primary occipital lobe offers an alternative method to produce phosphenes non-invasively. A main challenge facing blind individuals involves navigation. Within the scientific community, methods to evaluate the ability of a visual prosthesis to facilitate in navigation has been neglected. In this study, we investigate the effectiveness of evoking lateralized phosphenes to navigate a computer simulated virtual environment. More importantly, we demonstrate how virtual environments along with the development of a visual prosthesis share a mutual relationship benefiting both patients and researchers. Using two TMS devices, a pair of 40mm figure-of-eight coils were placed over each occipital hemisphere resulting in lateralized phosphene perception. Participants were tasked with making a series of left and right turns using peripheral devices depending on the visual hemifield in which a phosphene is present. If a participant was able to accurately perceive all ten phosphenes, the simulated target is able to advance and fully exit the virtual environment. Our findings demonstrate that participants can interpret lateralized phosphenes while highlighting the integration of computer based virtual environments to evaluate the capability of a visual prosthesis during navigation.

Background Cocaine use disorder (CUD) is a global health issue with no effective treatment. Repetitive Transcranial Magnetic Stimulation (rTMS) is a recently proposed therapy for CUD. Methods We conducted a single-center, randomised, sham-controlled, blinded, parallel-group research with patients randomly allocated to rTMS (15 Hz) or Sham group (1:1) using a computerised block randomisation process. We enrolled 62 of 81 CUD patients in two years. Patients were followed for eight weeks after receiving 15 15 Hz rTMS/sham sessions over the left dorsolateral prefrontal cortex (DLPFC) during the first three weeks of the study. We targeted the DLFPC following the 5 cm method. Cocaine lapses in twice a week urine tests were the primary outcome. The secondary outcomes were craving severity, cocaine use pattern, and psychometric assessments. Findings We randomly allocated patients to either an active rTMS group (32 subjects) or a sham treatment group (30 subjects). Thirteen (42%) and twelve (43.3%) of the subjects in rTMS and sham groups, respectively, completed the full trial regimen, displaying a high dropout rate. Ten/30 (33%) of rTMS-treated patients tested negative for cocaine in urine, in contrast to 4/27 of placebo controls (p = 0.18, odd ratio 2.88, CI 0.9–10). The Kaplan-Meier survival curve did not state a significant change between the treated and sham groups in the time of cocaine urine negativisation (p = 0.20). However, the severity of cocaine-related cues mediated craving (VAS peak) was substantially decreased in the rTMS treated group (p Conclusions In CUD, rTMS could be a useful tool for lowering cocaine craving and consumption. Trial registration The study number on clinicalTrials.gov is NCT03607591.

Electroencephalography (EEG) likely reflects activity of cortical neurocircuits, making it an insightful estimation for mental health in patients with substance use disorder (SUD). EEG signals are recorded as sinusoidal waves, containing spectral amplitudes across several frequency bands with high spatio-temporal resolution. Prior work on EEG signal analysis has been made mainly at individual electrodes. These signals can be evaluated from advanced aspects, including sub-regional and hemispheric analyses. Due to limitation of computational techniques, few studies in earlier work could conduct data analyses from these aspects. Therefore, EEG in patients with SUD is not fully understood. In the present retrospective study, spectral powers from a data house containing opioid (OUD), methamphetamine/stimulants (MUD), and alcohol use disorder (AUD) were extracted, and then converted into five distinct topographic data (i.e., electrode-based, cortical subregion-based, left-right hemispheric, anterior-posterior based, and total cortex-based analyses). We found that data conversion and reorganization in the topographic way had an impact on EEG spectral powers in patients with OUD significantly different from those with MUD or AUD. Differential changes were observed from multiple perspectives, including individual electrodes, subregions, hemispheres, anterior-posterior cortices, and across the cortex as a whole. Understanding the differential changes in EEG signals may be useful for future work with machine learning and artificial intelligence (AI), not only for diagnostic but also for prognostic purposes in patients with SUD.

Individuals with autistic traits display impaired social interaction and communication in everyday life, but the underlying cognitive neural mechanisms remain very unclear and still remain controversial. The mind-blindness hypothesis suggests that social difficulties in individuals with autistic traits are caused by empathy impairment in individuals; however, the intense world theory suggests that these social difficulties are caused by sensory hyper-reactivity and sensory overload, rather than empathy impairment. To further test these two theories, this study investigated event-related potentials (ERPs) to explore the cognitive neural processing of repetitive expressions in individuals with autistic traits. This study employed the Mandarin version of the autism-spectrum quotient (AQ) to assess autistic traits in 2,502 healthy adults. Two subset groups were used, e.g., the participants of a high-AQ group were randomly selected among the 10% of individuals with the highest AQ scores; similarly, the participants in the low-AQ group were randomly selected from the 10% of participants with the lowest AQ scores. In an experiment, three different facial expressions (positive, neutral, or negative) of the same person were presented successively and pseudo-randomly in each trial. Participants needed to define the expression of the face that was presented last. The results showed that compared with the low-AQ group, the high-AQ group exhibited higher P1 amplitudes induced by the second and third presented expressions, as well as higher P3 amplitudes induced by the third presented negative expressions. This indicates that individuals with autistic traits may experience overly strong perception, attention, and cognitive evaluation to repetitive expressions, particularly negative expressions. This result supports the intense world theory more strongly than the mind-blindness hypothesis.

In current anesthesiology practice, anesthesiologists infer the state of unconsciousness without directly monitoring the brain. Drug- and patient-specific electroencephalographic (EEG) signatures of anesthesia-induced unconsciousness have been identified previously. We applied machine learning approaches to construct classification models for real-time tracking of unconscious state during anesthesia-induced unconsciousness. We used cross-validation to select and train the best performing models using 33,159 2s segments of EEG data recorded from 7 healthy volunteers who received increasing infusions of propofol while responding to stimuli to directly assess unconsciousness. Cross-validated models of unconsciousness performed very well when tested on 13,929 2s EEG segments from 3 left-out volunteers collected under the same conditions (median volunteer AUCs 0.99-0.99). Models showed strong generalization when tested on a cohort of 27 surgical patients receiving solely propofol collected in a separate clinical dataset under different circumstances and using different hardware (median patient AUCs 0.95—0.98), with model predictions corresponding with actions taken by the anesthesiologist during the cases. Performance was also strong for 17 patients receiving sevoflurane (alone or in addition to propofol) (median AUCs 0.88—0.92). These results indicate that EEG spectral features can predict unconsciousness, even when tested on a different anesthetic that acts with a similar neural mechanism. With high performance predictions of unconsciousness, we can accurately monitor anesthetic state, and this approach may be used to engineer infusion pumps to intelligibly respond to patients’ neural activity.

In recent decades reported findings regarding gender differences in reading achievement, cognitive abilities and maturation process in boys and girls are conflicting. As reading is one of the most important processes in the maturation of an individual, the aim of the study was to better understand gender differences between primary school students. The study evaluates differences in Heart Rate Variability (HRV), Electroencephalography (EEG), Electrodermal Activities (EDA) and eye movement of participants during the reading task. Taking into account that colour may affect reading skills, in that it affects the emotional and physiological state of the body, the research attempts to provide a better understanding of gender differences in reading through examining the effect of colour, as applied to reading content. The physiological responses of 50 children (25 boys and 25 girls) to 12 different background and overlay colours of reading content were measured and summarised during the reading process. Our findings show that boys have shorter reading duration scores and a longer Saccade Count, Saccade Duration Total, and Saccade Duration Average when reading on a coloured background, especially purple, which could be caused by their motivation and by the type of reading task. Also, the boys had higher values for the Delta band and the Whole Range of EEG measurements in comparison to the girls when reading on coloured backgrounds, which could reflect the faster maturation of the girls. Regarding EDA measurements we did not find systematic differences between groups either on white or on coloured/overlay background. We found the most significant differences arose in the HRV parameters, namely (SDNN (ms), STD HR (beats/min), RMSSD (ms), NN50 (beats), pNN50 (%), CVRR) when children read the text on coloured/overlay backgrounds, where the girls showed systematically higher values on HRV measurements in comparison to the boys, mostly with yellow, red, and orange overlay colours.

Wearable Cognitive Assistants (WCA) are anticipated to become a widely-used application class, in conjunction with emerging network infrastructures like 5G that incorporate edge computing capabilities. While prototypical studies of such applications exist today, the relationship between infrastructure service provisioning and its implication for WCA usability is largely unexplored despite the relevance that these applications have for future networks. This paper presents an experimental study assessing how WCA users react to varying end-to-end delays induced by the application pipeline or infrastructure. Participants interacted directly with an instrumented task-guidance WCA as delays were introduced into the system in a controllable fashion. System and task state were tracked in real time, and biometric data from wearable sensors on the participants were recorded. Our results show that periods of extended system delay cause users to correspondingly (and substantially) slow down in their guided task execution, an effect that persists for a time after the system returns to a more responsive state. Furthermore, the slow-down in task execution is correlated with a personality trait, neuroticism, associated with intolerance for time delays. We show that our results implicate impaired cognitive planning, as contrasted with resource depletion or emotional arousal, as the reason for slowed user task executions under system delay. The findings have several implications for the design and operation of WCA applications as well as computational and communication infrastructure, and additionally for the development of performance analysis tools for WCA., 27 pages, 14 figures. Submitted to PLOS ONE on October 15, 2020

Some research suggests that positive and negative valence stimuli may be processed differently. For example, negative material may capture and hold attention more readily than equally arousing positive material. This is called the negativity bias, and it has been observed as both behavioural and electroencephalographic (EEG) effects. Consequently, it has been attributed to both automatic and elaborative processes. However, at the lowest levels of arousal, faster reaction times and stronger EEG responses to positive material have been observed. This is called the positivity offset, and the underlying cognitive mechanism is less understood. To study the role of selective attention in the positivity offset, participants completed a negative affective priming (NAP) task modified to dissociate priming for positive and negative words. The task required participants to indicate the valence of a target word, while simultaneously ignoring a distractor. In experiment 1, a behavioural facilitation effect (faster response time) was observed for positive words, in stark contrast to the original NAP task. These results were congruent with a previously reported general categorization advantage for positive material. In experiment 2, participants performed the task while EEG was recorded. In additional to replicating the behavioural results from experiment 1, positive words elicited a larger Late Positive Potential (LPP) component on ignored repetition relative to control trials. Surprisingly, negative words elicited a larger LPP than positive words on control trials. These results suggest that the positivity offset may reflect a greater sensitivity to priming effects due to a more flexible attentional set.

Children with Congenital Zika Syndrome and microcephaly are at high risk for epilepsy; however, the risk is unclear in normocephalic children with prenatal Zika virus (ZIKV) exposure [Exposed Children (EC)]. In this prospective cohort study, we performed epilepsy screening in normocephalic EC alongside a parallel group of normocephalic unexposed children [Unexposed Children (UC)]. We compared the incidence rate of epilepsy among EC and UC at one year of life to global incidence rates. Pregnant women were recruited from public health centers during the ZIKV outbreak in Grenada, West Indies and assessed for prior ZIKV infection using a plasmonic-gold platform that measures IgG antibodies in serum. Normocephalic children born to mothers with positive ZIKV results during pregnancy were classified as EC and those born to mothers with negative ZIKV results during and after pregnancy were classified as UC. Epilepsy screening procedures included a pediatric epilepsy screening questionnaire and video electroencephalography (vEEG). vEEG was collected using a multi-channel microEEG® system for a minimum of 20 minutes along with video recording of participant behavior time-locked to the EEG. vEEGs were interpreted independently by two pediatric epileptologists, who were blinded to ZIKV status, via telemedicine platform. Positive screening cases were referred to a local pediatrician for an epilepsy diagnostic evaluation. Epilepsy screens were positive in 2/71 EC (IR: 0.028; 95% CI: 0.003–0.098) and 0/71 UC. In both epilepsy-positive cases, questionnaire responses and interictal vEEGs were consistent with focal, rather than generalized, seizures. Both children met criteria for a clinical diagnosis of epilepsy and good seizure control was achieved with carbamazepine. Our results indicate that epilepsy rates are modestly elevated in EC. Given our small sample size, results should be considered preliminary. They support the use of epilepsy screening procedures in larger epidemiological studies of children with congenital ZIKV exposure, even in the absence of microcephaly, and provide guidance for conducting epilepsy surveillance in resource limited settings., Author summary Epilepsy is a clinical concern in children with Congenital Zika Syndrome and microcephaly; however, it is unknown whether epilepsy rates are elevated in normocephalic children with prenatal Zika virus exposure. We found a modest elevation of epilepsy rates in the first year of life of exposed, relative to unexposed, children, despite no other neurological manifestations. Seizures in exposed children had features of focal, rather than generalized, epilepsy and were well controlled with carbamazepine. Our findings suggest that epilepsy surveillance should be included in the neurodevelopmental assessment of children with prenatal Zika virus exposure, even in the absence of neurologic manifestations at birth.

Birds and mammals share specialized forms of sleep including slow wave sleep (SWS) and rapid eye movement sleep (REM), raising the question of why and how specialized sleep evolved. Extensive prior studies concluded that avian sleep lacked many features characteristic of mammalian sleep, and therefore that specialized sleep must have evolved independently in birds and mammals. This has been challenged by evidence of more complex sleep in multiple songbird species. To extend this analysis beyond songbirds, we examined a species of parrot, the sister taxon to songbirds. We implanted adult budgerigars (Melopsittacus undulatus) with electroencephalogram (EEG) and electrooculogram (EOG) electrodes to evaluate sleep architecture, and video monitored birds during sleep. Sleep was scored with manual and automated techniques, including automated detection of slow waves and eye movements. This can help define a new standard for how to score sleep in birds. Budgerigars exhibited consolidated sleep, a pattern also observed in songbirds, and many mammalian species, including humans. We found that REM constituted 26.5% of total sleep, comparable to humans and an order of magnitude greater than previously reported. Although we observed no spindles, we found a clear state of intermediate sleep (IS) similar to non-REM (NREM) stage 2. Across the night, SWS decreased and REM increased, as observed in mammals and songbirds. Slow wave activity (SWA) fluctuated with a 29-min ultradian rhythm, indicating a tendency to move systematically through sleep states as observed in other species with consolidated sleep. These results are at variance with numerous older sleep studies, including for budgerigars. Here, we demonstrated that lighting conditions used in the prior budgerigar study—and commonly used in older bird studies—dramatically disrupted budgerigar sleep structure, explaining the prior results. Thus, it is likely that more complex sleep has been overlooked in a broad range of bird species. The similarities in sleep architecture observed in mammals, songbirds, and now budgerigars, alongside recent work in reptiles and basal birds, provide support for the hypothesis that a common amniote ancestor possessed the precursors that gave rise to REM and SWS at one or more loci in the parallel evolution of sleep in higher vertebrates. We discuss this hypothesis in terms of the common plan of forebrain organization shared by reptiles, birds, and mammals., Extensive prior studies concluded that avian sleep lacked many features characteristic of mammalian sleep, and therefore that specialized sleep must have evolved independently in birds and mammals. However, this study shows that the architecture of sleep in budgerigars, a species of parrot, is surprisingly similar to that in human adults, raising new questions about the evolution of complex mammalian-like sleep structure.

The International League Against Epilepsy (ILAE) groups seizures into “focal”, “generalized” and “unknown” based on whether the seizure onset is confined to a brain region in one hemisphere, arises in several brain region simultaneously, or is not known, respectively. This separation fails to account for the rich diversity of clinically and experimentally observed spatiotemporal patterns of seizure onset and even less so for the properties of the brain networks generating them. We consider three different patterns of domino-like seizure onset in Idiopathic Generalized Epilepsy (IGE) and present a novel approach to classification of seizures. To understand how these patterns are generated on networks requires understanding of the relationship between intrinsic node dynamics and coupling between nodes in the presence of noise, which currently is unknown. We investigate this interplay here in the framework of domino-like recruitment across a network. In particular, we use a phenomenological model of seizure onset with heterogeneous coupling and node properties, and show that in combination they generate a range of domino-like onset patterns observed in the IGE seizures. We further explore the individual contribution of heterogeneous node dynamics and coupling by interpreting in-vitro experimental data in which the speed of onset can be chemically modulated. This work contributes to a better understanding of possible drivers for the spatiotemporal patterns observed at seizure onset and may ultimately contribute to a more personalized approach to classification of seizure types in clinical practice., Author summary Epilepsy is a serious neurological condition encompassing a variety of syndromes that affect around 65 million people worldwide. Seizure type in epilepsy is characterized by onset pattern and brain network involved into three categories that do not fully capture the complexity of observed onset patterns. Ambiguity of seizure onset observed in the clinic could result in significant diagnostic delay and inappropriate treatment for an individual. We show how a variety of recruitment patterns across a network arise as the result of interplay between heterogeneous node dynamics and heterogeneous coupling among nodes. Our results demonstrate the important role of brain network dynamics in driving spatiotemporal patterns of seizure onset and provide a dynamic mechanism that could inform novel classifications of seizure types in clinical practice.

Brain networks are complex dynamical systems in which directed interactions between different areas evolve at the sub-second scale of sensory, cognitive and motor processes. Due to the highly non-stationary nature of neural signals and their unknown noise components, however, modeling dynamic brain networks has remained one of the major challenges in contemporary neuroscience. Here, we present a new algorithm based on an innovative formulation of the Kalman filter that is optimized for tracking rapidly evolving patterns of directed functional connectivity under unknown noise conditions. The Self-Tuning Optimized Kalman filter (STOK) is a novel adaptive filter that embeds a self-tuning memory decay and a recursive regularization to guarantee high network tracking accuracy, temporal precision and robustness to noise. To validate the proposed algorithm, we performed an extensive comparison against the classical Kalman filter, in both realistic surrogate networks and real electroencephalography (EEG) data. In both simulations and real data, we show that the STOK filter estimates time-frequency patterns of directed connectivity with significantly superior performance. The advantages of the STOK filter were even clearer in real EEG data, where the algorithm recovered latent structures of dynamic connectivity from epicranial EEG recordings in rats and human visual evoked potentials, in excellent agreement with known physiology. These results establish the STOK filter as a powerful tool for modeling dynamic network structures in biological systems, with the potential to yield new insights into the rapid evolution of network states from which brain functions emerge., Author summary During normal behavior, brains transition between functional network states several times per second. This allows humans to quickly read a sentence, and a frog to catch a fly. Understanding these fast network dynamics is fundamental to understanding how brains work, but up to now it has proven very difficult to model fast brain dynamics for various methodological reasons. To overcome these difficulties, we designed a new Kalman filter (STOK) by innovating on previous solutions from control theory and state-space modelling. We show that STOK accurately models fast network changes in simulations and real neural data, making it an essential new tool for modelling fast brain networks in the time and frequency domain.

In this study, we propose a new open-source simulation platform that comprises computer-aided design and computer-aided engineering tools for highly automated evaluation of electric field distribution and neural activation during Deep Brain Stimulation (DBS). It will be shown how a Volume Conductor Model (VCM) is constructed and examined using Python-controlled algorithms for generation, discretization and adaptive mesh refinement of the computational domain, as well as for incorporation of heterogeneous and anisotropic properties of the tissue and allocation of neuron models. The utilization of the platform is facilitated by a collection of predefined input setups and quick visualization routines. The accuracy of a VCM, created and optimized by the platform, was estimated by comparison with a commercial software. The results demonstrate no significant deviation between the models in the electric potential distribution. A qualitative estimation of different physics for the VCM shows an agreement with previous computational studies. The proposed computational platform is suitable for an accurate estimation of electric fields during DBS in scientific modeling studies. In future, we intend to acquire SDA and EMA approval. Successful incorporation of open-source software, controlled by in-house developed algorithms, provides a highly automated solution. The platform allows for optimization and uncertainty quantification (UQ) studies, while employment of the open-source software facilitates accessibility and reproducibility of simulations., Author summary Volume conductor models for the computation of the potential and current distribution resulting from deep brain stimulation can help research to gain a deeper understanding of the underlying processes as well as in optimization studies. On the other hand, they are extremely valuable for patient-specific therapy planning while avoiding side effects as far as possible. Despite existing high-quality models, further potential exists to increase their level of realism, precision and reliability and to allow robust optimization. Our approach enables high-precision, patient- or atlas-based results for deep brain stimulation while simultaneously exploiting different measures to achieve high computational efficiency. In the development of the simulation software, we follow the goals of Open Science—in particular the principles of open-source, open data and reproducibility. In two benchmark examples, one on the human brain, the other on the rat brain, we were able to clearly demonstrate the accuracy and efficiency of our simulation results in comparison to a high-resolution simulation using a commercial software. The developed platform provides both the scientific community and clinicians with a precise yet easy-to-use simulation tool for scientific optimization studies and patient-specific therapy planning in context of deep brain stimulation.

Attention deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental condition characterized by diminished attentional control. Critically, these difficulties are related to negative consequences in real-life functioning both during development and into adulthood. There is now growing evidence that modulating the underlying neural circuits related to attention can improve behavior and brain function in children with ADHD. We have previously shown that game-based digital therapeutics targeting a key neural marker of attention–midline frontal theta (MFT)–yield positive effects on attentional control in several populations. However, the effects of such digital therapeutics in children with ADHD and no other comorbidities has not been yet examined. To address this gap, we assessed a sample of 25 children with ADHD (8–12 years old) on neural, behavioral, and clinical metrics of attention before and after a 4-week at-home intervention on an iPad targeting MFT circuitry. We found that children showed enhancements on a neural measure of attention (MFT power), as well as on objective behavioral measures of attention and parent reports of clinical ADHD symptoms. Importantly, we observed relationships between the neural and behavioral cognitive improvements, demonstrating that those children who showed the largest intervention-related neural gains were also those that improved the most on the behavioral tasks indexing attention. These findings provide support for using targeted, digital therapeutics to enhance multiple features of attentional control in children with ADHD. Study registration: ClinicalTrials.gov registry (NCT03844269) https://clinicaltrials.gov/ct2/show/NCT03844269.

In this paper, the algebraic topological characteristics of brain networks composed of electroencephalogram(EEG) signals induced by different quality images were studied, and on that basis, a neurophysiological image quality assessment approach was proposed. Our approach acquired quality perception-related neural information via integrating the EEG collection with conventional image assessment procedures, and the physiologically meaningful brain responses to different distortion-level images were obtained by topological data analysis. According to the validation experiment results, statistically significant discrepancies of the algebraic topological characteristics of EEG data evoked by a clear image compared to that of an unclear image are observed in several frequency bands, especially in the beta band. Furthermore, the phase transition difference of brain network caused by JPEG compression is more significant, indicating that humans are more sensitive to JPEG compression other than Gaussian blur. In general, the algebraic topological characteristics of EEG signals evoked by distorted images were investigated in this paper, which contributes to the study of neurophysiological assessment of image quality.

Paired associative corticospinal-motoneuronal stimulation (PCMS) induces plasticity at synapses between corticospinal tracts (CSTs) and spinal motoneurons (SMs). We investigated the effects of peripheral nerve electrical stimulation (PNS) intensity on PCMS-induced plasticity. PCMS consisted of 180 paired stimuli of transcranial magnetic stimulation (TMS) over the left primary motor cortex with PNS on the right ulnar nerve at the wrist. We compared effects induced by different PNS intensities: supramaximal, twice and three times sensory threshold intensities. For evaluating efficacy of the synapse between CSTs and SMs, single-pulse TMS was delivered at cervicomedullary junction level, and cervicomedullary motor-evoked potentials (CMEPs) were recorded from the right first-dorsal interosseous muscle before and after PCMS. PCMS with the supramaximal PNS intensity increased CMEP amplitude. The facilitatory effect of PCMS with the supramaximal PNS was larger than those of PCMS with weaker PNS intensities. Sham TMS with the supramaximal PNS showed no CMEP changes after the intervention. PNS intensity of PCMS influences the magnitude of synaptic plasticity induction between the CSTs and SMs at the spinal level, and the supramaximal intensity is the best for induction of long-term potentiation-like effects. The PNS intensity may influence the number of activated SMs by axonal backpropagating pulses with PNS which must overlap with descending volleys induced by TMS.

In the early visual system, suppression occurs between neurons representing different stimulus properties. This includes features such as orientation (cross-orientation suppression), eye-of-origin (interocular suppression) and spatial location (surround suppression), which are thought to involve distinct anatomical pathways. We asked if these separate routes to suppression can be differentiated by their pattern of gain control on the contrast response function measured in human participants using steady-state electroencephalography. Changes in contrast gain shift the contrast response function laterally, whereas changes in response gain scale the function vertically. We used a Bayesian hierarchical model to summarise the evidence for each type of gain control. A computational meta-analysis of 16 previous studies found the most evidence for contrast gain effects with overlaid masks, but no clear evidence favouring either response gain or contrast gain for other mask types. We then conducted two new experiments, comparing suppression from four mask types (monocular and dichoptic overlay masks, and aligned and orthogonal surround masks) on responses to sine wave grating patches flickering at 5Hz. At the occipital pole, there was strong evidence for contrast gain effects in all four mask types at the first harmonic frequency (5Hz). Suppression generally became stronger at more lateral electrode sites, but there was little evidence of response gain effects. At the second harmonic frequency (10Hz) suppression was stronger overall, and involved both contrast and response gain effects. Although suppression from different mask types involves distinct anatomical pathways, gain control processes appear to serve a common purpose, which we suggest might be to suppress less reliable inputs., Author summary Suppression is a ubiquitous process in the brain that acts to regulate neural activity. In the visual system, there are multiple suppressive pathways, which normalize neural responses across dimensions such as spatial location, eye of origin, and feature (e.g. stimulus orientation). In this study we ask how we can characterise suppression from these different sources by examining the effect on the contrast response function (the function mapping the physical stimulus intensity to the neural response), measured using steady-state electroencephalography (EEG). Using a Bayesian computational model, we estimate the likely range of model parameter values summarising contributions from contrast gain (which shifts the contrast response function laterally) and response gain (which scales it vertically). A meta analysis of 16 previous studies provided inconclusive evidence, but generally supported a greater contribution from contrast gain control. Data from two new studies showed convincing effects of contrast gain control for four different mask types at the first harmonic (stimulus flicker frequency), and both contrast and response gain at the second harmonic (twice the flicker frequency). We discuss these findings in the context of work using other experimental methodologies, and speculate about the purpose of suppression in the nervous system.

Humans are constantly exposed to a rich tapestry of visual information in a potentially changing environment. To cope with the computational burden this engenders, our perceptual system must use prior context to simultaneously prioritise stimuli of importance and suppress irrelevant surroundings. This study investigated the influence of prediction and attention in visual perception by investigating event-related potentials (ERPs) often associated with these processes, N170 and N2pc for prediction and attention, respectively. A contextual trajectory paradigm was used which violated visual predictions and neglected to predetermine areas of spatial interest, to account for the potentially unpredictable nature of a real-life visual scene. Participants (N=36) viewed a visual display of cued and non-cued shapes rotating in a five-step predictable trajectory, with the fifth and final position of either the cued or non-cued shape occurring in a predictable or unpredictable spatial location. To investigate the predictive coding theory of attention we used factors of attention and prediction, whereby attention was manipulated as either cued or non-cued conditions, and prediction manipulated in either predictable or unpredictable conditions. Results showed both enhanced N170 and N2pc amplitudes to unpredictable compared to predictable stimuli. Stimulus cueing status also increased N170 amplitude, but this did not interact with stimulus predictability. The N2pc amplitude was not affected by stimulus cueing status. In accordance with previous research these results suggest the N170 is in part a visual prediction error response with respect to higher-level visual processes, and furthermore the N2pc may index attention reorientation. The results demonstrate prior context influences the sensitivity of the N170 and N2pc electrophysiological responses. These findings add further support to the role of N170 as a prediction error signal and suggest that the N2pc may reflect attentional reorientation in response to unpredicted stimulus locations.

The human brain tracks amplitude fluctuations of both speech and music, which reflects acoustic processing in addition to the encoding of higher-order features and one’s cognitive state. Comparing neural tracking of speech and music envelopes can elucidate stimulus-general mechanisms, but direct comparisons are confounded by differences in their envelope spectra. Here, we use a novel method of frequency-constrained reconstruction of stimulus envelopes using EEG recorded during passive listening. We expected to see music reconstruction match speech in a narrow range of frequencies, but instead we found that speech was reconstructed better than music for all frequencies we examined. Additionally, models trained on all stimulus types performed as well or better than the stimulus-specific models at higher modulation frequencies, suggesting a common neural mechanism for tracking speech and music. However, speech envelope tracking at low frequencies, below 1 Hz, was associated with increased weighting over parietal channels, which was not present for the other stimuli. Our results highlight the importance of low-frequency speech tracking and suggest an origin from speech-specific processing in the brain., Author summary The time-varying amplitude of sounds such as speech and music provides information about phrasing and rhythm, and previous research has shown that the brain continuously tracks these variations. Is a common neural mechanism responsible for tracking both sounds? We used a technique that reconstructs these amplitude fluctuations from the fluctuations in recorded EEG to quantify the strength of neural tracking. Our hypothesis was that neural tracking for music would match speech in a narrow frequency range associated with syllables and musical beats. Though our results did suggest a common mechanism involved in tracking both speech and music at these higher frequencies, we instead found that speech was tracked better than the rock, orchestral, and vocals stimuli at all of the frequencies we examined. Moreover, low-frequency fluctuations at the rate of phrases were associated with increased EEG weightings over parietal scalp, which did not appear during the neural tracking of music. These results suggest that, unlike syllable- and beat-tracking, phrase-level tracking of amplitude variations in speech may be speech-specific.

Ultra-high field MRI at 7 T can produce much better visualization of sub-cortical structures compared to lower field, which can greatly help target verification as well as overall treatment monitoring for patients with deep brain stimulation (DBS) implants. However, use of 7 T MRI for such patients is currently contra-indicated by guidelines from the device manufacturers due to the safety issues. The aim of this study was to provide an assessment of safety and image quality of ultra-high field magnetic resonance imaging at 7 T in patients with deep brain stimulation implants. We performed experiments with both lead-only and complete DBS systems implanted in anthropomorphic phantoms. RF heating was measured for 43 unique patient-derived device configurations. Magnetic force measurements were performed according to ASTM F2052 test method, and device integrity was assessed before and after experiments. Finally, we assessed electrode artifact in a cadaveric brain implanted with an isolated DBS lead. RF heating remained below 2°C, similar to a fever, with the 95% confidence interval between 0.38°C-0.52°C. Magnetic forces were well below forces imposed by gravity, and thus not a source of concern. No device malfunctioning was observed due to interference from MRI fields. Electrode artifact was most noticeable on MPRAGE and T2*GRE sequences, while it was minimized on T2-TSE images. Our work provides the safety assessment of ultra-high field MRI at 7 T in patients with DBS implants. Our results suggest that 7 T MRI may be performed safely in patients with DBS implants for specific implant models and MRI hardware.