Repetitive Transcranial Alternating Current Stimulation to Improve Working Memory: An EEG-fNIRS Study.

Transcranial electrical stimulation has demonstrated the potential to enhance cognitive functions such as working memory, learning capacity, and attentional allocation. Recently, it was shown that periodic stimulation within a specific duration could augment the human brain's neuroplasticity. This study investigates the effects of repetitive transcranial alternating current stimulation (tACS; 1 mA, 5 Hz, 2 min duration) on cognitive function, functional connectivity, and topographic changes using both electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS). Fifteen healthy subjects were recruited to measure brain activity in the pre-, during-, and post-stimulation sessions under tACS and sham stimulation conditions. Fourteen trials of working memory tasks and eight repetitions of tACS/sham stimulation with a 1-minute intersession interval were applied to the frontal cortex of the participants. The working memory score, EEG band-wise powers, EEG topography, concentration changes of oxygenated hemoglobin, and functional connectivity (FC) were individually analyzed to quantify the behavioral and neurophysiological effects of tACS. Our results indicate that tACS increases: i) behavioral scores (i.e., 15.08, ) and EEG band-wise powers (i.e., theta and beta bands) compared to the sham stimulation condition, ii) FC of both EEG-fNIRS signals, especially in the large-scale brain network communication and interhemispheric connections, and iii) the hemodynamic response in comparison to the pre-stimulation session and the sham condition. Conclusively, the repetitive theta-band tACS stimulation improves the working memory capacity regarding behavioral and neuroplasticity perspectives. Additionally, the proposed fNIRS biomarkers (mean, slope), EEG band-wise powers, and FC can be used as neuro-feedback indices for closed-loop brain stimulation.

Effectiveness assessment of repetitive transcranial alternating current stimulation with concurrent EEG and fNIRS measurement.

Transcranial alternating current stimulation (tACS) exhibits the capability to interact with endogenous brain oscillations using an external low-intensity sinusoidal current and influences cerebral function. Despite its potential benefits, the physiological mechanisms and effectiveness of tACS are currently a subject of debate and disagreement. The aims of our study are to (i) evaluate the neurological and behavioral impact of tACS by conducting repetitive sham-controlled experiments and (ii) propose criteria to evaluate effectiveness, which can serve as a benchmark to determine optimal individual-based tACS protocols. In this study, 15 healthy adults participated in the experiment over two visiting: sham and tACS (i.e., 5 Hz, 1 mA). During each visit, we used multimodal recordings of the participants' brain, including simultaneous electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS), along with a working memory (WM) score to quantify neurological effects and cognitive changes immediately after each repetitive sham/tACS session. Our results indicate increased WM scores, hemodynamic response strength, and EEG power in theta and delta bands both during and after the tACS period. Additionally, the observed effects do not increase with prolonged stimulation time, as the effects plateau towards the end of the experiment. In conclusion, our proposed closed-loop scheme offers a promising advance for evaluating the effectiveness of tACS during the stimulation session. Specifically, the assessment criteria use participant-specific brain-based signals along with a behavioral output. Moreover, we propose a feedback efficacy score that can aid in determining the optimal stimulation duration based on a participant-specific brain state, thereby preventing the risk of overstimulation.

Motion artifacts removal and evaluation techniques for functional near-infrared spectroscopy signals: A review.

With the emergence of an increasing number of functional near-infrared spectroscopy (fNIRS) devices, the significant deterioration in measurement caused by motion artifacts has become an essential research topic for fNIRS applications. However, a high requirement for mathematics and programming limits the number of related researches. Therefore, here we provide the first comprehensive review for motion artifact removal in fNIRS aiming to (i) summarize the latest achievements, (ii) present the significant solutions and evaluation metrics from the perspective of application and reproduction, and (iii) predict future topics in the field. The present review synthesizes information from fifty-one journal articles (screened according to three criteria). Three hardware-based solutions and nine algorithmic solutions are summarized, and their application requirements (compatible signal types, the availability for online applications, and limitations) and extensions are discussed. Five metrics for noise suppression and two metrics for signal distortion were synthesized to evaluate the motion artifact removal methods. Moreover, we highlight three deficiencies in the existing research: (i) The balance between the use of auxiliary hardware and that of an algorithmic solution is not clarified; (ii) few studies mention the filtering delay of the solutions, and (iii) the robustness and stability of the solution under extreme application conditions are not discussed.

Concurrent fNIRS and EEG for Brain Function Investigation: A Systematic, Methodology-Focused Review.

Electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) stand as state-of-the-art techniques for non-invasive functional neuroimaging. On a unimodal basis, EEG has poor spatial resolution while presenting high temporal resolution. In contrast, fNIRS offers better spatial resolution, though it is constrained by its poor temporal resolution. One important merit shared by the EEG and fNIRS is that both modalities have favorable portability and could be integrated into a compatible experimental setup, providing a compelling ground for the development of a multimodal fNIRS-EEG integration analysis approach. Despite a growing number of studies using concurrent fNIRS-EEG designs reported in recent years, the methodological reference of past studies remains unclear. To fill this knowledge gap, this review critically summarizes the status of analysis methods currently used in concurrent fNIRS-EEG studies, providing an up-to-date overview and guideline for future projects to conduct concurrent fNIRS-EEG studies. A literature search was conducted using PubMed and Web of Science through 31 August 2021. After screening and qualification assessment, 92 studies involving concurrent fNIRS-EEG data recordings and analyses were included in the final methodological review. Specifically, three methodological categories of concurrent fNIRS-EEG data analyses, including EEG-informed fNIRS analyses, fNIRS-informed EEG analyses, and parallel fNIRS-EEG analyses, were identified and explained with detailed description. Finally, we highlighted current challenges and potential directions in concurrent fNIRS-EEG data analyses in future research.

Maize Shrek1 encodes a WD40 protein that regulates pre-rRNA processing in ribosome biogenesis.

Ribosome biogenesis is a fundamental and highly orchestrated process that involves hundreds of ribosome biogenesis factors. Despite advances that have been made in yeast, the molecular mechanism of ribosome biogenesis remains largely unknown in plants. We uncovered a WD40 protein, Shrunken and Embryo Defective Kernel 1 (SHREK1), and showed that it plays a crucial role in ribosome biogenesis and kernel development in maize (Zea mays). The shrek1 mutant shows an aborted embryo and underdeveloped endosperm and embryo-lethal in maize. SHREK1 localizes mainly to the nucleolus and accumulates to high levels in the seed. Depleting SHREK1 perturbs pre-rRNA processing and causes imbalanced profiles of mature rRNA and ribosome. The expression pattern of ribosomal-related genes is significantly altered in shrek1. Like its yeast (Saccharomyces cerevisiae) ortholog Periodic tryptophan protein 1 (PWP1), SHREK1 physically interacts with ribosomal protein ZmRPL7a, a transient component of the PWP1-subcomplex involved in pre-rRNA processing in yeast. Additionally, SHREK1 may assist in the A3 cleavage of the pre-rRNA in maize by interacting with the nucleolar protein ZmPOP4, a maize homolog of the yeast RNase mitochondrial RNA-processing complex subunit. Overall, our work demonstrates a vital role of SHREK1 in pre-60S ribosome maturation, and reveals that impaired ribosome function accounts for the embryo lethality in shrek1.

DEK48 Is Required for RNA Editing at Multiple Mitochondrial Sites and Seed Development in Maize.

In flowering plants, C-to-U RNA editing can be critical to normal functions of mitochondrion-encoded proteins. Mitochondrial C-to-U RNA editing is facilitated by many factors from diverse protein families, of which the pentatricopeptide repeat (PPR) proteins play an important role. Owing to their large number and frequent embryo lethality in mutants, functions of many PPRs remain unknown. In this study, we characterized a mitochondrion-localized DYW-type PPR protein, DEK48, functioning in the C-to-U RNA editing at multiple mitochondrial transcripts in maize. Null mutation of Dek48 severely arrests embryo and endosperm development, causing a defective kernel (dek) phenotype, named dek48. DEK48 loss of function abolishes the C-to-U editing at nad3-185, -215, and nad4-376, -977 sites and decreases the editing at 11 other sites, resulting in the alteration of the corresponding amino acids. Consequently, the absence of editing caused reduced assembly and activity of complex I in dek48. Interestingly, we identified a point mutation in dek48-3 causing a deletion of the Tryptophan (W) residue in the DYW motif that abolishes the editing function. In sum, this study reveals the function of DEK48 in the C-to-U editing in mitochondrial transcripts and seed development in maize, and it demonstrates a critical role of the W residue in the DYW triplet motif of DEK48 for the C-to-U editing function in vivo.

Neuromodulatory Effects of HD-tACS/tDCS on the Prefrontal Cortex: A Resting-State fNIRS-EEG Study.

Transcranial direct and alternating current stimulation (tDCS and tACS, respectively) can modulate human brain dynamics and cognition. However, these modalities have not been compared using multiple imaging techniques concurrently. In this study, 15 participants participated in an experiment involving two sessions with a gap of 10 days. In the first and second sessions, tACS and tDCS were administered to the participants. The anode for tDCS was positioned at point FpZ, and four cathodes were positioned over the left and right prefrontal cortices (PFCs) to target the frontal regions simultaneously. tDCS was administered with 1 mA current. tACS was supplied with a current of 1 mA (zero-to-peak value) at 10 Hz frequency. Stimulation was applied concomitantly with functional near-infrared spectroscopy and electroencephalography acquisitions in the resting-state. The statistical test showed significant alteration (p < 0.001) in the mean hemodynamic responses during and after tDCS and tACS periods. Between-group comparison revealed a significantly less (p < 0.001) change in the mean hemodynamic response caused by tACS compared with tDCS. As hypothesized, we successfully increased the hemodynamics in both left and right PFCs using tDCS and tACS. Moreover, a significant increase in alpha-band power (p < 0.01) and low beta band power (p < 0.05) due to tACS was observed after the stimulation period. Although tDCS is not frequency-specific, it increased but not significantly (p > 0.05) the powers of most bands including delta, theta, alpha, low beta, high beta, and gamma. These findings suggest that both hemispheres can be targeted and that both tACS and tDCS are equally effective in high-definition configurations, which may be of clinical relevance.

Systemic Review on Transcranial Electrical Stimulation Parameters and EEG/fNIRS Features for Brain Diseases.

BACKGROUND: Brain disorders are gradually becoming the leading cause of death worldwide. However, the lack of knowledge of brain disease's underlying mechanisms and ineffective neuropharmacological therapy have led to further exploration of optimal treatments and brain monitoring techniques. OBJECTIVE: This study aims to review the current state of brain disorders, which utilize transcranial electrical stimulation (tES) and daily usable noninvasive neuroimaging techniques. Furthermore, the second goal of this study is to highlight available gaps and provide a comprehensive guideline for further investigation. METHOD: A systematic search was conducted of the PubMed and Web of Science databases from January 2000 to October 2020 using relevant keywords. Electroencephalography (EEG) and functional near-infrared spectroscopy were selected as noninvasive neuroimaging modalities. Nine brain disorders were investigated in this study, including Alzheimer's disease, depression, autism spectrum disorder, attention-deficit hyperactivity disorder, epilepsy, Parkinson's disease, stroke, schizophrenia, and traumatic brain injury. RESULTS: Sixty-seven studies (1,385 participants) were included for quantitative analysis. Most of the articles (82.6%) employed transcranial direct current stimulation as an intervention method with modulation parameters of 1 mA intensity (47.2%) for 16-20 min (69.0%) duration of stimulation in a single session (36.8%). The frontal cortex (46.4%) and the cerebral cortex (47.8%) were used as a neuroimaging modality, with the power spectrum (45.7%) commonly extracted as a quantitative EEG feature. CONCLUSION: An appropriate stimulation protocol applying tES as a therapy could be an effective treatment for cognitive and neurological brain disorders. However, the optimal tES criteria have not been defined; they vary across persons and disease types. Therefore, future work needs to investigate a closed-loop tES with monitoring by neuroimaging techniques to achieve personalized therapy for brain disorders.

Quantitative Assessment of Resting-State for Mild Cognitive Impairment Detection: A Functional Near-Infrared Spectroscopy and Deep Learning Approach.

BACKGROUND: Mild cognitive impairment (MCI) is considered a prodromal stage of Alzheimer's disease. Early diagnosis of MCI can allow for treatment to improve cognitive function and reduce modifiable risk factors. OBJECTIVE: This study aims to investigate the feasibility of individual MCI detection from healthy control (HC) using a minimum duration of resting-state functional near-infrared spectroscopy (fNIRS) signals. METHODS: In this study, nine different measurement durations (i.e., 30, 60, 90, 120, 150, 180, 210, 240, and 270 s) were evaluated for MCI detection via the graph theory analysis and traditional machine learning approach, such as linear discriminant analysis, support vector machine, and K-nearest neighbor algorithms. Moreover, feature representation- and classification-based transfer learning (TL) methods were applied to identify MCI from HC through the input of connectivity maps with 30 and 90 s duration. RESULTS: There was no significant difference among the nine various time windows in the machine learning and graph theory analysis. The feature representation-based TL showed improved accuracy in both 30 and 90 s cases (i.e., 30 s: 81.27% and 90 s: 76.73%). Notably, the classification-based TL method achieved the highest accuracy of 95.81% using the pre-trained convolutional neural network (CNN) model with the 30 s interval functional connectivity map input. CONCLUSION: The results indicate that a 30 s measurement of the resting-state with fNIRS could be used to detect MCI. Moreover, the combination of neuroimaging (e.g., functional connectivity maps) and deep learning methods (e.g., CNN and TL) can be considered as novel biomarkers for clinical computer-assisted MCI diagnosis.

A Bipolar-Channel Hybrid Brain-Computer Interface System for Home Automation Control Utilizing Steady-State Visually Evoked Potential and Eye-Blink Signals.

The goal of this study was to develop and validate a hybrid brain-computer interface (BCI) system for home automation control. Over the past decade, BCIs represent a promising possibility in the field of medical (e.g., neuronal rehabilitation), educational, mind reading, and remote communication. However, BCI is still difficult to use in daily life because of the challenges of the unfriendly head device, lower classification accuracy, high cost, and complex operation. In this study, we propose a hybrid BCI system for home automation control with two brain signals acquiring electrodes and simple tasks, which only requires the subject to focus on the stimulus and eye blink. The stimulus is utilized to select commands by generating steady-state visually evoked potential (SSVEP). The single eye blinks (i.e., confirm the selection) and double eye blinks (i.e., deny and re-selection) are employed to calibrate the SSVEP command. Besides that, the short-time Fourier transform and convolution neural network algorithms are utilized for feature extraction and classification, respectively. The results show that the proposed system could provide 38 control commands with a 2 s time window and a good accuracy (i.e., 96.92%) using one bipolar electroencephalogram (EEG) channel. This work presents a novel BCI approach for the home automation application based on SSVEP and eye blink signals, which could be useful for the disabled. In addition, the provided strategy of this study-a friendly channel configuration (i.e., one bipolar EEG channel), high accuracy, multiple commands, and short response time-might also offer a reference for the other BCI controlled applications.

Detection of Mild Cognitive Impairment Using Convolutional Neural Network: Temporal-Feature Maps of Functional Near-Infrared Spectroscopy.

Mild cognitive impairment (MCI) is the clinical precursor of Alzheimer's disease (AD), which is considered the most common neurodegenerative disease in the elderly. Some MCI patients tend to remain stable over time and do not evolve to AD. It is essential to diagnose MCI in its early stages and provide timely treatment to the patient. In this study, we propose a neuroimaging approach to identify MCI using a deep learning method and functional near-infrared spectroscopy (fNIRS). For this purpose, fifteen MCI subjects and nine healthy controls (HCs) were asked to perform three mental tasks: N-back, Stroop, and verbal fluency (VF) tasks. Besides examining the oxygenated hemoglobin changes (ΔHbO) in the region of interest, ΔHbO maps at 13 specific time points (i.e., 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, and 65 s) during the tasks and seven temporal feature maps (i.e., two types of mean, three types of slope, kurtosis, and skewness) in the prefrontal cortex were investigated. A four-layer convolutional neural network (CNN) was applied to identify the subjects into either MCI or HC, individually, after training the CNN model with ΔHbO maps and temporal feature maps above. Finally, we used the 5-fold cross-validation approach to evaluate the performance of the CNN. The results of temporal feature maps exhibited high classification accuracies: The average accuracies for the N-back task, Stroop task, and VFT, respectively, were 89.46, 87.80, and 90.37%. Notably, the highest accuracy of 98.61% was achieved from the ΔHbO slope map during 20-60 s interval of N-back tasks. Our results indicate that the fNIRS imaging approach based on temporal feature maps is a promising diagnostic method for early detection of MCI and can be used as a tool for clinical doctors to identify MCI from their patients.

Evaluation of Neural Degeneration Biomarkers in the Prefrontal Cortex for Early Identification of Patients With Mild Cognitive Impairment: An fNIRS Study.

Mild cognitive impairment (MCI), a condition characterizing poor cognition, is associated with aging and depicts early symptoms of severe cognitive impairment, known as Alzheimer's disease (AD). Meanwhile, early detection of MCI can prevent progression to AD. A great deal of research has been performed in the past decade on MCI detection. However, availability of biomarkers for MCI detection requires greater attention. In our study, we evaluated putative and reliable biomarkers for diagnosing MCI by performing different mental tasks (i.e., N-back task, Stroop task, and verbal fluency task) using functional near-infrared spectroscopy (fNIRS) signals on a group of 15 MCI patients and 9 healthy control (HC). The 15 digital biomarkers (i.e., five means, seven slopes, peak, skewness, and kurtosis) and two image biomarkers (t-map, correlation map) in the prefrontal cortex (PFC) (i.e., left PFC, middle PFC, and right PFC) between the MCI and HC groups were investigated by the statistical analysis, linear discriminant analysis (LDA), and convolutional neural network (CNN) individually. The results reveal that the statistical analysis using digital biomarkers (with a p-value < 0.05) could not distinguish the MCI patients from the HC over 60% accuracy. Therefore, the current statistical analysis needs to be improved to be used for diagnosing the MCI patients. The best accuracy with LDA was 76.67% with the N-back and Stroop tasks. However, the CNN classification results trained by image biomarkers showed a high accuracy. In particular, the CNN results trained via t-maps revealed the best accuracy (90.62%) with the N-back task, whereas the CNN result trained by the correlation maps was 85.58% with the N-back task. Also, the results illustrated that investigating the sub-regions (i.e., right, middle, left) of the PFC for detecting MCI would be better than examining the whole PFC. The t-map (or/and the correlation map) is conclusively recommended as an image biomarker for early detection of AD. The combination of CNN and image biomarkers can provide a reliable clinical tool for diagnosing MCI patients.