Using transcranial alternating current stimulation to enhance working memory skills in youths with 22q11.2 deletion syndrome: A randomized double-blind sham-controlled study.

Abnormal cognitive development, particularly working memory (WM) deficits, is among the first apparent manifestations of psychosis. Yet, cognitive impairment only shows limited response to current pharmacological treatment. Alternative interventions to target cognition are highly needed in individuals at high risk for psychosis, like carriers of 22q11.2 deletion syndrome (22q11.2DS). Here we applied theta-tuned transcranial alternating current stimulation (tACS) between frontal and temporal regions during a visual WM task in 34 deletion carriers. We conducted a double-blind sham-controlled study over three consecutive days. The stimulation parameters were derived from individual structural MRI scan and HD-EEG data acquired at baseline (Day 1) to model current intensity and individual preferential theta peak. Participants were randomized to either sham or tACS (Days 2 and 3) and then completed a visual WM task and a control task. Our findings reveal that tACS was safe and well-tolerated among participants. We found a significantly increased accuracy in the visual WM but not the control task following tACS. Moreover, this enhancement in WM accuracy was greater after tACS than during tACS, indicating stronger offline effects than online effects. Our study therefore supports the application of repeated sessions of brain stimulation in 22q11.2DS.

Self-Regulation of Attention in Children in a Virtual Classroom Environment: A Feasibility Study.

Attention is a crucial cognitive function that enables us to selectively focus on relevant information from the surrounding world to achieve our goals. Impairments in sustained attention pose challenges, particularly in children with attention deficit hyperactivity disorder, a neurodevelopmental disorder characterized by impulsive and inattentive behavior. While psychostimulant medications are the most effective ADHD treatment, they often yield unwanted side effects, making it crucial to explore non-pharmacological treatments. We propose a groundbreaking protocol that combines electroencephalography-based neurofeedback with virtual reality (VR) as an innovative approach to address attention deficits. By integrating a virtual classroom environment, we aim to enhance the transferability of attentional control skills while simultaneously increasing motivation and interest among children. The present study demonstrates the feasibility of this approach through an initial assessment involving a small group of healthy children, showcasing its potential for future evaluation in ADHD children. Preliminary results indicate high engagement and positive feedback. Pre- and post-protocol assessments via EEG and fMRI recordings suggest changes in attentional function. Further validation is required, but this protocol is a significant advancement in neurofeedback therapy for ADHD. The integration of EEG-NFB and VR presents a novel avenue for enhancing attentional control and addressing behavioral challenges in children with ADHD.

Electroencephalography microstates imbalance across the spectrum of early psychosis, autism, and mood disorders.

BACKGROUND: Electroencephalography (EEG) microstates translate resting-state temporal dynamics of neuronal networks throughout the brain and could constitute possible markers of psychiatric disorders. We tested the hypothesis of an increased imbalance between a predominant self-referential mode (microstate C) and a decreased attentional mode (microstate D) in psychosis, mood, and autism spectrum disorders. METHODS: We retrospectively included 135 subjects from an early psychosis outpatient unit, with available eyes-closed resting-state 19 electrodes EEG. Individual-level then group-level modified K-means clustering in controls provided four microstate maps that were then backfitted to all groups. Differences between microstate parameters (occurrence, coverage, and mean duration) were computed between controls and each group, and between disease groups. RESULTS: Microstate class D parameters were systematically decreased in disease groups compared with controls, with an effect size increasing along the psychosis spectrum, but also in autism. There was no difference in class C. C/D ratios of mean duration were increased only in SCZ compared with controls. CONCLUSIONS: The decrease in microstate class D may be a marker of stage of psychosis, but it is not specific to it and may rather reflect a shared dimension along the schizophrenia-autism spectrum. C/D microstate imbalance may be more specific to schizophrenia.

Spectral decomposition of EEG microstates in post-traumatic stress disorder.

Microstates offer a promising framework to study fast-scale brain dynamics in the resting-state electroencephalogram (EEG). However, microstate dynamics have yet to be investigated in post-traumatic stress disorder (PTSD), despite research demonstrating resting-state alterations in PTSD. We performed microstate-based segmentation of resting-state EEG in a clinical population of participants with PTSD (N = 61) and a non-traumatized, healthy control group (N = 61). Microstate-based measures (i.e., occurrence, mean duration, time coverage) were compared group-wise using broadband (1-30 Hz) and frequency-specific (i.e., delta, theta, alpha, beta bands) decompositions. In the broadband comparisons, the centro-posterior maximum microstate (map E) occurred significantly less frequently (d = -0.64, pFWE = 0.03) and had a significantly shorter mean duration in participants with PTSD as compared to controls (d = -0.71, pFWE < 0.01). These differences were reflected in the narrow frequency bands as well, with lower frequency bands like delta (d = -0.78, pFWE < 0.01), theta (d = -0.74, pFWE = 0.01), and alpha (d = -0.65, pFWE = 0.02) repeating these group-level trends, only with larger effect sizes. Interestingly, a support vector machine classification analysis comparing broadband and frequency-specific measures revealed that models containing only alpha band features significantly out-perform broadband models. When classifying PTSD, the classification accuracy was 76 % and 65 % for the alpha band and the broadband model, respectively (p = 0.03). Taken together, we provide original evidence supporting the clinical utility of microstates as diagnostic markers of PTSD and demonstrate that filtering EEG into distinct frequency bands significantly improves microstate-based classification of a psychiatric disorder.

Aberrant Developmental Patterns of Gamma-Band Response and Long-Range Communication Disruption in Youths With 22q11.2 Deletion Syndrome.

OBJECTIVE: Brain oscillations play a pivotal role in synchronizing responses of local and global ensembles of neurons. Patients with schizophrenia exhibit impairments in oscillatory response, which are thought to stem from abnormal maturation during critical developmental stages. Studying individuals at genetic risk for psychosis, such as 22q11.2 deletion carriers, from childhood to adulthood may provide insights into developmental abnormalities. METHODS: The authors acquired 106 consecutive T1-weighted MR images and 40-Hz auditory steady-state responses (ASSRs) with high-density (256 channel) EEG in a group of 58 22q11.2 deletion carriers and 48 healthy control subjects. ASSRs were analyzed with 1) time-frequency analysis using Morlet wavelet decomposition, 2) intertrial phase coherence (ITPC), and 3) theta-gamma phase-amplitude coupling estimated in the source space between brain regions activated by the ASSRs. Additionally, volumetric analyses were performed with FreeSurfer. Subanalyses were conducted in deletion carriers who endorsed psychotic symptoms and in subgroups with different age bins. RESULTS: Deletion carriers had decreased theta and late-latency 40-Hz ASSRs and phase synchronization compared with control subjects. Deletion carriers with psychotic symptoms displayed a further reduction of gamma-band response, decreased ITPC, and decreased top-down modulation of gamma-band response in the auditory cortex. Reduced gamma-band response was correlated with the atrophy of auditory cortex in individuals with psychotic symptoms. In addition, a linear increase of theta and gamma power from childhood to adulthood was found in control subjects but not in deletion carriers. CONCLUSIONS: The results suggest that while all deletion carriers exhibit decreased gamma-band response, more severe local and long-range communication abnormalities are associated with the emergence of psychotic symptoms and gray matter loss. Additionally, the lack of age-related changes in deletion carriers indexes a potential developmental impairment in circuits underlying the maturation of neural oscillations during adolescence. The progressive disruption of gamma-band response in 22q11.2 deletion syndrome supports a developmental perspective toward understanding and treating psychotic disorders.

Beyond broadband: Towards a spectral decomposition of electroencephalography microstates.

Originally applied to alpha oscillations in the 1970s, microstate (MS) analysis has since been used to decompose mainly broadband electroencephalogram (EEG) signals (e.g., 1-40 Hz). We hypothesised that MS decomposition within separate, narrow frequency bands could provide more fine-grained information for capturing the spatio-temporal complexity of multichannel EEG. In this study, using a large open-access dataset (n = 203), we first filtered EEG recordings into four classical frequency bands (delta, theta, alpha and beta) and thereafter compared their individual MS segmentations using mutual information as well as traditional MS measures (e.g., mean duration and time coverage). Firstly, we confirmed that MS topographies were spatially equivalent across all frequencies, matching the canonical broadband maps (A, B, C, D and C'). Interestingly, however, we observed strong informational independence of MS temporal sequences between spectral bands, together with significant divergence in traditional MS measures. For example, relative to broadband, alpha/beta band dynamics displayed greater time coverage of maps A and B, while map D was more prevalent in delta/theta bands. Moreover, using a frequency-specific MS taxonomy (e.g., Ï´A and αC), we were able to predict the eyes-open versus eyes-closed behavioural state significantly better using alpha-band MS features compared with broadband ones (80 vs. 73% accuracy). Overall, our findings demonstrate the value and validity of spectrally specific MS analyses, which may prove useful for identifying new neural mechanisms in fundamental research and/or for biomarker discovery in clinical populations.

Electroencephalographic Microstates as Novel Functional Biomarkers for Adult Attention-Deficit/Hyperactivity Disorder.

BACKGROUND: Research on the electroencephalographic (EEG) signatures of attention-deficit/hyperactivity disorder (ADHD) has historically concentrated on its frequency spectrum or event-related evoked potentials. In this work, we investigate EEG microstates (MSs), an alternative framework defined by the clustering of recurring topographical patterns, as a novel approach for examining large-scale cortical dynamics in ADHD. METHODS: Using k-means clustering, we studied the spatiotemporal dynamics of ADHD during the rest condition by comparing the MS segmentations between adult patients with ADHD and neurotypical control subjects across two independent datasets: the first dataset consisted of 66 patients with ADHD and 66 control subjects, and the second dataset comprised 22 patients with ADHD and 22 control subjects and was used for out-of-sample validation. RESULTS: Spatially, patients with ADHD and control subjects displayed equivalent MS topographies (canonical maps), indicating the preservation of prototypical EEG generators in patients with ADHD. However, this concordance was accompanied by significant differences in temporal dynamics. At the group level, and across both datasets, ADHD diagnosis was associated with longer mean durations of a frontocentral topography (MS D), indicating that its electrocortical generator(s) could be acting as pronounced attractors of global cortical dynamics. In addition, its spatiotemporal metrics were correlated with sleep disturbance, the latter being known to have a strong relationship with ADHD. Finally, in the first (larger) dataset, we also found evidence of decreased time coverage and mean duration of a left-right diagonal topography (MS A), which inversely correlated with ADHD scores. CONCLUSIONS: Overall, our study underlines the value of EEG MSs as promising functional biomarkers for ADHD, offering an additional lens through which to examine its neurophysiological mechanisms.

A portable neurofeedback device for treating chronic subjective tinnitus: Feasibility and results of a pilot study.

BACKGROUND: Several clinical studies have shown that neurofeedback (NFB) has the potential to significantly improve the quality of life of patients complaining of chronic subjective tinnitus. Yet the clinical applicability of such a therapeutic approach in the everyday practice has not been tested so far. OBJECTIVE: This study aims at investigating the feasibility and efficacy of a semi-automated NFB intervention by means of a portable device that eventually could be used by the patients at home on an everyday basis. The duration of setup procedures is minimized through the use of a dry electrodes electroencephalography (EEG) headset and an automated user-interface. METHODS: We conducted a pilot clinical study (non-controlled, single arm, NCT03773926). According to a predetermined power calculation, a homogeneous population of 33 subjects with strict inclusion criteria was enrolled. After inclusion, all patients underwent 10 NFB sessions lasting 50min each, over a period of 5 weeks and a 3-month follow-up period. According to previous studies, the NFB training aimed at increasing the alpha-band power (8-12Hz) in the EEG power spectrum on the averaged signal of leads FC1, FC2, F3 and F4. Tinnitus handicap inventory (THI) was used as a primary outcome measure. Secondary outcome measures were the visual analog scales (VAS) and the change of the alpha-band power within sessions and across training. Time points of assessment were before intervention (T1), after intervention (T2) and at the 3-month follow-up (T3). RESULTS: Patient exhibited a clinically significant decrease of the THI score, with a 23% decrease (N=28) on average between T1 and T2 and a 31% decrease (N=25) between T1 and T3. A significant increase of the alpha-band power within sessions was observed. No significant increase of the alpha-band power across sessions was observed. For the 19 subjects where sufficient data were exploitable, a significant correlation was found between the evolution of the alpha-band training across sessions and the evolution of the THI between T1 and T2. The sessions were well tolerated and no adverse effect was reported. CONCLUSION: This study suggests that neurofeedback has potential to suit everyday clinical practice with the goal to significantly reduce tinnitus intrusiveness. The merits and limitations of this NFB procedure are discussed, especially with respect to the choice of EEG electrodes to ensure a good signal quality.