Closed-Loop Transcranial Electrical Neurostimulation for Sustained Attention Enhancement: A Pilot Study towards Personalized Intervention Strategies.

Sustained attention is pivotal for tasks like studying and working for which focus and low distractions are necessary for peak productivity. This study explores the effectiveness of adaptive transcranial direct current stimulation (tDCS) in either the frontal or parietal region to enhance sustained attention. The research involved ten healthy university students performing the Continuous Performance Task-AX (AX-CPT) while receiving either frontal or parietal tDCS. The study comprised three phases. First, we acquired the electroencephalography (EEG) signal to identify the most suitable metrics related to attention states. Among different spectral and complexity metrics computed on 3 s epochs of EEG, the Fuzzy Entropy and Multiscale Sample Entropy Index of frontal channels were selected. Secondly, we assessed how tDCS at a fixed 1.0 mA current affects attentional performance. Finally, a real-time experiment involving continuous metric monitoring allowed personalized dynamic optimization of the current amplitude and stimulation site (frontal or parietal). The findings reveal statistically significant improvements in mean accuracy (94.04 vs. 90.82%) and reaction times (262.93 vs. 302.03 ms) with the adaptive tDCS compared to a non-stimulation condition. Average reaction times were statistically shorter during adaptive stimulation compared to a fixed current amplitude condition (262.93 vs. 283.56 ms), while mean accuracy stayed similar (94.04 vs. 93.36%, improvement not statistically significant). Despite the limited number of subjects, this work points out the promising potential of adaptive tDCS as a tailored treatment for enhancing sustained attention.

Corrigendum: Alpha-synuclein oligomers alter the spontaneous firing discharge of cultured midbrain neurons.

[This corrects the article DOI: 10.3389/fncel.2023.1078550.].

Connectivity Analysis in EEG Data: A Tutorial Review of the State of the Art and Emerging Trends.

Understanding how different areas of the human brain communicate with each other is a crucial issue in neuroscience. The concepts of structural, functional and effective connectivity have been widely exploited to describe the human connectome, consisting of brain networks, their structural connections and functional interactions. Despite high-spatial-resolution imaging techniques such as functional magnetic resonance imaging (fMRI) being widely used to map this complex network of multiple interactions, electroencephalographic (EEG) recordings claim high temporal resolution and are thus perfectly suitable to describe either spatially distributed and temporally dynamic patterns of neural activation and connectivity. In this work, we provide a technical account and a categorization of the most-used data-driven approaches to assess brain-functional connectivity, intended as the study of the statistical dependencies between the recorded EEG signals. Different pairwise and multivariate, as well as directed and non-directed connectivity metrics are discussed with a pros-cons approach, in the time, frequency, and information-theoretic domains. The establishment of conceptual and mathematical relationships between metrics from these three frameworks, and the discussion of novel methodological approaches, will allow the reader to go deep into the problem of inferring functional connectivity in complex networks. Furthermore, emerging trends for the description of extended forms of connectivity (e.g., high-order interactions) are also discussed, along with graph-theory tools exploring the topological properties of the network of connections provided by the proposed metrics. Applications to EEG data are reviewed. In addition, the importance of source localization, and the impacts of signal acquisition and pre-processing techniques (e.g., filtering, source localization, and artifact rejection) on the connectivity estimates are recognized and discussed. By going through this review, the reader could delve deeply into the entire process of EEG pre-processing and analysis for the study of brain functional connectivity and learning, thereby exploiting novel methodologies and approaches to the problem of inferring connectivity within complex networks.

Alpha-synuclein oligomers alter the spontaneous firing discharge of cultured midbrain neurons.

The aim of this work was to monitor the effects of extracellular α-synuclein on the firing activity of midbrain neurons dissociated from substantia nigra TH-GFP mice embryos and cultured on microelectrode arrays (MEA). We monitored the spontaneous firing discharge of the network for 21 days after plating and the role of glutamatergic and GABAergic inputs in regulating burst generation and network synchronism. Addition of GABA A , AMPA and NMDA antagonists did not suppress the spontaneous activity but allowed to identify three types of neurons that exhibited different modalities of firing and response to applied L-DOPA: high-rate (HR) neurons, low-rate pacemaking (LR-p), and low-rate non-pacemaking (LR-np) neurons. Most HR neurons were insensitive to L-DOPA, while the majority of LR-p neurons responded with a decrease of the firing discharge; less defined was the response of LR-np neurons. The effect of exogenous α-synuclein (α-syn) on the firing discharge of midbrain neurons was then studied by varying the exposure time (0-48 h) and the α-syn concentration (0.3-70 µM), while the formation of α-syn oligomers was monitored by means of AFM. Independently of the applied concentration, acute exposure to α-syn monomers did not exert any effect on the spontaneous firing rate of HR, LR-p, and LR-np neurons. On the contrary, after 48 h exposure, the firing activity was drastically altered at late developmental stages (14 days in vitro, DIV, neurons): α-syn oligomers progressively reduced the spontaneous firing discharge (IC50 = 1.03 µM), impaired burst generation and network synchronism, proportionally to the increased oligomer/monomer ratio. Different effects were found on early-stage developed neurons (9 DIV), whose firing discharge remained unaltered, regardless of the applied α-syn concentration and the exposure time. Our findings unravel, for the first time, the variable effects of exogenous α-syn at different stages of midbrain network development and provide new evidence for the early detection of neuronal function impairment associated to aggregated forms of α-syn.