Ivan Alekseichuk

Transcranial electrical stimulation of the occipital cortex during visual perception modifies the magnitude of BOLD activity: A combined tES–fMRI approach

The aim of this study was to investigate if the blood oxygenation level-dependent (BOLD) changes in the visual cortex can be used as biomarkers reflecting the online and offline effects of transcranial electrical stimulation (tES). Anodal transcranial direct current stimulation (tDCS) and 10Hz transcranial alternating current stimulation (tACS) were applied for 10min duration over the occipital cortex of healthy adults during the presentation of different visual stimuli, using a crossover, double-blinded design. Control experiments were also performed, in which sham stimulation as well as another electrode montage were used. Anodal tDCS over the visual cortex induced a small but significant further increase in BOLD response evoked by a visual stimulus; however, no aftereffect was observed. Ten hertz of tACS did not result in an online effect, but in a widespread offline BOLD decrease over the occipital, temporal, and frontal areas. These findings demonstrate that tES during visual perception affects the neuronal metabolism, which can be detected with functional magnetic resonance imaging (fMRI).

Separating Recognition Processes of Declarative Memory via Anodal tDCS: Boosting Old Item Recognition by Temporal and New Item Detection by Parietal Stimulation

There is emerging evidence from imaging studies that parietal and temporal cortices act together to achieve successful recognition of declarative information; nevertheless, the precise role of these regions remains elusive. To evaluate the role of these brain areas in declarative memory retrieval, we applied bilateral tDCS, with anode over the left and cathode over the right parietal or temporal cortices separately, during the recognition phase of a verbal learning paradigm using a balanced old-new decision task. In a parallel group design, we tested three different groups of healthy adults, matched for demographic and neurocognitive status: two groups received bilateral active stimulation of either the parietal or the temporal cortex, while a third group received sham stimulation. Accuracy, discriminability index (d’) and reaction times of recognition memory performance were measurements of interest. The d’ sensitivity index and accuracy percentage improved in both active stimulation groups, as compared with the sham one, while reaction times remained unaffected. Moreover, the analysis of accuracy revealed a different effect of tDCS for old and new item recognition. While the temporal group showed enhanced performance for old item recognition, the parietal group was better at correctly recognising new ones. Our results support an active role of both of these areas in memory retrieval, possibly underpinning different stages of the recognition process.

Intrahemispheric theta rhythm desynchronization impairs working memory

BACKGROUND There is a growing interest in large-scale connectivity as one of the crucial factors in working memory. Correlative evidence has revealed the anatomical and electrophysiological players in the working memory network, but understanding of the effective role of their connectivity remains elusive. OBJECTIVE In this double-blind, placebo-controlled study we aimed to identify the causal role of theta phase connectivity in visual-spatial working memory. METHODS The frontoparietal network was over- or de-synchronized in the anterior-posterior direction by multi-electrode, 6 Hz transcranial alternating current stimulation (tACS). RESULTS A decrease in memory performance and increase in reaction time was caused by frontoparietal intrahemispheric desynchronization. According to the diffusion drift model, this originated in a lower signal-to-noise ratio, known as the drift rate index, in the memory system. The EEG analysis revealed a corresponding decrease in phase connectivity between prefrontal and parietal areas after tACS-driven desynchronization. The over-synchronization did not result in any changes in either the behavioral or electrophysiological levels in healthy participants. CONCLUSION Taken together, we demonstrate the feasibility of manipulating multi-site large-scale networks in humans, and the disruptive effect of frontoparietal desynchronization on theta phase connectivity and visual-spatial working memory.

The metabolomic approach to the assessment of cultivar specificity of Brassica napus L. seeds

The recent biomolecular studies tend to involve combinations of different methods and approaches that allow analyzing organisms at the genomic and proteomic levels, as well as at the level of metabolomics. However, in order to justify the use of the metabolomics techniques in plant breeding, it is important to comprehensively analyze a broad range of species and varieties. In this study, we evaluated the contents of low-molecular-weight substances in seeds of different rapeseed cultivars by the gas chromatography–mass spectrometry (GC–MS) technique. For every metabolomic profile, we estimated 168 target substances, and 52 of them were unambiguously identified. These compounds included amino acids, organic and fatty acids, tocopherols, and phytosterols. In order to keep the data assay within the context of multivariate statistics, we used principal component analysis (PCA), partial least square discriminant analysis (PLS-DA), and partial least square regression (PLS-R). The subsequent analysis revealed a significant difference between the metabolomic profiles of the investigated rapeseed cultivars, with the primary role of the amino acids and organic acids. Noticeably, the PCA and PLS-DA models showed 65% of the explained variance and, according to the Venetian blinds’ cross-validation test, 91.67% accuracy. Thus, we demonstrated the effectiveness of the metabolomic approach for the varietal identification of seeds. This strategy can be further improved with a continuously updated database of the metabolomic profiles of different species and cultivars. Application of the PLS-DA method will make it possible to compare metabolites of unknown seed samples with the existing metabolomic profiles and, subsequently, identify new seed samples.

Perturbation of theta-gamma coupling at the temporal lobe hinders verbal declarative memory

BACKGROUND Phase-amplitude cross-frequency coupling (PAC) is characterized by the modulation of the power of a fast brain oscillation (e.g., gamma) by the phase of a slow rhythm (e.g., theta). PAC in different sub- and neocortical regions is known to underlie effective neural communication and correlates with successful long-term memory formation. OBJECTIVE/HYPOTHESIS The present work aims to extend earlier observational data, by probing the functional role of theta-gamma PAC in the left temporal cortex in humans during verbal long-term memory encoding. METHODS In three double-blinded, placebo-controlled experiments (n = 72), we employed cross-frequency transcranial alternating current stimulation (tACS) to externally modulate ongoing PAC during a verbal-associative learning task. Three types of cross-frequency tACS protocols were used: bursts of high gamma tACS were coupled to the peak or trough of the theta tACS cycle, and a control condition where gamma tACS was continuously superimposed at theta tACS cycles. RESULTS Gamma bursts coupled to the trough of theta tACS induced robust behavioral impairment in memory performance (p < .01), whereas gamma burst coupled to the peak or continuously superimposed with theta tACS had no significant behavioral effects. CONCLUSIONS Our results demonstrate direct evidence regarding the importance of theta-gamma coupling in verbal long-term memory formation.

On ways to overcome the magical capacity limit of working memory

The ability to simultaneously process and maintain multiple pieces of information is limited. Over the past 50 years, observational methods have provided a large amount of insight regarding the neural mechanisms that underpin the mental capacity that we refer to as “working memory.” More than 20 years ago, a neural coding scheme was proposed for working memory. As a result of technological developments, we can now not only observe but can also influence brain rhythms in humans. Building on these novel developments, we have begun to externally control brain oscillations in order to extend the limits of working memory.

Comparative Modeling of Transcranial Magnetic and Electric Stimulation in Mouse, Monkey, and Human

Transcranial magnetic stimulation (TMS) and transcranial electric stimulation (TES) are increasingly popular methods to noninvasively affect brain activity. However, their mechanism of action and dose-response characteristics remain under active investigation. Translational studies in animals play a pivotal role in these efforts due to a larger neuroscientific toolset enabled by invasive recordings. In order to translate knowledge gained in animal studies to humans, it is crucial to generate comparable stimulation conditions with respect to the induced electric field in the brain. Here, we conduct a finite element method (FEM) modeling study of TMS and TES electric fields in a mouse, capuchin monkey, and human model. We systematically evaluate the induced electric fields and analyze their relationship to head and brain anatomy. We find that with increasing head size, TMS-induced electric field strength first increases and then decreases according to a two-term exponential function. TES-induced electric field strength strongly decreases from smaller to larger specimen with up to 100x fold differences across species. Our results can serve as a basis to compare and match stimulation parameters across studies in animals and humans. HIGHLIGHTS Translational research in brain stimulation should account for large differences in induced electric fields in different organisms We simulate TMS and TES electric fields using anatomically realistic finite element models in three species: mouse, monkey, and human TMS with a 70 mm figure-8 coil creates an approximately 2-times weaker electric field in a mouse brain than in monkey and human brains, where electric field strength is comparable Two-electrode TES creates an approximately 100-times stronger electric field in a mouse brain and 3.5-times stronger electric field in a monkey brain than in a human brain

transcranial Direct Current Stimulation Studies Open Database (tDCS-OD)

Transcranial direct current stimulation (tDCS) is increasingly evaluated for a myriad of clinical indications and performance enhancement mainly related to cognitive and motor applications. As a result tDCS has been tested with diverse inclusion criteria and subject populations. tDCS is customized for applications by many factors, including stimulation dose (montage, current, time), associated training and subject inclusion/exclusion criteria. The rapid proliferation of applications, technological advancements and emerging scientific discoveries presents challenges to the organization and consolidation of tDCS data – which can lead to scientific, clinical and public confusions. In this paper, we develop a system to summarize and consolidate methodological aspects of tDCS, concentrating on study design and the physical parameters of the stimulation. We introduce a community-driven, open access database, where these parameters, including stimulation intensities, duration, electrode sizes, montages, and subject information, are noted for relevant tDCS publications. The transcranial Direct Current Stimulation Studies Open Database (tDCS-OD) (http://tdcsdatabase.com) will support constructive dialogue on research and clinical tDCS applications, critical evaluation of past work, and identification of promising protocols, while reducing ambiguity about stimulation methodology. The database design allows ongoing updates and editing, with transparent version control. At the moment, the database includes information about 56,613 tDCS sessions.

Electric field dynamics in the brain during multi-electrode transcranial electric stimulation

Neural oscillations play a crucial role in communication between remote brain areas. Transcranial electric stimulation with alternating currents (TACS) can manipulate these brain oscillations in a non-invasive manner. Of particular interest, TACS protocols using multiple electrodes with phase shifted stimulation currents were developed to alter the connectivity between two or more brain regions. Typically, an increase in coordination between two sites is assumed when they experience an in-phase stimulation and a disorganization through an anti-phase stimulation. However, the underlying biophysics of multi-electrode TACS has not been studied in detail, thus limiting our ability to develop a mechanistic understanding. Here, we leverage direct invasive recordings from two non-human primates during multi-electrode TACS to show that the electric field magnitude and phase depend on the phase of the stimulation currents in a non-linear manner. Further, we report a novel phenomenon of a “traveling wave” stimulation where the location of the electric field maximum changes over the stimulation cycle. Our results provide a basis for a mechanistic understanding of multi-electrode TACS, necessitating the reevaluation of previously published studies, and enable future developments of novel stimulation protocols.

The New Modalities of Transcranial Electric Stimulation: tACS, tRNS, and Other Approaches

The most frequently used low-intensity transcranial electrical stimulation (tES) techniques are transcranial direct current (tDCS), alternating current (tACS), and random noise stimulation (tRNS). During tES, currents are applied with intensities ranging between 0.4 and 2 mA through the human scalp. It has been suggested that tACS interacts with cortical oscillations in a frequency-specific manner at single and using tRNS, at multiple frequencies. All techniques might affect homeostatic mechanisms or the signal-to-noise ratio in the brain. The aim of this review is to summarize basic aspects of tACS and tRNS, their possible neuronal mechanisms and clinical applications.