Optimal parameters for rapid (invisible) frequency tagging using MEG.

Frequency tagging has been demonstrated to be a useful tool for identifying representational-specific neuronal activity in the auditory and visual domains. However, the slow flicker (<30 Hz) applied in conventional frequency tagging studies is highly visible and might entrain endogenous neuronal oscillations. Hence, stimulation at faster frequencies that is much less visible and does not interfere with endogenous brain oscillatory activity is a promising new tool. In this study, we set out to examine the optimal stimulation parameters of rapid frequency tagging (RFT/RIFT) with magnetoencephalography (MEG) by quantifying the effects of stimulation frequency, size and position of the flickering patch. Rapid frequency tagging using flickers above 50 Hz results in almost invisible stimulation which does not interfere with slower endogenous oscillations; however, the signal is weaker as compared to tagging at slower frequencies so certainty over the optimal parameters of stimulation delivery are crucial. The here presented results examining the frequency range between 60 Hz and 96 Hz suggest that RFT induces brain responses with decreasing strength up to about 84 Hz. In addition, even at the smallest flicker patch (2°) focally presented RFT induces a significant and measurable oscillatory brain signal (steady state visual evoked potential/field, SSVEP/F) at the stimulation frequency (66 Hz); however, the elicited response increases with patch size. While focal RFT presentation elicits the strongest response, off-centre presentations do generally mainly elicit a measureable response if presented below the horizontal midline. Importantly, the results also revealed considerable individual differences in the neuronal responses to RFT stimulation. Finally, we discuss the comparison of oscillatory measures (coherence and power) and sensor types (planar gradiometers and magnetometers) in order to achieve optimal outcomes. Based on our extensive findings we set forward concrete recommendations for using rapid frequency tagging in human cognitive neuroscience investigations.

FLUX: A pipeline for MEG analysis.

Magnetoencephalography (MEG) allows for quantifying modulations of human neuronal activity on a millisecond time scale while also making it possible to estimate the location of the underlying neuronal sources. The technique relies heavily on signal processing and source modelling. To this end, there are several open-source toolboxes developed by the community. While these toolboxes are powerful as they provide a wealth of options for analyses, the many options also pose a challenge for reproducible research as well as for researchers new to the field. The FLUX pipeline aims to make the analyses steps and setting explicit for standard analysis done in cognitive neuroscience. It focuses on quantifying and source localization of oscillatory brain activity, but it can also be used for event-related fields and multivariate pattern analysis. The pipeline is derived from the Cogitate consortium addressing a set of concrete cognitive neuroscience questions. Specifically, the pipeline including documented code is defined for MNE Python (a Python toolbox) and FieldTrip (a Matlab toolbox), and a data set on visuospatial attention is used to illustrate the steps. The scripts are provided as notebooks implemented in Jupyter Notebook and MATLAB Live Editor providing explanations, justifications and graphical outputs for the essential steps. Furthermore, we also provide suggestions for text and parameter settings to be used in registrations and publications to improve replicability and facilitate pre-registrations. The FLUX can be used for education either in self-studies or guided workshops. We expect that the FLUX pipeline will strengthen the field of MEG by providing some standardization on the basic analysis steps and by aligning approaches across toolboxes. Furthermore, we also aim to support new researchers entering the field by providing education and training. The FLUX pipeline is not meant to be static; it will evolve with the development of the toolboxes and with new insights. Furthermore, with the anticipated increase in MEG systems based on the Optically Pumped Magnetometers, the pipeline will also evolve to embrace these developments.

Theta:gamma phase coupling and evoked gamma activity reflect the fidelity of mental templates during memory matching in visual perception.

Top-down predictions of future events shaped by prior experience are an important control mechanism to allocate limited attentional resources more efficiently and are thought to be implemented as mental templates stored in memory. Increased evoked gamma activity and theta:gamma phase-phase coupling over parieto-occipital areas have previously been observed when mental templates meet matching visual stimuli. Here, we investigated how these signatures evolve during the formation of new mental templates and how they relate to the fidelity of such. Based on single-trial feedback, participants learned to classify target shapes as matching or mismatching with preceding cue sequences. In the end of the experiment, they were asked to freely reproduce targets as means of template fidelity. We observed fidelity-dependent increments of matching-related gamma phase locking and theta:gamma phase coupling in early visual areas around 100-200-ms poststimulus over time. Theta:gamma phase synchronization and evoked gamma activity might serve as complementary signatures of memory matching in visual perception; theta:gamma phase synchronization seemingly most important in early phases of learning and evoked gamma activity being essential for transition of mental templates into long-term memory.

EEG cross-frequency phase synchronization as an index of memory matching in visual search.

Visual perception is influenced by our expectancies about incoming sensory information. It is assumed that mental templates of expected sensory input are created and compared to actual input, which can be matching or not. When such mental templates are held in working memory, cross-frequency phase synchronization (CFS) between theta and gamma band activity has been proposed to serve matching processes between prediction and sensation. We investigated how this is affected by the number of activated templates that could be matched by comparing conditions where participants had to keep either one or multiple templates in mind for successful visual search. We found a transient CFS between EEG theta and gamma activity in an early time window around 150 ms after search display presentation, in right hemispheric parietal cortex. Our results suggest that for single template conditions, stronger transient theta-gamma CFS at posterior sites contralateral to target presentation can be observed than for multiple templates. This can be interpreted as evidence to the idea of sequential attentional templates. But mainly, it is understood in line with previous theoretical accounts strongly arguing for transient synchronization between posterior theta and gamma phase as a neural correlate of matching incoming sensory information with contents from working memory and as evidence for limitations in memory matching during multiple template search.

The involvement of alpha oscillations in voluntary attention directed towards encoding episodic memories.

Forming episodic memories is often driven by top-down processes of allocating attention towards voluntarily remembering the details of an episode. This attention orientation is needed to make sure that information is encoded for later remembering. Here we designed an episodic long-term memory (LTM) EEG experiment where we examined brain oscillatory activity associated with attention allocation towards the temporal link between an item and its context. The remembering of this temporal conjunction is crucial for item-context binding and hence for the formation of episodic memories. Participants saw a background picture and a word in a central position on a computer screen and were instructed to memorise (a) the picture only, (b) the word, (c) both individually (i.e. ignoring their co-occurrence) and (d) both with them being presented together. Attention allocation towards item-context binding was associated with oscillatory alpha desynchronization in the upper alpha band (10-13 Hz) over dominantly left posterior brain areas. The results highlight the role of alpha desynchronization in voluntary attention allocation towards the temporal conjunction of item and its context in episodic binding and the involvement of posterior brain areas. The pattern of results suggest that they most likely reflect additional visual processes recruited by attentional mechanisms and do not tap into neural processes of item-context binding per se. Moreover, it indicates that the involvement of alpha oscillations in cognitive processes may be more complex.

Brain Oscillatory Correlates of Altered Executive Functioning in Positive and Negative Symptomatic Schizophrenia Patients and Healthy Controls.

Working Memory and executive functioning deficits are core characteristics of patients suffering from schizophrenia. Electrophysiological research indicates that altered patterns of neural oscillatory mechanisms underpinning executive functioning are associated with the psychiatric disorder. Such brain oscillatory changes have been found in local amplitude differences at gamma and theta frequencies in task-specific cortical areas. Moreover, interregional interactions are also disrupted as signified by decreased phase coherence of fronto-posterior theta activity in schizophrenia patients. However, schizophrenia is not a one-dimensional psychiatric disorder but has various forms and expressions. A common distinction is between positive and negative symptomatology but most patients have both negative and positive symptoms to some extent. Here, we examined three groups-healthy controls, predominantly negative, and predominantly positive symptomatic schizophrenia patients-when performing a working memory task with increasing cognitive demand and increasing need for executive control. We analyzed brain oscillatory activity in the three groups separately and investigated how predominant symptomatology might explain differences in brain oscillatory patterns. Our results indicate that differences in task specific fronto-posterior network activity (i.e., executive control network) expressed by interregional phase synchronization are able to account for working memory dysfunctions between groups. Local changes in the theta and gamma frequency range also show differences between patients and healthy controls, and more importantly, between the two patient groups. We conclude that differences in oscillatory brain activation patterns related to executive processing can be an indicator for positive and negative symptomatology in schizophrenia. Furthermore, changes in cognitive and especially executive functioning in patients are expressed by alterations in a task-specific fronto-posterior connectivity even in the absence of behavioral impairment.

Effects of anodal transcranial direct current stimulation on visually guided learning of grip force control.

Anodal transcranial Direct Current Stimulation (tDCS) has been shown to be an effective non-invasive brain stimulation method for improving cognitive and motor functioning in patients with neurological deficits. tDCS over motor cortex (M1), for instance, facilitates motor learning in stroke patients. However, the literature on anodal tDCS effects on motor learning in healthy participants is inconclusive, and the effects of tDCS on visuo-motor integration are not well understood. In the present study we examined whether tDCS over the contralateral motor cortex enhances learning of grip-force output in a visually guided feedback task in young and neurologically healthy volunteers. Twenty minutes of 1 mA anodal tDCS were applied over the primary motor cortex (M1) contralateral to the dominant (right) hand, during the first half of a 40 min power-grip task. This task required the control of a visual signal by modulating the strength of the power-grip for six seconds per trial. Each participant completed a two-session sham-controlled crossover protocol. The stimulation conditions were counterbalanced across participants and the sessions were one week apart. Performance measures comprised time-on-target and target-deviation, and were calculated for the periods of stimulation (or sham) and during the afterphase respectively. Statistical analyses revealed significant performance improvements over the stimulation and the afterphase, but this learning effect was not modulated by tDCS condition. This suggests that the form of visuomotor learning taking place in the present task was not sensitive to neurostimulation. These null effects, together with similar reports for other types of motor tasks, lead to the proposition that tDCS facilitation of motor learning might be restricted to cases or situations where the motor system is challenged, such as motor deficits, advanced age, or very high task demand.

Interacting memory systems-does EEG alpha activity respond to semantic long-term memory access in a working memory task?

Memory consists of various individual processes which form a dynamic system co-ordinated by central (executive) functions. The episodic buffer as direct interface between episodic long-term memory (LTM) and working memory (WM) is fairly well studied but such direct interaction is less clear in semantic LTM. Here, we designed a verbal delayed-match-to-sample task specifically to differentiate between pure information maintenance and mental manipulation of memory traces with and without involvement of access to semantic LTM. Task-related amplitude differences of electroencephalographic (EEG) oscillatory brain activity showed a linear increase in frontal-midline theta and linear suppression of parietal beta amplitudes relative to memory operation complexity. Amplitude suppression at upper alpha frequency, which was previously found to indicate access to semantic LTM, was only sensitive to mental manipulation in general, irrespective of LTM involvement. This suggests that suppression of upper EEG alpha activity might rather reflect unspecific distributed cortical activation during complex mental processes than accessing semantic LTM.

EEG oscillatory phase-dependent markers of corticospinal excitability in the resting brain.

Functional meaning of oscillatory brain activity in various frequency bands in the human electroencephalogram (EEG) is increasingly researched. While most research focuses on event-related changes of brain activity in response to external events there is also increasing interest in internal brain states influencing information processing. Several studies suggest amplitude changes of EEG oscillatory activity selectively influencing cortical excitability, and more recently it was shown that phase of EEG activity (instantaneous phase) conveys additional meaning. Here we review this field with many conflicting findings and further investigate whether corticospinal excitability in the resting brain is dependent on a specific spontaneously occurring brain state reflected by amplitude and instantaneous phase of EEG oscillations. We applied single pulse transcranial magnetic stimulation (TMS) over the left sensorimotor cortex, while simultaneously recording ongoing oscillatory activity with EEG. Results indicate that brain oscillations reflect rapid, spontaneous fluctuations of cortical excitability. Instantaneous phase but not amplitude of oscillations at various frequency bands at stimulation site at the time of TMS-pulse is indicative for brain states associated with different levels of excitability (defined by size of the elicited motor evoked potential). These results are further evidence that ongoing brain oscillations directly influence neural excitability which puts further emphasis on their role in orchestrating neuronal firing in the brain.