Paul Sauseng

Theta-gamma phase synchronization during memory matching in visual working memory

In most cases, object recognition is related to the matching of internal memory contents and bottom-up external sensory stimulation. The aim of this study was to investigate the electrophysiological correlates of memory matching based on EEG oscillatory phase synchronization analysis. Healthy subjects completed a delayed-match to sample task in which items stored in visual-spatial short-term memory had to be compared with a matching or non-matching probe. The results show that memory matching appears as transient phase-synchronization over parieto-occipital regions between theta (4-8 Hz) and high gamma (50-70 Hz) oscillations, 150-200 ms post probe presentation. When memory representation and visual information match, phase-synchronization is stronger in the right hemisphere; conversely, when they do not match, stronger phase synchronization is observed in the left hemisphere. The present results reveal the integrative role of oscillatory activity in the memory matching process.

Right Prefrontal TMS Disrupts Interregional Anticipatory EEG Alpha Activity during Shifting of Visuospatial Attention

Visual attention can be shifted in space without moving the eyes. Amplitude decrease of rhythmical brain activity around 10 Hz (so called alpha activity) at contralateral posterior sites has been reported during covered shifts of visuospatial attention to one visual hemi-field. Alpha amplitude increase, on the other hand, can be found at ipsilateral visual cortex. There is some evidence suggesting an involvement of prefrontal brain areas during the control of attention-related anticipatory alpha amplitude asymmetry. This open question has been studied in detail using a multimodal approach combining transcranial magnetic stimulation (TMS) and multichannel electroencephalography (EEG) in healthy humans. Slow (1 Hz) repetitive TMS leading to reduced excitability of the stimulation site was delivered either to right frontal eye field (FEF) or a control site (vertex). Subsequently, participants had to perform a spatial cuing task in which covert shifts of attention were required to either the left or the right visual hemi-field. After stimulation at the vertex (control condition) a pattern of anticipatory, attention-related ipsilateral alpha increase/contralateral alpha decrease over posterior recording sites could be obtained. Additionally, there was pronounced coupling between (in particular right) FEF and posterior brain sites at EEG alpha frequency. When, however, right prefrontal cortex had been virtually lesioned preceding the task, these EEG correlates of visuospatial attention were attenuated. Notably, the effect of TMS at the right FEF on interregional fronto-parietal alpha coupling predicted the effect of TMS on response times. This suggests that visual attention processes associated with posterior EEG alpha activity are at least partly top-down controlled by the prefrontal cortex.

Two brakes are better than one: the neural bases of inhibitory control of motor memory traces

Inhibitory control of actions is one important aspect in daily life to warrant adequate context related behavior. Alpha activity (oscillatory brain activity around 10Hz) has been suggested to play a major role for the implementation of inhibitory control. In the present study electrophysiological correlates of voluntary suppression of acquired, memorized motor actions have been compared to the suppression of novel motor actions. Multichannel EEG analyses of alpha power and alpha phase coherence were used. Healthy subjects were asked to inhibit the execution of either well-trained, memorized or untrained, novel sequential finger movements depending on the respective context. An increase of focal upper alpha activity at bilateral sensorimotor cortices was found during suppression of movements independent of whether these were memorized or novel. This represents a memory unspecific mechanism of motor cortical inhibition. In contrast, interregional phase synchronization between frontal and (left) central recording sites showed a differential effect with decoupling during suppression of memorized movements which was not the case with novel ones. Increase of fronto-central coupling at upper alpha frequency during retrieval of the memory trace and decrease during suppression of retrieval were obtained. This further supports the view of the functional relevance of upper alpha oscillations as a mechanism of context-dependent sustained inhibition of memory contents.

Anodal transcranial direct current stimulation (tDCS) increases frontal–midline theta activity in the human EEG: A preliminary investigation of non-invasive stimulation

Rhythmical brain activity in the range between four and eight Hz acquired over frontal-midline EEG recording sites - so called frontal-midline theta activity - is regarded as one of the most prominent neural signatures of sustained attention. It is reported to parametrically increase with cognitive load and is thought to be generated in medial prefrontal cortex. Here we explored the possibility of using anodal transcranial direct current stimulation over frontal sites to enhance frontal-midline theta activity and to increase sustained attention performance. We used a small preliminary sample to test a novel direct current stimulation electrode configuration by which we were able to significantly increase frontal-midline theta amplitude in a resting condition after the end of the stimulation period. Using standardised low resolution electromagnetic tomography analysis the effect in the surface EEG was localised to right prefrontal and left medial prefrontal brain areas. Transcranial direct current stimulation did, however, not have any impact on behavioural performance during a sustained attention task. This most likely was due to a very fast washout of the stimulations after effect on theta activity. Although these are only preliminary results from a rather small sample, this study demonstrates that transcranial direct current stimulation can be used to rather selectively enhance frontal-midline theta amplitude.

EEG theta phase coupling during executive control of visual working memory investigated in individuals with schizophrenia and in healthy controls

In healthy humans, it has been shown that executive functions are associated with increased frontal-midline EEG theta activity and theta phase coupling between frontal and posterior brain regions. In individuals with schizophrenia, central executive functions are supposed to be heavily impaired. Given that theta phase coupling is causally involved in central executive functions, one would expect that patients with an executive function deficit should display abnormal EEG theta synchronization. We therefore investigated executive functioning in 21 healthy controls and 21 individuals with schizophrenia while they performed a visuospatial delayed match to sample task. The task required either high executive demands (manipulation of content in working memory [WM]) or low executive demands (retention of WM content). In addition, WM load (one vs. three items) was varied. Results indicated higher frontal theta activity for manipulation processes than for retention processes in patients with schizophrenia, as compared with healthy controls, independently of WM load. Furthermore, individuals with schizophrenia revealed a reduction in theta phase coupling during early stages of the delay period for retention, as well as for manipulation processes at high-WM loads. Deviations in theta phase coupling in individuals with schizophrenia were mainly characterized by aberrant fronto-posterior connections, but also by attenuated posterior connections during manipulation of high-WM load. To conclude, fronto-parietal theta coupling seems to be substantially involved in executive control, whereas frontal theta activity seems to reflect general task demands, such as deployment of attentional resources during WM.

The Importance of Sample Size for Reproducibility of tDCS Effects

Cheap, easy to apply, well-tolerable, with the potential of altering cortical excitability, and for testing causalities—these are attributes that have made transcranial direct current stimulation (tDCS) a highly popular research tool in cognitive neuroscience. Since its reintroduction over 15 years ago by Nitsche and Paulus (2000), the number of publications reporting tDCS results has risen exponentially (a Scopus® literature search indicates over 500 such journal articles published in 2015 alone). Recently however, the efficacy of tDCS to alter cognitive performance has been called into question, in particular among healthy participants, but also in certain clinical samples (Horvath et al., 2015; Hill et al., 2016; Mancuso et al., 2016). A number of empirical studies reported not having been able to detect any facilitatory effects of anodal tDCS or inhibitory effects of cathodal tDCS on various cognitive processes (e.g., Wiethoff et al., 2014; Minarik et al., 2015; Sahlem et al., 2015; Horvath et al., 2016; Vannorsdall et al., 2016). In fact, in a recent meta-analysis Horvath et al. (2015) argue that in young, healthy participants there is no effect of tDCS on cognition whatsoever, whereas other meta- analyses do find specific modulation of cognitive processes by tDCS; however, these effects seem to be rather weak (Hill et al., 2016; Mancuso et al., 2016). In a recent commentary the field of tDCS research was even called a research area of bad science (Underwood, 2016) in desperate need of further meticulous evaluation. Although there seems to be some inconsistency of effects there is also current work by Cason and Medina (2016) suggesting no evidence for p-hacking (strategic testing and analysis procedures to increase likelihood of obtaining significant effects) in tDCS research. However, Cason and Medina (2016) find average statistical power in tDCS studies to be below 50%. Therefore, one potential reason for the reported inconsistencies might be that sample size is usually very small in most tDCS studies (including those from our research group). Whilst this issue is not specific to tDCS studies (in fact Button et al., 2013 estimate the median statistical power in neuroscience in general being only 21%), it could lead to weaker effects often not being detected, and consequently meta- analyses suggesting small or no efficacy of tDCS. In addition, the assessment of the real effect of tDCS is further complicated by potential publication bias (file drawer problem) leading to over-reporting significant tDCS findings. That is, a publication bias favoring studies with significant effects might lead to an inflation of the reported efficacy of tDCS. Thus, depending on which studies are included in systematic reviews and meta- analyses (i.e., findings published in peer-reviewed journals; unpublished nil-effects; nil-effects reported as an additional finding in papers with the actual focus on another, significant, effect, etc.), small sample size in tDCS research could lead to both under—and overestimation of tDCS efficacy. Some current meta- analyses (e.g., Mancuso et al., 2016), however, include an estimation of publication bias (e.g., using the “trim and fill” procedure in which funnel plots are used for determining whether there is a bias toward studies with significant effects in the literature included in the meta- analysis); and overall effect size can then be adjusted accordingly. Taking publication bias into account it becomes evident that efficacy of tDCS is rather weak (Mancuso et al., 2016). As indicated by quite some inconsistency in literature on the efficacy of the stimulation, the field of tDCS research is clearly struck by the replication crisis that we also find in psychology and neurosciences in general (Button et al., 2013; Open Science Collaboration, 2015). But how to estimate efficacy of tDCS, if it is not clear, how many unsuccessful experimental attempts end up in the file drawer? As discussed above, one possibility is to adjust for publication bias in meta- analyses. Another strategy is pre-registering tDCS studies and reporting their outcome, independent of whether the results are significant or not—be it in peer reviewed journals or platforms such as the Open Science Framework (https://osf.io); this can result in more accurate estimates of efficacy. Moreover, allowing open access to the acquired data (open data) offers the opportunity that researchers could pool raw data from experiments with small samples but similar experimental designs. By doing so, they overcome the problem of under-powering, an issue that seems so fundamental in tDCS research. Therefore, to investigate the effect of sample size on tDCS efficacy and to contribute to increased research transparency we designed a simple, pre-registered study (https://osf.io/eb9c5/?view_only=2743a0c4600943c998c2c37fbfb25846) with a sufficiently large number of young, healthy volunteers estimated with a priori power analysis. Furthermore, we make all the acquired data publicly available. In a choice reaction time task (CRT) participants underwent either anodal or cathodal tDCS applied to the sensorimotor cortex. Jacobson et al. (2012) suggest that for the motor domain with tDCS over sensorimotor cortex anodal-excitation and cathodal-inhibition effects (AeCi) are quite straight forward, whereas in other cognitive domains AeCi effects seem not particularly robust. Since we stimulated the sensorimotor cortex we decided to contrast anodal with cathodal tDCS (instead of sham stimulation) for obtaining the largest possible effect. We expected anodal stimulation to result in faster response times compared to cathodal tDCS in accordance with findings by Garcia-Cossio et al. (2015). To demonstrate the importance of sample size for finding the predicted effect, random samples of different sizes were drawn from the data pool and tested statistically. This way the probability of identifying the predicted effect was obtained as a function of sample size.

Alpha coherence predicts accuracy during a visuomotor tracking task

It has been shown that synchrony of neuronal oscillations plays a critical role in effective communication between functionally distinct brain areas involving motor-sensory integration. However, the patterns of cortico-cortical coupling and their relation to behavioural success are widely unknown. Here, we analysed changes in cortico-cortical coherence during an unimanual visuomotor task and their correlation with performance. A 28-channel-EEG was attained in 27 healthy subjects during the tracking of an irregularly fluctuating target on a screen by manipulating a force sensor with the right index finger and thumb. For oscillatory power in the alpha (8-12 Hz) and the lower beta-band (beta1, 13-20 Hz), we found a decrease in central and occipital areas during performance. Interregional coherence between contralateral frontal and central areas was enhanced in the alpha band. In beta1, we observed a marked increase of coherence in centroparietal regions of both hemispheres extending to occipital and frontal regions in beta2 (21-30 Hz). Most prominently, correlation analysis between alpha coherence and performance accuracy indicated that higher occipitocentral (i.e. visuomotor) coherence is associated with better visuomotor performance whereas high tracking error is associated with enhanced frontocentral coupling, suggesting additional activation of a frontoparietal control network. These results provide further evidence that coherent brain oscillations in alpha and beta bands significantly contribute to effective functional integration of visual and motor areas.

Stuck in default mode: inefficient cross-frequency synchronization may lead to age-related short-term memory decline

Aging-related decline in short-term memory capacity seems to be caused by deficient balancing of task-related and resting state brain networks activity; however, the exact neural mechanism underlying this deficit remains elusive. Here, we studied brain oscillatory activity in healthy young and old adults during visual information maintenance in a delayed match-to-sample task. Particular emphasis was on long range phase:amplitude coupling of frontal alpha (8-12 Hz) and posterior fast oscillatory activity (>30 Hz). It is argued that through posterior fast oscillatory activity nesting into the excitatory or the inhibitory phase of frontal alpha wave, long-range networks can be efficiently coupled or decoupled, respectively. On the basis of this mechanism, we show that healthy, elderly participants exhibit a lack of synchronization in task-relevant networks while maintaining synchronized regions of the resting state network. Lacking disconnection of this resting state network is predictive of aging-related short-term memory decline. These results support the idea of inefficient orchestration of competing brain networks in the aging human brain and identify the neural mechanism responsible for this control breakdown.

Neural correlates of visuo-spatial working memory encoding-An EEG study.

The aim of the present electroencephalographic (EEG) study was to investigate neuronal correlates of working memory encoding in a visuo-spatial serial delayed match-to-sample task. A rapid serial visual presentation approach was used to dissociate brain activity related to encoding of visuo-spatial targets and cortical activity evoked by suppression of distracting information. During the task EEG was recorded and steady-state visually evoked potentials (SSVEPs) were calculated. Finally, standardized low-resolution electromagnetic tomography (sLORETA) was used to determine brain regions involved in visuo-spatial working memory encoding. A distributed task-relevant network comprising right temporal, parietal, and occipital areas was identified. Results suggest that activity of this network is amplified during actual encoding of targets into visual working memory, whereas the same network is attenuated in its activation when distracting visual information should be suppressed. Left prefrontal and anterior cingulate cortices do not seem to be involved in encoding of targets but only in suppression of distracting information, likely reflecting activity of an attention-based supervisory system. These results strongly emphasise the linkage between visuo-spatial attention and working memory during amplification of selected and suppression of irrelevant information.

Distributed Cortical Phase Synchronization in the EEG Reveals Parallel Attention and Working Memory Processes Involved in the Attentional Blink

Attentional blink (AB) describes a visuo-perceptual phenomenon in which the second of 2 targets within a rapid serial visual presentation stream is not detected. There are several cognitive models attempting to explain the fundamentals of this information processing bottleneck. Here, we used electroencephalographic recordings and the analysis of interregional phase synchronization of rhythmical brain activity to investigate the neural bases of the AB. By investigating the time course of interregional phase synchronization separately for trials in which participants failed to report the second target correctly (AB trials) and trials in which no AB occurred, and by clustering interregional connections based on their functional similarity, it was possible to define several distinct cortical networks. Analyzing these networks comprising phase synchronization--over a large spectrum of brain frequencies from theta to gamma activity--it was possible to identify neural correlates for cognitive subfunctions involved in the AB, such as the encoding of targets into working memory, tuning of attentional filters, and the recruitment of general cognitive resources. This parallel activation of functionally distinct neural processes substantiates the eligibility of several cognitive models on the AB.