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Objective: To further evaluate the potential of slew-rate limiting amplifiers to record electrophysiological signals in spite of concurrent transcranial magnetic stimulation (TMS), and to explore the effects of single-pulse TMS on electroencephalographic (EEG) correlates of functional brain activity.Methods: Visual-evoked potentials (VEPs) to checkerboards were recorded in 7 right-handed subjects, while single-pulse TMS was applied to the occipital pole either at visual stimulus onset, during the build-up or at the expected peak of the early VEP component P1 (VIS&TMS). Timing of TMS was individually adjusted based on each subject''s VEP-latency. A condition of TMS without concurrent visual stimulation (TMSalone) served for subtraction purposes (VIS&TMS minus TMSalone) to partial out TMS-related contaminations of the EEG signal.Results: When TMS was applied at visual stimulus onset, VEPs (as calculated by subtraction) perfectly matched control VEPs to visual stimulation alone. TMS at around P1, in contrast, modified the targeted (P1) and the subsequent VEP component (N1), independently of whether TMS was given at build-up or peak.Conclusions: The retrieval of regular VEPs with concomitant TMS at visual stimulus onset suggests that the employed EEG system and subtraction procedure are suited for combined EEG-TMS studies. The VEP changes following TMS at around P1 provide direct clues on the temporal dynamics of TMS pulse effects on functional activity in the human brain. Our data suggest effects of relatively long duration (∼100 ms) when TMS is applied while functional neuronal activity evolves. [Copyright &y& Elsevier]

Objective: To investigate a modulation of the N170 face-sensitive component related to the perception of other-race (OR) and same-race (SR) faces, as well as differences in face and non-face object processing, by combining different methods of event-related potential (ERP) signal analysis.Methods: Sixty-two channel ERPs were recorded in 12 Caucasian subjects presented with Caucasian and Asian faces along with non-face objects. Surface data were submitted to classical waveforms and ERP map topography analysis. Underlying brain sources were estimated with two inverse solutions (BESA and LORETA).Results: The N170 face component was identical for both race faces. This component and its topography revealed a face specific pattern regardless of race. However, in this time period OR faces evoked significantly stronger medial occipital activity than SR faces. Moreover, in terms of maps, at around 170 ms face-specific activity significantly preceded non-face object activity by 25 ms. These ERP maps were followed by similar activation patterns across conditions around 190–300 ms, most likely reflecting the activation of visually derived semantic information.Conclusions: The N170 was not sensitive to the race of the faces. However, a possible pre-attentive process associated to the relatively stronger unfamiliarity for OR faces was found in medial occipital area. Moreover, our data provide further information on the time-course of face and non-face object processing. [Copyright &y& Elsevier]

Visual-induced alpha desynchronization (VID) and visual-evoked potentials (VEPs) characterize occipital activation in response to visual stimulation but their exact relationship is unclear. Here, we tested the hypothesis that VID and VEPs reflect different aspects of cortical activation. For this purpose, we determined whether VID and VEPs are differentially modulated by low-frequency repetitive transcranial magnetic stimulation (rTMS) over the occipital pole. Scalp EEG responses to visual stimuli (flashed either to the left or to the right visual field) were recorded for 8 min in six healthy subjects (1) before, (2) immediately following, and (3) 20 min after left occipital rTMS (1 Hz, 10 min). The parameters aimed to reduce cortical excitability beyond the end of the TMS train. In addition, simple reaction times to visual stimulation were recorded (left or right hand in separate blocks). In all subjects, VID was significantly and prominently reduced by rTMS (P = 0.0001). In contrast, rTMS failed to modulate early VEP components (P1/N1). A moderate effect was found on a late VEP component close to manual response onset (P = 0.014) but this effect was in the opposite direction to the VID change. All changes were restricted to the targeted left occipital cortex. The effects were present only after right visual field stimulation when a right hand response was required, were associated with a behavioral effect, and had washed out 20 min after rTMS. We conclude that VID and early VEPs represent different aspects of cortical activation. The findings that rTMS did not change early VEPs and selectively affected VID and late VEPs in conditions where the visual input must be transferred intrahemispherically for visuomotor integration (right visual field/right hand) are suggestive of rTMS interference with higher-order visual functions beyond visual input. This is consistent with the idea that alpha desynchronization serves an integrative role through a corticocortical “gating function.” [Copyright &y& Elsevier]

Cognitive deficits are a fundamental feature of schizophrenia for which currently no effective treatments exist. This paper examines the possibility to use transcranial direct current stimulation (tDCS) to target cognitive deficits in schizophrenia as evidence from studies in healthy participants suggests that tDCS may improve cognitive functions and associated neural processes. We carried out a systematic review with the following search terms: 'tDCS', 'electric brain stimulation', 'schizophrenia', 'cognitive', 'cognition' until March 2019. 659 records were identified initially, 612 of which were excluded after abstract screening. The remaining 47 articles were assessed for eligibility based on our criteria and 26 studies were excluded. In addition, we compared several variables, such as online vs. offline-stimulation protocols, stimulation type and intensity on mediating positive vs. negative study outcomes. The majority of studies (n = 21) identified significant behavioural and neural effects on a range of cognitive functions (versus n = 11 with null results), including working memory, attention and social cognition. However, we could not identify tDCS parameters (electrode montage, stimulation protocol, type and intensity) that clearly mediated effects on cognitive deficits. There is preliminary evidence for the possibility that tDCS may improve cognitive deficits in schizophrenia. We discuss the rationale and strength of evidence for using tDCS for targeting cognitive deficits in schizophrenia as well as methodological issues and potential mechanisms of action. [ABSTRACT FROM AUTHOR]

This talk will consider to what extent specificity of TMS (and TACS) interventions can be enhanced by adding a temporal to the usual spatial dimension of targeting. The studies I will present take into account temporal patterns of ongoing electrical brain activity for tailoring TMS to interfere with brain functions. The emphasis will be on brain oscillations as potential targets, and entrainment by rhythmic stimulation as a potential approach, which corresponds to an interaction of brain stimulation with brain activity, as opposed to a simple perturbation. My talk will cover studies that use frequency-tuned rhythmic TMS (or tACS), combined with EEG/MEG recordings, to guide and document the effects of stimulation. It will highlight concepts as well as empirical support for entrainment of brain oscillations, associated performance changes in the context of parietal TMS to bias visual perception, and outline differences between online and offline effects. [ABSTRACT FROM AUTHOR]

Introduction: Simultaneous transcranial magnetic stimulation (TMS) and electroencephalography (EEG) allows the direct assessment of cortico-thalamic responsiveness by TMS-evoked EEG potentials (TEPs). Notably, the frequency composition of TEPs corresponds to the dominant spontaneous oscillation at the respective stimulation site, e.g. ′alpha′ in the visual cortex (Rosanova et al., J Neurosci 2009). Furthermore, TEPs change dramatically with shifts in neuromodulatory levels during sleep (Massimini et al., Science 2005; Bergmann et al., J Neurosci 2012), suggesting that both are generated by the same neuronal mechanisms. Indeed, rhythmic TMS of the parieto-occipital cortex can mimic alpha band (8–12Hz) oscillations in the EEG (Thut et al., Curr Biol 2011) as well as their known impact on perceptual performance (Romei et al., J Neurosci 2010) due to gating by inhibition (Jensen et al., TICS 2012). However, does the alpha-like TEP as response to visual cortex stimulation actually resemble spontaneous alpha oscillations or rather visual evoked potentials (VEPs)? Importantly, VEPs are amplified by visual attention (Rajagovindan and Ding, J Cog Neurosci, 2011), whereas spontaneous alpha oscillations are suppressed (Foxe et al., Neurorep 1998; Fu et al., Cog Brain Res 2001). Objectives: To test the similarity between transcranially evoked and spontaneous alpha oscillations, we currently investigate whether they show comparable responses to covert shifts in attention, i.e., decrease and increase in amplitude when attending the visual and auditory modality, respectively (Foxe and Snyder, Front Psychol 2011). Methods: Here, we measure TEPs my means of simultaneously applied 61-channel EEG and neuronavigated single-pulse TMS to the visual cortex while subjects attend to either visual or auditory noise patterns in order to detect slight contrast modulations. Since auditory stimuli have been shown to evoke an alpha-like response in the visual cortex (Romei, Gross and Thut, Curr Biol 2012), we use a constant stream of auditory masking noise as well as sham TMS to control for these effects. Results and conclusion: Preliminary results suggest that the TMS-evoked alpha oscillation is in fact modulated by top-down visual attention in analogy to spontaneous alpha oscillations, suggesting that both are generated by the same underlying neural mechanisms. [Copyright &y& Elsevier]

Brain oscillations reflect interactions between neuronal elements which functionally assemble through synchronization in specific frequency bands, depending on the state of the brain and on the task that is currently being executed. This gives rise to brain rhythms that can be measured on the scalp by electroencephalography (EEG). Transcranial magnetic stimulation (TMS) can be used to stimulate cortical areas in rhythmic pulse-trains, at frequencies that characterize EEG-signals. This raises two intriguing questions: Could frequency-tuned TMS be used to transiently entrain brain oscillations, and would this result in behavioural consequences? My talk covers (1) EEG-signatures that carry information on the excitability of visual cortex (amenable to attention control) and predict perception of an upcoming visual event. It then addresses the questions whether (2) these signatures can be transiently entrained by frequency-tuned rhythmic TMS, and whether (3) this alters perception in expected directions, i.e. in line with the proposed functional roles of these oscillations in perception and attention. [Copyright &y& Elsevier]

Introduction TDCS studies have recently faced strong criticism for exhibiting both a large intra- and inter-subject response variability and a low reproducibility of effects. We here attempt to replicate one of our own recent studies. In this study, we found a rightward shift of spatial attention bias, relative to a leftward (“pseudoneglect”) bias at baseline (as indexed by the landmark task ) using a bi-hemispheric montage (P5-aTCS/P6-cTDCS, Dual tDCS) to affect the balance of activity between the left versus right posterior parietal cortices (PPCs). This effect was overall weak (near significant trend in 40 participants), but displayed a complex, non-linear interaction between current strength and baseline task performance, indicating inter-individual variability in sensitivity to tDCS according to baseline state and intensity. Objectives Using a within-subjects design (vs between-subjects in our previous study) to further test and replicate baseline state- and intensity-dependency of tDCS outcome. Methods 20 adults received 1 mA & 2 mA Dual, and Sham tDCS, counterbalanced across different days. In each session, 6 blocks of the landmark task were completed (2 pre-tDCS, 2 during-tDCS and 2 post-tDCS). Dual tDCS was applied for 15 min (Sham = 30 s). Subjects were divided into good/poor baseline performance groups. Results We found no overall effects of tDCS on landmark task performance, nor any interaction with the factors baseline state or tDCS intensity. Our data are however not fully conclusive as there are group-level spatial bias differences at baseline between the 3 testing sessions that may confound the results (and were not present in our previous study). Further recordings are needed to resolve this point (that we hope to present at the conference). Conclusion We believe more replication studies (within- or across participants) are needed to establish reproducibility of tDCS effects. [ABSTRACT FROM AUTHOR]

Introduction Iconic memory represents the registration of visual information in a high-capacity but fast decaying visuo-sensory buffer. It has recently been shown that the primary visual cortex contributes to this memory function. Objectives In this TMS study, we investigated visual priming effects when TMS is applied over the primary visual cortex after prime presentation to see whether TMS could reactivate or “replay” the prime information stored in the sensory buffer. Methods Prime and probe maintained the same shape (square) but varied in colours of the same mean luminance, leading to congruent vs incongruent prime-probe conditions. Observers (n = 14) were asked to identify the colour of the probe as accurately and as fast as possible. Each trial started by a fixation cross lasting between 500–2000 ms. A prime was then flashed for 10 ms within the lower RVF at the location of TMS-induced phosphenes. A probe was displayed 400 ms after the prime for 40 ms at a mirrored location in the lower LVF. In TMS blocks, single-pulse TMS below phosphene thresholds was randomly delivered at 100 ms or 300 ms after the prime onset and intermingled with no TMS trials. Control trials (with no TMS) aiming at emulating a possible TMS-induced replay consisted of a physical redisplay of the prime at 300 ms i) in the same but faint colour, ii) in the opponent colour or iii) of a grey mask while responses to probes were recorded. The design was the same in SHAM blocks. Results Results showed that the significant priming effect (reaction times, RTs congruent < incongruent) observed in absence of stimulation was disrupted by TMS at 100 ms after the prime onset. Notably, this priming effect reverted to negative priming (RTs incongruent < congruent) for TMS at 300 ms. Comparison with the control trials attempting to emulate a physical re-appearance of the prime was suggestive of TMS at 300 ms inducing a recall of the prime in the colour opponent colour of the prime (no RT differences to opponent colour redisplays). Conclusion This is evidence that a memory trace stored in the sensory buffer in V1/V2 can be reactivated by TMS. The study is supported by a Wellcome Trust Award to Gregor Thut and Joachim Gross [grant number 098434, 098433] and by a Biological Sciences Research Council (BB /I006494/1) grant. [ABSTRACT FROM AUTHOR]

Models on the mechanisms underlying letter-colour synaesthesia diverge on a central question: whether triggered sensations reflect (a) quantitatively or (b) qualitatively deviant brain organization. We previously found evidence for (a) after observing synaesthesia-like letter-colour binding in adult non-synaesthetes following execution of a visual letter search task which employed likelihood manipulations of letter-colour pairings to implicitly train letter-colour associations (Kusnir and Thut, 2012). The newly-formed associations were synaesthesia-like, since correlating with the synaesthetic-Stroop and showing the colour-opponency effect, present in synaesthetes (Nikolić et al., 2007). This latter effect manifests as increased synaesthetic-Stroop interference when the real colour of a letter is opponent to the synaesthetic/associated colour, in line with involvement of visual/colour areas in letter-colour binding. Here, we investigated the brain areas involved in the formation of these synesthetic associations. Based on (Kadosh and Iuculano, 2006) revealing reciprocal involvement of the PPC and dlPFC in distinct aspects of learning in a numerical conception task, we hypothesized that these two areas may also be differentially implicated in the learning of synaesthesia-like letter-colour associations by non-synaesthetes. Previous results would predict that while PPC supports processing of these associations after learning (see also Esterman et al., 2006), dlPFC shows a reciprocal function, i.e., suppressing these associations under normal conditions. Using bilateral tDCS, we interfered with either PPC or dlPFC in two groups while they performed the letter-colour association task as in (Kusnir and Thut, 2012). A third group performed the same task but without tDCS (control group). All three groups used non-opponent colour pairs for letter-colour association learning, to avoid ceiling effects. In comparison to the control group, dlPFC-stimulation significantly enhanced letter-colour binding. This enhancement was substantial, leading to interference between learned and real colours in the order of the colour-opponency effect (despite the use of non-opponent colour pairs). No such effect was observed with PPC stimulation. This provides novel information regarding the network of areas implicated in the formation of automatic (letter-colour) associations. Synaesthesia-like binding of colours to letters by non-synaesthetes seems to be suppressed by dlPFC under normal conditions, and may be released by modulation of the dlPFC. We speculate that dlPFC-stimulation facilitates the formation of letter-colour binding, possibly by emphasizing relevant associations during task performance and/or by disinhibiting other brain areas (i.e., posterior parietal) involved in automatic, perceptual letter-colour binding. [Copyright &y& Elsevier]

Question Oscillatory brain activity in specific frequency bands has been related to cognitive processes such as attention (Foxe and Snyder (2011) Front Psychology 2:154). While in the domain of endogenous top-down control of visuospatial attention, occipito-parietal oscillations in the alpha band have been causally implicated (Romei et al. (2010) Journal of Neurosci. 30(25):8692–8697), the oscillatory signatures underlying reflexively driven orienting of spatial attention and its time course remain unclear. In this study, we employed electrophysiology (EEG) and concurrent single pulse transcranial magnetic stimulation (TMS) during a cued visuospatial detection task, known to induce reflexive shifts of attention and inhibition-of-return (IOR). Methods Participants ( n = 13) performed an exogenously cued dot detection task while the time course of the IOR was measured at four different cue-target delays (from 105.8–705.8 ms). The cue consisted of a brief flash in the left or right visual field and was task-irrelevant and uninformative as to forthcoming target location. In one quarter of the trials a single pulse TMS was delivered over the right intraparietal sulcus (IPS) at the longest cue-target delay (705.8 ms) whilst changes in brain activity were measured with EEG. Results The behavioural analysis revealed significantly faster reaction times to targets at cued relative to uncued positions at the early cue-target delay, which reversed to significantly faster reaction times to uncued relative to cued positions (i.e, an IOR) at the later cue-target delays. Ongoing analyses of the EEG measurements focuses on identifying the key frequency bands implicated in reflexive shifts of attention in TMS-free trials, complemented by analyses of the oscillatory response to single-pulse TMS over the right parietal cortex at the maximal time of IOR. Conclusions Our behavioural findings reveal that our experimental manipulation induced a reflexive shift of attention as expected, allowing us to examine the EEG/TMS-EEG data for underlying oscillatory brain activities. [ABSTRACT FROM AUTHOR]

Question Transcranial electrical stimulation is under investigation as an experimental and clinical interventional technique in both healthy participants and patients. While the technique is promising in many regards, important limitations have been identified, including weak effects as well as high inter- and intra-individual variability, hence the effort of many studies to enhance its effectivity. Here, we directly compared two “inhibitory” tES techniques with supposedly different mechanisms of action as to their effectivity of intervention into a cognitive task. Methods Nineteen healthy participants underwent transcranial alternating current stimulation at alpha frequency (10 Hz-tACS) shown to entrain the “inhibitory” alpha oscillation or cathodal transcranial direct current stimulation (c-tDCS) known to supress neuronal spiking activity, as well as a tES control (sham). tES was applied for 10 min with a right parietal stimulation - left frontal return montage (electrode sizes: 3 × 3 cm–7 × 5 cm), while participants were performing a perceptual line bisection (landmark) task. The tES protocols were compared as to their ability to interfere with left pseudoneglect in healthy participant, the latter thought to be under control of the right hemisphere. Results: The results revealed that only right parietal 10 Hz-tACS led to the expected changes in spatial attention bias, namely a rightward shift in line bisection (as compares to sham). No effects of right parietal c-tDCS were observed. While the rightward attention shifts by 10 Hz-tACS were observed in the majority of participants ( n = 14), the mean amplitude of this shift was small (as compared to the range of spatial attention biases in the healthy population), speaking for weak, albeit significant changes. Conclusions Our study suggests that more direct comparisons across protocols are needed in an attempt to improve tES techniques. [ABSTRACT FROM AUTHOR]

Question Previous TMS studies have shown that attention-regulated changes in posterior brain rhythms are under FEF control (Capotosto, JNeurosci 2009) and that FEF-TMS affects the probability of perceiving phosphenes (Silvanto, JNeurophysiol 2006). However the oscillatory nature of the latter changes has never been examined. Here we specifically tested whether FEF-TMS causes visual cortex excitability to phase align at the frequency of brain rhythms. Methods To this end we used bifocal TMS. The first pulse was used to activate FEF projections to visual areas, the second pulse to test the resulting excitability changes in primary visual cortex (V1) or extrastriate cortex (V5) in terms of phosphenes perception as a function of the interval between pulses. If FEF activation phase-aligns oscillatory activity over the occipital cortex, one would expect a periodicity in phosphenes perception locked to the FEF-TMS pulse. Thirteen participants were enrolled to assess right FEF-right V1 (rFEF-rV1) or rFEF-rV5 interactions at 19 time delays (30 to 300 ms). The specificity of FEF-V1/V5 interactions was controlled for by means of two control conditions (Cz-rV1, Cz-rV5). To test for a cyclical pattern in phosphene perception, we fitted cosine waves between 7 and 25 Hz, extracted the R-squared values for each frequency and statistically evaluated the difference between each main condition and its control (FEF-V5 vs Cz-V5; FEF-V1 vs Cz-V5) using a bootstrapping procedure. Results When comparing rFEF-rV5 and Cz-rV5, we found beta-frequency (from 14 to 19 Hz) to better fit the rFEF-rV5 than its control condition. Notably, when testing for phase locking, we found significant results in the beta band (16–17 Hz) for the rFEF-rV5 condition. When comparing rFEF-rV1 and Cz-rV1 we found no significant difference in the R-squared values at any frequency. Conclusions Our data are in line with FEFs controlling V5 excitability by phase resetting oscillatory activity in the beta band, which accords with findings suggesting that beta oscillations are involved in top-down interactions within cortical networks (Buschman, Science 2007). [ABSTRACT FROM AUTHOR]