Transcranial Alternating Current Stimulation over Frontal Eye Fields Mimics Attentional Modulation of Visual Processing.

Attentional control over sensory processing has been linked to neural alpha oscillations and related inhibition of cerebral cortex. Despite the wide consensus on the functional relevance of alpha oscillations for attention, precise neural mechanisms of how alpha oscillations shape perception and how this top-down modulation is implemented in cortical networks remain unclear. Here, we tested the hypothesis that alpha oscillations in frontal eye fields (FEFs) are causally involved in the top-down regulation of visual processing in humans (male and female). We applied sham-controlled, intermittent transcranial alternating current stimulation (tACS) over bilateral FEF at either 10 Hz (alpha) or 40 Hz (gamma) to manipulate attentional preparation in a visual discrimination task. Under each stimulation condition, we measured psychometric functions for contrast perception and introduced a novel linear mixed modeling approach for statistical control of neurosensory side effects of the electric stimulation. tACS at alpha frequency reduced the slope of the psychometric function, resulting in improved subthreshold and impaired superthreshold contrast perception. Side effects on the psychometric functions were complex and showed large interindividual variability. Controlling for the impact of side effects on the psychometric parameters by using covariates in the linear mixed model analysis reduced this variability and strengthened the perceptual effect. We propose that alpha tACS over FEF mimicked a state of endogenous attention by strengthening a fronto-occipitoparietal network in the alpha band. We speculate that this network modulation enhanced phasic gating in occipitoparietal cortex leading to increased variability of single-trial psychometric thresholds, measurable as a reduction of psychometric slope.

Cerebellar Modulation of Sensorimotor Associative Plasticity Is Impaired in Cervical Dystonia.

BACKGROUND: In recent years, cervical dystonia (CD) has been recognized as a network disorder that involves not only the basal ganglia but other brain regions, such as the primary motor and somatosensory cortex, brainstem, and cerebellum. So far, the role of the cerebellum in the pathophysiology of dystonia is only poorly understood. OBJECTIVE: The objective of this study was to investigate the role of the cerebellum on sensorimotor associative plasticity in patients with CD. METHODS: Sixteen patients with CD and 13 healthy subjects received cerebellar transcranial direct current stimulation (ctDCS) followed by a paired associative stimulation (PAS) protocol based on transcranial magnetic stimulation that induces sensorimotor associative plasticity. Across three sessions the participants received excitatory anodal, inhibitory cathodal, and sham ctDCS in a double-blind crossover design. Before and after the intervention, motor cortical excitability and motor symptom severity were assessed. RESULTS: PAS induced an increase in motor cortical excitability in both healthy control subjects and patients with CD. In healthy subjects this effect was attenuated by both anodal and cathodal ctDCS with a stronger effect of cathodal stimulation. In patients with CD, anodal stimulation suppressed the PAS effect, whereas cathodal stimulation had no influence on PAS. Motor symptom severity was unchanged after the intervention. CONCLUSIONS: Cerebellar modulation with cathodal ctDCS had no effect on sensorimotor associative plasticity in patients with CD, in contrast with the net inhibitory effect in healthy subjects. This is further evidence that the cerebello-thalamo-cortical network plays a role in the pathophysiology of dystonia. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Personalized alpha-tACS targeting left posterior parietal cortex modulates visuo-spatial attention and posterior evoked EEG activity.

BACKGROUND: Covert visuo-spatial attention is marked by the anticipatory lateralization of neuronal alpha activity in the posterior parietal cortex. Previous applications of transcranial alternating current stimulation (tACS) at the alpha frequency, however, were inconclusive regarding the causal contribution of oscillatory activity during visuo-spatial attention. OBJECTIVE: Attentional shifts of behavior and electroencephalography (EEG) after-effects were assessed in a cued visuo-spatial attention paradigm. We hypothesized that parietal alpha-tACS shifts attention relative to the ipsilateral visual hemifield. Furthermore, we assumed that modulations of behavior and neurophysiology are related to individual electric field simulations. METHODS: We applied personalized tACS at alpha and gamma frequencies to elucidate the role of oscillatory neuronal activity for visuo-spatial attention. Personalized tACS montages were algorithmically optimized to target individual left and right parietal regions that were defined by an EEG localizer. RESULTS: Behavioral performance in the left hemifield was specifically increased by alpha-tACS compared to gamma-tACS targeting the left parietal cortex. This hemisphere-specific effect was observed despite the symmetry of simulated electric fields. In addition, visual event-related potential (ERP) amplitudes showed a reduced lateralization over posterior sites induced by left alpha-tACS. Neuronal sources of this effect were localized in the left premotor cortex. Interestingly, accuracy modulations induced by left parietal alpha-tACS were directly related to electric field magnitudes in the left premotor cortex. CONCLUSION: Overall, results corroborate the notion that alpha lateralization plays a causal role in covert visuo-spatial attention and indicate an increased susceptibility of parietal and premotor brain regions of the left dorsal attention network to subtle tACS-neuromodulation.

Optimizing the montage for cerebellar transcranial alternating current stimulation (tACS): a combined computational and experimental study.

Objective. The application of cerebellar transcranial alternating current stimulation (tACS) is limited by the absence of commonly agreed montages and also the presence of unpleasant side effects. We aimed to find the most effective cerebellar tACS montage with minimum side effects (skin sensations and phosphenes).Approach. We first simulated cerebellar tACS with five montages (return electrode on forehead, buccinator, jaw, and neck positions, additionally focal montage with high-definition ring electrodes) to compare induced cerebellar current, then stimulated healthy participants and evaluated side effects for different montages and varying stimulation frequencies.Main results. The simulation revealed a descending order of current density in the cerebellum from forehead to buccinator, jaw, neck and ring montage respectively. Montages inducing higher current intensity in the eyeballs during the simulation resulted in stronger and broader phosphenes during tACS sessions. Strong co-stimulation of the brainstem was observed for the neck. Skin sensations did not differ between montages or frequencies. We propose the jaw montage as an optimal choice for maximizing cerebellar stimulation while minimizing unwanted side effects.Significance. These findings contribute to adopting a standard cerebellar tACS protocol. The combination of computational modelling and experimental data offers improved experimental control, safety, effectiveness, and reproducibility to all brain stimulation practices.

tACS phase-specifically biases brightness perception of flickering light.

BACKGROUND: Visual phenomena like brightness illusions impressively demonstrate the highly constructive nature of perception. In addition to physical illumination, the subjective experience of brightness is related to temporal neural dynamics in visual cortex. OBJECTIVE: Here, we asked whether biasing the temporal pattern of neural excitability in visual cortex by transcranial alternating current stimulation (tACS) modulates brightness perception of concurrent rhythmic visual stimuli. METHODS: Participants performed a brightness discrimination task of two flickering lights, one of which was targeted by same-frequency electrical stimulation at varying phase shifts. tACS was applied with an occipital and a periorbital active control montage, based on simulations of electrical currents using finite element head models. RESULTS: Experimental results reveal that flicker brightness perception is modulated dependent on the phase shift between sensory and electrical stimulation, solely under occipital tACS. Phase-specific modulatory effects by tACS were dependent on flicker-evoked neural phase stability at the tACS-targeted frequency, recorded prior to electrical stimulation. Further, the optimal timing of tACS application leading to enhanced brightness perception was correlated with the neural phase delay of the cortical flicker response. CONCLUSIONS: Our results corroborate the role of temporally coordinated neural activity in visual cortex for brightness perception of rhythmic visual input in humans. Phase-specific behavioral modulations by tACS emphasize its efficacy to transfer perceptually relevant temporal information to the cortex. These findings provide an important step towards understanding the basis of visual perception and further confirm electrical stimulation as a tool for advancing controlled modulations of neural activity and related behavior.

Sensory capability and information integration independently explain the cognitive status of healthy older adults.

While there is evidence that sensory processing and multisensory integration change with age, links between these alterations and their relation to cognitive status remain unclear. In this study, we assessed sensory thresholds and performance of healthy younger and older adults in a visuotactile delayed match-to-sample task. Using Bayesian structural equation modelling (BSEM), we explored the factors explaining cognitive status in the group of older adults. Additionally, we applied transcranial alternating current stimulation (tACS) to a parieto-central network found to underlie visuotactile interactions and working memory matching in our previous work. Response times and signal detection measures indicated enhanced multisensory integration and enhanced benefit from successful working memory matching in older adults. Further, tACS caused a frequency-specific speeding (20 Hz) and delaying (70 Hz) of responses. Data exploration suggested distinct underlying factors for sensory acuity and sensitivity d' on the one side, and multisensory and working memory enhancement on the other side. Finally, BSEM showed that these two factors labelled 'sensory capability' and 'information integration' independently explained cognitive status. We conclude that sensory decline and enhanced information integration might relate to distinct processes of ageing and discuss a potential role of the parietal cortex in mediating augmented integration in older adults.

Phase-specific manipulation of rhythmic brain activity by transcranial alternating current stimulation.

BACKGROUND: Oscillatory phase has been proposed as a key parameter defining the spatiotemporal structure of neural activity. To enhance our understanding of brain rhythms and improve clinical outcomes in pathological conditions, modulation of neural activity by transcranial alternating current stimulation (tACS) emerged as a promising approach. However, the phase-specificity of tACS effects in humans is still critically debated. OBJECTIVE: Here, we investigated the phase-specificity of tACS on visually evoked steady state responses (SSRs) in 24 healthy human participants. METHODS: We used an intermittent electrical stimulation protocol and assessed the influence of tACS on SSR amplitude in the interval immediately following tACS. A neural network model served to validate the plausibility of experimental findings. RESULTS: We observed a modulation of SSR amplitudes dependent on the phase shift between flicker and tACS. The tACS effect size was negatively correlated with the strength of flicker-evoked activity. Supported by simulations, data suggest that strong network synchronization limits further neuromodulation by tACS. Neural sources of phase-specific effects were localized in the parieto-occipital cortex within flicker-entrained regions. Importantly, the optimal phase shift between flicker and tACS associated with strongest SSRs was correlated with SSR phase delays in the tACS target region. CONCLUSIONS: Overall, our data provide electrophysiological evidence for phase-specific modulations of rhythmic brain activity by tACS in humans. As the optimal timing of tACS application was dependent on cortical SSR phase delays, our data suggest that tACS effects were not mediated by retinal co-stimulation. These findings highlight the potential of tACS for controlled, phase-specific modulations of neural activity.

Frontal and parietal alpha oscillations reflect attentional modulation of cross-modal matching.

Multisensory perception is shaped by both attentional selection of relevant sensory inputs and exploitation of stimulus-driven factors that promote cross-modal binding. Underlying mechanisms of both top-down and bottom-up modulations have been linked to changes in alpha/gamma dynamics in primary sensory cortices and temporoparietal cortex. Accordingly, it has been proposed that alpha oscillations provide pulsed inhibition for gamma activity and thereby dynamically route cortical information flow. In this study, we employed a recently introduced multisensory paradigm incorporating both bottom-up and top-down aspects of cross-modal attention in an EEG study. The same trimodal stimuli were presented in two distinct attentional conditions, focused on visual-tactile or audio-visual components, for which cross-modal congruence of amplitude changes had to be evaluated. Neither top-down nor bottom-up cross-modal attention modulated alpha or gamma power in primary sensory cortices. Instead, we found alpha band effects in bilateral frontal and right parietal cortex. We propose that frontal alpha oscillations reflect the origin of top-down control regulating perceptual gains and that modulations of parietal alpha oscillations relates to intersensory re-orienting. Taken together, we suggest that the idea of selective cortical routing via alpha oscillations can be extended from sensory cortices to the frontoparietal attention network.

Modulation of large-scale cortical coupling by transcranial alternating current stimulation.

BACKGROUND: Long-range functional connectivity in the brain is considered fundamental for cognition and is known to be altered in many neuropsychiatric disorders. To modify such coupling independent of sensory input, noninvasive brain stimulation could be of utmost value. OBJECTIVE: First, we tested if transcranial alternating current stimulation (tACS) is able to influence functional connectivity in the human brain. Second, we investigated the specificity of effects in frequency and space. METHODS: Participants were stimulated bifocally with high-definition tACS in counterbalanced order (1) in-phase, with identical electric fields in both hemispheres, (2) anti-phase, with phase-reversed electric fields in the two hemispheres, and (3) jittered-phase, generated by subtle frequency shifts continuously changing the phase relation between the two fields. EEG aftereffects were analyzed systematically in sensor and source space. RESULTS: While total power and spatial distribution of the fields were comparable between conditions, global pre-post stimulation changes in EEG connectivity were larger after in-phase stimulation than after anti-phase or jittered-phase stimulation. Those differences in connectivity were restricted to the stimulated frequency band and decayed within the first 120 s after stimulation offset. Source reconstruction localized the maximum effect between the stimulated occipito-parietal areas. CONCLUSION: The relative phase of bifocal alpha-tACS modulated alpha-band connectivity between the targeted regions. As side effects are not expected to differ between the stimulation conditions, we conclude that neural activity was phase-specifically influenced by the electric fields. We thus suggest bifocal high-definition tACS as a tool to manipulate long-range cortico-cortical coupling which outlasts the stimulation period.

Synchronization of Sensory Gamma Oscillations Promotes Multisensory Communication.

Rhythmic neuronal activity in the gamma range is a signature of cortical processing and its synchronization across distant sites has been proposed as a fundamental mechanism of network interactions. While this has been shown within sensory streams, we tested whether cross talk between the senses relies on similar mechanisms. Direct sensory interactions in humans (male and female) were studied with a visual-tactile amplitude matching paradigm. In this task, congruent stimuli are associated with behavioral benefits, which are proposed to be mediated by increased binding between sensory cortices through coherent gamma oscillations. We tested this hypothesis by applying 4-in-1 multi-electrode transcranial alternating current stimulation (tACS) with 40 Hz over visual and somatosensory cortices. In phase stimulation (0°) was expected to strengthen binding and thereby enhance the congruence effect, while anti-phase (180°) stimulation was expected to have opposite effects. Gamma tACS was controlled by alpha (10 Hz) and sham stimulation, as well as by applying tACS unilaterally while visual-tactile stimuli were presented lateralized. Contrary to our expectations, gamma tACS over the relevant hemisphere delayed responses to congruent trials. Additionally, reanalysis of EEG data revealed decoupling of sensory gamma oscillations during congruent trials. We propose that gamma tACS prevented sensory decoupling and thereby limited the congruence effect. Together, our results favor the perspective that processing multisensory congruence involves corticocortical communication rather than feature binding. Furthermore, we found control stimulation over the irrelevant hemisphere to speed responses under alpha stimulation and to delay responses under gamma stimulation, consistent with the idea that contralateral alpha/gamma dynamics regulate cortical excitability.

A matter of attention: Crossmodal congruence enhances and impairs performance in a novel trimodal matching paradigm.

A novel crossmodal matching paradigm including vision, audition, and somatosensation was developed in order to investigate the interaction between attention and crossmodal congruence in multisensory integration. To that end, all three modalities were stimulated concurrently while a bimodal focus was defined blockwise. Congruence between stimulus intensity changes in the attended modalities had to be evaluated. We found that crossmodal congruence improved performance if both, the attended modalities and the task-irrelevant distractor were congruent. If the attended modalities were incongruent, the distractor impaired performance due to its congruence relation to one of the attended modalities. Between attentional conditions, magnitudes of crossmodal enhancement or impairment differed. Largest crossmodal effects were seen in visual-tactile matching, intermediate effects for audio-visual and smallest effects for audio-tactile matching. We conclude that differences in crossmodal matching likely reflect characteristics of multisensory neural network architecture. We discuss our results with respect to the timing of perceptual processing and state hypotheses for future physiological studies. Finally, etiological questions are addressed.