Transcranial temporal interference stimulation (tTIS) influences event-related alpha activity during mental rotation.

Non-invasive brain stimulation techniques offer therapeutic potential for neurological and psychiatric disorders. However, current methods are often limited in their stimulation depth. The novel transcranial temporal interference stimulation (tTIS) aims to overcome this limitation by non-invasively targeting deeper brain regions. In this study, we aimed to evaluate the efficacy of tTIS in modulating alpha activity during a mental rotation task. The effects of tTIS were compared with transcranial alternating current stimulation (tACS) and a sham control. Participants were randomly assigned to a tTIS, tACS, or sham group. They performed alternating blocks of resting and mental rotation tasks before, during, and after stimulation. During the stimulation blocks, participants received 20 min of stimulation adjusted to their individual alpha frequency (IAF). We assessed shifts in resting state alpha power, event-related desynchronization (ERD) of alpha activity during mental rotation, as well as resulting improvements in behavioral performance. Our results indicate tTIS and tACS to be effective in modulating cortical alpha activity during mental rotation, leading to an increase in ERD from pre- to poststimulation as well as compared to sham stimulation. However, this increase in ERD was not correlated with enhanced mental rotation performance, and resting state alpha power remained unchanged. Our findings underscore the complex nature of tTIS and tACS efficacy, indicating that stimulation effects are more observable during active cognitive tasks, while their impacts are less pronounced on resting neuronal systems.

Combined multi-session transcranial alternating current stimulation (tACS) and language skills training improves individual gamma band activity and literacy skills in developmental dyslexia.

Developmental dyslexia is characterized by the pathologically diminished ability to acquire reading and spelling skills. Accurate processing of acoustic information at the phonemic scale is crucial for successful sound-to-letter-mapping which, in turn, is elemental in reading and spelling. Altered activation patterns in the auditory cortex are thought to provide the neurophysiological basis for the inaccurate phonemic perception. Recently, transcranial electrical stimulation has been shown to be an effective method to ameliorate cortical activation patterns in the auditory cortex. In a sample of children and adolescents with dyslexia, we investigated the effect of multi-session transcranial alternating current stimulation delivered concurrently with a phonological training and in combination with a behavioral literacy skills training. Over a 5-week period the participants received 10 training sessions while gamma-tACS was administered over bilateral auditory cortex. We found that gamma-tACS shifted the peak frequency of auditory gamma oscillations reflecting a more fine-grained processing of time-critical acoustic information. This amelioration was accompanied by increased phonemic processing skills. Moreover, individuals who received gamma-tACS showed significant improvements in their spelling skills four months after the intervention. Our results demonstrate that multi-session gamma-tACS enhances the effects of a behavioral intervention and induces long-term improvement on literacy skills in dyslexia.

Effects of transcutaneous auricular vagus nerve stimulation paired with tones on electrophysiological markers of auditory perception.

BACKGROUND: Transcutaneous auricular vagus nerve stimulation (taVNS) has been introduced as a non-invasive alternative to invasive vagus nerve stimulation (iVNS). While iVNS paired with tones has been highlighted as a potential effective therapy for the treatment of auditory disorders such as tinnitus, there is still scarce data available confirming the efficacy of non-invasive taVNS. Here, we assessed the effect of taVNS paired with acoustic stimuli on sensory-related electrophysiological responses. METHODS: A total of 22 healthy participants were investigated with a taVNS tone-pairing paradigm using a within-subjects design. In a single session pure tones paired with either active taVNS or sham taVNS were repeatedly presented. Novel tones without electrical stimulation served as control condition. Auditory event related potentials and auditory cortex oscillations were compared before and after the tone pairing procedure between stimulation conditions. RESULTS: From pre to post pairing, we observed a decrease in the N1 amplitude and in theta power to tones paired with sham taVNS while these electrophysiological measures remained stable for tones paired with active taVNS a pattern mirroring auditory sensory processing of novel, unpaired control tones. CONCLUSION: Our results demonstrate the efficacy of a short-term application of non-invasive taVNS to modulate auditory processing in healthy individuals and, thereby, have potential implications for interventions in auditory processing deficits.

Dysfunctional auditory gamma oscillations in developmental dyslexia: A potential target for a tACS-based intervention.

Interventions in developmental dyslexia typically consist of orthography-based reading and writing trainings. However, their efficacy is limited and, consequently, the symptoms persist into adulthood. Critical for this lack of efficacy is the still ongoing debate about the core deficit in dyslexia and its underlying neurobiological causes. There is ample evidence on phonological as well as auditory temporal processing deficits in dyslexia and, on the other hand, cortical gamma oscillations in the auditory cortex as functionally relevant for the extraction of linguistically meaningful information units from the acoustic signal. The present work aims to shed more light on the link between auditory gamma oscillations, phonological awareness, and literacy skills in dyslexia. By mean of EEG, individual gamma frequencies were assessed in a group of children and adolescents diagnosed with dyslexia as well as in an age-matched control group with typical literacy skills. Furthermore, phonological awareness was assessed in both groups, while in dyslexic participants also reading and writing performance was measured. We found significantly lower gamma peak frequencies as well as lower phonological awareness scores in dyslexic participants compared to age-matched controls. Additionally, results showed a positive correlation between the individual gamma frequency and phonological awareness. Our data suggest a hierarchical structure of neural gamma oscillations, phonological awareness, and literacy skills. Thereby, the results emphasize altered gamma oscillation not only as a core deficit in dyslexia but also as a potential target for future causal interventions. We discuss these findings considering non-invasive brain stimulation techniques and suggest transcranial alternating current stimulation as a promising approach to normalize dysfunctional oscillations in dyslexia.

The internal time keeper: Causal evidence for the role of the cerebellum in anticipating regular acoustic events.

Most acoustic events in our environment do not appear randomly but are rather predictable due to the temporal regularity in that they occur. Besides sensory-related cortical areas, the cerebellum has been suggested as a key structure in temporal processing and in the anticipation of future events. Hence, patients with cerebellum lesions show impaired precision in temporal processing as reflected in the reduced ability to exploit temporal regularity. Using transcranial direct current stimulation (tDCS), we here aimed to draw further causal conclusions on the human cerebellum as functionally relevant in temporal processing of acoustic events. We focused on the electrophysiologic P3b, a large positive wave apparent in the electroencephalography (EEG), that represents encoding of task-relevant events and that has been demonstrated as sensitive to the exploitation of temporal regularities. Participants received 30 min of anodal, cathodal or sham tDCS over the cerebellum while they performed two oddball paradigms with different temporal regularities in that the acoustic stimuli were presented. Following clinical observations, we hypothesized that tDCS-effects will be present in the regular oddball paradigm only, thus, in the condition that allows anticipating the occurrence of subsequent stimuli. In result, we found that cathodal tDCS over the cerebellum reduced the P3b-amplitude specifically in response to target stimuli in the regular paradigm. Thereby, tDCS-induced changes mirror the effects of cerebellar lesions in clinical samples. Our data provides direct evidence for a causal link between the human cerebellum and auditory processing of temporal regularity and emphasize future work on a potential benefit of cerebellar-tDCS in clinical samples.

Pulsed transcranial electric brain stimulation enhances speech comprehension.

BACKGROUND: One key mechanism thought to underlie speech processing is the alignment of cortical brain rhythms to the acoustic input, a mechanism termed entrainment. Recent work showed that transcranial electrical stimulation (tES) in speech relevant frequencies or adapted to the speech envelope can in fact enhance speech processing. However, it is unclear whether an oscillatory tES is necessary, or if transients in the stimulation (e.g., peaks in the tES signal) at relevant times are sufficient. OBJECTIVE: In this study we used a novel pulsed-tES-protocol and tested behaviorally if a transiently pulsed - instead of a persistently oscillating - tES signal, can improve speech processing. METHODS: While subjects listened to spoken sentences embedded in noise, brief electric direct current pulses aligned to speech transients (syllable onsets) were applied to auditory cortex regions to modulate comprehension. Additionally, we modulated the temporal delay between tES-pulses and speech transients to test for periodic modulations of behavior, indicative of entrainment by tES. RESULTS: Speech comprehension was improved when tES-pulses were applied with a delay of 100 ms in respect to the speech transients. Contradictory to previous reports we find no periodic modulation of behavior. However, we find indications that periodic modulations can be spurious results of sampling behavioral data too coarsely. CONCLUSIONS: Subject's speech comprehension benefits from pulsed-tES, yet behavior is not modulated periodically. Thus, pulsed-tES can aid cortical entrainment to speech input, which is especially relevant in a noisy environment. Yet, pulsed-tES does not seem to entrain brain oscillations by itself.

Inconsistent effects of stochastic resonance on human auditory processing.

It has been demonstrated that, while otherwise detrimental, noise can improve sensory perception under optimal conditions. The mechanism underlying this improvement is stochastic resonance. An inverted U-shaped relationship between noise level and task performance is considered as the signature of stochastic resonance. Previous studies have proposed the existence of stochastic resonance also in the human auditory system. However, the reported beneficial effects of noise are small, based on a small sample, and do not confirm the proposed inverted U-shaped function. Here, we investigated in two separate studies whether stochastic resonance may be present in the human auditory system by applying noise of different levels, either acoustically or electrically via transcranial random noise stimulation, while participants had to detect acoustic stimuli adjusted to their individual hearing threshold. We find no evidence for behaviorally relevant effects of stochastic resonance. Although detection rate for near-threshold acoustic stimuli appears to vary in an inverted U-shaped manner for some subjects, it varies in a U-shaped manner or in other manners for other subjects. Our results show that subjects do not benefit from noise, irrespective of its modality. In conclusion, our results question the existence of stochastic resonance in the human auditory system.

Transcranial electrical stimulation improves phoneme processing in developmental dyslexia.

BACKGROUND: About 10% of the western population suffers from a specific disability in the acquisition of reading and writing skills, known as developmental dyslexia (DD). Even though DD starts in childhood it frequently continuous throughout lifetime. Impaired processing of acoustic features at the phonematic scale based on dysfunctional auditory temporal resolution is considered as one core deficit underlying DD. Recently, the efficacy of transcranial electrical stimulation (tES) to modulate auditory temporal resolution and phoneme processing in healthy individuals has been demonstrated. OBJECTIVE: The present work aims to investigate online effects of tES on phoneme processing in individuals with DD. METHOD: Using an established phoneme-categorization task, we assessed the immediate behavioral and electrophysiological effects of transcranial alternating current stimulation (tACS) and transcranial random noise stimulation (tRNS) over bilateral auditory cortex in children and adolescents with DD (study 1) and adults with DD (study 2) on auditory phoneme processing acuity. RESULTS: Our data revealed that tACS improved phoneme categorization in children and adolescents with DD, an effect that was paralleled by an increase in evoked brain response patterns representing low-level sensory processing. In the adult sample we replicated these findings and additionally showed a more pronounced impact of tRNS on phoneme-categorization acuity. CONCLUSION: These results provide compelling evidence for the potential of both tACS and tRNS to increase temporal precision of the auditory system in DD and suggest transcranial electrical stimulation as potential intervention in DD to foster the effect of standard phonology-based training.

Modulation of Working Memory Using Transcranial Electrical Stimulation: A Direct Comparison Between TACS and TDCS.

Transcranial electrical stimulation (TES) has been considered a promising tool for improving working memory (WM) performance. Recent studies have demonstrated modulation of networks underpinning WM processing through application of transcranial alternating current (TACS) as well as direct current (TDCS) stimulation. Differences between study designs have limited direct comparison of the efficacy of these approaches, however. Here we directly compared the effects of theta TACS (6 Hz) and anodal TDCS on WM, applying TACS to the frontal-parietal loop and TDCS to the dorsolateral prefrontal cortex (DLPFC). WM was evaluated using a visual 2-back WM task. A within-subject, crossover design was applied (N = 30) in three separate sessions. TACS, TDCS, and sham stimulation were administered in a counterbalanced order, and the WM task was performed before, during, and after stimulation. Neither reaction times for hits (RT-hit) nor accuracy differed according to stimulation type with this study design. A marked practice effect was noted, however, with improvement in RT-hit irrespective of stimulation type, which peaked at the end of the second session. Pre-stimulation RT-hits in session three returned to the level observed pre-stimulation in session two, irrespective of stimulation type. The participants who received sham stimulation in session one and had therefore improved their performance due to practice alone, had thus reached a plateau by session two, enabling us to pool RT-hits from sessions two and three for these participants. The pooling allowed implementation of a within-subject crossover study design, with a direct comparison of the effects of TACS and TDCS in a subgroup of participants (N = 10), each of whom received both stimulation types, in a counterbalanced order, with pre-stimulation performance the same for both sessions. TACS resulted in a greater improvement in RT-hits than TDCS (F(2,18) = 4.31 p = 0.03). Our findings suggest that future work optimizing the application of TACS has the potential to facilitate WM performance.

Modulating auditory selective attention by non-invasive brain stimulation: Differential effects of transcutaneous vagal nerve stimulation and transcranial random noise stimulation.

Selective attention is a basic process required to maintain goal-directed behavior by appropriately responding to target stimuli and suppressing reactions to non-target stimuli. It has been proposed that auditory selective attention is linked to the activity of the locus coeruleus-norepinergic (LC-NE) system and a large-scale fronto-parietal cortical network, but there is still sparse causal evidence for these assumptions. By applying transcutaneous vagal nerve stimulation (tVNS) and transcranial random noise stimulation (tRNS) over the frontal cortex, we systematically assessed the involvement of these subcortical and cortical components in the regulation of auditory selective attention. Using a single-blinded, sham-controlled, within-subject design we analyzed online effects of tVNS and tRNS in 20 healthy participants during an auditory oddball paradigm. We show significant stimulation-dependent modulations of auditory selective attention on the behavioral and electrophysiological level. Compared to sham, tVNS increased the P3 amplitude, while tRNS reduced the reaction time to target stimuli. Moreover, both techniques reduced the P3 latency. Our data provide evidence for the functional relevance of the subcortical NE system in the regulation of neural resources that allows a phasic response to incoming target stimuli. They indicate that frontal cortex structures are crucially involved in the successful evaluation of the respective information. Moreover, our results are in favor of the LC-P3 hypothesis claiming the vital role of the NE system in auditory selective attention and in the generation of the P3. Of note, the effects of tVNS on auditory selective attention are comparable with those evoked by pharmacological interventions and invasive vagal nerve stimulation.

Electrophysiological and behavioral effects of frontal transcranial direct current stimulation on cognitive fatigue in multiple sclerosis.

Fatigue is one of the most common and debilitating symptoms affecting patients with multiple sclerosis (MS). Sustained cognitive effort induces cognitive fatigue, operationalized as subjective exhaustion and fatigue-related objective alertness decrements with time-on-task. During prolonged cognitive testing, MS patients show increased simple reaction times (RT) accompanied by lower amplitudes and prolonged latencies of the P300 event-related potential. Previous studies suggested a major role of structural and functional abnormalities in the frontal cortex including a frontal hypo-activation in fatigue pathogenesis. In the present study we investigated the neuromodulatory effect of transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (DLPFC) on objective measures of fatigue-related decrements in cognitive performance in MS patients. P300 during an auditory oddball task and simple reaction times in an alertness test were recorded at baseline, during and after stimulation. Compared to sham, anodal tDCS caused an increase in P300 amplitude that persisted after the end of stimulation and eliminated the fatigue-related increase in RT over the course of a testing session. Our findings demonstrate that anodal tDCS over the left DLPFC can counteract performance decrements associated with fatigue thereby leading to an improvement in the patient's ability to cope with sustained cognitive demands. This provides causal evidence for the functional relevance of the left DLPFC in fatigue pathophysiology. The results indicate that tDCS-induced modulations of frontal activity can be an effective therapeutic option for the treatment of fatigue-related declines in cognitive performance in MS patients.

Transcranial Random Noise Stimulation (tRNS) Shapes the Processing of Rapidly Changing Auditory Information.

Neural oscillations in the gamma range are the dominant rhythmic activation pattern in the human auditory cortex. These gamma oscillations are functionally relevant for the processing of rapidly changing acoustic information in both speech and non-speech sounds. Accordingly, there is a tight link between the temporal resolution ability of the auditory system and inherent neural gamma oscillations. Transcranial random noise stimulation (tRNS) has been demonstrated to specifically increase gamma oscillation in the human auditory cortex. However, neither the physiological mechanisms of tRNS nor the behavioral consequences of this intervention are completely understood. In the present study we stimulated the human auditory cortex bilaterally with tRNS while EEG was continuously measured. Modulations in the participants' temporal and spectral resolution ability were investigated by means of a gap detection task and a pitch discrimination task. Compared to sham, auditory tRNS increased the detection rate for near-threshold stimuli in the temporal domain only, while no such effect was present for the discrimination of spectral features. Behavioral findings were paralleled by reduced peak latencies of the P50 and N1 component of the auditory event-related potentials (ERP) indicating an impact on early sensory processing. The facilitating effect of tRNS was limited to the processing of near-threshold stimuli while stimuli clearly below and above the individual perception threshold were not affected by tRNS. This non-linear relationship between the signal-to-noise level of the presented stimuli and the effect of stimulation further qualifies stochastic resonance (SR) as the underlying mechanism of tRNS on auditory processing. Our results demonstrate a tRNS related improvement in acoustic perception of time critical auditory information and, thus, provide further indices that auditory tRNS can amplify the resonance frequency of the auditory system.

Transcranial Alternating Current Stimulation (tACS) differentially modulates speech perception in young and older adults.

BACKGROUND: Normal aging is accompanied by a functional decline in processing temporal features of spoken language, such as voice onset time (VOT). On an electrophysiological level, this finding is paralleled by altered patterns of gamma oscillations. OBJECTIVE: Using 40 Hz transcranial alternating current stimulation (tACS) over the bilateral auditory cortex, this study aims to compare the effect of tACS to modulate VOT-processing in samples of healthy young and older adults. METHODS: Twenty-five healthy young (age 20-35 years) and 20 older adults (age 60-75 years) participated in this study. Presented with an auditory phoneme categorization task participants received 40 Hz and 6 Hz tACS on two consecutive sessions. RESULTS: While 40 Hz tACS diminished task accuracy in young adults, older adults benefitted from this stimulation resulting in a more precise phonetic categorization. CONCLUSION: The results of the study are discussed with respect to the non-linear relationship between gamma oscillations in the vicinity of the auditory cortex and VOT-processing. The present findings are promising in the context of an intervention for subjects with impaired ability to process temporal acoustic features in the speech signal.

Modulating Human Auditory Processing by Transcranial Electrical Stimulation.

Transcranial electrical stimulation (tES) has become a valuable research tool for the investigation of neurophysiological processes underlying human action and cognition. In recent years, striking evidence for the neuromodulatory effects of transcranial direct current stimulation, transcranial alternating current stimulation, and transcranial random noise stimulation has emerged. While the wealth of knowledge has been gained about tES in the motor domain and, to a lesser extent, about its ability to modulate human cognition, surprisingly little is known about its impact on perceptual processing, particularly in the auditory domain. Moreover, while only a few studies systematically investigated the impact of auditory tES, it has already been applied in a large number of clinical trials, leading to a remarkable imbalance between basic and clinical research on auditory tES. Here, we review the state of the art of tES application in the auditory domain focussing on the impact of neuromodulation on acoustic perception and its potential for clinical application in the treatment of auditory related disorders.

40Hz-Transcranial alternating current stimulation (tACS) selectively modulates speech perception.

The present study investigated the functional relevance of gamma oscillations for the processing of rapidly changing acoustic features in speech signals. For this purpose we analyzed repetition-induced perceptual learning effects in 18 healthy adult participants. The participants received either 6Hz or 40Hz tACS over the bilateral auditory cortex, while repeatedly performing a phoneme categorization task. In result, we found that 40Hz tACS led to a specific alteration in repetition-induced perceptual learning. While participants in the non-stimulated control group as well as those in the experimental group receiving 6Hz tACS considerably improved their perceptual performance, the application of 40Hz tACS selectively attenuated the repetition-induced improvement in phoneme categorization abilities. Our data provide causal evidence for a functional relevance of gamma oscillations during the perceptual learning of acoustic speech features. Moreover, we demonstrate that even less than twenty minutes of alternating current stimulation below the individual perceptual threshold is sufficient to affect speech perception. This finding is relevant in that this novel approach might have implications with respect to impaired speech processing in dyslexics and older adults.

Age-Related Neural Oscillation Patterns During the Processing of Temporally Manipulated Speech.

This EEG-study aims to investigate age-related differences in the neural oscillation patterns during the processing of temporally modulated speech. Viewing from a lifespan perspective, we recorded the electroencephalogram (EEG) data of three age samples: young adults, middle-aged adults and older adults. Stimuli consisted of temporally degraded sentences in Swedish-a language unfamiliar to all participants. We found age-related differences in phonetic pattern matching when participants were presented with envelope-degraded sentences, whereas no such age-effect was observed in the processing of fine-structure-degraded sentences. Irrespective of age, during speech processing the EEG data revealed a relationship between envelope information and the theta band (4-8 Hz) activity. Additionally, an association between fine-structure information and the gamma band (30-48 Hz) activity was found. No interaction, however, was found between acoustic manipulation of stimuli and age. Importantly, our main finding was paralleled by an overall enhanced power in older adults in high frequencies (gamma: 30-48 Hz). This occurred irrespective of condition. For the most part, this result is in line with the Asymmetric Sampling in Time framework (Poeppel in Speech Commun 41:245-255, 2003), which assumes an isomorphic correspondence between frequency modulations in neurophysiological patterns and acoustic oscillations in spoken language. We conclude that speech-specific neural networks show strong stability over adulthood, despite initial processes of cortical degeneration indicated by enhanced gamma power. The results of our study therefore confirm the concept that sensory and cognitive processes undergo multidirectional trajectories within the context of healthy aging.