Interindividual variability of electric fields during transcranial temporal interference stimulation (tTIS).

Transcranial temporal interference stimulation (tTIS) is a novel non-invasive brain stimulation technique for electrical stimulation of neurons at depth. Deep brain regions are generally small in size, making precise targeting a necessity. The variability of electric fields across individual subjects resulting from the same tTIS montages is unknown so far and may be of major concern for precise tTIS targeting. Therefore, the aim of the current study is to investigate the variability of the electric fields due to tTIS across 25 subjects. To this end, the electric fields of different electrode montages consisting of two electrode pairs with different center frequencies were simulated in order to target selected regions-of-interest (ROIs) with tTIS. Moreover, we set out to compare the electric fields of tTIS with the electric fields of conventional tACS. The latter were also based on two electrode pairs, which, however, were driven in phase at a common frequency. Our results showed that the electric field strengths inside the ROIs (left hippocampus, left motor area and thalamus) during tTIS are variable on single subject level. In addition, tTIS stimulates more focally as compared to tACS with much weaker co-stimulation of cortical areas close to the stimulation electrodes. Electric fields inside the ROI were, however, comparable for both methods. Overall, our results emphasize the potential benefits of tTIS for the stimulation of deep targets, over conventional tACS. However, they also indicate a need for individualized stimulation montages to leverage the method to its fullest potential.

Temporal Expectation Modulates the Cortical Dynamics of Short-Term Memory.

Increased memory load is often signified by enhanced neural oscillatory power in the alpha range (8-13 Hz), which is taken to reflect inhibition of task-irrelevant brain regions. The corresponding neural correlates of memory decay, however, are not yet well understood. In the current study, we investigated auditory short-term memory decay in humans using a delayed matching-to-sample task with pure-tone sequences. First, in a behavioral experiment, we modeled memory performance over six different delay-phase durations. Second, in a MEG experiment, we assessed alpha-power modulations over three different delay-phase durations. In both experiments, the temporal expectation for the to-be-remembered sound was manipulated so that it was either temporally expected or not. In both studies, memory performance declined over time, but this decline was weaker when the onset time of the to-be-remembered sound was expected. Similarly, patterns of alpha power in and alpha-tuned connectivity between sensory cortices changed parametrically with delay duration (i.e., decrease in occipitoparietal regions, increase in temporal regions). Temporal expectation not only counteracted alpha-power decline in heteromodal brain areas (i.e., supramarginal gyrus), but also had a beneficial effect on memory decay, counteracting memory performance decline. Correspondingly, temporal expectation also boosted alpha connectivity within attention networks known to play an active role during memory maintenance. The present data show how patterns of alpha power orchestrate short-term memory decay and encourage a more nuanced perspective on alpha power across brain space and time beyond its inhibitory role.SIGNIFICANCE STATEMENT Our sensory memories of the physical world fade quickly. We show here that this decay of short-term memory can be counteracted by so-called temporal expectation; that is, knowledge of when to expect a sensory event that an individual must remember. We also show that neural oscillations in the "alpha" (8-13 Hz) range index both the degree of memory decay (for brief sound patterns) and the respective memory benefit from temporal expectation. Spatially distributed cortical patterns of alpha power show opposing effects in auditory versus visual sensory cortices. Moreover, alpha-tuned connectivity changes within supramodal attention networks reflect the allocation of neural resources as short-term memory representations fade.

Transcranial alternating current stimulation with speech envelopes modulates speech comprehension.

Cortical entrainment of the auditory cortex to the broadband temporal envelope of a speech signal is crucial for speech comprehension. Entrainment results in phases of high and low neural excitability, which structure and decode the incoming speech signal. Entrainment to speech is strongest in the theta frequency range (4-8 Hz), the average frequency of the speech envelope. If a speech signal is degraded, entrainment to the speech envelope is weaker and speech intelligibility declines. Besides perceptually evoked cortical entrainment, transcranial alternating current stimulation (tACS) entrains neural oscillations by applying an electric signal to the brain. Accordingly, tACS-induced entrainment in auditory cortex has been shown to improve auditory perception. The aim of the current study was to modulate speech intelligibility externally by means of tACS such that the electric current corresponds to the envelope of the presented speech stream (i.e., envelope-tACS). Participants performed the Oldenburg sentence test with sentences presented in noise in combination with envelope-tACS. Critically, tACS was induced at time lags of 0-250 ms in 50-ms steps relative to sentence onset (auditory stimuli were simultaneous to or preceded tACS). We performed single-subject sinusoidal, linear, and quadratic fits to the sentence comprehension performance across the time lags. We could show that the sinusoidal fit described the modulation of sentence comprehension best. Importantly, the average frequency of the sinusoidal fit was 5.12 Hz, corresponding to the peaks of the amplitude spectrum of the stimulated envelopes. This finding was supported by a significant 5-Hz peak in the average power spectrum of individual performance time series. Altogether, envelope-tACS modulates intelligibility of speech in noise, presumably by enhancing and disrupting (time lag with in- or out-of-phase stimulation, respectively) cortical entrainment to the speech envelope in auditory cortex.

4-Hz Transcranial Alternating Current Stimulation Phase Modulates Hearing.

BACKGROUND: Non-invasive brain stimulation with transcranial alternating currents (tACS) has been shown to entrain slow cortical oscillations and thereby influence various aspects of visual perception. Much less is known about its potential effects on auditory perception. OBJECTIVE: In the present study, we apply a novel variant that enables near-equivalent stimulation of both auditory cortices to investigate the causal role of the phase of 4-Hz cortical oscillations for auditory perception. METHODS: We measured detection performance for near-threshold auditory stimuli (4-Hz click trains) that were presented at various moments during ongoing tACS (two synchronous 4-Hz alternating currents applied transcranially to the two cerebral hemispheres). RESULTS: We found that changes in the relative timing of acoustic and electric stimulation cause corresponding perceptual changes that oscillate predominantly at the 4-Hz frequency of the electric stimulation, which is consistent with previous results based on 10-Hz tACS. CONCLUSION: TACS at various frequencies can affect auditory perception. Together with converging previous results based on acoustic stimulation (rather than tACS), this finding implies that fundamental aspects of auditory cognition are mediated by the temporal coherence of sound-induced cortical activity with ongoing cortical oscillations at multiple time scales.

Association of Concurrent fNIRS and EEG Signatures in Response to Auditory and Visual Stimuli.

Functional near-infrared spectroscopy (fNIRS) has been proven reliable for investigation of low-level visual processing in both infants and adults. Similar investigation of fundamental auditory processes with fNIRS, however, remains only partially complete. Here we employed a systematic three-level validation approach to investigate whether fNIRS could capture fundamental aspects of bottom-up acoustic processing. We performed a simultaneous fNIRS-EEG experiment with visual and auditory stimulation in 24 participants, which allowed the relationship between changes in neural activity and hemoglobin concentrations to be studied. In the first level, the fNIRS results showed a clear distinction between visual and auditory sensory modalities. Specifically, the results demonstrated area specificity, that is, maximal fNIRS responses in visual and auditory areas for the visual and auditory stimuli respectively, and stimulus selectivity, whereby the visual and auditory areas responded mainly toward their respective stimuli. In the second level, a stimulus-dependent modulation of the fNIRS signal was observed in the visual area, as well as a loudness modulation in the auditory area. Finally in the last level, we observed significant correlations between simultaneously-recorded visual evoked potentials and deoxygenated hemoglobin (DeoxyHb) concentration, and between late auditory evoked potentials and oxygenated hemoglobin (OxyHb) concentration. In sum, these results suggest good sensitivity of fNIRS to low-level sensory processing in both the visual and the auditory domain, and provide further evidence of the neurovascular coupling between hemoglobin concentration changes and non-invasive brain electrical activity.

Individual musical tempo preference correlates with EEG beta rhythm.

Every individual has a preferred musical tempo, which peaks slightly above 120 beats per minute and is subject to interindividual variation. The preferred tempo is believed to be associated with rhythmic body movements as well as motor cortex activity. However, a long-standing question is whether preferred tempo is determined biologically. To uncover the neural correlates of preferred tempo, we first determined an individual's preferred tempo using a multistep procedure. Subsequently, we correlated the preferred tempo with a general EEG timing parameter as well as perceptual and motor EEG correlates-namely, individual alpha frequency, auditory evoked gamma band response, and motor beta activity. Results showed a significant relation between preferred tempo and the frequency of motor beta activity. These findings suggest that individual tempo preferences result from neural activity in the motor cortex, explaining the interindividual variation.

Analyzing the auditory scene: neurophysiologic evidence of a dissociation between detection of regularity and detection of change.

Detecting regularity and change in the environment is crucial for survival, as it enables making predictions about the world and informing goal-directed behavior. In the auditory modality, the detection of regularity involves segregating incoming sounds into distinct perceptual objects (stream segregation). The detection of change from this within-stream regularity is associated with the mismatch negativity, a component of auditory event-related brain potentials (ERPs). A central unanswered question is how the detection of regularity and the detection of change are interrelated, and whether attention affects the former, the latter, or both. Here we show that the detection of regularity and the detection of change can be empirically dissociated, and that attention modulates the detection of change without precluding the detection of regularity, and the perceptual organization of the auditory background into distinct streams. By applying frequency spectra analysis on the EEG of subjects engaged in a selective listening task, we found distinct peaks of ERP synchronization, corresponding to the rhythm of the frequency streams, independently of whether the stream was attended or ignored. Our results provide direct neurophysiological evidence of regularity detection in the auditory background, and show that it can occur independently of change detection and in the absence of attention.

Modulation of frontal-midline theta by neurofeedback.

Cortical oscillations demonstrate a relationship with cognition. Moreover, they also exhibit associations with task performance and psychiatric mental disorders. This being the case, the modification of oscillations has become one of the key interests of neuroscientific approaches for cognitive enhancement. For such kind of alterations, neurofeedback (NF) of brain activity constitutes a promising tool. Concerning specific higher cognitive functions, frontal-midline theta (fm-theta) has been suggested as an important indicator of relevant brain processes. This paper presents a novel approach for an individualized, eight-session NF training to enhance fm-theta. An individual's dominant fm-theta frequency was determined based on experiments tapping executive functions. Effects of the actual NF training were compared to a pseudo-NF training. Participants of the pseudo-NF training experienced a comparable degree of motivation and commitment as the subjects of the actual NF training, but found the "training" slightly easier. In comparison to the pseudo-NF training, proper NF training significantly enhanced fm-theta amplitude in the actual training sessions, as well as during the whole course of training. However, unspecific changes in the alpha and beta frequency ranges found with both the actual NF and the pseudo-NF training groups emphasize the relevance of active control groups for neurofeedback studies.

Brain-computer interfaces for EEG neurofeedback: peculiarities and solutions.

Neurofeedback training procedures designed to alter a person's brain activity have been in use for nearly four decades now and represent one of the earliest applications of brain-computer interfaces (BCI). The majority of studies using neurofeedback technology relies on recordings of the electroencephalogram (EEG) and applies neurofeedback in clinical contexts, exploring its potential as treatment for psychopathological syndromes. This clinical focus significantly affects the technology behind neurofeedback BCIs. For example, in contrast to other BCI applications, neurofeedback BCIs usually rely on EEG-derived features with only a minimum of additional processing steps being employed. Here, we highlight the peculiarities of EEG-based neurofeedback BCIs and consider their relevance for software implementations. Having reviewed already existing packages for the implementation of BCIs, we introduce our own solution which specifically considers the relevance of multi-subject handling for experimental and clinical trials, for example by implementing ready-to-use solutions for pseudo-/sham-neurofeedback.

Musical expertise affects attention as reflected by auditory-evoked gamma-band activity in human EEG.

Musical expertise has been shown to induce widespread structural and functional alterations in the brain, even-handedly affecting top-down and bottom-up factors. At the same time, it is known that the early evoked gamma-band response (GBR) can be modulated by top-down as well as bottom-up factors such as attention and sound intensity. In this study, we examined the effects of musicianship and attention on the intensity modulation of the auditory-evoked GBR. We compared the electroencephalogram of 17 professional musicians with that of 17 musical laymen obtained during either a forced-choice discrimination task (active) or a passive listening condition. Pure 1000 Hz sine tones were presented at three systematically varied sound intensities (40, 60, and 80 dB sound pressure levels). The results of auditory-evoked potentials and evoked GBRs obtained in the active condition predominantly corresponded to the findings of previous studies. Besides the already known augmentation of the early evoked GBR because of enhanced intertrial phase coherence with increasing sound intensity, we also observed stronger GBRs and enhanced phase locking under the active condition compared with passive listening, whereas the general shape of intensity modulation was comparable between the two conditions. In addition, phase locking to stimulus onset was increased for stimuli of all three intensities when attended, whereas in musicians, only stimuli of the highest intensity (80 dB) induced significantly increased phase locking under the active condition. Taken together, our results suggest that musical expertise influences attention effects on the intensity-modulated early auditory-evoked GBR with respect to intertrial phase coherence.

Boosting brain functions: Improving executive functions with behavioral training, neurostimulation, and neurofeedback.

Cognitive enhancement is a popular topic, attracting attention both from the general public and the scientific research community. Higher cognitive functions are involved in various aspects of everyday life and have been associated with manifest behavioral and psychiatric mental impairments when deteriorated. The improvement of these so-called executive functions (EFs) is of high individual, social, and economic relevances. This review provides a synopsis of two lines of research, investigating the enhancement of capabilities in executive functioning: a) computerized behavioral trainings, and b) approaches for direct neuromodulation (neurofeedback and transcranial electrostimulation). Task switching, memory updating, response inhibition, and dual task performance are addressed in terms of cognitive functions. It has been shown that behavioral cognitive training leads to enhanced performance in task switching, memory updating, and dual tasks. Similarly, direct neurocognitive modulation of brain regions that are crucially involved in specific EFs also leads to behavioral benefits in response inhibition, task switching, and memory updating. Response inhibition performance has been shown to be improved by neurostimulation of the right inferior frontal cortex, whereas neurostimulation of the dorsolateral prefrontal cortex exerts effects on task switching and memory updating. Due to a lack of consistency in experimental methods and findings, a comparison of different training approaches concerning their effectiveness is not yet possible. So far, current data suggest that training gains may indeed generalize to untrained tasks aiming at the same cognitive process, as well as across cognitive domains within executive control.

Neurophysiological studies of auditory verbal hallucinations.

We discuss 3 neurophysiological approaches to study auditory verbal hallucinations (AVH). First, we describe "state" (or symptom capture) studies where periods with and without hallucinations are compared "within" a patient. These studies take 2 forms: passive studies, where brain activity during these states is compared, and probe studies, where brain responses to sounds during these states are compared. EEG (electroencephalography) and MEG (magnetoencephalography) data point to frontal and temporal lobe activity, the latter resulting in competition with external sounds for auditory resources. Second, we discuss "trait" studies where EEG and MEG responses to sounds are recorded from patients who hallucinate and those who do not. They suggest a tendency to hallucinate is associated with competition for auditory processing resources. Third, we discuss studies addressing possible mechanisms of AVH, including spontaneous neural activity, abnormal self-monitoring, and dysfunctional interregional communication. While most studies show differences in EEG and MEG responses between patients and controls, far fewer show symptom relationships. We conclude that efforts to understand the pathophysiology of AVH using EEG and MEG have been hindered by poor anatomical resolution of the EEG and MEG measures, poor assessment of symptoms, poor understanding of the phenomenon, poor models of the phenomenon, decoupling of the symptoms from the neurophysiology due to medications and comorbidites, and the possibility that the schizophrenia diagnosis breeds truer than the symptoms it comprises. These problems are common to studies of other psychiatric symptoms and should be considered when attempting to understand the basic neural mechanisms responsible for them.

Auditory event-related response in visual cortex modulates subsequent visual responses in humans.

Growing evidence from electrophysiological data in animal and human studies suggests that multisensory interaction is not exclusively a higher-order process, but also takes place in primary sensory cortices. Such early multisensory interaction is thought to be mediated by means of phase resetting. The presentation of a stimulus to one sensory modality resets the phase of ongoing oscillations in another modality such that processing in the latter modality is modulated. In humans, evidence for such a mechanism is still sparse. In the current study, the influence of an auditory stimulus on visual processing was investigated by measuring the electroencephalogram (EEG) and behavioral responses of humans to visual, auditory, and audiovisual stimulation with varying stimulus-onset asynchrony (SOA). We observed three distinct oscillatory EEG responses in our data. An initial gamma-band response around 50 Hz was followed by a beta-band response around 25 Hz, and a theta response around 6 Hz. The latter was enhanced in response to cross-modal stimuli as compared to either unimodal stimuli. Interestingly, the beta response to unimodal auditory stimuli was dominant in electrodes over visual areas. The SOA between auditory and visual stimuli--albeit not consciously perceived--had a modulatory impact on the multisensory evoked beta-band responses; i.e., the amplitude depended on SOA in a sinusoidal fashion, suggesting a phase reset. These findings further support the notion that parameters of brain oscillations such as amplitude and phase are essential predictors of subsequent brain responses and might be one of the mechanisms underlying multisensory integration.

Neurofeedback training of the upper alpha frequency band in EEG improves cognitive performance.

In this study, the individually determined upper alpha frequency band in EEG (electroencephalogram) was investigated as a neurofeedback parameter. Fourteen subjects were trained on five sessions within 1 week by means of feedback dependent on the current upper alpha amplitude. On the first and fifth session, cognitive ability was tested by a mental rotation test. As a result, eleven of the fourteen subjects showed significant training success. Individually determined upper alpha was increased independently of other frequency bands. The enhancement of cognitive performance was significantly larger for the neurofeedback group than for a control group who did not receive feedback. Thus, enhanced cognitive control went along with an increased upper alpha amplitude that was found in the neurofeedback group only.

Altered evoked γ-band responses as a neurophysiological marker of schizophrenia?

Evoked gamma-band responses (GBRs) were shown to be involved in different aspects of human cognition and behavior. They have been linked to the integration and processing of incoming information leading to an adequate behavioral outcome. Consequently, altered evoked GBRs have been associated with impaired cognitive and behavioral states present in a variety of psychiatric disorders. However, to the best of our knowledge, there are no reports directly comparing evoked GBRs of different clinical groups in the same experimental setting. Thus, the purpose of the present study was to shed light on the question, whether evoked GBRs, as a kind of a neurophysiological biomarker of pathological states, might serve for characterization and distinguishing of groups suffering from diverse psychiatric disorders. We measured EEG during a passive auditory oddball-paradigm. Participants were patients diagnosed with schizophrenia, mood disorder, and personality disorders as well as a fourth group consisting of healthy participants. Our results indicate that evoked GBRs significantly differed from healthy participants only in schizophrenic patients whereas no difference could be observed for the other clinical groups. Our findings support the notion that early evoked GBRs could be indeed a trait variable of schizophrenia and are not a general marker of pathological brain states.

Pre-attentive spectro-temporal feature processing in the human auditory system.

In the present study, we investigated the pre-attentive processing of low-level acoustic properties and the impact of this mechanism on functional lateralization in the human auditory system. Mismatch negativity (MMN) of the event-related potentials (ERP) were recorded in 19 adult humans who passively listened to a standard stimulus and spectrally and temporally deviant sounds. We predicted modulations of the MMN amplitude in response to spectrally and temporally graded deviants. Based on recent models of functional hemispheric lateralisation, we further hypothesized a left-lateralized source of the MMN in response to temporal deviants and, in contrast, a right-lateralized source of the MMN in response to spectral deviants. In agreement with our hypothesis, we showed that spectrally and temporally deviant sounds lead to robust MMNs recorded from frontocentral scalp electrodes. The amplitudes of the MMNs were modulated by the grade of spectral and temporal deviation from the standard sound. Furthermore, by using an assumption-free source localization approach (LORETA) we demonstrated functionally lateralized activations with dominance of the right hemisphere for the processing of spectral characteristics and of the left hemisphere for the processing of temporal acoustic properties. Results of our study further contribute to the ongoing debate on the role of low-level acoustic feature perception in functional hemispheric lateralization in the context of auditory and speech processing. Our data indicate that the pre-attentive feature-specific deviant processing is mediated by partly distinct neural subsystems for temporal and spectral information.

Auditory memory: a comparison between humans and starlings.

In this study, we compare the processing of acoustic signals in European starlings (Sturnus vulgaris) and in human listeners by observing the decay of short-term auditory memory in delayed non-matching-to-sample experiments. A series of identical "sample" stimuli and a final "test" stimulus were separated by variable delays (1 to 180.1 s). Subjects had to classify sample and test stimuli as being either the same or different. Test stimuli were pure tones that differed in a single signal feature, i.e., frequency, and song motifs that differed in multiple signal characteristics. We have tested several predictions concerning the memory performance of starlings and humans and we obtained the following outcome: (1) In contrast to our expectation, signal complexity had no effect. The overall analysis of the starling data did not show differences in memory performance for signals differing in single or multiple signal features. (2) Starling and human data supported the hypothesis that auditory memory impairs with increasing delay. This was also seen when interfering noise was added to the delay periods in an additional series with human subjects. (3) The starling data showed that the repetition of sample stimuli improved memory performance, compared to only a single presentation. Human memory performance, however, was similar for a single and for the repeated presentation of signals. (4) Differences in salience between sample and test stimuli were positively related to memory performance only for tonal stimuli but not for song motifs. Results are discussed with respect to a model based on signal detection theory and to requirements for the analysis of natural communication signals.

Sound level dependence of auditory evoked potentials: simultaneous EEG recording and low-noise fMRI.

The simultaneous recording of EEG and fMRI offers the advantage of combining precise spatial information about neuronal processing obtained by fMRI data with the high temporal resolution of EEG data. One problem for the analysis of auditory processing, however, is the noisy environment during fMRI measurements, especially when EPI sequences are employed. While EEG studies outside an MRI scanner repeatedly demonstrated a clear sound level-dependent increase of N1 amplitude, this finding was less obvious in simultaneous recordings inside a scanner. Based on the assumption that this inconsistency might be due to the confounding effect of the rather loud EPI noise, we employed a low-noise fMRI protocol. This method was previously used to reveal level-dependent fMRI activation in auditory cortex areas. We combined this method with simultaneous EEG recordings to investigate the effect of different sound intensities on the auditory evoked potentials. Eight participants without hearing deficits took part in our experiment. Frequency modulated tones (FM) were presented monaurally with two sound intensities (60 and 80 dB HL). The task of the participants was to categorize the FM-direction (rising vs. falling). Our results inside the scanner replicate the sound level dependence of AEPs from previous EEG studies outside the scanner. The data analysis revealed a significant shortening of N1 latency and an increase in the N1-P2 peak-to-peak amplitude for the higher sound intensity. On a descriptive level, the 80 dB HL stimulation yielded more activated voxels in fMRI and stronger activations. This effect was pronounced over the right hemisphere. Our results suggest that low-noise sequences might be advantageous for the examination of auditory processing in simultaneous EEG and fMRI recordings.

Analysis of a choice-reaction task yields a new interpretation of Libet's experiments.

Benjamin Libet has demonstrated that the readiness potential precedes the time at which participants consciously decide to perform an intentional motor act, and suggested that free will is an illusion. We performed an experiment where participants observed a stimulus on a computer monitor and were instructed to press one of two buttons, depending on the presented stimulus. We found neural activity preceding the motor response, similar to Libet's experiments. However, this activity was already present prior to stimulus presentation, and thus before participants could decide which button to press. Therefore, we argue that this activity does not specifically determine behaviour. Instead, it may reflect a general expectation. This interpretation would not interfere with the notion of free will.

Human EEG very high frequency oscillations reflect the number of matches with a template in auditory short-term memory.

Auditory perception comprises bottom-up as well as top-down processes. While research in the past has revealed many neural correlates of bottom-up processes, less is known about top-down modulation. Memory processes have recently been associated with oscillations in the gamma-band of human EEG (30 Hz and above) which are enhanced when incoming information matches a stored memory template. Therefore, we investigated event-related potentials (ERPs) and gamma-band activity in 17 healthy participants in a Go/NoGo-task. They listened to four frequency-modulated (FM) sounds which varied regarding the frequency range traversed and the direction of frequency modulation. One sound was defined as target and required a button press. The results of ERPs (N1, P2, N2, and P3) were consistent with previous studies. Analysis of evoked gamma-band responses yielded no significant task-dependent modulation, but we observed a stimulus dependency, which was also present in a control experiment: The amplitude of evoked gamma responses showed an inverted U-shape as a function of stimulus frequency. Investigation of total gamma activity revealed functionally relevant responses at high frequencies (90 Hz to 250 Hz), which showed significant modulations by matches with STM: Complete matches led to the strongest enhancements (starting around 100 ms after stimulus onset) and partial matches resulted in intermediate ones. The results support the conclusion that very high frequency oscillations (VHFOs) are markers of active stimulus discrimination in STM matching processes and are attributable to higher cognitive functions.