Theta and alpha oscillatory signatures of auditory sensory and cognitive loads during complex listening.

The neuronal signatures of sensory and cognitive load provide access to brain activities related to complex listening situations. Sensory and cognitive loads are typically reflected in measures like response time (RT) and event-related potentials (ERPs) components. It's, however, strenuous to distinguish the underlying brain processes solely from these measures. In this study, along with RT- and ERP-analysis, we performed time-frequency analysis and source localization of oscillatory activity in participants performing two different auditory tasks with varying degrees of complexity and related them to sensory and cognitive load. We studied neuronal oscillatory activity in both periods before the behavioral response (pre-response) and after it (post-response). Robust oscillatory activities were found in both periods and were differentially affected by sensory and cognitive load. Oscillatory activity under sensory load was characterized by decrease in pre-response (early) theta activity and increased alpha activity. Oscillatory activity under cognitive load was characterized by increased theta activity, mainly in post-response (late) time. Furthermore, source localization revealed specific brain regions responsible for processing these loads, such as temporal and frontal lobe, cingulate cortex and precuneus. The results provide evidence that in complex listening situations, the brain processes sensory and cognitive loads differently. These neural processes have specific oscillatory signatures and are long lasting, extending beyond the behavioral response.

Using reciprocity for relating the simulation of transcranial current stimulation to the EEG forward problem.

To explore the relationship between transcranial current stimulation (tCS) and the electroencephalography (EEG) forward problem, we investigate and compare accuracy and efficiency of a reciprocal and a direct EEG forward approach for dipolar primary current sources both based on the finite element method (FEM), namely the adjoint approach (AA) and the partial integration approach in conjunction with a transfer matrix concept (PI). By analyzing numerical results, comparing to analytically derived EEG forward potentials and estimating computational complexity in spherical shell models, AA turns out to be essentially identical to PI. It is then proven that AA and PI are also algebraically identical even for general head models. This relation offers a direct link between the EEG forward problem and tCS. We then demonstrate how the quasi-analytical EEG forward solutions in sphere models can be used to validate the numerical accuracies of FEM-based tCS simulation approaches. These approaches differ with respect to the ease with which they can be employed for realistic head modeling based on MRI-derived segmentations. We show that while the accuracy of the most easy to realize approach based on regular hexahedral elements is already quite high, it can be significantly improved if a geometry-adaptation of the elements is employed in conjunction with an isoparametric FEM approach. While the latter approach does not involve any additional difficulties for the user, it reaches the high accuracies of surface-segmentation based tetrahedral FEM, which is considerably more difficult to implement and topologically less flexible in practice. Finally, in a highly realistic head volume conductor model and when compared to the regular alternative, the geometry-adapted hexahedral FEM is shown to result in significant changes in tCS current flow orientation and magnitude up to 45° and a factor of 1.66, respectively.

[Transcranial alternating current stimulation. Entrainment and function control of neuronal networks]. / Transkranielle Wechselstromstimulation. Entrainment und Funktionssteuerung neuronaler Netzwerke.

Transcranial alternating current stimulation (tACS) is a new technique for the modulation of oscillatory brain activity as measured in the electroencephalogram (EEG). In contrast to well-established stimulation techniques, such as transcranial direct current stimulation and transcranial magnetic stimulation, tACS applies a sinusoidal alternating current at a specific frequency. This enables the modulation of the amplitude and frequency of endogenous brain oscillations as well as related cognitive processes. Therefore, the use of tACS has the possibility to evaluate well-known correlations between brain oscillations and cognitive processes in terms of causality. Such causal relationships have been documented in numerous neurocognitive studies on sensory, motor and perceptual processes; however, the clinical application of tACS is still in its infancy. In principle, any pathology that can reliably be connected with brain oscillations of a defined frequency is treatable. A current main focus of clinical research is on symptoms of Parkinson's disease and to a lesser degree, tinnitus. For an effective application of tACS it is important to choose the electrode positions as well as the frequency, intensity and duration of the stimulation in a theory-based and symptom-related manner. A successful therapeutic intervention requires the persistence of the tACS effect after stimulation has ceased. A mechanism that offers not only an explanation to the origin of persistent tACS effects but is also of high therapeutic benefit is neural plasticity. Therefore, one current focus of research aims at a better understanding of tACS after effects.

Good vibrations: oscillatory phase shapes perception.

In the current study, we provide compelling evidence to answer the long-standing question whether perception is continuous or periodic. Spontaneous brain oscillations are assumed to be the underlying mechanism of periodic perception. Depending on the phase angle of the oscillations, an identical stimulus results in different perceptual outcomes. Past results, however, can only account for a correlation of perception with the phase of the ongoing brain oscillations. Therefore, it is desirable to demonstrate a causal relation between phase and perception. One way to address this question is to entrain spontaneous brain oscillations by applying an external oscillation and then demonstrate behavioral consequences of this oscillation. We conducted an auditory detection experiment with humans, recorded the electroencephalogram (EEG) concurrently and simultaneously applied oscillating transcranial direct current stimulation at 10Hz (α-tDCS). Our approach revealed that detection thresholds were dependent on the phase of the oscillation that was entrained by α-tDCS. This behavioral effect was accompanied by an electrophysiological effect: α-power was enhanced after α-tDCS as compared to a pre-stimulation period. By showing a causal relation between phase and perception, our results extend findings of previous studies that were only able to demonstrate a correlation. We found that manipulation of the phase resulted in different detection thresholds, which supports the notion that perception can be periodically modulated by oscillatory processes. This demonstrates that tDCS can serve as a tool in neuroscience to extend the knowledge of the functional significance of brain oscillations.

Resonance phenomena in the human auditory cortex: individual resonance frequencies of the cerebral cortex determine electrophysiological responses.

The brain can be considered a dynamical system which is able to oscillate at multiple frequencies. To study the brain's preferred oscillation frequencies, the resonance frequencies in the frequency response of the system can be assessed by stimulating the brain at various stimulation frequencies. Furthermore, the event-related potential (ERP) can be considered as the brain's impulse response. For linear dynamical systems, the frequency response should be equivalent to the frequency transform of the impulse response. The present study test whether this fundamental relation is also true for the frequency transform of the ERP and the frequency response of the brain. Results show that the spectral characteristics of both impulse and frequency response in the gamma frequency range are significantly correlated. Thus, we speculate that the resonance frequencies determine the frequency spectrum of the impulse response. This, in turn, implies that both measures are determined by the same, individually specific, neuronal generator mechanisms.

Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines.

Low intensity transcranial electrical stimulation (TES) in humans, encompassing transcranial direct current (tDCS), transcutaneous spinal Direct Current Stimulation (tsDCS), transcranial alternating current (tACS), and transcranial random noise (tRNS) stimulation or their combinations, appears to be safe. No serious adverse events (SAEs) have been reported so far in over 18,000 sessions administered to healthy subjects, neurological and psychiatric patients, as summarized here. Moderate adverse events (AEs), as defined by the necessity to intervene, are rare, and include skin burns with tDCS due to suboptimal electrode-skin contact. Very rarely mania or hypomania was induced in patients with depression (11 documented cases), yet a causal relationship is difficult to prove because of the low incidence rate and limited numbers of subjects in controlled trials. Mild AEs (MAEs) include headache and fatigue following stimulation as well as prickling and burning sensations occurring during tDCS at peak-to-baseline intensities of 1-2mA and during tACS at higher peak-to-peak intensities above 2mA. The prevalence of published AEs is different in studies specifically assessing AEs vs. those not assessing them, being higher in the former. AEs are frequently reported by individuals receiving placebo stimulation. The profile of AEs in terms of frequency, magnitude and type is comparable in healthy and clinical populations, and this is also the case for more vulnerable populations, such as children, elderly persons, or pregnant women. Combined interventions (e.g., co-application of drugs, electrophysiological measurements, neuroimaging) were not associated with further safety issues. Safety is established for low-intensity 'conventional' TES defined as <4mA, up to 60min duration per day. Animal studies and modeling evidence indicate that brain injury could occur at predicted current densities in the brain of 6.3-13A/m2 that are over an order of magnitude above those produced by tDCS in humans. Using AC stimulation fewer AEs were reported compared to DC. In specific paradigms with amplitudes of up to 10mA, frequencies in the kHz range appear to be safe. In this paper we provide structured interviews and recommend their use in future controlled studies, in particular when trying to extend the parameters applied. We also discuss recent regulatory issues, reporting practices and ethical issues. These recommendations achieved consensus in a meeting, which took place in Göttingen, Germany, on September 6-7, 2016 and were refined thereafter by email correspondence.

A technical guide to tDCS, and related non-invasive brain stimulation tools.

Transcranial electrical stimulation (tES), including transcranial direct and alternating current stimulation (tDCS, tACS) are non-invasive brain stimulation techniques increasingly used for modulation of central nervous system excitability in humans. Here we address methodological issues required for tES application. This review covers technical aspects of tES, as well as applications like exploration of brain physiology, modelling approaches, tES in cognitive neurosciences, and interventional approaches. It aims to help the reader to appropriately design and conduct studies involving these brain stimulation techniques, understand limitations and avoid shortcomings, which might hamper the scientific rigor and potential applications in the clinical domain.

Human EEG gamma oscillations in neuropsychiatric disorders.

Due to their small amplitude, the importance of high-frequency EEG oscillations with respect to cognitive functions and disorders is often underestimated as compared to slower oscillations. This article reviews the literature on the alterations of gamma oscillations (about 30-80 Hz) during the course of neuropsychiatric disorders and relates them to a model for the functional role of these oscillations for memory matching. The synchronous firing of neurons in the gamma-band has been proposed to bind multiple features of an object, which are coded in a distributed manner in the brain, and is modulated by cognitive processes such as attention and memory. In certain neuropsychiatric disorders the gamma activity shows significant changes. In schizophrenic patients, negative symptoms correlate with a decrease of gamma responses, whereas a significant increase in gamma amplitudes is observed during positive symptoms such as hallucinations. A reduction is also observed in Alzheimer's Disease (AD), whereas an increase is found in epileptic patients, probably reflecting both cortical excitation and perceptual distortions such as déjà vu phenomena frequently observed in epilepsy. ADHD patients also exhibit increased gamma amplitudes. A hypothesis of a gamma axis of these disorders mainly based on the significance of gamma oscillations for memory matching is formulated.

Mechanisms of human attention: event-related potentials and oscillations.

Electrophysiological and hemodynamical responses of the brain allow investigation of the neural origins of human attention. We review attention-related brain responses from auditory and visual tasks employing oddball and novelty paradigms. Dipole localization and intracranial recordings as well as functional magnetic resonance imaging reveal multiple areas involved in generating and modulating attentional brain responses. In addition, the influence of brain lesions of circumscribed areas of the human cortex onto attentional mechanisms are reviewed. While it is obvious that damaged brain tissue no longer functions properly, it has also been shown that functions of non-lesioned brain areas are impaired due to loss of modulatory influence of the lesioned area. Both early (P1 and N1) and late (P3) event-related potentials are modulated by excitatatory and inhibitory mechanisms. Oscillatory EEG-correlates of attention in the alpha and gamma frequency range also show attentional modulation.

Gestalt perception modulates early visual processing.

We examined whether early visual processing reflects perceptual properties of a stimulus in addition to physical features. We recorded event-related potentials (ERPs) of 13 subjects in a visual classification task. We used four different stimuli which were all composed of four identical elements. One of the stimuli constituted an illusory Kanizsa square, another was composed of the same number of collinear line segments but the elements did not form a Gestalt. In addition, a target and a control stimulus were used which were arranged differently. These stimuli allow us to differentiate the processing of colinear line elements (stimulus features) and illusory figures (perceptual properties). The visual N170 in response to the illusory figure was significantly larger as compared to the other collinear stimulus. This is taken to indicate that the visual N170 reflects cognitive processes of Gestalt perception in addition to attentional processes and physical stimulus properties.

Noise affects auditory and linguistic processing differently: an MEG study.

We investigated the influence of noise on brain responses to spoken sentences in MEG. Sixteen subjects had to listen to acoustically presented sentences and judge their syntactic correctness. Sentences were either presented on a silent background or with noise. Noise had differential effects on early auditory and syntactic processes. While noise affected early auditory processes only in the right hemisphere, noise had a general effect on syntactical processes. The evoked responses to syntactic violations compared with correct sentences, namely an early left anterior negativity, were significantly suppressed when noise was present The noise suppression effect, however, was not lateralized.

Gamma responses and ERPs in a visual classification task.

OBJECTIVE: We examined event-related potentials (ERPs) and gamma range EEG activity in a visual classification task to assess which variables affect these responses. METHODS: Ten subjects silently counted the occurrence of rare Kanizsa squares (targets) among Kanizsa triangles and non-Kanizsa figures (standards). By applying a time-frequency analysis to the data and selectively calculating topographical maps of certain frequencies. RESULTS: We were able to find 3 different types of gamma responses to Kanizsa figures: an early phase-locked gamma response at 40 Hz in the N100 time range, late phase-locked gamma activity (200-300 ms) at 40 Hz and a continuous phase-locked gamma response at 80 Hz due to the monitor refresh frequency. The two 40 Hz responses were significantly higher for Kanizsa figures than for non-Kanizsa figures and within the Kanizsa figures were higher for the target figure than for the non-target. CONCLUSION: The phase-locking of these two responses, previously found also as non-phase-locked activity, could be synchronized due to the monitor flicker frequency. Also, our findings suggest that the gamma responses are not solely associated with the binding of stimulus features, but reflect some processes related to target processing.

Sleep stage dependant changes of the high-frequency part of the somatosensory evoked potentials at the thalamus and cortex.

OBJECTIVES: It is known that the high-frequency oscillations (above 400 Hz) of the somatosensory evoked potentials (SEPs) diminish during sleep while the N20 persists (Neurology 38 (1988) 64; Electroenceph clin Neurophysiol 70 (1988) 126; Electroenceph clin Neurophysiol 100 (1996) 189). We investigated possible differential effects of sleep on the 600 Hz SEPs at the thalamus and cortex. METHODS: SEPs from 10 subjects were recorded using 64 channels following electric stimulation at the wrist during awake state and sleep stages II, IV and REM. Dipole source analysis was applied to separate brain-stem, thalamic and cortical activity in the low-frequency (20-450 Hz) and the high-frequency (450-750 Hz) part of the signal. RESULTS: The low-frequency SEPs showed a non-significant increase of the latency of the N20 and a bifid change of the waveform in 3 subjects. The high-frequency SEPs showed a significant decrease of their amplitude at the level of the thalamus and cortex but not at the brain-stem. This decrease in amplitude at the thalamus and cortex were significantly correlated. There was no effect on the latency of the signal. In addition, at the cortex, differential effects on early and late parts of the 600 Hz oscillations were found by time-frequency analysis using a wavelet transformation. CONCLUSIONS: Sleep dependent decrease of the high-frequency SEPs were first observed at the thalamus pointing to the known function of the reticular thalamic nucleus regulating arousal. The results presented here provide further evidence for a thalamic origin of the 600 Hz oscillations. In addition, on the basis of the differential effects on early (up to the N20 peak) and late (between 20 and 25 ms) parts of the signal, at least one intracortical generator of these oscillations is proposed. In general, the high-frequency SEPs (600 Hz oscillations) are supposed to reflect activity of a somatosensory arousal system.

Perception of pain coincides with the spatial expansion of electroencephalographic dynamics in human subjects.

The dynamics of cortex driven by painful median nerve stimulation were investigated in event-related oscillation (ERO). We applied a wavelet time-frequency analysis to differentiate the brain dynamics between painful and non-painful somatosensory stimulation. The observed pattern to pain-induced effects exhibited a stepwise decrease of frequencies over time, starting around 26 ms over somatosensory cortex at 80 Hz, intermediate oscillations at 40 and 20 Hz around 40 ms, and reaching down to 10 Hz after 160 ms. This step-wise frequency decrease of ERO, coincident with spatial shift from the contralateral somatosensory area at 80 Hz to the centro-frontal brain at 40/20 Hz and final spatial expansion to the large region of centro-parietal areas at 10 Hz, may represent the cortical processes necessary to transfer sensory information from perceptual stages to subsequent cognitive stages in consciousness.

Magnetoencephalographic responses to illusory figures: early evoked gamma is affected by processing of stimulus features.

We examined evoked and induced responses in event-related fields and gamma activity in the magnetoencephalogram (MEG) during a visual classification task. The objective was to investigate the effects of target classification and the different levels of discrimination between certain stimulus features. We performed two experiments, which differed only in the subjects' task while the stimuli were identical. In Experiment 1, subjects responded by a button-press to rare Kanizsa squares (targets) among Kanizsa triangles and non-Kanizsa figures (standards). This task requires the processing of both stimulus features (colinearity and number of inducer disks). In Experiment 2, the four stimuli of Experiment 1 were used as standards and the occurrence of an additional stimulus without any feature overlap with the Kanizsa stimuli (a rare and highly salient red fixation cross) had to be detected. Discrimination of colinearity and number of inducer disks was not necessarily required for task performance. We applied a wavelet-based time-frequency analysis to the data and calculated topographical maps of the 40 Hz activity. The early evoked gamma activity (100-200 ms) in Experiment 1 was higher for targets as compared to standards. In Experiment 2, no significant differences were found in the gamma responses to the Kanizsa figures and non-Kanizsa figures. This pattern of results suggests that early evoked gamma activity in response to visual stimuli is affected by the targetness of a stimulus and the need to discriminate between the features of a stimulus.

The loci of oscillatory visual-object priming: a combined electroencephalographic and reaction-time study.

The detection of reaction-times (RTs) to a target Kanizsa-type square (an illusory square defined by the colinear arrangement of 90 degrees corner junctions) within a matrix of distractor junctions are expedited when the target display is preceded by a 40-Hz flickering display of premask crosses presented prior to, and at the locations subsequently occupied by the junctions of the target display. Priming effects were obtained when four crosses (which together matched the Gestalt arrangement of the target) were presented at the display locations subsequently occupied by the junctions forming the target Kanizsa square (Elliott and Müller, 1998, 2000). The present study was conducted with the aim of replicating the 40-Hz RT priming effects, while simultaneously recording the observers EEG in order to establish the presence and location of Gestalt priming in the brain. The statistical pattern obtained in the RT data corresponded well with previous studies and was matched by the pattern of target P300 latencies across bilateral central and posterior electrodes. Planned analyses focused upon the evoked 40-Hz activity that co-occurs with the P300, revealing a more specific pattern of 40-Hz priming over the visual cortex. A subsequent series of cross-correlational analyses examined the cortical distribution and timing of Gestalt-prime generation during and subsequent to premask-display presentation. Correlations were revealed between stimulus related 40-Hz activity over a range of cortical loci, including the right temporal lobe, which is considered important for figure coding. Taken together, these findings not only support the role of a distributed 40-Hz mechanism during Gestalt-figure priming, but also suggest that patterns of oscillatory brain activity may be directly influenced by, and interpretable in terms of equivalent temporal patterns of stimulus activity.

Auditory novelty oddball allows reliable distinction of top-down and bottom-up processes of attention.

An auditory novelty-oddball task, which is known to evoke a P3 event-related potential (ERP) in a target condition and a novelty-P3 ERP in response to task-irrelevant unique environmental sounds, was repeatedly applied to healthy participants (n = 14) on two separate recording sessions, 7 days apart. Both target-P3 and novelty-P3 were internally consistent and test-retest reliable. Interestingly, novelty-P3 amplitude declined from the first to the second half of each recording session, whereas no systematic alteration between both sessions occurred. The target-P3 showed the opposite pattern, i.e. a reduced amplitude from the first to the second session, but no systematic change within each session. These findings suggest that novelty-P3 amplitude changes reflect habituation, whereas target-P3 session effects may indicate the adjusted amount of processing resources invested into the task. In general, the results support the interpretation of the novelty-P3 as indicating automatic, bottom-up related aspects of attention, whereas the target-P3, in the present paradigm, seems to reflect voluntary, top-down related aspects of attention.

Adaptive frequency decomposition of EEG with subsequent expert system analysis.

We present a hybrid system for automatic analysis of clinical routine EEG, comprising a spectral analysis and an expert system. EEG raw data are transformed into the time-frequency domain by the so-called adaptive frequency decomposition. The resulting frequency components are converted into pseudo-linguistic facts via fuzzification. Finally, an expert system applies symbolic rules formulated by the neurologist to evaluate the extracted EEG features. The system detects artefacts, describes alpha rhythm by frequency, amplitude, and stability and after artefact rejection detects pathologic slow activity. All results are displayed as linguistic terms, numerical values and maps of temporal extent, giving an overview about the clinical routine EEG.

Investigation of tDCS volume conduction effects in a highly realistic head model.

OBJECTIVE: We investigate volume conduction effects in transcranial direct current stimulation (tDCS) and present a guideline for efficient and yet accurate volume conductor modeling in tDCS using our newly-developed finite element (FE) approach. APPROACH: We developed a new, accurate and fast isoparametric FE approach for high-resolution geometry-adapted hexahedral meshes and tissue anisotropy. To attain a deeper insight into tDCS, we performed computer simulations, starting with a homogenized three-compartment head model and extending this step by step to a six-compartment anisotropic model. MAIN RESULTS: We are able to demonstrate important tDCS effects. First, we find channeling effects of the skin, the skull spongiosa and the cerebrospinal fluid compartments. Second, current vectors tend to be oriented towards the closest higher conducting region. Third, anisotropic WM conductivity causes current flow in directions more parallel to the WM fiber tracts. Fourth, the highest cortical current magnitudes are not only found close to the stimulation sites. Fifth, the median brain current density decreases with increasing distance from the electrodes. SIGNIFICANCE: Our results allow us to formulate a guideline for volume conductor modeling in tDCS. We recommend to accurately model the major tissues between the stimulating electrodes and the target areas, while for efficient yet accurate modeling, an exact representation of other tissues is less important. Because for the low-frequency regime in electrophysiology the quasi-static approach is justified, our results should also be valid for at least low-frequency (e.g., below 100 Hz) transcranial alternating current stimulation.