40-Hz Auditory Steady-State Responses in Schizophrenia: Toward a Mechanistic Biomarker for Circuit Dysfunctions and Early Detection and Diagnosis.

There is converging evidence that 40-Hz auditory steady-state responses (ASSRs) are robustly impaired in schizophrenia and could constitute a potential biomarker for characterizing circuit dysfunctions as well as enable early detection and diagnosis. Here, we provide an overview of the mechanisms involved in 40-Hz ASSRs, drawing on computational, physiological, and pharmacological data with a focus on parameters modulating the balance between excitation and inhibition. We will then summarize findings from electro- and magnetoencephalographic studies in participants at clinical high risk for psychosis, patients with first-episode psychosis, and patients with schizophrenia to identify the pattern of deficits across illness stages, the relationship with clinical variables, and the prognostic potential. Finally, data on genetics and developmental modifications will be reviewed, highlighting the importance of late modifications of 40-Hz ASSRs during adolescence, which are closely related to the underlying changes in GABA (gamma-aminobutyric acid) interneurons. Together, our review suggests that 40-Hz ASSRs may constitute an informative electrophysiological approach to characterize circuit dysfunctions in psychosis that could be relevant for the development of mechanistic biomarkers.

Application of rapid invisible frequency tagging for brain computer interfaces.

BACKGROUND: Brain-computer interfaces (BCI) based on steady-state visual evoked potentials (SSVEPs/SSVEFs) are among the most commonly used BCI systems. They require participants to covertly attend to visual objects flickering at specified frequencies. The attended location is decoded online by analysing the power of neuronal responses at the flicker frequency. NEW METHOD: We implemented a novel rapid invisible frequency-tagging technique, utilizing a state-of-the-art projector with refresh rates of up to 1440 Hz. We flickered the luminance of visual objects at 56 and 60 Hz, which was invisible to participants but produced strong neuronal responses measurable with magnetoencephalography (MEG). The direction of covert attention, decoded from frequency-tagging responses, was used to control an online BCI PONG game. RESULTS: Our results show that seven out of eight participants were able to play the pong game controlled by the frequency-tagging signal, with average accuracies exceeding 60 %. Importantly, participants were able to modulate the power of the frequency-tagging response within a 1-second interval, while only seven occipital sensors were required to reliably decode the neuronal response. COMPARISON WITH EXISTING METHODS: In contrast to existing SSVEP-based BCI systems, rapid frequency-tagging does not produce a visible flicker. This extends the time-period participants can use it without fatigue, by avoiding distracting visual input. Furthermore, higher frequencies increase the temporal resolution of decoding, resulting in higher communication rates. CONCLUSION: Using rapid invisible frequency-tagging opens new avenues for fundamental research and practical applications. In combination with novel optically pumped magnetometers (OPMs), it could facilitate the development of high-speed and mobile next-generation BCI systems.

20 Hz Steady-State Response in Somatosensory Cortex During Induction of Tactile Perceptual Learning Through LTP-Like Sensory Stimulation.

The induction of synaptic plasticity requires the presence of temporally patterned neural activity. Numerous cellular studies in animals and brain slices have demonstrated that long-term potentiation (LTP) enhances synaptic transmission, which can be evoked by high-frequency intermittent stimulation. In humans, plasticity processes underlying perceptual learning can be reliably induced by repetitive, LTP-like sensory stimulation. These protocols lead to improvement of perceptual abilities parallel to widespread remodeling of cortical processing. However, whether maintained rhythmic cortical activation induced by the LTP-like stimulation is also present during human perceptual learning experiments, remains elusive. To address this question, we here applied a 20 Hz intermittent stimulation protocol for 40 min to the index-, middle- and ring-fingers of the right hand, while continuously recording EEG over the hand representation in primary somatosensory cortex in young adult participants. We find that each train of stimulation initiates a transient series of sensory-evoked potentials which accumulate after about 500 ms into a 20 Hz steady-state response persisting over the entire period of the 2-s-train. During the inter-train interval, no consistent evoked activity can be detected. This response behavior is maintained over the whole 40 min of stimulation without any indication of habituation. However, the early stimulation evoked potentials (SEPs) and the event-related desynchronization (ERD) during the steady-state response change over the 40 min of stimulation. In a second experiment, we demonstrate in a separate cohort of participants that the here-applied pneumatic type of stimulation results in improvement of tactile acuity as typically observed for electrically applied 20 Hz intermittent stimulation. Our data demonstrate that repetitive stimulation using a 20 Hz protocol drives rhythmic activation in the hand representation of somatosensory cortex, which is sustained during the entire stimulation period. At the same time, cortical excitability increases as indicated by altered ERD and SEP amplitudes. Our results, together with previous data underlining the dependence of repetitive sensory stimulation effects on NMDA-receptor activation, support the view that repetitive sensory stimulation elicits LTP-like processes in the cortex, thereby facilitating perceptual learning processes.

Somatosensory alpha oscillations gate perceptual learning efficiency.

Cognition and perception are closely coupled to alpha power, but whether there is a link between alpha power and perceptual learning efficacy is unknown. Here we show that somatosensory alpha power can be successfully up- and down-regulated with short-term neurofeedback training, which in turn controls subsequent tactile perceptual learning. We find that neurofeedback-induced increases in alpha power lead to enhanced learning, whereas reductions in alpha power impede learning. As a consequence, interindividual learning variability is substantially reduced. No comparable impact is observed for oscillatory power in theta, beta, and lower gamma frequency bands. Our results demonstrate that high pre-learning alpha levels are a requirement for reaching high learning efficiency. These data provide further evidence that alpha oscillations shape the functional architecture of the brain network by gating neural resources and thereby modulating levels of preparedness for upcoming processing.