Auditory steady-state responses in the auditory cortex of mice during estrus cycle.

Auditory-steady state responses (ASSRs) disclose the brain's potency to oscillate and have been suggested to serve as biomarkers in various psychiatric disorders. GABAergic neurotransmission, a critical component of brain oscillations, is strongly influenced by sex hormones. In line, the severity of symptoms in psychiatric disorders has been linked to changes in sex hormones during the menstrual cycle. However, how these sex hormones affect ASSRs remain largely unknown. This was addressed by performing chronic recordings of ASSRs in mice while monitoring its estrus cycle. Here, the stability of ASSRs during long-term recordings was validated and showed good reliability. 40 Hz ASSRs showed changes throughout the estrus cycle where it decreased in the metestrus phase compared to the diestrus phase. In contrast, other frequency ASSRs did not show significant changes throughout the estrus cycle. Taken together, our findings illustrate that the estrus cycle may influence the generation of ASSRs and that the phase of the estrus cycle should be taken into consideration when ASSRs are recorded in females.

Extraction of Individual EEG Gamma Frequencies from the Responses to Click-Based Chirp-Modulated Sounds.

Activity in the gamma range is related to many sensory and cognitive processes that are impaired in neuropsychiatric conditions. Therefore, individualized measures of gamma-band activity are considered to be potential markers that reflect the state of networks within the brain. Relatively little has been studied in respect of the individual gamma frequency (IGF) parameter. The methodology for determining the IGF is not well established. In the present work, we tested the extraction of IGFs from electroencephalogram (EEG) data in two datasets where subjects received auditory stimulation consisting of clicks with varying inter-click periods, covering a 30-60 Hz range: in 80 young subjects EEG was recorded with 64 gel-based electrodes; in 33 young subjects, EEG was recorded using three active dry electrodes. IGFs were extracted from either fifteen or three electrodes in frontocentral regions by estimating the individual-specific frequency that most consistently exhibited high phase locking during the stimulation. The method showed overall high reliability of extracted IGFs for all extraction approaches; however, averaging over channels resulted in somewhat higher reliability scores. This work demonstrates that the estimation of individual gamma frequency is possible using a limited number of both the gel and dry electrodes from responses to click-based chirp-modulated sounds.

Spectral Characteristics of EEG during Active Emotional Musical Performance.

The research on neural correlates of intentional emotion communication by the music performer is still limited. In this study, we attempted to evaluate EEG patterns recorded from musicians who were instructed to perform a simple piano score while manipulating their manner of play to express specific contrasting emotions and self-rate the emotion they reflected on the scales of arousal and valence. In the emotional playing task, participants were instructed to improvise variations in a manner by which the targeted emotion is communicated. In contrast, in the neutral playing task, participants were asked to play the same piece precisely as written to obtain data for control over general patterns of motor and sensory activation during playing. The spectral analysis of the signal was applied as an initial step to be able to connect findings to the wider field of music-emotion research. The experimental contrast of emotional playing vs. neutral playing was employed to probe brain activity patterns differentially involved in distinct emotional states. The tasks of emotional and neutral playing differed considerably with respect to the state of intended-to-transfer emotion arousal and valence levels. The EEG activity differences were observed between distressed/excited and neutral/depressed/relaxed playing.

Auditory steady-state response to chirp-modulated tones: A pilot study in patients with disorders of consciousness.

OBJECTIVE: Due to the problems with behavioral diagnosis of patients with prolonged DOC (disorders of consciousness), complementary approaches based on objective measurement of neural function are necessary. In this pilot study, we assessed the sensitivity of auditory chirp-evoked responses to the state of patients with severe brain injury as measured with CRS-R (Coma Recovery Scale - Revised). METHODS: A convenience sample of fifteen DOC patients was included in the study. Auditory stimuli, chirp-modulated at 1-120 Hz were used to evoke auditory steady-state response (ASSR). Phase-locking index (PLI) estimates within low gamma and high gamma windows were evaluated. RESULTS: The PLI estimates within a narrow low gamma 38-42 Hz window positively correlated with the CRS-R total score and with the scores of the Auditory and Visual Function subscales. In the same low gamma window, significant difference in the PLIs was found between minimally conscious (MCS) and vegetative state (VS) patients. We did not observe any between-group differences nor any significant correlations with CRS-R scores in the high gamma window (80-110 Hz). CONCLUSIONS: Our results support the notion that the activity around 40 Hz may serve as a possible marker of the integrity of thalamocortical networks in prolonged DOC patients. SIGNIFICANCE: Auditory steady-state responses at gamma-band frequencies highlight the role of upper parts of auditory system in evaluation of the level of consciousness in DOC patients.

Low and high gamma auditory steady-states in response to 440 Hz carrier chirp-modulated tones show no signs of attentional modulation.

Auditory steady-state responses (ASSRs) are increasingly used as a neurodiagnostical tool and in neurotechnological applications where it is important to test responses at different frequencies. We aimed to evaluate EEG responses to a low-frequency carrier (440 Hz) tone modulated with 500 ms chirps at 1-120 Hz and to test the ability of stimulation to highlight the low and high gamma band activity. Increasing and decreasing modulation rates were applied. Subjective pleasantness of chirps and attentional effects on ASSRs to chirps were assessed. Our results suggest that brief low-frequency tones modulated with chirps can be used to evoke ASSRs and to test responses at low and high gamma frequencies. Moreover, chirps are perceived as moderately arousing and neutrally pleasant, while ASSRs to these sounds are not sensitive to attentional modulation. The abovementioned findings make chirp stimulation suitable for use in populations with increased perceptual sensitivity to auditory stimuli, for instance like patients with schizophrenia.

Global field synchronization of 40 Hz auditory steady-state response: Does it change with attentional demands?

Auditory steady-state responses (ASSRs) are increasingly used in research of neuropsychiatric disorders and for brain-computer interface applications. However, results on attentional modulation of ASSRs are inconclusive. The evaluation of large-scale effects of task-related modulation on ASSRs might give better estimation of the induced changes. The aim of the study was to test global field synchronization - a reference-independent evaluation of the amount of phase-locking among all active regions at a given frequency - during tasks differing in attentional demands to 40 Hz auditory stimulation. Twenty seven healthy young males participated in the EEG study with concurrent 40 Hz binaural click stimulation and three experimental tasks: 1) to count presented stimuli (focused attention); 2) to silently read a text (distraction); 3) to stay awake with closed eyes (resting). We showed that during auditory 40 Hz stimulation, the global field synchronization of the EEG increased as compared to the silent baseline period and the largest increase was observed when subjects counted stimuli or rested with closed eyes. Our results provide insights that depending on the method of assessment, the 40 Hz ASSR might be an indicator of both local and complex synchronization processes that are affected by the state (task performed or psychopathology) of the participants.

Psilocybin disrupts sensory and higher order cognitive processing but not pre-attentive cognitive processing-study on P300 and mismatch negativity in healthy volunteers.

RATIONALE: Disruption of auditory event-related evoked potentials (ERPs) P300 and mismatch negativity (MMN), electrophysiological markers of attentive and pre-attentive cognitive processing, is repeatedly described in psychosis and schizophrenia. Similar findings were observed in a glutamatergic model of psychosis, but the role of serotonergic 5-HT2A receptors in information processing is less clear. OBJECTIVES: We studied ERPs in a serotonergic model of psychosis, induced by psilocybin, a psychedelic with 5-HT2A/C agonistic properties, in healthy volunteers. METHODS: Twenty subjects (10M/10F) were given 0.26 mg/kg of psilocybin orally in a placebo-controlled, double-blind, cross-over design. ERPs (P300, MMN) were registered during the peak of intoxication. Correlations between measured electrophysiological variables and psilocin serum levels and neuropsychological effects were also analyzed. RESULTS: Psilocybin induced robust psychedelic effects and psychotic-like symptoms, decreased P300 amplitude (p = 0.009) but did not affect the MMN. Psilocybin's disruptive effect on P300 correlated with the intensity of the psychedelic state, which was dependent on the psilocin serum levels. We also observed a decrease in N100 amplitude (p = 0.039) in the P300 paradigm and a negative correlation between P300 and MMN amplitude (p = 0.014). CONCLUSIONS: Even though pre-attentive cognition (MMN) was not affected, processing at the early perceptual level (N100) and in higher-order cognition (P300) was significantly disrupted by psilocybin. Our results have implications for the role of 5-HT2A receptors in altered information processing in psychosis and schizophrenia.

40 Hz Auditory Steady-State Response: The Impact of Handedness and Gender.

The 40 Hz auditory steady-state response (ASSR) is a periodic response to a periodic stimulation. Its sources are located in the primary auditory cortex and the asymmetry of the planum temporale has previously been associated with hand preference and gender-related differences; thus subject's handedness and gender could potentially influence ASSRs. Nevertheless, electrophysiological studies of ASSRs are mainly dominated by right-handed participants and the observed findings can only be generalized to the right-handed populations. However, for a potential use of 40 Hz ASSR as a translational biomarker of neuropsychiatric disorders, it is important to investigate the response in association to handedness and gender. We included an equal number of left-handed and right-handed males and females and recorded EEG responses during left-ear, right-ear and both ears stimulation. The results of the study suggest that the processing of 40 Hz auditory stimulation depends on the subjects' gender and handedness: significantly lower phase-locking and strength of 40 Hz ASSRs were observed in left-handed females as compared to left-handed males, but right-handers did not differ in 40 Hz ASSRs. Our observation of the opposite impact of gender in the examined handedness groups stresses the importance of careful consideration of handedness and gender factors when evaluating the determinants of inter individual variability of 40 Hz ASSRs. This finding is of particular importance for clinical studies in psychiatry and neurology.

40Hz auditory steady-state response in schizophrenia: Sensitivity to stimulation type (clicks versus flutter amplitude-modulated tones).

Auditory steady-state response (ASSR) at 40Hz has been proposed as a potential biomarker for schizophrenia. The ASSR studies in patients have used click stimulation or amplitude-modulated tones. However, the sensitivity of 40Hz ASSRs to different stimulation types in the same group of patients has not been previously evaluated. Two stimulation types for ASSRs were tested in this study: (1) 40Hz clicks and (2) flutter-amplitude modulated tones. The mean phase-locking index, evoked amplitude and event-related spectral perturbation values were compared between schizophrenia patients (n=26) and healthy controls (n=20). Both stimulation types resulted in the observation of impaired phase-locking and power measures of late (200-500ms) 40Hz ASSR in patients compared to healthy controls. The early-latency (0-100ms) 40Hz ASSR part was diminished in the schizophrenia group in response to clicks only. The late-latency 40Hz ASSR parameters obtained through different stimulation types correlated in healthy subjects but not in patients. We conclude that flutter amplitude-modulated tone stimulation, due to its potential to reveal late-latency entrainment deficits, is suitable for use in clinical populations. Careful consideration of experimental stimulation settings can contribute to the interpretation of ASSR deficits and utilization as a potential biomarker.

Sex differences in equiprobable auditory Go/NoGo task: effects on N2 and P3.

The Go/NoGo variants of the auditory event-related potentials were shown promising for clinical researches; however, prior to the wider application, it is important to evaluate potential modulating factors. We aimed to evaluate gender effect on the behavioral and electrophysiological responses in an auditory equiprobable Go/NoGo task. The auditory equal probability Go/NoGo paradigm with two types of stimuli was presented to 79 healthy subjects (40 females and 39 males, age 18-30 years) during EEG recording. Behavioral performance, latency and amplitude of N2 and P3 waves in the Go and the NoGo conditions were evaluated and compared between genders. The response times did not differ between genders; however, females were less accurate on the task. They also exhibited slower N2s and P3s in both Go and NoGo conditions and higher P3 amplitudes. Our results suggest that females require longer times for monitoring of response conflict (N2s) and outcome inhibition (NoGo-P3) and more neural resources and longer processing times for motor response execution (Go-P3). The research provides evidence that gender factor is important in the Go/NoGo studies employing auditory equiprobable paradigm.

Effect of attention on 40Hz auditory steady-state response depends on the stimulation type: Flutter amplitude modulated tones versus clicks.

Auditory steady-state responses (ASSRs) are used to test the ability of local cortical networks to generate gamma frequency activity in patients with psychiatric disorders. For the effective use of ASSRs in research and clinical applications, it is necessary to find a comfortable stimulation type and to know how ASSRs are modulated by the tasks given to the subjects during the recording session. We aimed to evaluate the suitability of flutter amplitude modulated tone (FAM) stimulation for generation of ASSRs: subjective pleasantness of FAMs and attentional effects on FAM-elicited 40Hz ASSRs were assessed. Commonly used click stimulation was used for comparison. FAMs produced ASSRs that were stable over the variety of tasks - they were not modulated by attentional demands during the task; responses to clicks were reduced and less synchronized during distraction. FAM stimuli were rated as less unpleasant and less arousing than click stimuli, thus being more pleasant to the subjects. Our findings suggest that FAM stimulation might be more suitable in conditions, where attention is difficult to control, i.e. in clinical settings.

Go and NoGo: modulation of electrophysiological correlates by female sex steroid hormones.

RATIONALE: The behavioral and electrophysiological responses in a Go/NoGo task are objective measures of executive functioning that may be impaired in clinical conditions. Prior to the wider application of Go/NoGo tasks in clinics, it is tempting to evaluate factors causing modulation of the responses. OBJECTIVE: We aimed to evaluate the effect of different levels of female sex steroids on Go/NoGo task-related ERPs in healthy females. METHODS: Thirty-four young healthy females performed an equiprobable (50/50) auditory Go/NoGo task. Amplitudes and latencies of N2 and P3 peaks from Fz, Cz, and Pz electrodes were evaluated. 17ß-estradiol and progesterone levels in saliva samples were measured. Electrophysiological measures were correlated to 17ß-estradiol and progesterone concentrations. RESULTS: The diverse pattern of modulation of P3 latencies was shown: higher levels of 17ß-estradiol contributed to Go-P3 latency prolongation, and higher levels of progesterone contributed to NoGo-P3 latency shortening. Higher levels of 17ß-estradiol were associated with more negative frontal N2 amplitude in both conditions. CONCLUSIONS: The relationship between electrophysiological correlates of executive functioning to individual hormonal levels points to a broader range of variation sources in healthy subjects which might mask or pronounce between-group differences in clinical studies.

Phase-locking index and power of 40-Hz auditory steady-state response are not related to major personality trait dimensions.

Although a number of studies have demonstrated state-related dependence of auditory steady-state responses (ASSRs), the investigations assessing trait-related ASSR changes are limited. Five consistently identified major trait dimensions, also referred to as "big five" (Neuroticism, Extraversion, Openness, Agreeableness and Conscientiousness), are considered to account for virtually all personality variances in both healthy people and those with psychiatric disorders. The purpose of the present study was, for the first time, to establish the link between 40-Hz ASSR and "big five" major personality trait dimensions in young healthy adults. Ninety-four young healthy volunteers participated (38 males and 56 females; mean age ± SD 22.180 ± 2.75). The 40-Hz click trains were presented for each subject 30 times with an inter-train interval of 1-1.5 s. The EEG responses were recorded from F3, Fz, F4, C3, Cz, C4, P3, Pz and P4 locations according to 10/20 electrode placement system. Phase-locking index (PLI) and event-related power perturbation (ERSP) were calculated, each providing the following characteristics: peak time, entrainment frequency, peak value and mean value. For assessing "big five" personality traits, NEO Personality Inventory Revised (NEO-PI-R) was used. No significant correlation between 40-Hz ASSR PLI or ERSP and "big five" personality traits was observed. Our results indicate that there is no dependence between 40-Hz ASSR entrainment and personality traits, demonstrating low individual 40-Hz variability in this domain. Our results support further development of 40-Hz ASSR as a neurophysiological marker allowing distinguishing between healthy population and patients with psychiatric disorders.

40 Hz auditory steady-state response in females: When is it better to entrain?

Auditory steady-state responses (ASSRs) are widely applied to test brain's ability to follow external stimulation in neuropsychiatric disorders. It is known that ASSRs are related to GABAergic transmission. Female sex steroid homones - both estrogens and progesterone - affect functioning of GABAergic system. However, it is not known how these hormones affect brain's ability to entrain. This study was designed to test the ability to synchronize to 40 Hz stimulation during different phases of the menstrual cycle. Twenty-eight healthy females participated in the research during one of the menstrual cycle phases: (1) early follicular; (2) late follicular; (3) and mid-luteal. Auditory 40 Hz trains of 500 ms were delivered binaurally and EEG was recorded. Time-frequency analysis of the data was performed and phase-locking index, evoked amplitude and total intensity measures were extracted and decomposed by non-negative multi-way factorization. Additionally, alpha power of the baseline period was calculated. Parameters of ASSR were increasing in a linear manner with increasing levels of 17ß-estradiol and largest estimates of ASSR parameters were obtained in the late follicular phase, smallest - in the mid-luteal phase. Alpha power values were highest in the late follicular phase and lowest in the mid-luteal phase, pointing to lower arousal level in the late follicular phase. We speculate that increased 40 Hz ASSRs during mid-cycle might be related to the level of general arousal and specific GABA-mediated changes during the menstrual cycle. The results suggest that the ability to entrain to 40 Hz stimulation depends on the phase of menstrual cycle. This should be taken into account, particularly when ASSRs are used in clinical practice, comparing patients and healthy subjects.

Does brain ability to synchronize with 40 Hz auditory stimulation change with age?

Auditory steady-state responses (ASSRs) are widely applied to test brain ability to follow external stimulation and this appeared to be a promising method in neuropsychiatric disorders. Nevertheless, there is no established conclusion on the way aging affects phase-locking measures of ASSRs in healthy subjects. We aimed to identify the effects of aging on phaselocking measures of 40 Hz ASSR. The effect of aging was tested in a sample of 46 healthy male subjects (20-58 years old) during eyes open condition. Stimuli were 500 ms trains, consisting of 20 identical clicks (1.5 ms burst of white noise) delivered binaurally. Time-frequency analysis of the data was performed and phase-locking index, evoked amplitude and total intensity measures were extracted and decomposed by non-negative multi-way factorization. As shown by curve-fitting analyses, phase-locking index and evoked amplitudes were diminishing with age in the linear manner. This was also proven by ANOVA testing when sample was divided into age groups. No effect of age on the total intensity was found. The complexity of the factors modulating the 40 Hz ASSR is not entirely solved; nevertheless, the current results suggest that the ability to synchronize to high frequency external stimulation diminishes with age. This should be taken into account, particularly when ASSRs are used in clinical practice, comparing patients and healthy subjects.

Closed eyes condition increases auditory brain responses in schizophrenia.

The 40-Hz auditory steady-state responses (ASSRs) of 14 medicated schizophrenic patients were recorded in eyes-open and eyes-closed conditions as previously done in healthy volunteers. Patients show significantly increased precision of the evoked response with eyes closed, and a significant increase of broad-band noise activity when eyes are open.

P50 potential-associated gamma band activity: modulation by distraction.

We aimed to evaluate the effect of changing attentional demands towards stimulation in healthy subjects on P50 potential-related high-frequency beta and gamma oscillatory responses, P50 and N100 peak amplitudes and their gating measures. There are no data showing effect of attention on P50 potential-related beta and gamma oscillatory responses and previous results of attention effects on P50 and N100 amplitudes and gating measures are inconclusive. Nevertheless the variation in the level of attention may be a source of variance in the recordings as well as it may provide additional information about the pathology under study. Nine healthy volunteers participated in the study. A standard paired stimuli auditory P50 potential paradigm was applied. Four stimulation conditions were selected: focused attention (stimuli pair counting), unfocused attention (sitting with open eyes), easy distraction (reading a magazine article), and difficult distraction (searching for Landolt rings with appropriate gap orientation). Time-frequency responses to both S1 and S2 were evaluated in slow beta (13-16 Hz, 45-175 ms window); fast beta (20-30 Hz, 45-105 ms window) and gamma (32-46 Hz, 45-65 ms window) ranges. P50 and N100 peak amplitudes in response to both S1 and S2 and their ratio were evaluated. The phase-locked P50 potential-associated gamma activity was attenuated during distraction tasks as compared to focused attention and an unfocused attention condition. The amplitudes and gating measures of P50 and N100 waves and beta activity were not sensitive to the competing distraction task performance. The use of a distraction task is not favorable when phase-locked gamma range activity is a key interest in auditory potential studies.

The level of arousal modulates P50 peak amplitude.

We aimed to evaluate the effect of arousal level in healthy subjects on P50 potential, as the variation in the level of arousal may be a source of variance in the recordings as well as it may provide additional information about the pathology under study. Eleven healthy volunteers participated in the study. A standard auditory P50 potential paradigm was applied. Two stimulation conditions were selected: eyes-open, i.e., high arousal level condition and eyes-closed, i.e., low arousal level condition. P50 component amplitudes in response to both the first (S1) and second stimulus (S2) of the pair, their ratio and difference were evaluated. P50 amplitude in response to S1 was significantly higher during the low arousal closed eyes condition as compared to high arousal open eyes condition. There was no P50 amplitude difference in response to S2 and no arousal effect on gating measures. This prompts for more careful evaluation of patients' arousal level when performing P50 studies and interpreting the results.

Distraction task rather than focal attention modulates gamma activity associated with auditory steady-state responses (ASSRs).

OBJECTIVE: To explore the modulation of auditory steady-state response (ASSR) by experimental tasks, differing in attentional focus and arousal level. METHODS: 20 Hz and 40 Hz click trains were used to elicit ASSRs. Experiment 1 consisted of two runs of closed eyes and two runs of open eyes. Experiment 2 consisted of six tasks: counting 20 Hz and 40 Hz stimuli, sitting with closed and open eyes, reading an article, and performing a search task. Phase locking factor, evoked amplitude and total intensity were decomposed by non-negative multi-way factorization. RESULTS: The total intensity of 40 Hz ASSR was enhanced during closed eyes condition in comparison to the open eyes condition. The evoked amplitude and phase locking factor of 40 Hz ASSR were attenuated during distraction, while there were no differences between attention to stimulation and no task. 20 Hz ASSR and 20 Hz ASSR-related 40 Hz activity were not modulated by the tasks. CONCLUSIONS: The phase-locked measures of 40 Hz ASSR are attenuated when attention to the stimulation is low, i.e. the subject is effortfully focused on the competitive "distraction" task performance. Lower arousal level increases the total intensity of 40 Hz ASSRs. SIGNIFICANCE: Improvements of the practical use of ASSRs are suggested: a careful monitoring for arousal fluctuations during ASSR recordings should be performed; when ASSRs are applied to investigate the ability to generate high frequency cortical activity a "distraction" task is not favorable.