The beta component of gamma-band auditory steady-state responses in patients with schizophrenia

The mechanisms underlying circuit dysfunctions in schizophrenia (SCZ) remain poorly understood. Auditory steady-state responses (ASSRs), especially in the gamma and beta band, have been suggested as a potential biomarker for SCZ. While the reduction of 40 Hz power for 40 Hz drive has been well established and replicated in SCZ patients, studies are inconclusive when it comes to an increase in 20 Hz power during 40 Hz drive. There might be several factors explaining the inconsistencies, including differences in the sensitivity of the recording modality (EEG vs MEG), differences in stimuli (click-trains vs amplitude-modulated tones) and large differences in the amplitude of the stimuli. Here, we used a computational model of ASSR deficits in SCZ and explored the effect of three SCZ-associated microcircuit alterations: reduced GABA activity, increased GABA decay times and NMDA receptor hypofunction. We investigated the effect of input strength on gamma (40 Hz) and beta (20 Hz) band power during gamma ASSR stimulation and saw that the pronounced increase in beta power during gamma stimulation seen experimentally could only be reproduced in the model when GABA decay times were increased and only for a specific range of input strengths. More specifically, when the input was in this specific range, the rhythmic drive at 40 Hz produced a strong 40 Hz rhythm in the control network; however, in the ‘SCZ-like’ network, the prolonged inhibition led to a so-called ‘beat-skipping’, where the network would only strongly respond to every other input. This mechanism was responsible for the emergence of the pronounced 20 Hz beta peak in the power spectrum. The other two microcircuit alterations were not able to produce a substantial 20 Hz component but they further narrowed the input strength range for which the network produced a beta component when combined with increased GABAergic decay times. Our finding that the beta component only existed for a specific range of input strengths might explain the seemingly inconsistent reporting in experimental studies and suggests that future ASSR studies should systematically explore different amplitudes of their stimuli. Furthermore, we provide a mechanistic link between a microcircuit alteration and an electrophysiological marker in schizophrenia and argue that more complex ASSR stimuli are needed to disentangle the nonlinear interactions of microcircuit alterations. The computational modelling approach put forward here is ideally suited to facilitate the development of such stimuli in a theory-based fashion.

Detection of the 40-Hz Auditory Steady-state Response with Optically Pumped Magnetometers

Magnetoencephalography (MEG) is a functional neuroimaging technique that noninvasively detects the brain magnetic field from neuronal activations. Conventional MEG measures brain signals using superconducting quantum interference devices (SQUIDs). SQUID based MEG requires a cryogenic environment involving a bulky non-magnetic dewar and the consumption of liquid helium, which restricts the variability of the sensor array and the gap between the cortical sources and sensors. Recently, miniature optically pumped magnetometers (OPMs) have been developed and commercialized. OPMs do not require cryogenic cooling and can be placed within millimeters from the scalp. In the present study, we arranged six OPM sensors on the temporal area to detect auditory related brain responses in a two layer magnetically shielded room. We presented the auditory stimuli of 1 kHz pure tone bursts with 200 ms duration and obtained the M50 and M100 components of auditory evoked fields. We delivered the periodic stimuli with a 40 Hz repetition rate and observed the gamma band power changes and inter trial phase coherence of auditory steady state responses at 40 Hz. We found that the OPM sensors have a performance comparable to that of conventional SQUID based MEG sensors, and our results suggest the feasibility of using OPM sensors for functional neuroimaging and brain computer interface applications.

The Application of ASSRs, P50, and MMN in the Exploration of Cognitive Dysfunction Involving Inputs and Processing in Insomnia Patients

Objective cognitive dysfunction has been commonly found in patients with insomnia, such as attention, memory, speed of information processing, and executive functions. Auditory steady-state responses (ASSRs), P50, mismatch negativity (MMN) can meet varied need and estimate such different cognitive dysfunction. Thus, we can examine whether insomnia is associated with different cognitive dysfunction by such multiple event-related potential (ERP) tasks. Methods we used polysomnography (PSG) to record such objective PSG parameters. ASSR, P50, and MMN were performed in sequence, different ERP components have been analyzed such as latency or amplitude between insomnia group and control group. And we chosed person correlation to make correlation analysis between different ERP components and gender, education, and sleep characteristics. Results there is a significant gender difference of ASSR latency found in insomnia group, and the similar result has been found in suppression ratio of amplitudes (S2:S1) for P50. Additionally, a significant correlation between sleep characteristics and ASSR, P50 has been found. Furthermore, there was a significant difference of MMN latency between insomnia and control group, and between sleep characteristics and varied MMN parameters as latency and amplitude. Discussion our results suggested robust electrophysiological abnormalities as ASSR, P50, and MMN in insomnia patients. Such abnormalities included gender difference, education difference, difference in depressive tendency, and difference in sleep parameters. That results revealed varied cognitive dysfunction involving inputs and processing in insomnia patients. And at the same time, we have also explored the neuropsychological mechanisms underlying the cognitive dysfunction with such different ERP tasks.

Gamma-Range Auditory Steady-State Responses and Cognitive Performance: A Systematic Review

The auditory steady-state response (ASSR) is a result of entrainment of the brain’s oscillatory activity to the frequency and phase of temporally modulated stimuli. Gamma-range ASSRs are utilized to observe the dysfunctions of brain-synchronization abilities in neuropsychiatric and developmental disorders with cognitive symptoms. However, the link between gamma-range ASSRs and cognitive functioning is not clear. We systematically reviewed existing findings on the associations between gamma-range ASSRs and cognitive functions in patients with neuropsychiatric or developmental disorders and healthy subjects. The literature search yielded 1597 articles. After excluding duplicates and assessing eligibility, 22 articles were included. In healthy participants, the gamma-range ASSR was related to cognitive flexibility and reasoning as measured by complex tasks and behavioral indicators of processing speed. In patients with schizophrenia, the studies that reported correlations found a higher ASSR to be accompanied by better performance on short-term memory tasks, long-term/semantic memory, and simple speeded tasks. The main findings indicate that individual differences in the gamma-range ASSR reflect the level of attentional control and the ability to temporary store and manipulate the information, which are necessary for a wide range of complex cognitive activities, including language, in both healthy and impaired populations.

The beta component of gamma-band auditory steady-state responses in patients with schizophrenia

The mechanisms underlying circuit dysfunctions in schizophrenia (SCZ) remain poorly understood. Auditory steady-state responses (ASSRs), especially in the gamma and beta band, have been suggested as a potential biomarker for SCZ. While the reduction of 40Hz power for 40Hz drive has been well established and replicated in SCZ patients, studies are inconclusive when it comes to an increase in 20Hz power during 40Hz drive. There might be several factors explaining the inconsistencies, including differences in the sensitivity of the recording modality (EEG vs MEG), differences in stimuli (click-trains vs amplitude-modulated tones) and large differences in the amplitude of the stimuli. Here, we used a computational model of ASSR deficits in SCZ and explored the effect of three SCZ-associated microcircuit alterations: reduced GABA activity, increased GABA decay times and NMDA receptor hypofunction. We investigated the effect of input strength on gamma (40 Hz) and beta (20 Hz) band power during gamma ASSR stimulation and saw that the pronounced increase in beta power during gamma stimulation seen experimentally could only be reproduced in the model when GABA decay times were increased and only for a specific range of input strengths. More specifically, when the input was in this specific range, the rhythmic drive at 40Hz produced a strong 40Hz rhythm in the control network; however, in the ‘SCZ-like’ network, the prolonged inhibition led to a so-called ‘beat-skipping’, where the network would only strongly respond to every other input. This mechanism was responsible for the emergence of the pronounced 20Hz beta peak in the power spectrum. The other two microcircuit alterations were not able to produce a substantial 20 Hz component but they further narrowed the input strength range for which the network produced a beta component when combined with increased GABAergic decay times. Our finding that the beta component only existed for a specific range of input strengths might explain the seemingly inconsistent reporting in experimental studies and suggests that future ASSR studies should systematically explore different amplitudes of their stimuli. Furthermore, we provide a mechanistic link between a microcircuit alterations and an electrophysiological marker in schizophrenia and argue that more complex ASSR stimuli are needed to disentangle the nonlinear interactions of microcircuit alterations. The computational modelling approach put forward here is ideally suited to facilitate the development of such stimuli in a theory-based fashion.

Σύγκριση των click Auditory Brainstem Responses (ABR) και των chirp Auditory Steady-State Responses (ASSR), ηλεκτροφυσιολογικών (αντικειμενικών) μεθόδων που χρησιμοποιούνται για τον έλεγχο και τη διάγνωση της παιδικής βαρηκοΐας

Τα προκλητά δυναμικά κατέχουν σημαντική θέση στον προσδιορισμό των ουδών της ακοής σε παιδιά πολύ μικρά για να εξεταστούν με τις συμβατικές συμπεριφορικές μεθόδους και σε άλλους πληθυσμούς που παρουσιάζουν δυσκολίες κατά την εξέταση. Το ABR (Auditory Brainstem Response), μέθοδος που χρησιμοποιείται κατά τα τελευταία 50 χρόνια, έχει σήμερα ευρέως αναγνωριστεί ως η πιο αποτελεσματική τεχνική προκλητών δυναμικών και χρησιμοποιείται καθημερινά, με click και tone burst ως ερεθίσματα, για την εκτίμηση της ακουστικής ικανότητας σε βρέφη και παιδιά πολύ μικρά για άλλες εξεταστικές μεθόδους. Η καταγραφή του ABR, ωστόσο, υπόκειται σε περιορισμούς ως προς το ανώτερο επίπεδο έντασης χορήγησης του ερεθίσματος, όπως επίσης και εξαιτίας της υποκειμενικής μεθόδου ελέγχου για τον προσδιορισμό του ουδού, ενώ οι καταγραφές με tone burst ερεθίσματα είναι συχνά πιο απαιτητικές ως προς την ερμηνεία τους, λόγω του ότι οι κυματομορφές μπορεί να είναι λιγότερο χαρακτηριστικές. Το ASSR (Auditory Steady-State Response) αποτελεί μια πιο πρόσφατη εναλλακτική πρόταση έναντι των καθιερωμένων ABR τεχνικών καταγραφής. Σε αντίθεση με το παροδικού τύπου ερέθισμα click που χρησιμοποιείται στις ABR καταγραφές, το διαμορφωμένο συνεχούς τύπου ερέθισμα του ASSR εκλύει μια περιοδική ή “steady-state” κυματομορφή, της οποίας τα φασματικά χαρακτηριστικά (εύρος και φάση) αναλύονται στο frequency ή και στο time domain για τον προσδιορισμό της παρουσίας ή της απουσίας απάντησης. Το αυτόματο σύστημα ανίχνευσης της απάντησης που χρησιμοποιείται στην καταγραφή του ASSR εξαλείφει την ανάγκη για υποκειμενικό τρόπο ελέγχου των απαντήσεων. Ο τύπος του ASSR ερεθίσματος που χρησιμοποιήθηκε σε αυτήν την μελέτη ήταν το narrowband CE-chirp, ένα είδος chirp που εισήλθε σχετικά πολύ πρόσφατα στις συσκευές που διατίθενται στο εμπόριο. Σκοπός αυτής της μελέτης ήταν να συγκρίνει αυτές τις δύο ηλεκτροφυσιολογικές μεθόδους και τον βαθμό στον οποίο συσχετίζονται, σε ένα μεγάλο πληθυσμό παιδιών με διάφορου βαθμού νευροαισθητήρια βαρηκοΐα, που εξετάστηκαν με φαρμακευτικό ύπνο στο Ακοολογικό Κέντρο της Κλινικής μας κατά το διάστημα 2010-14. Εξετάστηκαν συνολικά 130 παιδιά, 90 άρρενα και 40 θήλεα (n = 260 αυτιά), ηλικίας 5 έως 79 μηνών (μέση ηλικία: 32.7 ± 14.0 μήνες), με μια ποικιλία προβλημάτων και διαταραχών. Η τελική στατιστική ανάλυση για σύγκριση των δύο μεθόδων περιέλαβε αφ’ ενός τις τιμές ουδών που αποκτήθηκαν από το click ABR και αφ’ ετέρου τους μέσους όρους των ουδών που αποκτήθηκαν από το chirp ASSR στις συχνότητες 1, 2 και 4 kHz και 2 και 4 kHz. Τα αποτελέσματα αυτής της μελέτης ανέδειξαν ισχυρές συσχετίσεις μεταξύ των click ABR ουδών και των μέσων όρων των chirp ASSR ουδών στα 1000, 2000 και 4000 Hz (rs = .826, p < .001) και στα 2000 και 4000 Hz (rs = .824, p < .001) και συμφωνούν γενικά με τα αποτελέσματα παρόμοιων μελετών της διεθνούς βιβλιογραφίας. Συμπερασματικά φαίνεται ότι το ASSR είναι αναγκαίο για την ακριβή ποσοτικοποίηση της υπολειπόμενης ακοής στην ζώνη της μεγάλου προς πολύ μεγάλου βαθμού βαρηκοΐας, σε περιοχές εντάσεων άνω των ορίων των περισσοτέρων ABR συσκευών. Η «ακοολογική πληροφορία» που αποκτάται με το ASSR τεστ, ειδικά στην ανωτέρω περιοχή, είναι πολύτιμη στην λήψη αποφάσεων για περαιτέρω παρέμβαση σε παιδιά με νευροαισθητήρια βαρηκοΐα (ενίσχυση, κοχλιακή εμφύτευση), ιδίως για τα παιδιά εκείνα που δεν μπορούν να μετρηθούν με συμπεριφορικές μεθόδους. Τα αποτελέσματα αυτά ενισχύουν την χρήση του ASSR ως εναλλακτικού τεστ σε σχέση με το ABR στην εκτίμηση και αντιμετώπιση της παιδικής βαρηκοΐας.