Impaired Sensory Processing During Low-Oxygen Exposure: A Noninvasive Approach to Detecting Changes in Cognitive States

Abstract

The ability to detect novelty in our environment is a critical sensory function. A reliable set of event-related potentials (ERP), known as the auditory deviance response (ADR), are elicited in the absence of directed attention and indexes functionally relevant networks. The ADR consists of three peaks: mismatch negativity (MMN), P3a, and reorienting negativity (RON) that are sequentially evoked in response to unattended changes in repetitive background stimulation. While previous studies have established the ADR's sensitivity to a range of pharmacologic and nonpharmacologic interventions and are leading candidate biomarkers of perturbations of the central nervous system (CNS), here we sought to determine if ADR peaks are sensitive to decreases in breathable oxygen. Participants performed a visuomotor tracking task while EEG was recorded during two 27-min sessions. The two sessions differed in the amount of environmental oxygen available: 10.6% O 2 (hypoxia) versus 20.4% O 2 (normoxia). ERPs were measured while a series of identical, or "standard," tones combined with occasional "oddball," tones, were presented. MMN, P3a, and RON were assessed in response to the oddball compared to the standard stimuli. Behavioral impairment during hypoxia was demonstrated by a deficit in tracking performance compared to the normoxia condition. Whereas no changes were detected in the MMN or RON, the amplitude of the P3a component was significantly reduced during hypoxia compared to normoxia, within the first 9 min of exposure. To our knowledge, this is the first study to demonstrate the effect of low oxygen exposure on passively elicited neural measures of early sensory processing. This study demonstrates that passively elicited EEG measures, reflecting preattentive auditory processing, are disrupted by acute hypoxia. Results have implications for the development of biomarkers for the noninvasive assessment of CNS perturbations.

Phase 1 randomized study on the safety, tolerability, and pharmacodynamic cognitive and electrophysiological effects of a dopamine D1 receptor positive allosteric modulator in patients with schizophrenia

“…A passive auditory oddball paradigm was used to elicit MMN and P3a. Consistent with Seech et al [ 21 ], 85% of the tones were standards (50 ms, 1000 Hz, n = 2754) and 15% were deviants (7.5%, n = 243 per deviant type) that differed in stimulus duration (100 ms, 1000 Hz) or both duration and frequency (i.e., “double deviant” 100 ms, 1100 Hz). All tones had 5-ms rise/fall times and were presented with a fixed 500-ms stimulus onset asynchrony.…”

“…Results of the present study support the continued use of highdensity EEG recording of ASSR, MMN, and P3a as pharmacodynamic endpoints in clinical trials. These measures were selected based on several criteria described in the literature [25][26][27][28], including ease of rapid assessment with high-density montages [19,20] for characterization of neural substrates, substantial test-retest reliability [29], relationships to cognition and daily functioning [17,20,[30][31][32][33][34][35], and sensitivity to pharmacologic [19,22] and non-pharmacologic interventions [36][37][38][39]/perturbations [21]. The primary limitation of this study is the small patient population because of which it is underpowered for detection of treatment-induced effects for the key physiological biomarkers or cognitive assessments.…”

“…Electroencephalographic (EEG) data were continuously recorded during baseline visit, and on days 1 (pre-dose), 7, and 14 with a 64-channel Brain Products ActiChamp2 system at a sampling rate of 2000 Hz. Data processing was performed offline using Matlab, EEGlab, and BrainVision Analyzer and as per established methods [17][18][19][20][21][22]. All auditory stimuli were presented to participants at 85-dB sound pressure levels using a NeuroSig stimulation unit with custom EEG acquisition software.…”

Effects of Acute Hypoxia on Early Visual and Auditory Evoked Potentials

“…The MMN/P3a complex is a reliable neural index of automatic and preattentive stages of information processing. Previous work has demonstrated that these ERPs are disrupted both within the auditory ( Seech et al, 2020 ; Blacker and McHail, 2021 ) and visual ( Blacker et al, 2021 ) domains. Broadly speaking, ERPs are often classified as “cognitive” or “sensory” ERPs.…”

“…Previous work has demonstrated that hypoxic exposure disrupts the mismatch negativity (MMN) and P3a event-related potentials (ERP; Seech et al, 2020 ; Blacker and McHail, 2021 ; Blacker et al, 2021 ). The MMN/P3a complex is a reliable neural index of automatic and preattentive stages of information processing.…”