EEG/ECoG/EMG publications

Purpose: In anesthesia research and clinical practice, the level of consciousness is often assessed by stimulating subjects and observing their responses. It is possible that such stimulation alters the very state of consciousness being assessed. Whether this phenomenon is accompanied by specific cortical activities remains unknown. Here, we tested the effects of behavioral assessments on neuronal activity in the rat primary auditory cortex (A1) and perirhinal cortex (PrC). Methods: Neuronal spiking activity was recorded from microwire arrays targeting A1 and/or PrC in rats (n = 9), whilst presenting 40 Hz click-trains and gradually increasing infusion rates of propofol, remifentanil, ketamine or dexmedetomidine. We assessed righting reflex, pain withdrawal, whisking reflex, and corneal reflex every 12 minutes (every 360 auditory trials). We searched for significant changes in baseline firing rate and stimulus-evoked activities (where present) due to the behavioral assessments, by comparing 4 min intervals before and after the behavioral tests. Results: Out of 1004 units in 20 sessions, we found significantly elevated activity (p < 0.01) following behavioral tests in 32% and 20% of A1 auditory-responsive units and 8.6% and 5.3% of auditory-unresponsive units under propofol and dexmedetomidine, respectively, but not under remifentanil or ketamine. A higher proportion of units modulated their firing following behavioral tests in A1 compared to PrC, with median gains ranging from +0.23 to +1.06, depending on the specific response feature. Conclusion: Behavioral testing increases ongoing firing rate and responses to sounds in some cortical neurons. This increase is more prevalent in A1 than in PrC, mirroring clinical observations that patients exhibit basic responses under sedation, while complex processing, such as memory encoding, is impaired. The degree of neuronal modulation due to behavioral testing varies between anesthetic agents, mirroring their clinical phenotypes.

Auditory evoked responses undergo notable changes during childhood, likely reflecting modifications in synaptic signaling in the auditory cortex. Particularly robust response, observed around 200 to 300 ms post stimulus (N/M250), has been consistently reported in children but is absent in adults. This long-latency response, evoked even in passive listening conditions, may indicate heightened sensory pathway responsiveness, facilitating experience-driven cortical plasticity. However, it remains unclear whether this delayed activation pattern is an intrinsic, species-general feature of brain development. We recorded cortical auditory evoked responses to monaural sine-wave tones/click sounds in 3 age groups (preadolescents, adolescents, and young adults) of human subjects and rats. Following short-lived early responses, both species exhibited a long-latency (150 to 450 ms) response in the auditory cortex. In both species, the relative amplitude of the long-latency response, compared to early responses, was increased in younger individuals. In human children, single-trial analysis demonstrated more consistent trial-by-trial timing of the response in this later time window than in the adult-typical 100-ms response in the earlier time window. Given its emergence in purely passive conditions, and across species, the robust current activity in late time window could represent a distinct synaptic event and may serve as a marker of the maturational stage, particularly in GABAergic cortical circuits.

During wake, sound‐evoked and spontaneous neural activity of the auditory cortex evolves in distinct subspaces, whereas anesthesia disrupts sound responses and merges these spaces. To evaluate if similar modifications of sound representation geometry explain sensory disconnection during sleep, large neural populations of the mouse auditory cortex are followed across slow‐wave sleep and wakefulness. It is observed that sleep dampens sound responses but preserves the geometry of sound representations such that they remain separate from spontaneous activity. Moreover, response dampening is strongly coordinated across neurons and varied throughout sleep, spanning from fully preserved response patterns to population response failures on a fraction of sound presentations. These failures rarely occurred in wakefulness and are more common during high spindle‐band activity. Therefore, in sleep, the auditory system preserves sound feature selectivity up to the cortex for detailed acoustic surveillance but concurrently implements an intermittent gating mechanism leading to local sensory disconnections.

The locus coeruleus–norepinephrine (LC-NE) system regulates arousal and awakening; however, it remains unclear whether the LC does this in a global or circuit-specific manner. We hypothesized that sensory-evoked awakenings are predominantly regulated by specific LC-NE efferent pathways. Anatomical, physiological, and functional modularities of LC-NE pathways involving the mouse basal forebrain (BF) and pontine reticular nucleus (PRN) were tested. We found partial anatomical segregation between the LC → PRN and LC → BF circuits. Extracellular NE dynamics in BF and PRN exhibited distinct sound-evoked activation during sleep, including a fast sound-evoked NE peak specific to PRN. Causal optogenetic interrogation of LC efferent pathways, by retro-channelrhodopsin (ChR2) activation or Platynereis dumerilii ciliary opsin (PdCO) silencing of synapses in target regions, revealed a role for early LC → PRN activity in driving arousal and sound-evoked awakenings. Together, our results uncover a role for early LC-NE PRN activity in connecting sensory and arousal pathways and establish LC heterogeneity in regulating arousal.

Sound‐evoked wakefulness from sleep is crucial in daily life, yet its neural mechanisms remain poorly understood. It is found that CaMKIIα+ neurons in the temporal association cortex (TeA) of mice are not essential for natural awakening from sleep. However, optogenetic activation of these neurons reliably induces wakefulness from non‐rapid eye movement (NREM) sleep but not from rapid eye movement (REM) sleep. In vivo electrophysiological and calcium recordings further demonstrated that TeA neurons are monotonically tuned to sound intensity but not frequency. More importantly, it is found that the activity of CaMKIIα+ neurons in TeA can gate sound‐evoked arousal from NREM sleep, which is further confirmed by optogenetic manipulations. Further investigation reveals that the baseline excitability of TeA CaMKIIα+ neurons and the delta oscillations in the electroencephalogram are particularly important in regulating the evoked activity of TeA neurons. Anatomical and functional screening of downstream targets of TeA reveals that excitatory projections from TeA glutamatergic neurons to glutamatergic neurons in the basolateral/lateral amygdala are critical for modulating sound‐evoked arousal from NREM sleep. These findings uncover a top‐down regulatory circuit that selectively governs sound‐evoked arousal from NREM sleep, with the TeA functioning as a key connecting cortex to subcortical regions.

The claustrum has been linked to attention and sleep. We hypothesized that this reflects a shared function, determining responsiveness to stimuli, which spans the axis of engagement. To test this hypothesis, we recorded claustrum population dynamics from male mice during both sleep and an attentional task (‘ENGAGE’). Heightened activity in claustrum neurons projecting to the anterior cingulate cortex (ACCp) corresponded to reduced sensory responsiveness during sleep. Similarly, in the ENGAGE task, heightened ACCp activity correlated with disengagement and behavioral lapses, while low ACCp activity correlated with hyper-engagement and impulsive errors. Chemogenetic elevation of ACCp activity reduced both awakenings during sleep and impulsive errors in the ENGAGE task. Furthermore, mice employing an exploration strategy in the task showed a stronger correlation between ACCp activity and performance compared to mice employing an exploitation strategy which reduced task complexity. Our results implicate ACCp claustrum neurons in restricting engagement during sleep and goal-directed behavior.

Auditory Residual Inhibition (ARI) is a temporary suppression of tinnitus that occurs in some people following the presentation of masking sounds. Differences in neural response to ARI stimuli may enable classification of tinnitus and a tailored approach to intervention in the future. In an exploratory study, we investigated the use of a brain-inspired artificial neural network to examine the effects of ARI on electroencephalographic function, as well as the predictive ability of the model. Ten tinnitus patients underwent two auditory stimulation conditions (constant and amplitude modulated broadband noise) at two time points and were then characterised as responders or non-responders, based on whether they experienced ARI or not. Using a spiking neural network model, we evaluated concurrent neural patterns generated across space and time from features of electroencephalographic data, capturing the neural dynamic changes before and after stimulation. Results indicated that the model may be used to predict the effect of auditory stimulation on tinnitus on an individual basis. This approach may aid in the development of predictive models for treatment selection.

Envelope following responses (EFRs) may be a useful tool for evaluating the audibility of speech sounds in infants. The present study aimed to evaluate the characteristics of speech-evoked EFRs in infants with normal hearing, relative to adults, and identify age-dependent changes in EFR characteristics during infancy. In 42 infants and 21 young adults, EFRs were elicited by the first (F1) and the second and higher formants (F2+) of the vowels /u/, /a/, and /i/, dominant in low and mid frequencies, respectively, and by amplitude-modulated fricatives /s/ and /∫/, dominant in high frequencies. In a subset of 20 infants, the in-ear stimulus level was adjusted to match that of an average adult ear (65 dB sound pressure level [SPL]). We found that (a) adult–infant differences in EFR amplitude, signal-to-noise ratio, and intertrial phase coherence were larger and spread across the frequency range when in-ear stimulus level was adjusted in infants, (b) adult–infant differences in EFR characteristics were the largest for low-frequency stimuli, (c) infants demonstrated adult-like phase coherence when they received a higher (i.e., unadjusted) stimulus level, and (d) EFR phase coherence and signal-to-noise ratio changed with age in the first year of life for a few F2+ vowel stimuli in a level-specific manner. Together, our findings reveal that development-related changes in EFRs during infancy likely vary by stimulus frequency, with low-frequency stimuli demonstrating the largest adult–infant differences. Consistent with previous research, our findings emphasize the significant role of stimulus level calibration methods while investigating developmental trends in EFRs.

Significance: Speech processing tasks can be used to assess the integrity and health of many functional and structural aspects of the brain. Despite the potential merits of such behavioral tests as clinical assessment tools, however, the underlying neural substrates remain relatively unclear. Aim: We aimed to obtain a more in-depth portrait of hemispheric asymmetry during dichotic listening tasks at the level of the prefrontal cortex, where prior studies have reported inconsistent results. Approach: To avoid central confounds that limited previous studies, we used diffuse correlation spectroscopy to optically monitor cerebral blood flow (CBF) in the dorsolateral prefrontal cortex during dichotic listening tasks in human subjects. Results: We found that dichotic listening tasks elicited hemispheric asymmetries in both amplitude as well as kinetics. When listening task blocks were repeated, there was an accommodative reduction in the response amplitude of the left, but not the right hemisphere. Conclusions: These heretofore unobserved trends depict a more nuanced portrait of the functional asymmetry that has been observed previously. To our knowledge, these results additionally represent the first direct measurements of CBF during a speech processing task recommended by the American Speech-Language-Hearing Association for diagnosing auditory processing disorders.

Do noises wake you up at night? Blame your locus coeruleus.