EEG/ECoG/EMG publications

When presented with an oscillatory sensory input at a particular frequency, F [Hz], neural systems respond with the corresponding frequency, f [Hz], and its multiples. When the input includes two frequencies ( F1 and F2 ) and they are nonlinearly integrated in the system, responses at intermodulation frequencies (i.e., n1 * f1 + n2 * f2 [Hz], where n1 and n2 are non-zero integers) emerge. Utilizing these properties, the steady state evoked potential (SSEP) paradigm allows us to characterize linear and nonlinear neural computation performed in cortical neurocircuitry. Here, we analyzed the steady state evoked local field potentials (LFPs) recorded from the primary (S1) and secondary (S2) somatosensory cortex of anesthetized cats (maintained with alfaxalone) while we presented slow ( F1 = 23Hz) and fast ( F2 = 200Hz) somatosensory vibration to the contralateral paw pads and digits. Over 9 experimental sessions, we recorded LFPs from N = 1620 and N = 1008 bipolar-referenced sites in S1 and S2 using electrode arrays. Power spectral analyses revealed strong responses at 1) the fundamental ( f1 , f2 ), 2) its harmonic, 3) the intermodulation frequencies, and 4) broadband frequencies (50-150Hz). To compare the computational architecture in S1 and S2, we employed simple computational modeling. Our modeling results necessitate nonlinear computation to explain SSEP in S2 more than S1. Combined with our current analysis of LFPs, our paradigm offers a rare opportunity to constrain the computational architecture of hierarchical organization of S1 and S2 and to reveal how a large-scale SSEP can emerge from local neural population activities.

Objective. Detection and early prediction of mental fatigue (i.e. shifts in vigilance), could be used to adapt neuromodulation strategies to effectively treat patients suffering from brain injury and other indications with prominent chronic mental fatigue. Approach. In this study, we analyzed electrocorticography (ECoG) signals chronically recorded from two healthy non-human primates (NHP) as they performed a sustained attention task over extended periods of time. We employed a set of spectrotemporal and connectivity biomarkers of the ECoG signals to identify periods of mental fatigue and a gradient boosting classifier to predict performance, up to several seconds prior to the behavioral response. Main results. Wavelet entropy and the instantaneous amplitude and frequency were among the best single features across sessions in both NHPs. The classification performance using higher order spectral-temporal (HOST) features was significantly higher than that of conventional spectral power features in both NHPs. Across the 99 sessions analyzed, average F1 scores of 77.5% ± 8.2% and 91.2% ± 3.6%, and accuracy of 79.5% ± 8.9% and 87.6% ± 3.9% for the classifier were obtained for each animal, respectively. Significance. Our results here demonstrate the feasibility of predicting performance and detecting periods of mental fatigue by analyzing ECoG signals, and that this general approach, in principle, could be used for closed-loop control of neuromodulation strategies.

Languages can use a common repertoire of vocal sounds to signify distinct meanings. In tonal languages, such as Mandarin Chinese, pitch contours of syllables distinguish one word from another, whereas in non-tonal languages, such as English, pitch is used to convey intonation. The neural computations underlying language specialization in speech perception are unknown. Here, we use a cross-linguistic approach to address this. Native Mandarin- and English- speaking participants each listened to both Mandarin and English speech, while neural activity was directly recorded from the non-primary auditory cortex. Both groups show language-general coding of speaker-invariant pitch at the single electrode level. At the electrode population level, we find language-specific distribution of cortical tuning parameters in Mandarin speakers only, with enhanced sensitivity to Mandarin tone categories. Our results show that speech perception relies upon a shared cortical auditory feature processing mechanism, which may be tuned to the statistics of a given language.

Serotonergic psychedelic drugs, such as psilocin (4-hydroxy-N,N-dimethyltryptamine), profoundly alter the quality of consciousness through mechanisms which are incompletely understood. Growing evidence suggests that a single psychedelic experience can positively impact long-term psychological well-being, with relevance for the treatment of psychiatric disorders, including depression. A prominent factor associated with psychiatric disorders is disturbed sleep, and the sleep-wake cycle is implicated in the regulation of neuronal firing and activity homeostasis. It remains unknown to what extent psychedelic agents directly affect sleep, in terms of both acute arousal and homeostatic sleep regulation. Here, chronic in vivo electrophysiological recordings were obtained in mice to track sleep-wake architecture and cortical activity after psilocin injection. Administration of psilocin led to delayed REM sleep onset and reduced NREM sleep maintenance for up to approximately 3 hours after dosing, and the acute EEG response was associated primarily with an enhanced oscillation around 4 Hz. No long-term changes in sleep-wake quantity were found. When combined with sleep deprivation, psilocin did not alter the dynamics of homeostatic sleep rebound during the subsequent recovery period, as reflected in both sleep amount and EEG slow wave activity. However, psilocin decreased the recovery rate of sleep slow wave activity following sleep deprivation in the local field potentials of electrodes targeting medial prefrontal and surrounding cortex. It is concluded that psilocin affects both global vigilance state control and local sleep homeostasis, an effect which may be relevant for its antidepressant efficacy.

Speech processing is built upon encoding by the auditory nerve and brainstem, yet we know very little about how these processes unfold in specific subcortical structures. These structures are deep and respond quickly, making them difficult to study during ongoing speech. Recent techniques have begun to address this problem, but yield temporally broad responses with consequently ambiguous neural origins. Here, we describe a method that pairs re-synthesized ‘peaky’ speech with deconvolution analysis of electroencephalography recordings. We show that in adults with normal hearing the method quickly yields robust responses whose component waves reflect activity from distinct subcortical structures spanning auditory nerve to rostral brainstem. We further demonstrate the versatility of peaky speech by simultaneously measuring bilateral and ear-specific responses across different frequency bands and discuss the important practical considerations such as talker choice. The peaky speech method holds promise as a tool for investigating speech encoding and processing, and for clinical applications.

For many peripheral neuro-modulation applications, the cuff electrode has become a preferred technology for delivering electrical current into targeted volumes of tissue. While basic cuffs with low spatial selectivity, having longitudinally arranged contacts, can be produced from relatively straightforward processes, the fabrication of more complex electrode configurations typically requires iterative design and clean-room fabrication with skilled technicians. Although facile methods for fabricating cuff electrodes exist, their inconsistent products have limited their adoption for rapid manufacturing. In this article, we report a fast, low-cost fabrication process for patterning of electrode contacts in an implantable peripheral nerve cuff. Using a laser cutter as we have prescribed, the designer can render precise contact geometries that are consistent between batches. This method is enabled by the use of silicone/carbon black (CB) composite electrodes, which integrate with the patterned surface of its substrate—tubular silicone insulation. The size and features of its products can be adapted to fit a wide range of nerve diameters and applications. In this study, we specifically documented the manufacturing and evaluation of circumpolar cuffs with radial arrays of three contacts for acute implantation on the rat sciatic nerve. As part of this method, we also detail protocols for verification—electrochemical characterization—and validation—electrophysiological evaluation—of implantable cuff electrodes. Applied to our circumpolar cuff electrode, we report favorable electrical characteristics. In addition, we report that it reproduces expected electrophysiological behaviors described in prior literature. No specialized equipment or fabrication experience was required in our production, and we encountered negligible costs relative to commercially available solutions. Since, as we demonstrate, this process generates consistent and precise electrode geometries, we propose that it has strong merits for use in rapid manufacturing.

Individuals differ in their ability to selectively attend to goal-relevant auditory stimuli. People with Attention-Deficit/Hyperactivity Disorder (ADHD) in particular tend to show cognitive deficits associated with distractibility and inefficiencies in inhibition and attention. We hypothesized that people with ADHD would exhibit poorer performance and weaker neural signatures of attentional control when undertaking a challenging auditory task that required strong top-down attention. Neurotypical (N = 20) and ADHD (N = 25) young adults with normal hearing listened to one of three concurrent, spatially separated speech streams and reported the order of the syllables presented while we recorded electroencephalography (EEG). We tested both the ability to sustain attentional focus on a single “target” stream and the ability to monitor the target but flexibly switch attention to an unpredictable “interrupter” stream from another direction if and when it appeared. Although both stimulus structure and task demands affected behavioral performance, ADHD status did not. In both groups, the interrupter evoked larger neural responses when it was to be attended compared to when it was irrelevant, including for the P3a “reorienting” response previously described as involuntary. This attentional modulation was weaker in ADHD listeners, even though their behavioral performance was no lower. Across the entire cohort, individual performance correlated with the degree of top-down modulation of neural responses. These results demonstrate that listeners differ in their ability to modulate neural representations of sound based on task goals. Adults with ADHD have weaker volitional control of attentional processes than their neurotypical counterparts. Significance Statement ADHD and neurotypical listeners attended to one speech stream among distractors while neural responses were measured with electroencephalography. Behavioral performance varied with stimulus structure and task demands, but not with ADHD status. In both groups, top-down attention modulated stimulus-evoked neural responses: interrupting sounds elicited weaker responses when the sounds were ignored compared to when they were attended. This modulation affected a late “orienting” response (P3a) that has been previously described as automatic and not dependent on internal state. Importantly, ADHD subjects showed weaker attentional filtering than did neurotypical controls. At the individual level, performance correlated with neural metrics. Our results demonstrate that people vary widely in how flexibly they can use attention to modulate sensory responses based on task goals.

Objectives: Prolonged cardiac arrest is known to cause global ischemic brain injury and functional impairment. Upon resuscitation, electroencephalographic recordings of brain activity begin to resume and can potentially be used to monitor neurologic recovery. We have previously shown that intrathecal orexin shows promise as a restorative drug and arousal agent in rodents. Our goal is to determine the electrophysiology effects of orexin in a rodent model of asphyxial cardiac arrest, focusing on the electroencephalographic activity in the gamma and super-gamma bands (indicative of return of higher brain function). Design: Experimental animal study. Setting: University-based animal research laboratory. Subjects: Adult male Wistar rats. Interventions: In an established model of asphyxial cardiac arrest ( n = 24), we treated half of Wistar rats with orexin administered intranasally by atomizer 30 minutes post return of spontaneous circulation in one of two dose levels (10 and 50 µM); the rest were treated with saline as control. Continuous electroencephalographic recording was obtained and quantitatively analyzed for the gamma fraction. Gamma and high-frequency super-gamma band measures were compared against clinical recovery according to Neuro-Deficit Score. Measurements and Main Results: Compared with the control cohort, the high-dose orexin cohort showed significantly better Neuro-Deficit Score 4 hours after return of spontaneous circulation (55.17 vs 47.58; p < 0.02) and significantly higher mean gamma fraction (0.251 vs 0.177; p < 0.02) in cerebral regions surveyed by rostral electrodes for the first 170 minutes after administration of orexin. Conclusions: Our findings support early and continuous monitoring of electroencephalography-based gamma activity as a marker of better functional recovery after intranasal administration of orexin as measured by Neuro-Deficit Score in an established animal model of asphyxial cardiac arrest.

Vision is the primary sense humans use to evaluate and respond to threats. Understanding the biological underpinnings of the human threat response has been hindered by lack of realistic in-lab threat paradigms. We established an immersive virtual reality (VR) platform to simultaneously measure behavior, physiological state, and neural activity from the human brain using chronically implanted electrodes. Subjects with high anxiety showed increased visual scanning in response to threats as compared to healthy controls. In both healthy and anxious subjects, the amount of scanning behavior correlated with the magnitude of physiological arousal, suggesting that visual scanning behavior is directly linked to internal state. Intracranial electroencephalography (iEEG) recordings from three subjects suggested that high-frequency gamma activity in the insula positively correlates with physiological arousal induced by visual threats and that low-frequency theta activity in the orbitofrontal cortex (OFC) negatively correlates with physiological arousal induced by visual threats. These findings reveal a key role of eye movements and suggest that distinct insula and OFC activation dynamics may be important for detecting and adjusting human stress in response to visually perceived threats.

The latency of the auditory steady-state response (ASSR) may provide valuable information regarding the integrity of the auditory system, as it could potentially reveal the presence of multiple intracerebral sources. To estimate multiple latencies from high-order ASSRs, we propose a novel two-stage procedure that consists of a nonparametric estimation method, called apparent latency from phase coherence (ALPC), followed by a heuristic sequential forward selection algorithm (SFS). Compared with existing methods, ALPC-SFS requires few prior assumptions, and is straightforward to implement for higher-order nonlinear responses to multi-cosine sound complexes with their initial phases set to zero. It systematically evaluates the nonlinear components of the ASSRs by estimating multiple latencies, automatically identifies involved ASSR components, and reports a latency consistency index. To verify the proposed method, we performed simulations for several scenarios: two nonlinear subsystems with different or overlapping outputs. We compared the results from our method with predictions from existing, parametric methods. We also recorded the EEG from ten normal-hearing adults by bilaterally presenting superimposed tones with four frequencies that evoke a unique set of ASSRs. From these ASSRs, two major latencies were found to be stable across subjects on repeated measurement days. The two latencies are dominated by low-frequency (LF) (near 40 Hz, at around 41–52 ms) and high-frequency (HF) (> 80 Hz, at around 21–27 ms) ASSR components. The frontal-central brain region showed longer latencies on LF components, but shorter latencies on HF components, when compared with temporal-lobe regions. In conclusion, the proposed nonparametric ALPC-SFS method, applied to zero-phase, multi-cosine sound complexes is more suitable for evaluating embedded nonlinear systems underlying ASSRs than existing methods. It may therefore be a promising objective measure for hearing performance and auditory cortex (dys)function.

Background Electrical stimulation of residual afferent nerve fibers can evoke sensations from a missing limb after amputation, and bionic arms endowed with artificial sensory feedback have been shown to confer functional and psychological benefits. Here we explore the extent to which artificial sensations can be discriminated based on location, quality, and intensity. Methods We implanted Utah Slanted Electrode Arrays (USEAs) in the arm nerves of three transradial amputees and delivered electrical stimulation via different electrodes and frequencies to produce sensations on the missing hand with various locations, qualities, and intensities. Participants performed blind discrimination trials to discriminate among these artificial sensations. Results Participants successfully discriminated cutaneous and proprioceptive sensations ranging in location, quality and intensity. Performance was significantly greater than chance for all discrimination tasks, including discrimination among up to ten different cutaneous location-intensity combinations (15/30 successes, p < 0.0001) and seven different proprioceptive location-intensity combinations (21/40 successes, p < 0.0001). Variations in the site of stimulation within the nerve, via electrode selection, enabled discrimination among up to five locations and qualities (35/35 successes, p < 0.0001). Variations in the stimulation frequency enabled discrimination among four different intensities at the same location (13/20 successes, p < 0.0005). One participant also discriminated among individual stimulation of two different USEA electrodes, simultaneous stimulation on both electrodes, and interleaved stimulation on both electrodes (20/24 successes, p < 0.0001). Conclusion Electrode location, stimulation frequency, and stimulation pattern can be modulated to evoke functionally discriminable sensations with a range of locations, qualities, and intensities. This rich source of artificial sensory feedback may enhance functional performance and embodiment of bionic arms endowed with a sense of touch.

Previous research with speech and non-speech stimuli suggested that in audiovisual perception, visual information starting prior to the onset of corresponding sound can provide visual cues, and form a prediction about the upcoming auditory sound. This prediction leads to audiovisual (AV) interaction. Auditory and visual perception interact and induce suppression and speeding up of the early auditory event-related potentials (ERPs) such as N1 and P2. To investigate AV interaction, previous research examined N1 and P2 amplitudes and latencies in response to audio only (AO), video only (VO), audiovisual, and control (CO) stimuli, and compared AV with auditory perception based on four AV interaction models (AV vs. AO+VO, AV-VO vs. AO, AV-VO vs. AO-CO, AV vs. AO). The current study addresses how different models of AV interaction express N1 and P2 suppression in music perception. Furthermore, the current study took one step further and examined whether previous musical experience, which can potentially lead to higher N1 and P2 amplitudes in auditory perception, influenced AV interaction in different models. Musicians and non-musicians were presented the recordings (AO, AV, VO) of a keyboard /C4/ key being played, as well as CO stimuli. Results showed that AV interaction models differ in their expression of N1 and P2 amplitude and latency suppression. The calculation of model (AV-VO vs. AO) and (AV-VO vs. AO-CO) has consequences for the resulting N1 and P2 difference waves. Furthermore, while musicians, compared to non-musicians, showed higher N1 amplitude in auditory perception, suppression of amplitudes and latencies for N1 and P2 was similar for the two groups across the AV models. Collectively, these results suggest that when visual cues from finger and hand movements predict the upcoming sound in AV music perception, suppression of early ERPs is similar for musicians and non-musicians. Notably, the calculation differences across models do not lead to the same pattern of results for N1 and P2, demonstrating that the four models are not interchangeable and are not directly comparable.

Sleep is intimately linked to cognitive performance and exposure to traumatic stress that leads to post-traumatic stress disorder (PTSD) impairs both sleep and cognitive function. However, the contribution of pre-trauma sleep loss to subsequent trauma-dependent fear-associated memory impairment remains unstudied. We hypothesized that sleep deprivation (SD) prior to trauma exposure may increase the severity of a PTSD-like phenotype in rats exposed to single prolonged stress (SPS), a rodent model of PTSD. Rats were exposed to SPS alone, SD alone, or a combination of SPS+SD and measures of fear-associated memory impairments and vigilance state changes were compared to a group of control animals not exposed to SPS or SD. We found that SPS, and SPS+SD animals showed impaired fear-associated memory processing and that the addition of SD to SPS did not further exaggerate the effect of SPS alone. Additionally, the combination of SPS with SD results in a unique homeostatic sleep duration phenotype when compared to SD, SPS, or control animals. SPS exposure following SD represses homeostatic rebound and eliminates sleep-deprivation-induced increases in NREM sleep delta power. This work identifies a unique time frame where trauma exposure and sleep interact and identifies this window of time as a potential therapeutic treatment window for staving off the negative consequences of trauma exposure.

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.

This work examines how sounds are held in auditory working memory (AWM) in humans by examining oscillatory local field potentials (LFPs) in candidate brain regions. Previous fMRI studies by our group demonstrated blood oxygenation level-dependent (BOLD) response increases during maintenance in auditory cortex, inferior frontal cortex and the hippocampus using a paradigm with a delay period greater than 10s. The relationship between such BOLD changes and ensemble activity in different frequency bands is complex, and the long delay period raised the possibility that long-term memory mechanisms were engaged. Here we assessed LFPs in different frequency bands in six subjects with recordings from all candidate brain regions using a paradigm with a short delay period of 3 s. Sustained delay activity was demonstrated in all areas, with different patterns in the different areas. Enhancement in low frequency (delta) power and suppression across higher frequencies (beta/gamma) were demonstrated in primary auditory cortex in medial Heschl's gyrus (HG) whilst non-primary cortex showed patterns of enhancement and suppression that altered at different levels of the auditory hierarchy from lateral HG to superior- and middle-temporal gyrus. Inferior frontal cortex showed increasing suppression with increasing frequency. The hippocampus and parahippocampal gyrus showed low frequency increases and high frequency decreases in oscillatory activity. This work demonstrates sustained activity patterns during AWM maintenance, with prominent low-frequency increases in medial temporal lobe regions.

In mammals, spinal cord injuries often result in muscle paralysis through the apoptosis of lower motor neurons and denervation of neuromuscular junctions. Previous research shows that the inflammatory response to a spinal cord injury can cause additional tissue damage after the initial trauma. To modulate this inflammatory response, we delivered lentiviral anti-inflammatory interleukin-10, via loading onto an implantable biomaterial scaffold, into a left-sided hemisection at the C5 vertebra in mice. We hypothesized that improved behavioral outcomes associated with anti-inflammatory treatment are due to the sparing of fine motor circuit components. We examined behavioral recovery using a ladder beam, tissue sparing using histology, and electromyogram recordings using intraspinal optogenetic stimulation at 2 weeks post-injury. Ladder beam analysis shows interleukin-10 treatment results in significant improvement of behavioral recovery at 2 and 12 weeks post-injury when compared to mice treated with a control virus. Histology shows interleukin-10 results in greater numbers of lower motor neurons, axons, and muscle innervation at 2 weeks post-injury. Furthermore, electromyogram recordings suggest that interleukin-10-treated animals have signal-to-noise ratios and peak-to-peak amplitudes more similar to that of uninjured controls than to that of control injured animals at 2 weeks post-injury. These data show that gene therapy using anti-inflammatory interleukin-10 can significantly reduce tissue damage and subsequent motor deficits after a spinal cord injury. Together, these results suggest that early modulation of the injury response can preserve muscle function with long-lasting benefits.

Elucidating changes in sensory processing across attentional and arousal states is a major focus in neuroscience. The local/global deviant (LGD) stimulus paradigm engages auditory predictive coding over short (local deviance, LD) and long (global deviance, GD) time scales, and has been used to assay disruption of auditory predictive coding upon loss of consciousness. Our previous work (Nourski et al., 2018, J Neurosci 38:8441-52) examined effects of general anesthesia on short- and long-term novelty detection. GD effects were suppressed at subhypnotic doses of propofol, suggesting that they may be more related to task engagement than consciousness per se. The present study addressed this hypothesis by comparing cortical responses to auditory novelty during passive versus active listening conditions in awake listeners. Subjects were seven adult neurosurgical patients undergoing chronic invasive monitoring for medically intractable epilepsy. LGD stimuli were sequences of four identical vowels followed by a fifth identical or different vowel. In the passive condition, the stimuli were presented to subjects as they watched a silent TV program and were instructed to attend to its content. In the active condition, stimuli were presented in the absence of a TV program, and subjects were instructed to press a button in response to GD target stimuli. Intracranial recordings were made from multiple brain regions, including core and non-core auditory, auditory-related, prefrontal and sensorimotor cortex. Metrics of task performance included hit rate, sensitivity index, and reaction times. Cortical activity was measured as averaged auditory evoked potentials (AEPs) and event-related band power in high gamma (70-150 Hz) and alpha (8-14 Hz) frequency bands. The vowel stimuli and LD elicited robust AEPs in all studied brain areas in both passive and active conditions. High gamma responses to stimulus onset and LD were localized predominantly to the auditory cortex in the superior temporal plane and had a comparable prevalence and spatial extent between the two conditions. In contrast, GD effects (AEPs, high gamma and alpha suppression) were greatly enhanced during the active condition in all studied brain areas. The prevalence of high gamma GD effects was positively correlated with individual subjects' task performance. The data demonstrate distinct task engagement-related effects on responses to auditory novelty across the auditory cortical processing hierarchy. The results motivate a closer examination of effective connectivity underlying attentional modulation of cortical sensory responses, and serve as a foundation for examining changes in sensory processing associated with general anesthesia, sleep and disorders of consciousness.

Predictive coding is an influential theory of neural processing underlying perceptual inference. However, it is unknown to what extent prediction violations of different sensory features are mediated in different regions in auditory cortex, with different dynamics, and by different mechanisms. This study investigates the neural responses to synthesized acoustic syllables, which could be expected or unexpected, along several features. By using electrocorticography (ECoG) in rat auditory cortex (subjects: adult female Wistar rats with normal hearing), we aimed at mapping regional differences in mismatch responses to different stimulus features. Continuous streams of morphed syllables formed roving oddball sequences in which each stimulus was repeated several times (thereby forming a standard) and subsequently replaced with a deviant stimulus which differed from the standard along one of several acoustic features: duration, pitch, interaural level differences (ILD), or consonant identity. Each of these features could assume one of several different levels, and the resulting change from standard to deviant could be larger or smaller. The deviant stimuli were then repeated to form new standards. We analyzed responses to the first repetition of a new stimulus (deviant) and its last repetition in a stimulus train (standard). For the ECoG recording, we implanted urethane-anaesthetized rats with 8 × 8 surface electrode arrays covering a 3 × 3 mm cortical patch encompassing primary and higher-order auditory cortex. We identified the response topographies and latencies of population activity evoked by acoustic stimuli in the rat auditory regions, and mapped their sensitivity to expectation violations along different acoustic features. For all features, the responses to deviant stimuli increased in amplitude relative to responses to standard stimuli. Deviance magnitude did not further modulate these mismatch responses. Mismatch responses to different feature violations showed a heterogeneous distribution across cortical areas, with no evidence for systematic topographic gradients for any of the tested features. However, within rats, the spatial distribution of mismatch responses varied more between features than the spatial distribution of tone-evoked responses. This result supports the notion that prediction error signaling along different stimulus features is subserved by different cortical populations, albeit with substantial heterogeneity across individuals.

Continuous acoustic streams, such as speech signals, can be chunked into segments containing reoccurring patterns (e.g., words). Noninvasive recordings of neural activity in humans suggest that chunking is underpinned by low-frequency cortical entrainment to the segment presentation rate, and modulated by prior segment experience (e.g., words belonging to a familiar language). Interestingly, previous studies suggest that also primates and rodents may be able to chunk acoustic streams. Here, we test whether neural activity in the rat auditory cortex is modulated by previous segment experience. We recorded subdural responses using electrocorticography (ECoG) from the auditory cortex of 11 anesthetized rats. Prior to recording, four rats were trained to detect familiar triplets of acoustic stimuli (artificial syllables), three were passively exposed to the triplets, while another four rats had no training experience. While low-frequency neural activity peaks were observed at the syllable level, no triplet-rate peaks were observed. Notably, in trained rats (but not in passively exposed and naïve rats), familiar triplets could be decoded more accurately than unfamiliar triplets based on neural activity in the auditory cortex. These results suggest that rats process acoustic sequences, and that their cortical activity is modulated by the training experience even under subsequent anesthesia.