Kinase signalling in excitatory neurons regulates sleep quantity and depth.

Progress has been made in the elucidation of sleep and wakefulness regulation at the neurocircuit level1,2. However, the intracellular signalling pathways that regulate sleep and the neuron groups in which these intracellular mechanisms work remain largely unknown. Here, using a forward genetics approach in mice, we identify histone deacetylase 4 (HDAC4) as a sleep-regulating molecule. Haploinsufficiency of Hdac4, a substrate of salt-inducible kinase 3 (SIK3)3, increased sleep. By contrast, mice that lacked SIK3 or its upstream kinase LKB1 in neurons or with a Hdac4S245A mutation that confers resistance to phosphorylation by SIK3 showed decreased sleep. These findings indicate that LKB1-SIK3-HDAC4 constitute a signalling cascade that regulates sleep and wakefulness. We also performed targeted manipulation of SIK3 and HDAC4 in specific neurons and brain regions. This showed that SIK3 signalling in excitatory neurons located in the cerebral cortex and the hypothalamus positively regulates EEG delta power during non-rapid eye movement sleep (NREMS) and NREMS amount, respectively. A subset of transcripts biased towards synaptic functions was commonly regulated in cortical glutamatergic neurons through the expression of a gain-of-function allele of Sik3 and through sleep deprivation. These findings suggest that NREMS quantity and depth are regulated by distinct groups of excitatory neurons through common intracellular signals. This study provides a basis for linking intracellular events and circuit-level mechanisms that control NREMS.

Delta- and theta-band cortical tracking and phase-amplitude coupling to sung speech by infants.

The amplitude envelope of speech carries crucial low-frequency acoustic information that assists linguistic decoding at multiple time scales. Neurophysiological signals are known to track the amplitude envelope of adult-directed speech (ADS), particularly in the theta-band. Acoustic analysis of infant-directed speech (IDS) has revealed significantly greater modulation energy than ADS in an amplitude-modulation (AM) band centred on ∼2 Hz. Accordingly, cortical tracking of IDS by delta-band neural signals may be key to language acquisition. Speech also contains acoustic information within its higher-frequency bands (beta, gamma). Adult EEG and MEG studies reveal an oscillatory hierarchy, whereby low-frequency (delta, theta) neural phase dynamics temporally organize the amplitude of high-frequency signals (phase amplitude coupling, PAC). Whilst consensus is growing around the role of PAC in the matured adult brain, its role in the development of speech processing is unexplored. Here, we examined the presence and maturation of low-frequency (<12 Hz) cortical speech tracking in infants by recording EEG longitudinally from 60 participants when aged 4-, 7- and 11- months as they listened to nursery rhymes. After establishing stimulus-related neural signals in delta and theta, cortical tracking at each age was assessed in the delta, theta and alpha [control] bands using a multivariate temporal response function (mTRF) method. Delta-beta, delta-gamma, theta-beta and theta-gamma phase-amplitude coupling (PAC) was also assessed. Significant delta and theta but not alpha tracking was found. Significant PAC was present at all ages, with both delta and theta -driven coupling observed.

Excitation of Putative Glutamatergic Neurons in the Rat Parabrachial Nucleus Region Reduces Delta Power during Dexmedetomidine but not Ketamine Anesthesia.

BACKGROUND: Parabrachial nucleus excitation reduces cortical delta oscillation (0.5 to 4 Hz) power and recovery time associated with anesthetics that enhance γ-aminobutyric acid type A receptor action. The effects of parabrachial nucleus excitation on anesthetics with other molecular targets, such as dexmedetomidine and ketamine, remain unknown. The hypothesis was that parabrachial nucleus excitation would cause arousal during dexmedetomidine and ketamine anesthesia. METHODS: Designer Receptors Exclusively Activated by Designer Drugs were used to excite calcium/calmodulin-dependent protein kinase 2α-positive neurons in the parabrachial nucleus region of adult male rats without anesthesia (nine rats), with dexmedetomidine (low dose: 0.3 µg · kg-1 · min-1 for 45 min, eight rats; high dose: 4.5 µg · kg-1 · min-1 for 10 min, seven rats), or with ketamine (low dose: 2 mg · kg-1 · min-1 for 30 min, seven rats; high dose: 4 mg · kg-1 · min-1 for 15 min, eight rats). For control experiments (same rats and treatments), the Designer Receptors Exclusively Activated by Designer Drugs were not excited. The electroencephalogram and anesthesia recovery times were recorded and analyzed. RESULTS: Parabrachial nucleus excitation reduced delta power in the prefrontal electroencephalogram with low-dose dexmedetomidine for the 150-min analyzed period, excepting two brief periods (peak median bootstrapped difference [clozapine-N-oxide - saline] during dexmedetomidine infusion = -6.06 [99% CI = -12.36 to -1.48] dB, P = 0.007). However, parabrachial nucleus excitation was less effective at reducing delta power with high-dose dexmedetomidine and low- and high-dose ketamine (peak median bootstrapped differences during high-dose [dexmedetomidine, ketamine] infusions = [-1.93, -0.87] dB, 99% CI = [-4.16 to -0.56, -1.62 to -0.18] dB, P = [0.006, 0.019]; low-dose ketamine had no statistically significant decreases during the infusion). Recovery time differences with parabrachial nucleus excitation were not statistically significant for dexmedetomidine (median difference for [low, high] dose = [1.63, 11.01] min, 95% CI = [-20.06 to 14.14, -20.84 to 23.67] min, P = [0.945, 0.297]) nor low-dose ketamine (median difference = 12.82 [95% CI: -3.20 to 39.58] min, P = 0.109) but were significantly longer for high-dose ketamine (median difference = 11.38 [95% CI: 1.81 to 24.67] min, P = 0.016). CONCLUSIONS: These results suggest that the effectiveness of parabrachial nucleus excitation to change the neurophysiologic and behavioral effects of anesthesia depends on the anesthetic's molecular target.

A heuristic perspective on non-variational free energy modulation at the sleep-like edge.

BACKGROUND: The variational Free Energy Principle (FEP) establishes that a neural system minimizes a free energy function of their internal state through environmental sensing entailing beliefs about hidden states in their environment. PROBLEM: Because sensations are drastically reduced during sleep, it is still unclear how a self-organizing neural network can modulate free energy during sleep transitions. GOAL: To address this issue, we study how network's state-dependent changes in energy, entropy and free energy connect with changes at the synaptic level in the absence of sensing during a sleep-like transition. APPROACH: We use simulations of a physically plausible, environmentally isolated neuronal network that self-organize after inducing a thalamic input to show that the reduction of non-variational free energy depends sensitively upon thalamic input at a slow, rhythmic Poisson (delta) frequency due to spike timing dependent plasticity. METHODS: We define a non-variational free energy in terms of the relative difference between the energy and entropy of the network from the initial distribution (prior to activity dependent plasticity) to the nonequilibrium steady-state distribution (after plasticity). We repeated the analysis under different levels of thalamic drive - as defined by the number of cortical neurons in receipt of thalamic input. RESULTS: Entraining slow activity with thalamic input induces a transition from a gamma (awake-like state) to a delta (sleep-like state) mode of activity, which can be characterized through a modulation of network's energy and entropy (non-variational free energy) of the ensuing dynamics. The self-organizing response to low and high thalamic drive also showed characteristic differences in the spectrum of frequency content due to spike timing dependent plasticity. CONCLUSIONS: The modulation of this non-variational free energy in a network that self-organizes, seems to be an organizational network principle. This could open a window to new empirically testable hypotheses about state changes in a neural network.

Cortical entrainment to hierarchical contextual rhythms recomposes dynamic attending in visual perception.

Temporal regularity is ubiquitous and essential to guiding attention and coordinating behavior within a dynamic environment. Previous researchers have modeled attention as an internal rhythm that may entrain to first-order regularity from rhythmic events to prioritize information selection at specific time points. Using the attentional blink paradigm, here we show that higher-order regularity based on rhythmic organization of contextual features (pitch, color, or motion) may serve as a temporal frame to recompose the dynamic profile of visual temporal attention. Critically, such attentional reframing effect is well predicted by cortical entrainment to the higher-order contextual structure at the delta band as well as its coupling with the stimulus-driven alpha power. These results suggest that the human brain involuntarily exploits multiscale regularities in rhythmic contexts to recompose dynamic attending in visual perception, and highlight neural entrainment as a central mechanism for optimizing our conscious experience of the world in the time dimension.

Mathematical Modeling of Brain Activity under Specific Auditory Stimulation.

Understanding the connection between different stimuli and the brain response represents a complex research area. However, the use of mathematical models for this purpose is relatively unexplored. The present study investigates the effects of three different auditory stimuli on cerebral biopotentials by means of mathematical functions. The effects of acoustic stimuli (S1, S2, and S3) on cerebral activity were evaluated by electroencephalographic (EEG) recording on 21 subjects for 20 minutes of stimulation, with a 5-minute period of silence before and after stimulation. For the construction of the mathematical models used for the study of the EEG rhythms, we used the Box-Jenkins methodology. Characteristic mathematical models were obtained for the main frequency bands and were expressed by 2 constant functions, 8 first-degree functions, a second-degree function, a fourth-degree function, 6 recursive functions, and 4 periodic functions. The values obtained for the variance estimator are low, demonstrating that the obtained models are correct. The resulting mathematical models allow us to objectively compare the EEG response to the three stimuli, both between the stimuli itself and between each stimulus and the period before stimulation.

Endogenous Oscillations Time-Constrain Linguistic Segmentation: Cycling the Garden Path.

Speech is transient. To comprehend entire sentences, segments consisting of multiple words need to be memorized for at least a while. However, it has been noted previously that we struggle to memorize segments longer than approximately 2.7 s. We hypothesized that electrophysiological processing cycles within the delta band (<4 Hz) underlie this time constraint. Participants' EEG was recorded while they listened to temporarily ambiguous sentences. By manipulating the speech rate, we aimed at biasing participants' interpretation: At a slow rate, segmentation after 2.7 s would trigger a correct interpretation. In contrast, at a fast rate, segmentation after 2.7 s would trigger a wrong interpretation and thus an error later in the sentence. In line with the suggested time constraint, the phase of the delta-band oscillation at the critical point in the sentence mirrored segmentation on the level of single trials, as indicated by the amplitude of the P600 event-related brain potential (ERP) later in the sentence. The correlation between upstream delta-band phase and downstream P600 amplitude implies that segmentation took place when an underlying neural oscillator had reached a specific angle within its cycle, determining comprehension. We conclude that delta-band oscillations set an endogenous time constraint on segmentation.

Delta/theta band EEG differentially tracks low and high frequency speech-derived envelopes.

The representation of speech in the brain is often examined by measuring the alignment of rhythmic brain activity to the speech envelope. To conveniently quantify this alignment (termed 'speech tracking') many studies consider the broadband speech envelope, which combines acoustic fluctuations across the spectral range. Using EEG recordings, we show that using this broadband envelope can provide a distorted picture on speech encoding. We systematically investigated the encoding of spectrally-limited speech-derived envelopes presented by individual and multiple noise carriers in the human brain. Tracking in the 1 to 6 Hz EEG bands differentially reflected low (0.2 - 0.83 kHz) and high (2.66 - 8 kHz) frequency speech-derived envelopes. This was independent of the specific carrier frequency but sensitive to attentional manipulations, and may reflect the context-dependent emphasis of information from distinct spectral ranges of the speech envelope in low frequency brain activity. As low and high frequency speech envelopes relate to distinct phonemic features, our results suggest that functionally distinct processes contribute to speech tracking in the same EEG bands, and are easily confounded when considering the broadband speech envelope.

Delta/Theta band EEG activity shapes the rhythmic perceptual sampling of auditory scenes.

Many studies speak in favor of a rhythmic mode of listening, by which the encoding of acoustic information is structured by rhythmic neural processes at the time scale of about 1 to 4 Hz. Indeed, psychophysical data suggest that humans sample acoustic information in extended soundscapes not uniformly, but weigh the evidence at different moments for their perceptual decision at the time scale of about 2 Hz. We here test the critical prediction that such rhythmic perceptual sampling is directly related to the state of ongoing brain activity prior to the stimulus. Human participants judged the direction of frequency sweeps in 1.2 s long soundscapes while their EEG was recorded. We computed the perceptual weights attributed to different epochs within these soundscapes contingent on the phase or power of pre-stimulus EEG activity. This revealed a direct link between 4 Hz EEG phase and power prior to the stimulus and the phase of the rhythmic component of these perceptual weights. Hence, the temporal pattern by which the acoustic information is sampled over time for behavior is directly related to pre-stimulus brain activity in the delta/theta band. These results close a gap in the mechanistic picture linking ongoing delta band activity with their role in shaping the segmentation and perceptual influence of subsequent acoustic information.

Non-rhythmic temporal prediction involves phase resets of low-frequency delta oscillations.

The phase of neural oscillatory signals aligns to the predicted onset of upcoming stimulation. Whether such phase alignments represent phase resets of underlying neural oscillations or just rhythmically evoked activity, and whether they can be observed in a rhythm-free visual context, however, remains unclear. Here, we recorded the magnetoencephalogram while participants were engaged in a temporal prediction task, judging the visual or tactile reappearance of a uniformly moving stimulus. The prediction conditions were contrasted with a control condition to dissociate phase adjustments of neural oscillations from stimulus-driven activity. We observed stronger delta band inter-trial phase consistency (ITPC) in a network of sensory, parietal and frontal brain areas, but no power increase reflecting stimulus-driven or prediction-related evoked activity. Delta ITPC further correlated with prediction performance in the cerebellum and visual cortex. Our results provide evidence that phase alignments of low-frequency neural oscillations underlie temporal predictions in a non-rhythmic visual and crossmodal context.

Electrocorticographic patterns dominated by low-frequency waves in camphor-induced seizures.

Camphor is an aromatic terpene compound found in the essential oils of many plants, which has been used for centuries as a herbal medicine, especially in children. However, many studies have shown that camphor may have major side effects, including neurological manifestation, such as seizures. In the present study, we investigated the electrocorticographic patterns of seizures induced by camphor in male adult Wistar rats. Each rat received 400 mg/kg (i.p.) of camphor prior to monitoring by electrocorticography. The application of camphor resulted a rapid evolution to seizure and marked changes in the electrocorticographic readings, which presented characteristics of epileptiform activity, with an increase in the total power wave. The decomposition of the cerebral waves revealed an increase in the delta and theta waves. The analysis of the camphor traces revealed severe ictal activity marked by an increase in the polyspike wave. Our data thus indicate that camphor may cause seizures, leading to tonic-clonic seizures. Clearly, further studies are necessary to better elucidate the mechanisms through which camphor acts on the brain, and to propose potential treatments with anticonvulsant drugs that are effective for the control of the seizures.

Linguistic Structure and Meaning Organize Neural Oscillations into a Content-Specific Hierarchy.

Neural oscillations track linguistic information during speech comprehension (Ding et al., 2016; Keitel et al., 2018), and are known to be modulated by acoustic landmarks and speech intelligibility (Doelling et al., 2014; Zoefel and VanRullen, 2015). However, studies investigating linguistic tracking have either relied on non-naturalistic isochronous stimuli or failed to fully control for prosody. Therefore, it is still unclear whether low-frequency activity tracks linguistic structure during natural speech, where linguistic structure does not follow such a palpable temporal pattern. Here, we measured electroencephalography (EEG) and manipulated the presence of semantic and syntactic information apart from the timescale of their occurrence, while carefully controlling for the acoustic-prosodic and lexical-semantic information in the signal. EEG was recorded while 29 adult native speakers (22 women, 7 men) listened to naturally spoken Dutch sentences, jabberwocky controls with morphemes and sentential prosody, word lists with lexical content but no phrase structure, and backward acoustically matched controls. Mutual information (MI) analysis revealed sensitivity to linguistic content: MI was highest for sentences at the phrasal (0.8-1.1 Hz) and lexical (1.9-2.8 Hz) timescales, suggesting that the delta-band is modulated by lexically driven combinatorial processing beyond prosody, and that linguistic content (i.e., structure and meaning) organizes neural oscillations beyond the timescale and rhythmicity of the stimulus. This pattern is consistent with neurophysiologically inspired models of language comprehension (Martin, 2016, 2020; Martin and Doumas, 2017) where oscillations encode endogenously generated linguistic content over and above exogenous or stimulus-driven timing and rhythm information.SIGNIFICANCE STATEMENT Biological systems like the brain encode their environment not only by reacting in a series of stimulus-driven responses, but by combining stimulus-driven information with endogenous, internally generated, inferential knowledge and meaning. Understanding language from speech is the human benchmark for this. Much research focuses on the purely stimulus-driven response, but here, we focus on the goal of language behavior: conveying structure and meaning. To that end, we use naturalistic stimuli that contrast acoustic-prosodic and lexical-semantic information to show that, during spoken language comprehension, oscillatory modulations reflect computations related to inferring structure and meaning from the acoustic signal. Our experiment provides the first evidence to date that compositional structure and meaning organize the oscillatory response, above and beyond prosodic and lexical controls.

Differential changes in visual and auditory event-related oscillations in dementia with Lewy bodies.

OBJECTIVE: Aside from the cognitive impairment, patients with dementia with Lewy bodies (DLB) have a high frequency of visual hallucinations and a number of other vision-related symptoms, whereas auditory hallucinations are less frequent. To better understand the differential dysfunction of the visual network in DLB, we compared auditory and visual event-related potentials and oscillations in patients with DLB. METHODS: Event-related potentials elicited by visual and auditory oddball tasks were recorded in 23 patients with DLB and 22 healthy controls and analyzed in time and time-frequency domain. RESULTS: DLB patients had decreased theta band activity related to both early sensory and later cognitive processing in the visual, but not in the auditory task. Patients had lower delta and higher alpha and beta bands power related to later cognitive processing in both auditory and visual tasks. CONCLUSIONS: In DLB visual event-related oscillations are characterized by a decrease in theta and lack of inhibition in alpha bands. SIGNIFICANCE: Decreased theta and a lack of inhibition in alpha band power might be an oscillatory underpinning of some classical DLB symptoms such as fluctuations in attention and high-level visual disturbances and a potential marker of dysfunction of the visual system in DLB.

Changes in cross-frequency coupling following closed-loop auditory stimulation in non-rapid eye movement sleep.

Regional changes of non-rapid eye movement (NREM) sleep delta and sigma activity, and their temporal coupling have been related to experience-dependent plastic changes during previous wakefulness. These sleep-specific rhythms seem to be important for brain recovery and memory consolidation. Recently, it was demonstrated that by targeting slow waves in a particular region at a specific phase with closed-loop auditory stimulation, it is possible to locally manipulate slow-wave activity and interact with training-induced neuroplastic changes. In our study, we tested whether closed-loop auditory stimulation targeting the up-phase of slow waves might not only interact with the main sleep rhythms but also with their coupling within the circumscribed region. We demonstrate that while closed-loop auditory stimulation globally enhances delta, theta and sigma power, changes in cross-frequency coupling of these oscillations were more spatially restricted. Importantly, a significant increase in delta-sigma coupling was observed over the right parietal area, located directly posterior to the target electrode. These findings suggest that closed-loop auditory stimulation locally modulates coupling between delta phase and sigma power in a targeted region, which could be used to manipulate sleep-dependent neuroplasticity within the brain network of interest.

Destabilization of light NREM sleep by thalamic PLCß4 deletion impairs sleep-dependent memory consolidation.

Sleep abnormality often accompanies the impairment of cognitive function. Both rapid eye movement (REM) and non-REM (NREM) sleep have associated with improved memory performance. However, the role of composition in NREM sleep, consisting of light and deep NREM, for memory formation is not fully understood. We investigated how the dynamics of NREM sleep states influence memory consolidation. Thalamocortical (TC) neuron-specific phospholipase C ß4 (PLCß4) knockout (KO) increased the total duration of NREM sleep, consisting of destabilized light NREM and stabilized deep NREM. Surprisingly, the longer NREM sleep did not improve memory consolidation but rather impaired it in TC-specific PLCß4 KO mice. Memory function was positively correlated with the stability of light NREM and spindle activity occurring in maintained light NREM period. Our study suggests that a single molecule, PLCß4, in TC neurons is critical for tuning the NREM sleep states and thus affects sleep-dependent memory formation.

Neurofeedback for tinnitus: study protocol for a randomised controlled trial assessing the specificity of an alpha/delta neurofeedback training protocol in alleviating both sound perception and psychological distress in a cohort of chronic tinnitus sufferers.

BACKGROUND: Tinnitus is a particularly common condition and can have debilitating psychological consequences for certain people. Although several interventions have been helpful in teaching individuals to better cope with tinnitus, no cure exists at present. Neurofeedback is an emerging treatment modality in tinnitus. Previous studies, utilising an alpha/delta training protocol, have shown promise. However, they were characterised by small sample sizes and a lack of neurofeedback control conditions. Therefore, the aim of this study is to investigate whether an alpha/delta neurofeedback training protocol, compared to beta/theta neurofeedback or a diary control group, is effective in reducing not only the tinnitus sound perception but also the psychological symptoms associated with the condition. METHODS: The study is designed as a three-armed randomised controlled trial. Participants are randomly assigned to a) an established neurofeedback protocol for tinnitus (alpha/delta training), b) an active control group (beta/theta training) or c) a diary control group. In the 4-week intervention period, participants in both neurofeedback groups undergo 10 sessions, whereas participants in the diary control group complete a bi-weekly diary. The primary outcomes are between group differences in tinnitus sound perception change, as measured with the Tinnitus Magnitude Index (TMI), and changes in tinnitus distress, measured with the Tinnitus Handicap Inventory (THI), 4 weeks after the start of the intervention. Secondary outcome measures include changes in tinnitus distress, sleep quality, depressive symptoms and whether neurofeedback leads to specific power changes in the trained frequency bands. DISCUSSION: This is the first randomised controlled trial examining the efficacy of an alpha/delta neurofeedback training protocol in reducing tinnitus sound perception and the distress associated with the condition. Compared to former studies, the present study is designed to assess both the specificity of an alpha/delta neurofeedback training protocol by including an active comparator and beta/theta neurofeedback training, in addition to controlling for placebo effects by the inclusion of a diary control group. This study aims to contribute to an understanding of the influences of both specific and non-specific effects in neurofeedback treatment for tinnitus. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03550430. Registered on 27 May 2018.

Prominence of delta oscillatory rhythms in the motor cortex and their relevance for auditory and speech perception.

In the motor cortex, beta oscillations (∼12-30 Hz) are generally considered a principal rhythm contributing to movement planning and execution. Beta oscillations cohabit and dynamically interact with slow delta oscillations (0.5-4 Hz), but the role of delta oscillations and the subordinate relationship between these rhythms in the perception-action loop remains unclear. Here, we review evidence that motor delta oscillations shape the dynamics of motor behaviors and sensorimotor processes, in particular during auditory perception. We describe the functional coupling between delta and beta oscillations in the motor cortex during spontaneous and planned motor acts. In an active sensing framework, perception is strongly shaped by motor activity, in particular in the delta band, which imposes temporal constraints on the sampling of sensory information. By encoding temporal contextual information, delta oscillations modulate auditory processing and impact behavioral outcomes. Finally, we consider the contribution of motor delta oscillations in the perceptual analysis of speech signals, providing a contextual temporal frame to optimize the parsing and processing of slow linguistic information.

Implicit temporal predictability enhances pitch discrimination sensitivity and biases the phase of delta oscillations in auditory cortex.

Can human listeners use implicit temporal contingencies in auditory input to form temporal predictions, and if so, how are these predictions represented endogenously? To assess this question, we implicitly manipulated temporal predictability in an auditory pitch discrimination task: unbeknownst to participants, the pitch of the standard tone could either be deterministically predictive of the temporal onset of the target tone, or convey no predictive information. Predictive and non-predictive conditions were presented interleaved in one stream, and separated by variable inter-stimulus intervals such that there was no dominant stimulus rhythm throughout. Even though participants were unaware of the implicit temporal contingencies, pitch discrimination sensitivity (the slope of the psychometric function) increased when the onset of the target tone was predictable in time (N = 49, 28 female, 21 male). Concurrently recorded EEG data (N = 24) revealed that standard tones that conveyed temporal predictions evoked a more negative N1 component than non-predictive standards. We observed no significant differences in oscillatory power or phase coherence between conditions during the foreperiod. Importantly, the phase angle of delta oscillations (1-3 Hz) in auditory areas in the post-standard and pre-target time windows predicted behavioral pitch discrimination sensitivity. This suggests that temporal predictions are encoded in delta oscillatory phase during the foreperiod interval. In sum, we show that auditory perception benefits from implicit temporal contingencies, and provide evidence for a role of slow neural oscillations in the endogenous representation of temporal predictions, in absence of exogenously driven entrainment to rhythmic input.

Neural Correlates of Music Listening and Recall in the Human Brain.

Previous neuroimaging studies have identified various brain regions that are activated by music listening or recall. However, little is known about how these brain regions represent the time course and temporal features of music during listening and recall. Here we analyzed neural activity in different brain regions associated with music listening and recall using electrocorticography recordings obtained from 10 epilepsy patients of both genders implanted with subdural electrodes. Electrocorticography signals were recorded while subjects were listening to familiar instrumental music or recalling the same music pieces by imagery. During the onset phase (0-500 ms), music listening initiated cortical activity in high-gamma band in the temporal lobe and supramarginal gyrus, followed by the precentral gyrus and the inferior frontal gyrus. In contrast, during music recall, the high-gamma band activity first appeared in the inferior frontal gyrus and precentral gyrus, and then spread to the temporal lobe, showing a reversed temporal sequential order. During the sustained phase (after 500 ms), delta band and high-gamma band responses in the supramarginal gyrus, temporal and frontal lobes dynamically tracked the intensity envelope of the music during listening or recall with distinct temporal delays. During music listening, the neural tracking by the frontal lobe lagged behind that of the temporal lobe; whereas during music recall, the neural tracking by the frontal lobe preceded that of the temporal lobe. These findings demonstrate bottom-up and top-down processes in the cerebral cortex during music listening and recall and provide important insights into music processing by the human brain.SIGNIFICANCE STATEMENT Understanding how the brain analyzes, stores, and retrieves music remains one of the most challenging problems in neuroscience. By analyzing direct neural recordings obtained from the human brain, we observed dispersed and overlapping brain regions associated with music listening and recall. Music listening initiated cortical activity in high-gamma band starting from the temporal lobe and ending at the inferior frontal gyrus. A reversed temporal flow was observed in high-gamma response during music recall. Neural responses of frontal and temporal lobes dynamically tracked the intensity envelope of music that was presented or imagined during listening or recall. These findings demonstrate bottom-up and top-down processes in the cerebral cortex during music listening and recall.

Laminar specificity of oscillatory coherence in the auditory cortex.

Empirical evidence suggests that, in the auditory cortex (AC), the phase relationship between spikes and local-field potentials (LFPs) plays an important role in the processing of auditory stimuli. Nevertheless, unlike the case of other sensory systems, it remains largely unexplored in the auditory modality whether the properties of the cortical columnar microcircuit shape the dynamics of spike-LFP coherence in a layer-specific manner. In this study, we directly tackle this issue by addressing whether spike-LFP and LFP-stimulus phase synchronization are spatially distributed in the AC during sensory processing, by performing laminar recordings in the cortex of awake short-tailed bats (Carollia perspicillata) while animals listened to conspecific distress vocalizations. We show that, in the AC, spike-LFP and LFP-stimulus synchrony depend significantly on cortical depth, and that sensory stimulation alters the spatial and spectral patterns of spike-LFP phase-locking. We argue that such laminar distribution of coherence could have functional implications for the representation of naturalistic auditory stimuli at a cortical level.