Publications using TDT

Reduction in neuronal firing from wake to sleep, i.e., sleep firing rate homeostasis (sFRH), is essential for restorative sleep. Sleep dysfunction is common in Parkinson's disease (PD), but sFRH has not been investigated. Here, using a within-subject design in the nonhuman primate model of PD, we report that thalamocortical sFRH is disrupted in parkinsonism. These findings can inform therapeutic approaches tailored to normalize sFRH and reestablish restorative sleep in PD.

Purpose Sound pressure recordings at different positions at the head such as ear canal, nasal cavity, or on the skin are effective tools to verify, fit, or follow up the output of bone conduction devices (BCDs) intra- and post-operatively. Here, we investigated the possibility of using a surface microphone (SM) as a non-invasive alternative to laser Doppler vibrometry (LDV) measuring cochlear promontory (CP) vibrations in human heads. Methods A percutaneous BCD (Ponto system) was implanted at the standard position in five human (four males/one female) cadaver heads (ten ears). CP vibration was measured using LDV in response to the BCD stimulation. Simultaneously, the sound pressure level (SPL) emitted by the skin was measured by the SM attached to the forehead of the specimens. A linear regression model estimated the vibration amplitudes based on the measured SPL. Results A frequency-independent linear regression between recorded SM SPL and CP velocity showed a significant correlation (slope = 1.012; r 2 = 0.535, p < 0.001). An enforced fixed slope (constant = 166.7 dB) of one resulted in a mean absolute error of MAE = 7.7 ± 2.7 dB across frequencies. Although the initial linear model with a fixed slope of one showed frequency-dependent deviations, applying a frequency-specific correction significantly improved the prediction accuracy ( r 2 = 0.557, MAE = 6.5 ± 1.5 dB). Conclusion Microphone-based recording of acoustic surface emissions offers a non-invasive alternative to LDV to assess BCD output.

Background: Otitis media (OM) is an inflammatory disease of the middle ear characterized by mucosal remodeling, effusion, and conductive hearing loss. Although antibiotics and surgical procedures remain standard treatments, their efficacy is often limited by recurrence, antibiotic resistance, and chronic progression. Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neuromodulatory technique that activates the cholinergic anti-inflammatory pathway through α7 nicotinic acetylcholine receptor (α7nAChR) signaling. This study aimed to evaluate the anti-inflammatory effects of taVNS in a lipopolysaccharide (LPS)-induced mouse model of acute otitis media (AOM) and to assess whether these effects may involve α7nAChR-dependent mechanisms. Methods: AOM was induced by transtympanic injection of LPS in BALB/c mice, followed by taVNS applied to the auricular concha using biphasic square pulses (0.3 mA, 20 Hz, 200 μs). Methyllycaconitine, a selective α7nAChR antagonist, was administered to assess receptor involvement. Auditory function, tympanic membrane morphology, and mucosal changes were assessed through auditory brainstem response testing, otoscopic imaging, and histological analysis. Cytokine levels in middle ear effusion and serum were quantified by ELISA, while inflammatory gene and protein expression were analyzed using qPCR and Western blotting. Statistical analyses were performed using one-way ANOVA or Kruskal-Wallis tests with post hoc comparisons. Results: taVNS significantly improved hearing thresholds and reduced mucosal thickening and goblet cell hyperplasia in AOM mice. It markedly decreased tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 levels in middle ear effusion, and mechanistically, this anti-inflammatory effect was associated with suppression of NF-κB activation without altering TLR4 or MYD88 expression. These effects were abolished by methyllycaconitine pretreatment. taVNS also reduced spleen enlargement and systemic cytokine concentrations, indicating modulation of both local and systemic inflammation. Conclusions: taVNS was associated with attenuation of LPS-induced acute otitis media and reduced NF-κB activation and downstream cytokine expression in a manner consistent with the involvement of α7nAChR-related signaling. By attenuating excessive inflammatory responses, taVNS was associated with improved auditory function and reduced middle ear injury, suggesting its potential as a non-invasive therapeutic strategy for LPS-induced acute otitis media.

How positive and negative affective stimuli interact in the brain to influence behavioral outcomes remains poorly understood. Here, we show that recall of a positively valenced reward-associated cue (reward-conditioned stimulus, CS Rew +) can prevent or reverse fear generalization in mice. Modification of generalized fear by recall of a CS Rew + is dependent on the midbrain dopamine system and the regulation of discriminatory fear encoding by the central amygdala (CeA). Precisely timed, transient elevations in dopamine are necessary to reverse fear generalization and nondiscriminatory fear encoding in the CeA. Recall of a positive association is also effective at enhancing the extinction of a conditioned fear response in a dopamine-dependent manner. These data demonstrate that recall of a positive experience can be an effective means to suppress generalized fear and show that dopamine projections to the CeA are an important neural substrate for this phenomenon.

Many people have trouble understanding speech in noisy environments despite normal audiometric thresholds, a condition referred to as “hidden hearing loss.” A leading hypothesis attributes this deficit to inner hair cell synaptic pathology (cochlear synaptopathy), which can persist after recovery from noise-induced temporary elevation of audiometric thresholds. This pathology impairs the temporally precise sound encoding necessary for spatial hearing, but direct evidence in primates, human or nonhuman, is lacking. Here, we show that a single noise exposure, producing only a temporary threshold elevation, induced long-lasting alterations in synaptic morphology, without synapse loss, resulting in persistent spatial hearing deficits for up to 11 months post-exposure in nonhuman primates of both sexes. These perceptual deficits were accompanied by a reduction in a neurophysiological measure of binaural processing - the binaural interaction component (BIC) of the auditory brainstem response (ABR). Both behavioral and neural deficits persisted despite full recovery of audiometric thresholds. Together, these findings provide the first evidence in primates that noise exposure disrupts spatial hearing and binaural neural circuit function without loss of hair cells or synapses. Because spatial hearing tests and the ABR/BIC are clinically accessible, this work also establishes translational biomarkers for early neural dysfunction underlying hidden hearing loss.

Humans and other animals can solve new problems, even on the first attempt. This capacity to generate novel problem-solving behavior has been hypothesized to depend on brain mechanisms for recombining units of knowledge using systems of procedural rules, or grammars . Yet, whether and how the brain represents and implements grammars remains unclear, in large part due to the lack of neural recordings (typically performed in animal models) during grammar-based problem solving (typically studied in humans). Here, we address that gap, and in turn identify an underlying neural basis of grammatical behavior. We designed a visual–motor construction task in which macaque monkeys trace complex, often novel, geometric figures by generating a sequence of strokes, each a distinct shape, like a circle, dash, or chevron (action symbols 1 ). Critically, sequencing was guided by a learned hierarchical action grammar A n B m C k , meaning “repeat shape A, then repeat shape B, then repeat shape C”, where the number of repetitions (n, m, and k) varied across problems. Behavior was internally generated (no cues guiding stroke order), problem-directed (to construct a specific image), and exhibited zero-shot generalization (successful on the first trial for novel problems, including harder ones)--key hallmarks of grammar use. To identify underlying neural substrates, we recorded from multiple frontal cortical areas previously implicated in rule use or action sequencing. Activity during drawing encoded key structural properties of the action grammar: (i) shape index (A, B, C), (ii) abstract role (e.g., the role A independent of the specific shape), and (iii) ordinal position within a shape repeat. Moreover, all three properties were strongest in a single region, the pre-supplementary motor area (preSMA). We suggest the possibility that this conjunction of representations is a signature of an implementation of an iterative algorithm resembling a “for-loop” program: internally tracking how many repetitions remain for each shape index and switching to the next when complete. Our study establishes a paradigm for studying the neural basis of grammar-guided novel behavior and identifies in preSMA a dynamic representation of grammatical structure supporting such behavior.

Proper orientation of the apical cytoskeleton in auditory and vestibular hair cells is essential for their sensory function. A recently identified regulator of hair cell orientation is the G protein-coupled receptor GPR156, which signals through inhibitory heterotrimeric G proteins. In hair cells expressing the transcription factor EMX2, GPR156 is apically enriched and polarized at cell junctions. There, GPR156 signaling reverses the interpretation of tissue-level core planar cell polarity cues, effectively reversing the orientation of Emx2 -positive compared to Emx2 -negative hair cells. This mechanism establishes key anatomical features, such as the correct alignment of auditory outer hair cells and the line of polarity reversal in the otolith organs of the vestibular system. Null mice with constitutive Gpr156 inactivation exhibit severe hearing loss, mirroring congenital hearing impairment in human patients with homozygous GPR156 variants. These null mutants also display impaired swimming and vestibulo-ocular reflexes, although the nature of these vestibular deficits differs from those reported in Emx2 mutants. Here, to determine the extent to which functional deficits arise from hair cell misorientation, we conditionally inactivated Gpr156 in postmitotic hair cells in the inner ear. This targeted deletion approach recapitulated the misorientation phenotype observed in null mutants. Notably, 30–40% of cochlear and utricular hair cells affected in the null background retained normal orientation in conditional mutants, likely due to the later timing of Gpr156 inactivation. Despite reduced efficiency, conditional mutants exhibited similar, albeit predictably milder, auditory and vestibular dysfunction. As hair cells can carry out mechano-electrical transduction without GPR156, we conclude that sensory deficits mainly result from its essential role in hair cell orientation.

Music listening is one of the most compelling and rewarding activities humans engage in spontaneously. But what exactly catches people”s attention when listening to music remains unclear. Musicologists have argued that tension - release dynamics in music constitute crucial features of the listening experience. They arise from the intertwining of different low-level and high-level features and sit at the core of music enjoyment by engaging listeners dynamically. This study aims to characterize the relationship between tension dynamics and engagement during naturalistic music listening. Using canonical correlation analysis, we decoded the music envelope from EEG and ECoG responses and found that musical tension patterns, as reported by listeners, were predictive of fluctuations in the coupling between the music and the neural response. Importantly, tension dynamics were significantly correlated with neural measures of envelope tracking even after controlling for loudness and musical expectations, confirming the specific and crucial role of musical tension in engaging listeners. These results shed new light on how musical structure gives rise to internal response modulations that, in turn, dynamically reflect musical engagement. This interplay may underlie the pervasive and emotionally rewarding nature of music. Significance Statement This work addresses a fundamental question in cognition: how engagement dynamically modulates complex auditory input processing. We investigate this issue within the well-controlled yet ecologically valid context of music perception. At the core of the musical experience lies the perception of tension – the shifting sense of expectancy, instability, and resolution that guides listening across time. We show that fluctuations in musical tension, shaped by musical structure, reliably predict modulations of auditory engagement, thereby illuminating an understudied phenomenon: what makes music engaging.

Hypothesis: In our study, we investigated the ototoxic interaction of Janus kinase (JAK) inhibition in combination with aminoglycosides. Background: The therapeutic landscape of JAK inhibitors has undergone a significant transformation since 2018, characterized by a rapid increase in FDA approvals for this class of drugs. Initially approved for conditions like myelofibrosis and polycythemia vera, the indications have expanded to include several inflammatory conditions, such as psoriatic arthritis, ulcerative colitis, and rheumatoid arthritis, leading to a substantial increase in patients exposed to these therapies. The potential interactions of this drug class with ototoxins are unknown. Methods: C57Bl/6N mice corrected for Cadherin23 (Cdh23 tm2.1/kjn ) were treated with kanamycin (KM), (500 mg/kg, subcutaneously, twice daily for 14 d) either alone or with lipopolysaccharide (LPS) (1 mg/kg, intraperitoneally, 3 times during the treatment) to mimic inflammation from gram-negative infections. A separate group also received momelotinib (MMB), a dual JAK1/JAK2 inhibitor, at 50 mg/kg or 20 mg/kg by oral gavage twice daily for 14 days alongside KM and LPS. Hearing function was assessed through auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE), while cochlear damage and hair cell loss were evaluated using whole mount staining for phalloidin and myosin 7a. Results: Inhibition of JAK1 and JAK2 by MMB caused a substantial increase in the hearing loss and cochlear damage in animals exposed KM and LPS as measured by ABR, DPOAE, and outer hair cell (OHC) counts. Conclusion: JAK1 and JAK2 inhibition worsens cochlear damage in mice exposed to aminoglycosides.

Background With age, even mild acoustic injuries can accumulate - ultimately leading to a characteristic clinical picture of age-related hearing loss with the risk of cognitive decline. Age-related hearing loss is currently attributed to the loss of a most vulnerable auditory fiber type contributing to hearing in background noise. Here, we investigated the potential of a new drug, a more stable chemical variant of Dendrogenin B (DX243) that is predicted to display a protective function on neurite outgrowth, rather than on cell survival. Methodology In the rat animal model, DX243 was tested on hearing thresholds, cortical local field potentials (LFP), auditory steady-state responses (ASSR), auditory brainstem responses (ABR), growth function of notched-noise stimuli, inner hair cell (IHC) ribbon numbers, and multi-click pulse responses (MCP) before and after auditory trauma (AT). Results No auditory evoked LFP response changes were seen in the prefrontal cortex, visual cortex, or hippocampus. In contrast, a permanent decline of auditory evoked LFP amplitudes in the auditory cortex (AC) was measured 2 weeks after AT. Daily injection of DX243 for 2 weeks prevented the AT-induced decline in LFP activity, a protective effect that continued for 6 weeks following the final injection. Through a protective effect of DX243 on a trauma-induced decline of LFP in response to amplitude-modulated tones >80 Hz, a subcortical origin of the drug-effect was suggested. DX243 showed no effect on hearing sensitivity and did not affect subcortical processing of sound features that depend on phase-locking at the stimulus onset (e.g., near-threshold ASSR responses, close-to-threshold ABR growth functions, or spontaneous cortical LFP responses). However, with the same dose-response dependency as shown for cortical LFP effects, DX243 significantly protected from AT-induced decreases in ABR growth functions for loud sound stimuli and in background noise, protected from AT-induced loss of IHC ribbons and AT-induced decline of fast ABRs with decreasing time intervals. Conclusion These findings suggest DX243 as a novel neuroprotective drug, that specifically protects auditory fibers contributing to the coding of the temporal envelope and detection of tones in masking noise, tasks of our auditory senses, both of which, if they fail, lead to age-related speech-in-noise comprehension deficits.

Introduction The abrupt cessation of chronic benzodiazepine administration is associated with the development of withdrawal symptoms like increased susceptibility to seizures or seizure development in both animals and humans. Although withdrawal phenomena have been studied in detail in adult animals, information about their development and nature in the immature brain is lacking. Substantial experimental evidence suggests that exposure to BZDs early in life permanently alters brain circuitry and functions. However, the possible long-term modification of seizure propensity has not yet been studied. Methods Clonazepam (CZP) was injected into rat pups daily at a dose of 1 mg/kg for five consecutive days, starting on postnatal day 7 (P7) and continuing until P11. Seizure susceptibility was assessed using a pentylenetetrazol (PTZ)-induced seizure model. PTZ induces three types of seizures in rodents that differ by developmental profile and manifestations: convulsive myoclonic seizures (mS) and generalized tonic-clonic seizures (GTCS), and absence-like rhythmic spike-and-wave EEG activity (RMA). Seizures were induced with a single threshold dose of 50–60 mg/kg on days 2, 4, 7, 10, or 14, or with three additive doses of 20 mg/kg on days 7 and 14, or 3 months after the end of treatment. Convulsions accompanying mS and GTCS were detected behaviorally, and RMA was detected in EEG recordings. Results The effects of early-life CZP exposure on susceptibility to PTZ-induced seizures were highly dependent on the interval after treatment cessation and the seizure type. Cessation of CZP after a single PTZ threshold dose resulted in an increase in seizure severity compared to controls that was driven by an increased incidence of GTCS lasting 1 week (up to P18). Early-life CZP exposure led to decreased latency to the first RMA and increased RMA frequency after the first PTZ dose of 20 mg/kg in adult (P90) animals, but it did not change RMA parameters in juvenile rats. Conclusion Abruptly ceasing clonazepam administration in infant rats results in the development of withdrawal phenomena, represented by a striking increase in seizure propensity. Interestingly, transient augmentation of GABAergic inhibition during critical periods of synaptogenesis and neural network formation and maturation permanently modifies susceptibility to PTZ-induced epileptiform activity.

This work presents three open datasets featuring various levels of processing, containing neural recordings from the auditory cortex of rats. These recordings were obtained during experiments using the auditory oddball paradigm before, during and after the local microiontophoretic application of acetylcholine. The primary objective of these datasets is to investigate how the brain processes predictable versus unexpected auditory stimuli, and the role of cholinergic inputs during such processing. The data include multi-unit recordings of neuronal activity during the presentation of standard and deviant tones, classified by stimulus type and cortical sub-region. These resources enable quantitative investigations of deviance detection, stimulus-specific adaptation, cholinergic modulation and predictive-coding mechanisms at multiple temporal scales.

Gap junction Beta 2 Protein (GJB2, Connexin26, Cx26), the primary genetic cause of hereditary hearing loss (25%–50% of cases), has been exclusively regarded as forming an intercellular channel that mediates rapid communication. Here, we redefine its biological role by discovering its nuclear localization and direct transcriptional regulatory function in cochlear structure development. We demonstrate that Cx26 could aggregate in the nucleus of cochlear support cell and cell lines. Cx26 can bind to the promoter transcription start point of genomic DNA and directly regulate gene transcription, thus controlling the structural development of the tunnel of Corti during cochlear development. Further, we provide strategies based on mechanisms to promote the TC development and hearing rescue in Cx26 deficient cochlea, which has important implications for the discovery and development of treatment strategies for hearing loss caused by Cx26 deficiency.

Facial gestures are one fundamental set of communicative behaviors in primates, generated through the dynamic arrangement of many fine muscles. Anatomy shows that facial muscles are under direct control from multiple cortical regions, and studies of patients with focal lesions suggest that lateral frontal cortices control voluntary movements and medial emotional expressions. By directly measuring single-neuron activity from both sets of areas, we found that lateral and medial cortical face motor regions encode both types of gestures. They do so through area-specific temporal activity patterns, distinguishable well prior to movement onset. Our results show that cortical regions projecting in parallel downstream form a continuum of gesture coding, from dynamic to temporally stable, to produce socially appropriate motor outputs during communication.

Adeno-associated virus (AAV) unequivocally emerges as one of the most powerful and promising delivery vectors for gene therapy targeting hereditary hearing loss. Following AAV transduction in the inner ear, varying degrees of natural immune responses are triggered, primarily characterized by macrophage activation and the secretion of pro-inflammatory factors. Additionally, the production of neutralizing antibodies may affect the efficacy of gene therapy. To evaluate immune dynamics, we injected AAV1 and AAV-ie (capsids with distinct transfection efficiencies) into murine cochleae and analyzed temporal transcriptomic profiles. Our results demonstrate that both capsids induce immune activity but with critical temporal and intensity differences that AAV1 elicits significantly later and milder immune reactions compared to AAV-ie. These findings establish that dynamic cochlear gene expression profiles directly inform the selection of immunologically optimized AAV vectors to minimize adverse responses in future hereditary hearing loss gene therapies.

Excessive daytime sleepiness, i.e., the inability to sustain wakefulness during the day, is a common Parkinson's disease (PD) non-motor symptom. Elevated cortico-basal ganglia beta oscillatory power (8-35 Hz) is a pathophysiological signature of PD motor signs. The relationship between beta oscillatory power and daytime sleepiness, however, remains unclear. Here, we examined the relationship between beta power and daytime vigilance in parkinsonian nonhuman primates. We administered dopaminergic medication to alter cortico-basal ganglia beta power and measured its effect on daytime vigilance. The beta power from motor cortex (MC) and subthalamic nucleus (STN), and wake quantity were derived in the following conditions: OFF-medication, ON-medication, and decay of medication effect. STN low-beta (8-20 Hz) power negatively correlated with wake quantity, suggesting that elevated STN low-beta power could disrupt sustenance of wakefulness. The cortical low-beta power did not correlate with wakefulness. Interestingly, STN and MC high-beta (21-35 Hz) power positively correlated with wake quantity. Our data provide evidence for an association between beta power and daytime vigilance in parkinsonism in addition to its known relationship with PD motor signs. These findings could inform targeted treatments to promote wakefulness in PD by selectively suppressing (e.g., low-beta) and/or amplifying (e.g., high-beta) cortico-basal ganglia beta oscillatory power.

The Rubber Voice Illusion is an auditory analogue of the classic Rubber Hand Illusion, a “mind-trick” for the voice. When speakers hear a stranger’s utterances that are perfectly time‑locked and syllable‑matched to their own voice, many momentarily adopt that alien voice as self‑generated. We used this illusion to probe the integrity of predictive auditory mechanisms across the psychosis continuum. Sixty healthy adults completed three Talk‑Listen conditions while high‑density EEG was recorded: veridical (live playback of own voice), stranger‑match (congruent stranger voice) and stranger‑mismatch (incongruent). Behaviorally, only the congruent condition evoked a sense of Ownership and Agency over the stranger’s voice, paired with an upward shift in fundamental frequency toward the higher-pitched stranger voice - an implicit indication of voice adaptation. Neurophysiologically, the canonical speaking-induced suppression was replicated, and suppression was significantly smaller in participants who scored high on Peters et al. Delusions Inventory. In controls, greater pitch shift was associated with stronger neural suppression, suggesting a functioning self-suppression mechanism; conversely, in high-schizotypy individuals, the relationship reversed, despite pitch shifting toward the stranger’s pitch, they exhibited reduced suppression, indicating decoupling between motor output and sensory prediction. The study provides further evidence to the intricate relationship of neural mechanisms underlying self-generated actions with sensory processing in the psychosis continuum.

Cisplatin is a broad-spectrum anticancer agent. Its main side effect - ototoxicity - may impact the quality of patient’s life. Eleutheroside E (EE), the main active component of Acanthopanax , exhibits antioxidant and anti-inflammatory properties. This study investigates the protective effects of EE against cisplatin-induced ototoxicity and its underlying mechanisms. We use C57BL/6 J mice, the House Ear Institute-Organ of Corti 1 (HEI-OC1) cells, and cultured cochlear basement membranes in our experiments. We employ network pharmacology and 4D-FastDIA quantitative proteomic analysis. Our results demonstrate that Cisplatin significantly impairs auditory function in mice. However, EE co-treatment preserves auditory function across most measured frequencies, correlating with reduced damage to cochlear hair cells and spiral ganglion neurons(SGNs). Here, we show that EE attenuates cisplatin-induced pro-inflammatory responses and cellular pyroptosis, possibly via downregulation of the MAPK/NF-κB/NLRP3 signaling pathway. In conclusion, EE may offer a promising strategy for reducing Cisplatin’s ototoxicity without affecting its antitumor efficacy.

Visual selective attention is not wired into the brain fully formed and immutable but is acquired and refined as animals learn by interacting with their environment. Here we investigated this process by studying neuronal activity in the superior colliculus (SC) of male and female mice that learned different meanings of the same visual stimuli. We recorded spiking activity of neurons across the superficial and deep SC layers in three cohorts of mice, each trained using a tailored set of task rules that attributed different levels of behavioral relevance to the visual stimuli. Experimental conditions across the three tasks were carefully matched for visual stimulation and task engagement. We found that several markers of attention-related activity depended on the level of learned behavioral relevance, with the strongest effects in deep SC. First, for activity evoked by cue onset, visual responses in superficial SC were larger in animals that exhibited higher learned relevance. In deep SC, the presence of visual onset responses depended entirely on the learned behavioral relevance. Second, traditional attention-related modulation, defined as enhanced steady-state activity for the visual stimulus at the cued location, was also stronger with higher learned relevance, and this effect was limited to deep SC. Finally, the response to the visual change at the cued location was virtually absent when learned behavioral relevance was low but was prominent after visual training. Together, these results reveal that several fundamental features of attention-related modulation depend on the behavioral relevance learned through task-specific training, including aspects of stimulus-driven attention.

Context modulates neural processing of sensory stimuli. Neural responses are suppressed to stimuli that are typical in their context and augmented to stimuli that deviate from their context. The latter has been conceptualized as a “prediction error”, which can serve to enhance the salience, direct attention, or support learning about behaviorally relevant events. Predictive coding theories posit that prediction errors act to signal the difference between internal predictions and actual sensory input, yet most paradigms simultaneously alter both predictions and input, so cannot test for a true difference signal. Increased neural responses to deviants could, instead, encode generalized surprise or augmented bottom-up signaling. Here we compare neural responses to auditory stimuli across oddball paradigm variants. We found that responses of putative excitatory neurons in primary auditory cortex (A1) to auditory deviants contain frequency change information and a memory trace of contextual information. Interestingly, in a fixed-deviant oddball paradigm where predictions are altered but deviant input remains constant, neural response patterns encoded standard-to-deviant frequency difference. These results support the interpretation that A1 deviance detection can be interpreted as a sensory prediction error that represents the difference between prediction and sensory input, a corollary of the predictive coding framework.