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Tziridis, K.

Publications and source records attributed to Tziridis, K..

9 recordsLinked to original sources

Chronic stress does not induce behavioural signs of tinnitus or cochlear synaptopathy in Mongolian gerbils

Tinnitus is commonly associated with psychosocial stress. However, it is unclear whether stress alone is sufficient to induce neural alterations resulting in tinnitus. In this study, we investigated the causal role of stress in tinnitus generation by experimentally isolating stress exposure as the sole independent variable in a well-established Mongolian gerbil model. Animals were subjected to repeated, inescapable electric foot shocks over three weeks to create a chronic, repeated stress paradigm. Behavioural, endocrine and histological measures were combined to assess tinnitus perception, stress system activation and cochlear synaptopathy. Repeated stress exposure reliably activated the endocrine stress response, as indicated by transient increases in serum cortisol following specific stress sessions. Basal cortisol levels returned to baseline values after the stress period. Behavioural assessment using gap-prepulse inhibition of the acoustic startle reflex revealed only isolated cases of behavioural signs of tinnitus, which occurred at a frequency consistent with false-positive detection and were evenly distributed between stress-exposed and control animals. Histological analyses revealed that ribbon synapse counts were preserved across the cochlea, with no evidence of stress-induced synaptopathy. No systematic relationships were observed between endocrine activation, behavioural outcomes and the number of inner hair cell ribbon synapses. Taken together, these findings suggest that, in the absence of acoustic trauma, repeated chronic stress is not sufficient to induce tinnitus or inner hair cell synaptopathy. These results argue against a primary causal role of stress alone in tinnitus generation and instead support models in which stress modulates symptom expression or perceptual salience in the context of pre-existing auditory dysfunction.

neuroscience↗

Prediction, Syntax and Semantic Grounding in the Brain and Large Language Models

Language comprehension involves continuous prediction of upcoming words, with syntactic structure and semantic meaning intertwined in the human brain. To date, few studies have used combined magnetoencephalography (MEG) and electroen-cephalography (EEG) measurements to investigate how syntactic processing, predictive coding, and semantic grounding interact in real time. Here we present the first combined MEG-EEG investigation of syntactic processing and semantic grounding under naturalistic conditions. Twenty-nine healthy participants listened to a German audio book while their neural responses were recorded. Event-related fields and event-related potentials for four word classes - nouns, verbs, adjectives, and proper nouns - showed highly reproducible, characteristic spatio-temporal signatures, including significant pre-onset activity for nouns, suggesting enhanced predictability of this word class. Source-space analyses revealed pronounced activation in the pre- and post-central gyri for nouns, suggesting a deeper semantic grounding of nouns in e.g. sensory experiences than verbs. To further investigate predictive mechanisms, we analyzed the hidden representations of the large language model Llama. By comparing the transformer-based representations to neural responses, we explored the relationship between computational language models and human brain activity, offering new insights into syntactic and semantic prediction. These findings highlight the power of simultaneous MEG-EEG recordings in unraveling the predictive, syntactic, and semantic mechanisms that underlie the comprehension of natural language.

neuroscience↗

Cognitive Dynamics of Verb-Particle Constructions: An Eye-Tracking Study

This study investigates the cognitive processing of verb-particle constructions (VPCs) using eye-tracking data analysis method to explore how English native speakers process different types of the sequence NP-verb-particle-NP during reading tasks. While previous research has focused on phrasal verbs, our study extends this examination to include patterns with prepositions, aiming to identify distinct cognitive engagement patterns and processing efficiencies associated with each. We employed the Provo Corpus to analyse eye movements while participants read sentences containing these constructions. we focused on metrics such as first fixation duration, gaze duration, go-past times, and total reading times. Our findings indicate similarities in the lexical verbs, and significant differences in particles, indicating how these two types of constructions are processed, with phrasal verbs sometimes processed more efficiently than the prepositional counterparts. This suggests that phrasal verbs might be more deeply entrenched in the linguistic repertoire of native speakers, possibly functioning as single lexical units. This research contributes to the understanding of complex structures processing and the cognitive mechanisms that support it, offering insights that could influence linguistic theory and language education.

neuroscience↗

Analyzing Differences in Processing Nouns and Verbs in the Human Brain using Combined EEG and MEG Measurements

Language and consequently the ability to transmit and spread complex information is unique to the human species. The disruptive event of the introduction of large language models has shown that the ability to process language alone leads to incredible abilities and, to some extent, to intelligence. However, how language is processed in the human brain remains elusive. Many insights originate from fMRI studies, as the high spatial resolution of fMRI devices provides valid information about where things happen. Nevertheless, the limited temporal resolution prevents us from gaining a deep understanding on the underlying mechanisms. In this study, we performed combined EEG and MEG measurements in 29 healthy right-handed human subjects during the presentation of continuous speech. We compared the evoked potentials (ERPs and ERFs) for different word types in source space and sensor space across the whole brain. We found characteristic spatio-temporal patterns for different word types (nouns, verbs) especially at latencies of 300ms to 1 s. This is further emphasized by the fact that we observe these effects in two pre-defined sub-samples of the data set (exploration and validation sample). We expect this study to be the starting point for further evaluations of semantic and syntactic processing in the brain.

neuroscience↗

Temporal and Hemispheric Dynamics in Neural Processing of Auditory and Speech Stimuli Across Linguistic Complexity: A MEG Source Space Study

In this study we investigated the neural processing of auditory stimuli of varying complexity: a non-linguistic (pure tone), a simple linguistic (phoneme) and a complex linguistic (word) stimulus. We recorded brain activity of 30 healthy, righthanded participants using magnetoencephalography (MEG), and compared the resulting evoked fields (ERFs) in source space in three different time intervals, i.e. early (0-250ms), mid (250-500ms) and late (500-750ms) responses. Our results reveal a bilateral activation during early response and rightlateralized activation in the mid-phase for all stimuli. Hoewever, the late response exhibited lateralization variations. The pure tone predominantly activated the right hemisphere, consistent with pitch processing theories. The phoneme primarily engaged the left hemisphere, supporting its role in phonemic processing. Notably, the word elicited activation in both hemispheres, reflecting phonemic processing on the left and stress patterns on the right. These findings highlight the intricate interplay between temporal processing and hemispheric lateralization in speech perception, emphasizing the importance of stimulus complexity and temporal dynamics in understanding auditory and speech processing.

neuroscience↗

Behavioral assessment of Zwicker tone percepts in rodents

The Zwicker tone illusion can serve as an interesting model for acute tinnitus, an auditory phantom percept still not fully understood. Recent mechanistic models suggest that the underlying neural mechanisms of both percepts are similar. However, to date it is not clear if animals do perceive the Zwicker tone at all, as up to now no behavioral paradigms are available to objectively assess the presence of this phantom percept. Here we introduce, for the first time, a modified version of the gap pre-pulse inhibition of the acoustic startle reflex (GPIAS) paradigm - usually used to assess the presence of a tinnitus percept in animals - to test if it is possible to induce a Zwicker tone percept in our rodent model, the Mongolian gerbil. Furthermore, we developed a new aversive conditioning shuttle box learning paradigm and compare the two approaches. We found a significant increase in the GPIAS effect when presenting a notched noise compared to flat white noise gap pre-pulse inhibition, indicating that the animals actually perceived a Zwicker tone. However, in the aversive conditioning learning paradigm, no clear effect could be observed in the discrimination performance of the tested animals. When investigating the CR+ responses, an effect of a possible Zwicker tone percept can be seen, i.e. animals show identical behavior as if a pure tone was presented, but the paradigm needs to be further improved.

neuroscience↗

The Stochastic Resonance model of auditory perception: A unified explanation of tinnitus development, Zwicker tone illusion, and residual inhibition.

Stochastic Resonance (SR) has been proposed to play a major role in auditory perception, and to maintain optimal information transmission from the cochlea to the auditory system. By this, the auditory system could adapt to changes of the auditory input at second or even sub-second timescales. In case of reduced auditory input, somatosensory projections to the dorsal cochlear nucleus would be disinhibited in order to improve hearing thresholds by means of SR. As a side effect, the increased somatosensory input corresponding to the observed tinnitus-associated neuronal hyperactivity is then perceived as tinnitus. In addition, the model can also explain transient phantom tone perceptions occurring after ear plugging, or the Zwicker tone illusion. Vice versa, the model predicts that via stimulation with acoustic noise, SR would not be needed to optimize information transmission, and hence somatosensory noise would be tuned down, resulting in a transient vanishing of tinnitus, an effect referred to as residual inhibition.

neuroscience↗

Acute and long-term circuit-level effects in the auditory cortex after sound trauma

Harmful environmental sounds are a prevailing source for chronic hearing impairments, including noise induced hearing loss, hyperacusis, or tinnitus. How these symptoms are related to pathophysiological damage to the sensory receptor epithelia and its effects along the auditory pathway, such as functional reorganizations in the auditory cortex (ACx), have been documented in numerous studies. An open question concerns the temporal evolution of maladaptive changes after damage and their manifestation in the balance between afferent thalamocortical input and corticocortical input to the ACx. To address this, we investigated the loci of plastic reorganizations across the tonotopic axis of the auditory cortex of male Mongolian gerbils (Meriones unguiculatus) acutely after a sound trauma and after several weeks. We used a laminar residual current-source density analysis to dissociate adaptations of intracolumnar input and horizontally relayed corticocortical input to synaptic populations across cortical layers in ACx. A pure tone-based sound trauma caused acute changes of subcortical inputs and corticocortical inputs at all tonotopic regions, particularly showing a broad elimination of tone-evoked inputs at tonotopic regions with a pre-trauma best frequency between 2-8 kHz. At other cortical sites, the overall columnar activity acutely decreased, while relative contributions of lateral corticocortical inputs increased. After 4-6 weeks, cortical activity to the altered sensory inputs showed a general increase of local thalamocortical input reaching levels higher than before the trauma. Hence, our results suggest a detailed mechanism for overcompensation of altered frequency input in the auditory cortex that relies on a changing balancing of thalamocortical and intracortical input and is confined to the spectral neighborhood of the trauma frequency. Significance statementHarmful noise exposure is a major anthropogenic cause of hearing disorders and is becoming an ever-increasing burden for human health and society. Damage to the sensory epithelia elicited by harmful sounds can subsequently lead to chronic hearing loss, hyperacusis or tinnitus. We still lack an understanding of the pathophysiological plastic processes and their evolution, particularly at the circuit level of the auditory cortex (ACx), which is fundamentally involved in auditory perception. We demonstrate that plastic changes in ACx after noise induced hearing loss (NIHL) occur over several weeks, and that changes in intracortical functional connectivity compensate the acute effects in the deafferentiated subcortical inputs. Such long-term changes may underlie the temporal evolution of hearing impairments or phantom sounds after NIHL.

neuroscience↗

Tinnitus development is associated with synaptopathy of inner hair cells in Mongolian gerbils

Human hearing loss (HL) is often accompanied by comorbidities like tinnitus which is affecting up to 15% of the adult population. Rodent animal studies could show that tinnitus may not only be a result of apparent HL due to cochlear hair cell damage but can also be a consequence of synaptopathy at the inner hair cells (IHC) already induced by moderate sound traumata. Here we investigate synaptopathy previously shown in mice in our animal model, the Mongolian gerbil, and relate it to behavioral signs of tinnitus. Tinnitus was induced by a mild monaural acoustic trauma leading to monaural noise induced HL in the animals, quantified by auditory brainstem response (ABR) audiometry. Behavioral signs of tinnitus percepts were detected by measurement of prepulse inhibition of the acoustic startle response in a gap-noise paradigm. 14 days after trauma, the cochleae of both ears were isolated and IHC synapses were counted within several spectral regions of the cochlea. Behavioral signs of tinnitus were only found in animals with IHC synaptopathy, independent of type of HL. On the other hand, animals with apparent HL but without behavioral signs of tinnitus showed a reduction in amplitudes of ABR waves I&II but no significant changes in the number of synapses at the IHC. We conclude - in line with the literature - that HL is caused by damage to the IHC or by other reasons but that the development of tinnitus, at least in our animal model, is closely linked to synaptopathy at the IHC.

neuroscience↗