The effects of acute and chronic noise trauma on stimulus-evoked activity across primary auditory cortex layers.

Exposure to intense noise environments is a major cause of sensorineural hearing loss and auditory perception disorders, such as tinnitus and hyperacusis, which may have a central origin. The effects of noise-induced hearing loss on the auditory cortex have been documented in many studies. One limitation of these studies, however, is that the effects of noise trauma have been mostly studied at the granular layer (i.e, the main cortical recipient of thalamic input), while the cortex is a very complex structure, with six different layers each having its own pattern of connectivity and role in sensory processing. The present study aims to investigate the effects of acute and chronic noise trauma on the laminar pattern of stimulus-evoked activity in the primary auditory cortex of the anesthetized guinea pig. We show that acute and chronic noise trauma are both followed by an increase in stimulus-evoked cortical responses, mostly in the granular and supragranular layers. The cortical responses are more monotonic as a function of the intensity level after noise trauma. There was minimal change, if any, in local field potential (LFP) amplitude after acute noise trauma, while LFP amplitude was enhanced after chronic noise trauma. Finally, LFP and the current source density analysis suggest that acute but more specifically chronic noise trauma is associated with the emergence of a new sink in the supragranular layer. This result suggests that supragranular layers become a major input recipient. We discuss the possible mechanisms and functional implications of these changes.NEW & NOTEWORTHY Our study shows that cortical activity is enhanced after trauma and that the sequence of cortical column activation during stimulus-evoked response is altered, i.e. the supragranular layer becomes a major input recipient. We speculate that these large cortical changes may play a key role in the auditory hypersensitivity (hyperacusis) that can be triggered after noise trauma in human subjects.

Noise-Induced Hearing Loss Alters Potassium-Chloride CoTransporter KCC2 and GABA Inhibition in the auditory centers.

Homeostatic plasticity, the ability of neurons to maintain their averaged activity constant around a set point value, is thought to account for the central hyperactivity after hearing loss. Here, we investigated the putative role of GABAergic neurotransmission in this mechanism after a noise-induced hearing loss larger than 50 dB in high frequencies in guinea pigs. The effect of GABAergic inhibition is linked to the normal functioning of K+-Cl- co-transporter isoform 2 (KCC2) which maintains a low intracellular concentration of chloride. The expression of membrane KCC2 were investigated before after noise trauma in the ventral and dorsal cochlear nucleus (VCN and DCN, respectively) and in the inferior colliculus (IC). Moreover, the effect of gabazine (GBZ), a GABA antagonist, was also studied on the neural activity in IC. We show that KCC2 is downregulated in VCN, DCN and IC 3 days after noise trauma, and in DCN and IC 30 days after the trauma. As expected, GBZ application in the IC of control animals resulted in an increase of spontaneous and stimulus-evoked activity. In the noise exposed animals, on the other hand, GBZ application decreased the stimulus-evoked activity in IC neurons. The functional implications of these central changes are discussed.

Offset responses in primary auditory cortex are enhanced after notched noise stimulation.

Sensory "aftereffects" are a subgroup of sensory illusions that can be defined as an illusory phenomenon triggered after prolonged exposure to a given sensory inducer. These phenomena are interesting because they can provide insights into the mechanisms of perception. In auditory modality, there is a special interest in the so-called "Zwicker tone" (ZT), an auditory aftereffect triggered after the presentation of a notched noise (NN, broadband noise with a missing frequency band). The ZT has been considered a plausible model of a specific tinnitus subtype since it presents some key characteristics in common with tinnitus. Indeed, both the tinnitus percept and ZT can be triggered by a relative "sensory deprivation," and their pitch corresponds to the frequency region that has been sensory deprived. The effects of a NN presentation on the central auditory system are still barely investigated, and the mechanisms of the ZT are elusive. In this study, we analyzed the laminar structure of the neural activity in the primary cortex of anesthetized and awake guinea pigs during and after white noise (WN) and NN stimulation. We found significantly increased offset responses, in terms of both spiking activity and local field potential amplitude, after NN compared with WN presentation. The offset responses were circumscribed to the granular and upper infragranular layers (input layers) and were maximal when the neuron's best frequency was within or near the missing frequency band. The mechanisms of the offset response and its putative link with the ZT are discussed.NEW & NOTEWORTHY Notched noise (white noise with embedded spectral gap) causes significant excitatory offset responses in the auditory cortex of awake and anesthetized guinea pigs. The largest offset responses were located in the infragranular/granular layers, and current source density analysis revealed that offset responses were associated with an early current sink localized in the upper infragranular layers. We discuss the possibility that the offset responses might be associated with an auditory phantom percept (Zwicker tone).

Doctoral Studies as part of an Innovative Training Network (ITN): Early Stage Researcher (ESR) experiences.

Background: The Marie-Sklodowska-Curie Actions' (MSCA) Innovative Training Network (ITN) is a doctoral training programme jointly implemented by academic institutions and industries from countries across Europe and beyond. To our knowledge no study has examined the experience of students participating in MSCA-ITNs. This study aims to evaluate and report MSCA-ITN Early Stage Researcher (ESR) experiences. Methods: The Innovative Training Network - Evaluation Questionnaire (ITN-EQ) was developed to assess supervision, training, collaborations and experiences of ESRs and forwarded to two tinnitus-related ITNs and seven ITNs of other disciplines. Results: Key advantages identified included better career prospects, multidisciplinary research opportunities/collaborations, international exposure, personal/professional development, plus generous salaries and research budgets. However, lack of a common EU framework resulted in the experience being largely dependent on the host institution, country and supervisor. Moreover, managing the dual requirements of ITNs and host institutions while completing a three-year PhD seemed challenging for most ESRs. ESR involvement in workshop and training school planning was desirable. More than 80% of ESRs rated the overall ITN experience favourably and 98.3% would recommend the same to prospective PhD students. Conclusions: This report could provide valuable insights in planning and management of future ITNs and could assist prospective students in their decision of joining an ITN for their PhD.

Photoacoustic-guided focused ultrasound for accurate visualization of brachytherapy seeds with the photoacoustic needle.

An important problem in minimally invasive photoacoustic (PA) imaging of brachytherapy seeds is reflection artifacts caused by the high signal from the optical fiber/needle tip reflecting off the seed. The presence of these artifacts confounds interpretation of images. In this letter, we demonstrate a recently developed concept called photoacoustic-guided focused ultrasound (PAFUSion) for the first time in the context of interstitial illumination PA imaging to identify and remove reflection artifacts. In this method, ultrasound (US) from the transducer is focused on the region of the optical fiber/needle tip identified in a first step using PA imaging. The image developed from the US diverging from the focus zone at the tip region visualizes only the reflections from seeds and other acoustic inhomogeneities, allowing identification of the reflection artifacts of the first step. These artifacts can then be removed from the PA image. Using PAFUSion, we demonstrate reduction of reflection artifacts and thereby improved interstitial PA visualization of brachytherapy seeds in phantom and