The neuroscience of tinnitus: Perspectives from human neuroimaging studies.

Conference (2012, November)

Investigating the tinnitus brain using resting-state fMRI

Conference (2012, June)

Auditory Resting-State Network Connectivity in Tinnitus: a Functionnal MRI Study.

in PLoS ONE (2012)

The underlying functional neuroanatomy of tinnitus remains poorly understood. Few studies have focused on functional cerebral connectivity changes in tinnitus patients. The aim of this study was to test ... [more ▼]

The underlying functional neuroanatomy of tinnitus remains poorly understood. Few studies have focused on functional cerebral connectivity changes in tinnitus patients. The aim of this study was to test if functional MRI ‘‘resting-state’’ connectivity patterns in auditory network differ between tinnitus patients and normal controls. Thirteen chronic tinnitus subjects and fifteen age-matched healthy controls were studied on a 3 tesla MRI. Connectivity was investigated using independent component analysis and an automated component selection approach taking into account the spatial and temporal properties of each component. Connectivity in extra-auditory regions such as brainstem, basal ganglia/NAc, cerebellum, parahippocampal, right prefrontal, parietal, and sensorimotor areas was found to be increased in tinnitus subjects. The right primary auditory cortex, left prefrontal, left fusiform gyrus, and bilateral occipital regions showed a decreased connectivity in tinnitus. These results show that there is a modification of cortical and subcortical functional connectivity in tinnitus encompassing attentional, mnemonic, and emotional networks. Our data corroborate the hypothesized implication of non-auditory regions in tinnitus physiopathology and suggest that various regions of the brain seem involved in the persistent awareness of the phenomenon as well as in the development of the associated distress. leading to disabling chronic tinnitus. [less ▲]

Novel association between vasoactive intestinal peptide and CRTH2 receptor in recruiting eosinophils: a possible biochemical mechanism for allergic eosinophilic inflammation of the airways.

in Journal of Biological Chemistry (2012)

We explored the relation between vasoactive intestinal peptide (VIP), CRTH2, and eosinophil recruitment. It is shown that CRTH2 expression by eosinophils from allergic rhinitis (AR) patients and ... [more ▼]

We explored the relation between vasoactive intestinal peptide (VIP), CRTH2, and eosinophil recruitment. It is shown that CRTH2 expression by eosinophils from allergic rhinitis (AR) patients and eosinophils cell line (Eol-1 cells) was up-regulated by VIP treatment. This was functional and resulted into exaggerated migratory response of cells against PGD2. Nasal challenge of AR patients resulted into significant increase of VIP contents in nasal secretion (ELISA), and the immunohistochemical studies of allergic nasal tissues, showed significant expression of VIP in association with intense eosinophil recruitment. Biochemical assays showed that VIP-induced eosinophils chemotaxis from AR patients and Eol-1 cells, was mediated through CRTH2 receptor. Cells migration against VIP was sensitive to protein kinase C (PKC) and protein kinase A (PKA) inhibition, but not to tyrosine kinase or P38 MAP-kinase inhibition, or calcium chelation. Western blot demonstrated a novel CRTH2 mediated cytosol to membrane translocation of PKC-epsilon, PKC-delta and PKA-alpha, gamma and IIalpha reg in Eol-1 cells upon stimulation with VIP. Confocal images and FACS demonstrated a strong association and co-localization between VIP peptide and CRTH2 molecules. Further, VIP induced PGD2 secretion from eosinophils. Our results demonstrate the first evidence of association between VIP and CRTH2 in recruiting eosinophils. [less ▲]

Resting-state activity in the tinnitus brain

Conference (2011, March)

2B4 (CD244) is involved in eosinophil adhesion and chemotaxis, and its surface expression is increased in allergic rhinitis after challenge.

in International Journal of Immunopathology and Pharmacology (2011), 24(4), 949-60

A role for the subtypes of CD2 Ig superfamily receptors has been recently demonstrated in eosinophilic inflammation in experimental asthma and atopic asthmatics. We investigated the functions of 2B4 ... [more ▼]

A role for the subtypes of CD2 Ig superfamily receptors has been recently demonstrated in eosinophilic inflammation in experimental asthma and atopic asthmatics. We investigated the functions of 2B4 (CD244) molecules in eosinophil adhesion and chemotaxis, and correlated the results to the pathophysiology of allergic rhinitis (AR). Herein, we show that agonistic stimulation of 2B4 by C1.7, the anti-human 2B4 functional grade purified antibody, resulted in significant increase of eosinophils and eosinophil cell line (Eol-1 cells) adhesion to collagen type IV, and random migration. These functions were associated with tyrosine kinase phosphorylation of several protein residues of low molecular weight. Flow cytometry (FACS) experiments demonstrated that Eol-1 cells, normal peripheral blood eosinophils and eosinophils from AR patients, express surface 2B4 molecules. In vitro AR model demonstrated that the CC-chemokine receptor CCR3 stimulation by eotaxin induced significant increase in the expression of surface 2B4 in eosinophils and Eol-1 cells. Immunofluorescence confocal microscopy images showed that eotaxin induces also redistribution of 2B4 molecules towards the pseudopods in eosinophils and Eol-1 cells, changing their shape. Blocking of 2B4 molecules by the corresponding neutralizing antibody inhibited eotaxin induced Eol-1-adhesion, chemotaxis and the cytoskeleton changes. Pretreatment of Eol-1 cells with 1 microM genistein blocked eotaxin-induced Eol-1 adhesion, chemotaxis and 2B4 up-regulated expression. In vivo correlation demonstrated the expression of 2B4 molecules in eosinophils from AR patients to be significantly increased, after nasal provocation challenge. These results identify a novel role for 2B4 molecules in eosinophil functional migratory response and may point to a novel tyrosine kinase-mediated ligation between CCR3 receptor and 2B4 co-receptor in eosinophil chemotaxis. If so, then 2B4 molecules would be a novel target for therapeutic modalities in diseases characterized by eosinophilia such as AR. [less ▲]

Resting-state auditory network in tinnitus: a fMRI study

Poster (2010, June)

Resting-state auditory network in tinnitus: a fMRI study

Conference (2010, March)

Implantation of Esterified Hyaluronic Acid in Microdissected Reinke's Space After Vocal Fold Microsurgery: Short- and Long-Term Results.

in Journal of Voice (2010)

In this study are reported the laryngeal and vocal results obtained after a microflap excision of benign vocal fold (VF) lesions and immediate implantation of esterified hyaluronic acid (EHA) in the ... [more ▼]

In this study are reported the laryngeal and vocal results obtained after a microflap excision of benign vocal fold (VF) lesions and immediate implantation of esterified hyaluronic acid (EHA) in the surgical wound. In a previous pilot study on 11 cases, we have shown an excellent tolerance of this bioimplant. The objectives are to confirm the innocuity of the technique, to demonstrate the laryngeal and vocal evolution at short and long term, and to evaluate the eventual positive impact of EHA implantation on the pliability of the superficial layer of the lamina propria (SLLP) and on voice. This is a prospective and comparative study on 83 patients suffering from various benign VF lesions. Thirty-three patients were implanted with EHA, whereas 50 patients did not undergo implantation at the end of the microsurgical procedure.All patients undergo rigid laryngoscopy and microflap excision procedure under general anesthesia. After freeing up of the Reinke's space and creation of a mucosal microflap, a few fibers of EHA are inserted in the surgical wound, before closure of the incision with fibrin glue. Serial laryngeal and vocal assessments are performed in all patients using videostroboscopy (Wolff and Xion), perceptual and objective voice evaluation (MDVP software, Kay Elemetrics), and phonatory function measurements (Aerophone II). Pre- and early postoperative means are compared by analysis of variance. Delayed and long-term evolution of laryngeal and vocal data are compared by means of nonparametric statistical methods. The longest follow-up in the implanted group is 4 years. Early postoperative results are similar in both groups: a significant improvement of a majority of laryngeal and vocal data is observed after microsurgery. In the long term, the two groups exhibit a different behavior: further improvement of voice, as an ongoing process, is only observed in the EHA implanted group, together with improvement of some videostroboscopic characteristics. The nonimplanted group remains stable, with no further improvement of the voice quality obtained after microsurgery. Excellent short- and long-term tolerance of EHA implantation is confirmed by this larger series. The use of EHA implant in microdissected SLLP is safe and leads to good laryngeal and vocal outcomes in the treated patients. More interestingly, treated cases exhibit a continuous improvement over a long period of time. [less ▲]

Hearing Preservation in Cochlear Implantation and Drug Treatment.

in Advances in Oto-Rhino-Laryngology (2010), 67

Insertion of an electrode array into the cochlea produces immediate damage to the inner ear, which is responsible for a hearing loss. In addition, a delayed hearing loss can be observed. In order to ... [more ▼]

Insertion of an electrode array into the cochlea produces immediate damage to the inner ear, which is responsible for a hearing loss. In addition, a delayed hearing loss can be observed. In order to maximize hearing preservation after insertion of an electrode and to enhance the performance of the cochlear implant, it has been proposed to deliver pharmacological agents to the inner ear. Molecules can be administered locally to the inner ear through a direct perilymphatic perfusion or through the round window membrane. These modalities of treatment have already been successfully applied to some patients with inner ear diseases. In this paper, we will review some basic aspects of drug delivery to the inner ear to prevent the degeneration of the neurosensory hair cells and auditory neurons, and the actual applicability to humans in order to maintain hearing function after the insertion of electrodes of a cochlear implant. [less ▲]