Is the effect of tinnitus on auditory steady-state response amplitude mediated by attention?

Objectives: Auditory steady-state response (ASSR) amplitude enhancement effects have been reported in tinnitus patients. As ASSR amplitude is also enhanced by attention, the effect of tinnitus on ASSR amplitude could be interpreted as an effect of attention mediated by tinnitus. As N1 attention effects are significantly larger than those on the ASSR, if the effect of tinnitus on ASSR amplitude were due to attention, there should be similar amplitude enhancement effects in tinnitus for the N1 component of the auditory-evoked response. Methods: MEG recordings which were previously examined for the ASSR (Diesch et al., 2010a) were analyzed with respect to the N1m component. Like the ASSR previously, the N1m was analyzed in the source domain (source space projection). Stimuli were amplitude-modulated (AM) tones with one of three carrier frequencies matching the tinnitus frequency or a surrogate frequency 1½ octave above the audiometric edge frequency in controls, the audiometric edge frequency, and a frequency below the audiometric edge. Single AM-tones were presented in a single condition and superpositions of three AM-tones differing in carrier and modulation frequency in a composite condition. Results: In the earlier ASSR study (Diesch et al., 2010a), the ASSR amplitude in tinnitus patients, but not in controls, was significantly larger in the (surrogate) tinnitus condition than in the edge condition. Patients showed less evidence than controls of reciprocal inhibition of component ASSR responses in the composite condition. In the present study, N1m amplitudes elicited by stimuli located at the audiometric edge and at the (surrogate) tinnitus frequency were smaller than N1m amplitudes elicited by sub-edge tones both in patients and controls. The relationship of the N1m response in the composite condition to the N1m response in the single condition indicated that reciprocal inhibition among component N1m responses was reduced in patients compared against controls. Conclusions: In the present study, no evidence was found for an N1-amplitude enhancement effect in tinnitus. Compared to controls, reciprocal inhibition is reduced in tinnitus patients. Thus, as there is no effect on N1m that could potentially be attributed to attention, it seems unlikely that the enhancement effect of tinnitus on ASSR amplitude could be accounted for in terms of attention induced by tinnitus

Structural changes of the corpus callosum in tinnitus

Objectives: In tinnitus, several brain regions seem to be structurally altered, including the medial partition of Heschl's gyrus (mHG), the site of the primary auditory cortex. The mHG is smaller in tinnitus patients than in healthy controls. The corpus callosum (CC) is the main interhemispheric commissure of the brain connecting the auditory areas of the left and the right hemisphere. Here, we investigate whether tinnitus status is associated with CC volume. Methods: The midsagittal cross-sectional area of the CC was examined in tinnitus patients and healthy controls in which an examination of the mHG had been carried out earlier. The CC was extracted and segmented into subregions which were defined according to the most common CC morphometry schemes introduced by Witelson (1989) and Hofer and Frahm (2006). Results: For both CC segmentation schemes, the CC posterior midbody was smaller in male patients than in male healthy controls and the isthmus, the anterior midbody, and the genou were larger in female patients than in female controls. With CC size normalized relative to mHG volume, the normalized CC splenium was larger in male patients than male controls and the normalized CC splenium, the isthmus and the genou were larger in female patients than female controls. Normalized CC segment size expresses callosal interconnectivity relative to auditory cortex volume. Conclusion: It may be argued that the predominant function of the CC is excitatory. The stronger callosal interconnectivity in tinnitus patients, compared to healthy controls, may facilitate the emergence and maintenance of a positive feedback loop between tinnitus generators located in the two hemispheres

Magnetic and Electric Brain Activity Evoked by the Processing of Tone and Vowel Stimuli

Sustained magnetic and electric brain waves may reflect linguistic processing when elicited by auditory speech stimuli. In the present study, only in the latency interval subsequent to the N1m/N1 has a sensitivity of brain responses to features of speech been demonstrated. We conclude this from studying the auditory-evoked magnetic field (AEF) and the corresponding evoked potential (AEP) in response to vowels and a tone. Brain activity was recorded from the left and the right hemisphere of 11 subjects. Three aspects of transient activity were examined: (1) the amplitudes and source characteristics of the N1m component of the AEF; (2) the amplitudes and source characteristics of the sustained field (SF), and (3) the corresponding amplitude characteristics of the AEP. Sustained potential amplitudes and SF root mean square amplitudes, as well as the dipole strength of the SF source, were found to be larger for vowel-evoked signals than for signals elicited by the tone stimulus. The amplitude and dipole strength effects had an interaction with hemisphere, with larger interhemispheric differences for the vowel condition, as well as larger tone-vowel differences of these parameters in the speech-dominant left hemisphere. No statistically significant hemisphere-by-stimulus-type interactions were found in N1/N1m amplitudes and N1m source parameters

A novel mouse model of atherosclerotic plaque instability for drug testing and mechanistic/therapeutic discoveries using gene and microRNA expression profiling

Rationale: The high morbidity/mortality of atherosclerosis is typically precipitated by plaque rupture and consequent thrombosis. However, research on underlying mechanisms and therapeutic approaches is limited by the lack of animal models that reproduce plaque instability observed in humans. Objective: Development and utilization of a mouse model of plaque rupture that reflects the end stage of human atherosclerosis. Methods and Results: Based on flow measurements and computational fluid dynamics, we applied a tandem stenosis to the carotid artery of ApoE-/- mice on high fat diet. At 7 weeks postoperatively, we observed intraplaque hemorrhage in ~50% of mice, as well as disruption of fibrous caps, intraluminal thrombosis, neovascularization and further characteristics typically seen in human unstable plaques. Administration of atorvastatin was associated with plaque stabilization and down regulation of MCP-1 and ubiquitin. Microarray profiling of mRNA and microRNA and in particular its combined analysis demonstrated major differences in the hierarchical clustering of genes and microRNAs between non-atherosclerotic arteries, stable and unstable plaques and allows the identification of distinct genes/microRNAs, potentially representing novel therapeutic targets for plaque stabilization. The feasibility of the described animal model as a discovery tool was established in a pilot approach, identifying ADAMTS4 and miR-322 as potential pathogenic factors of plaque instability in mice and validated in human plaques. Conclusions: The newly described mouse model reflects human atherosclerotic plaque instability and represents a discovery tool towards the development and testing of therapeutic strategies aimed at preventing plaque rupture. Distinctly expressed genes and microRNAs can be linked to plaque instability