Asymmetry in primary auditory cortex activity in tinnitus patients and controls.

Tinnitus is a bothersome phantom sound percept and its neural correlates are not yet disentangled. Previously published papers, using [(18)F]-fluoro-deoxyglucose positron emission tomography (FDG-PET), have suggested an increased metabolism in the left primary auditory cortex in tinnitus patients. This unilateral hyperactivity has been used as a target in localized treatments such as transcranial magnetic stimulation. The purpose of the current study was to test whether left-sided hyperactivity in the auditory cortex is specific to tinnitus or is a general characteristic of the auditory system unrelated to tinnitus. Therefore, FDG-PET was used to measure brain metabolism in 20 tinnitus patients and to compare their results to those in 19 control subjects without tinnitus. In contrast to our expectation, there was no hyperactivity associated with tinnitus. Nevertheless, the activity in the left primary auditory cortex was higher than in the right primary auditory cortex, but this asymmetry was present in both tinnitus patients and control subjects. In contrast, the lateralization in secondary auditory cortex was opposite, with higher activation in the right hemisphere. These data show that hemisphere asymmetries in the metabolic resting activity of the auditory cortex are present, but these are not associated with tinnitus and are a normal characteristic of the normal brain.

Neural correlates of human somatosensory integration in tinnitus.

Possible neural correlates of somatosensory modulation of tinnitus were assessed. Functional magnetic resonance imaging (fMRI) was used to investigate differences in neural activity between subjects that can modulate their tinnitus by jaw protrusion and normal hearing controls. We measured responses to bilateral sound and responses to jaw protrusion. Additionally we studied multimodal integration of somatosensory jaw protrusion and sound. The auditory system responded to both sound and jaw protrusion. Jaw responses were enhanced in the cochlear nucleus (CN) and the inferior colliculus (IC) in tinnitus patients. The responses of the auditory brain areas to jaw protrusion presumable account for the modulation of tinnitus as described by the patients. The somatosensory system responded to jaw protrusion and not to sound. These responses occurred both in subjects with tinnitus and controls. Unexpectedly, the cerebellum responded to sound in normal hearing subjects, but not in tinnitus patients. Together, these results provide a neurophysiological basis for the effect of jaw protrusion on tinnitus.

Neural activity underlying tinnitus generation: results from PET and fMRI.

Tinnitus is the percept of sound that is not related to an acoustic source outside the body. For many forms of tinnitus, mechanisms in the central nervous system are believed to play an important role in the pathology. Specifically, three mechanisms have been proposed to underlie tinnitus: (1) changes in the level of spontaneous neural activity in the central auditory system, (2) changes in the temporal pattern of neural activity, and (3) reorganization of tonotopic maps. The neuroimaging methods fMRI and PET measure signals that presumably reflect the firing rates of multiple neurons and are assumed to be sensitive to changes in the level of neural activity. There are two basic paradigms that have been applied in functional neuroimaging of tinnitus. Firstly, sound-evoked responses as well as steady state neural activity have been measured to compare tinnitus patients to healthy controls. Secondly, paradigms that involve modulation of tinnitus by a controlled stimulus allow for a within-subject comparison that identifies neural activity that may be correlated to the tinnitus percept. Even though there are many differences across studies, the general trend emerging from the neuroimaging studies, is that tinnitus in humans may correspond to enhanced neural activity across several centers of the central auditory system. Also, neural activity in non-auditory areas including the frontal areas, the limbic system and the cerebellum seems associated with the perception of tinnitus. These results indicate that in addition to the auditory system, non-auditory systems may represent a neural correlate of tinnitus. Although the currently published neuroimaging studies typically show a correspondence between tinnitus and enhanced neural activity, it will be important to perform future studies on subject groups that are closely matched for characteristics such as age, gender and hearing loss in order to rule out the contribution of these factors to the abnormalities specifically ascribed to tinnitus.

Functional imaging of unilateral tinnitus using fMRI.

CONCLUSIONS: This article shows that the inferior colliculus plays a key role in unilateral subjective tinnitus. OBJECTIVES: The major aim of this study was to determine tinnitus-related neural activity in the central auditory system of unilateral tinnitus subjects and compare this to control subjects without tinnitus. SUBJECTS AND METHODS: Functional MRI (fMRI) was performed in 10 patients (5 males) with unilateral tinnitus (5 left-sided, 5 right-sided) and 12 healthy subjects (6 males); both groups had normal hearing or mild hearing loss. fMRI experiments were performed using a 3T Philips Intera Scanner. Auditory stimuli were presented left or right and consisted of dynamically rippled broadband noise with a sound pressure level of 40 or 70 dB SPL. The responses of the inferior colliculus and the auditory cortex to the stimuli were measured. RESULTS: The response to sound in the inferior colliculus was elevated in tinnitus patients compared with controls without tinnitus.

Management of diabetes mellitus and hospital-related hyperglycemia in patients of a medical ICU, with the use of two "down-to-earth" protocols: a feasibility study.

OBJECTIVE: Optimal control of blood glucose in the ICU has been shown to significantly decrease mortality and morbidity of severely ill patients. The purpose of the present project was to develop and implement undemanding, "down-to-earth" protocols, enabling tight glucose control in critically ill patients, in the setting of a city hospital ICU with limited personnel and facilities. RESEARCH DESIGN AND METHODS: From January 2003 to January 2006, a total of 745 patients (3197 patient-days) were treated for hyperglycemia in our medical ICU. On July 2003 two different intensive insulin therapy protocols were implemented: A protocol of continuous intravenous insulin, including specific algorithms for calculation of initial insulin bolus, initial infusion rate and further adjustment plan, was used for patients with compromised peripheral tissue perfusion. For patients with stable circulation, a protocol of subcutaneous intensive insulin therapy, including a formula for calculation of daily insulin dosage in previously non-insulin-treated diabetics, was adopted. 134 patients were treated during the run-in phase of the project and 539 patients were treated during the main treatment phase. 72 patients treated for hyperglycemia in our ICU prior to the implementation of the two protocols (from January 2003 to July 2003) served as controls. RESULTS: After the implementation of the two protocols, a marked overall increase of normoglycemic blood glucose values (64.7% vs. 48.5%, P<0.001), a decrease of manifest hyperglycemias (6.4% vs. 17.4%, P<0.001) and an increase in hypoglycemic events (1.8% vs. 0.7%, P<0.001) was observed. Seven cases of severe hypoglycemia requiring glucose infusion were observed during the main treatment phase (0.3%). No hypoglycemia-associated deaths occurred. CONCLUSIONS: The combined implementation of the two protocols presents a simple, safe and effective way of pursuing normoglycemia in critically ill patients.

The behavior of evoked otoacoustic emissions during and after postural changes.

Click-evoked and stimulus frequency otoacoustic emissions (CEOAEs and SFOAEs, respectively) were studied in humans during and after postural changes. The subjects were tilted from upright to a recumbent position (head down 30 deg) and upright again. Due to the downward posture change, CEOAEs showed a phase increase (80 deg at 1 kHz) and a level decrease (0.5 at 1 kHz), especially for frequency components below 2 kHz. For SFOAEs, the typical ripple pattern showed a positive shift along the frequency axis, which can be interpreted as a phase shift of the inner-ear component of the microphone signal (90 deg at 1 kHz). This also occurred mainly for frequencies below 2 kHz. The altered posture is thought to cause an increase of the intracranial pressure, and consequently of the intracochlear fluid pressure, which results in an increased stiffness of the stapes system. The observed emission changes are in agreement with predictions from a model in which the stiffness of the cochlear windows was altered. For CEOAEs, the time to regain stability after a downward turn was of the order of 30 s, while this took about 20 s after an upward turn. For SFOAEs, this asymmetry was not found to be present (about 11 s, both for up- and downward turns).

The behavior of spontaneous otoacoustic emissions during and after postural changes.

Spontaneous otoacoustic emissions (SOAEs) were studied in humans during and after postural changes. The subjects were tilted from upright to a recumbent position (head down 30 degrees) and upright again in a 6-min period. The SOAEs were recorded continuously and analyzed off-line. The tilting caused a change in the SOAE spectrum for all subjects. Frequency shifts of 10 Hz, together with changes of amplitude (5 dB) and width (5 Hz), were typically observed. However, these changes were observed in both directions (including the appearance and disappearance of emission peaks). The most substantial changes occurred in the frequency region below 2 kHz. An increase of the intracranial pressure, and consequently of the intracochlear fluid pressure, is thought to result in an increased stiffness of the cochlear windows, which is probably mainly responsible for the SOAE changes observed after the downward turn. The time for the spectrum to regain stability after a postural change differed between the two maneuvers: 1 min for the downward and less than 10 s for the upward turn.

Audiogram fine structure and spontaneous otoacoustic emissions in patients with Menière's disease.

The incidence of and inter-relationship between audiogram fine structure and spontaneous otoacoustic emissions (SOAEs) was investigated in patients with Menière's disease. This project is a part of a comprehensive longitudinal study in which a range of tests of cochlear and vestibular function in patients who suffer from Menière's disease, is carried out and repeated over time. In this paper we present preliminary data from both ears (in most cases an affected and an unaffected ear) of 13 patients. The thresholds in these 26 ears ranged from normal to 80 dB HL. SOAEs could be measured in only four ears; these ears had near-normal thresholds. Data from seven ears had to be excluded because of the possibility of cross-over effects. In 16 out of the 19 remaining ears, audiogram fine structure was found. Our data confirm that (1) SOAEs correspond to behavioural sensitivity peaks. (2) There is no simple relationship between SOAE level and height of sensitivity peaks. (3) Sensitivity peaks may occur at frequencies without measurable SOAEs. In addition, our data show that: (1) Audiogram fine structure may occur in ears without observable SOAEs. (2) Fine structure can be present in ears without normal thresholds. (3) There is a weak tendency for fine structure to be more pronounced in ears with milder hearing loss.

A method to study the interaction between intraocular lens loops and anterior segment vasculature.

Gold-coated plastic casts of the anterior segment ocular microcirculation of the rabbit eye were studied by scanning electron microscopy to define the interaction between ciliary sulcus fixated intraocular lenses and the anterior segment vasculature. A detailed description of the technique is given. Interactions such as loop deformation by the tissue and loop erosion into the vascular tissue are shown. Possible clinical applications of this experimental model are discussed.