Tinnitus Perception in Light of a Parietal Operculo-Insular Involvement: A Review.

In tinnitus literature, researchers have increasingly been advocating for a clearer distinction between tinnitus perception and tinnitus-related distress. In non-bothersome tinnitus, the perception itself can be more specifically investigated: this has provided a body of evidence, based on resting-state and activation fMRI protocols, highlighting the involvement of regions outside the conventional auditory areas, such as the right parietal operculum. Here, we aim to conduct a review of available investigations of the human parietal operculo-insular subregions conducted at the microscopic, mesoscopic, and macroscopic scales arguing in favor of an auditory-somatosensory cross-talk. Both the previous literature and new results on functional connectivity derived from cortico-cortical evoked potentials show that these subregions present a dense tissue of interconnections and a strong connectivity with auditory and somatosensory areas in the healthy brain. Disrupted integration processes between these modalities may thus result in erroneous perceptions, such as tinnitus. More precisely, we highlight the role of a subregion of the right parietal operculum, known as OP3 according to the Jülich atlas, in the integration of auditory and somatosensory representation of the orofacial muscles in the healthy population. We further discuss how a dysfunction of these muscles could induce hyperactivity in the OP3. The evidence of direct electrical stimulation of this area eliciting auditory hallucinations further suggests its involvement in tinnitus perception. Finally, a small number of neuroimaging studies of therapeutic interventions for tinnitus provide additional evidence of right parietal operculum involvement.

Tracking white-matter brain modifications in chronic non-bothersome acoustic trauma tinnitus.

Subjective tinnitus is a symptom characterized by the perception of sound with no external acoustic source, most often accompanied by co-morbidities. To date, the specific role of white matter abnormalities related to tinnitus reaches no consensus in the literature. The goal of this study was to explore the structural connectivity related to tinnitus percept per se, thus focusing on a specific population presenting chronic non-bothersome tinnitus of similar etiology (noise induced) without co-morbidities. We acquired diffusion-weighted images with high angular resolution in a homogeneous group of mildly impacted tinnitus participants (n = 19) and their matched controls (n = 19). We focused the study on two subsets of fiber bundles of interest: on one hand, we extracted the acoustic radiation and further included any intersecting fiber bundles; on the other hand, we explored the tracts related to the limbic system. We modeled the diffusion signal using constrained spherical deconvolution. We conducted a deep-learning based tractography segmentation and mapped Apparent Fiber Density (AFD) on the bundles of interest. C, as well as Fractional Anisotropy (FA) and FOD peak amplitude for comparison. Between group statistical comparison was performed along the 27 tracts of interest controlling for confounding hearing loss, tinnitus severity, and duration since onset. We tested a potential correlation with hearing loss, tinnitus duration and tinnitus handicap score along these tracts. In the tinnitus group, we observed increased AFD related to chronic tinnitus percept after acoustic trauma in two main white matter regions. First, in the right hemisphere, in the isthmus between inferior temporal and inferior frontal cortices, in the uncinate fasciculus (UF), and in the inferior fronto-occipital bundle (IFO). Second, in the left hemisphere, underneath the superior parietal region in the thalamo parietal tract and parieto-occipital pontine tract. Between-group differences in the acoustic radiations were not significant with AFD but were with FA. Furthermore, significant correlations with hearing loss were found in the left hemisphere in the inferior longitudinal fasciculus and in the fronto-pontine tract. No additional correlation was found with tinnitus duration nor with tinnitus handicap, as reflected by THI scores. The regions that displayed tinnitus related increased AFD also displayed increased FA. The isthmus of the UF and IFO in the right hemisphere appear to be involved with a number of neuropsychiatric and traumatic disorders confirming the involvement of the limbic system even in chronic non-bothersome tinnitus subjects, potentially suggesting a common pathway between these pathologies. White matter changes underneath the superior parietal cortex found here in tinnitus participants supports the implication of an auditory-somatosensory pathway in tinnitus perception.

Functional Connectivity in Chronic Nonbothersome Tinnitus Following Acoustic Trauma: A Seed-Based Resting-State Functional Magnetic Resonance Imaging Study.

Background: Tinnitus and its mechanisms are an ongoing subject of interrogation in the neuroscientific community. Although most current models agree that it encompasses multiple structures within and outside the auditory system, evidence provided in the literature suffers from a lack of convergence. To further our understanding of contributions to tinnitus lying outside the auditory system, we explored a new model based on a proprioceptive hypothesis specifically in subjects experiencing chronic nonbothersome tinnitus due to acoustic trauma. The present study addresses the role of the right operculum 3 (OP3) involved in this model. It also investigates classical models of tinnitus. Methods: A seed-based resting-state magnetic resonance imaging study explored the functional connectivity in an acoustic trauma group presenting slight to mild nonbothersome chronic tinnitus and compared it with a control group. Results: Group differences were found with two networks: with the sensorimotor-auditory and the frontoparietal, but not with the default mode network nor the limbic regions. In the auditory pathway, the inferior colliculus displayed group differences in connectivity with the right superior parietal lobule. Exploratory analysis elicited a significant increase in connectivity between two seeds in the right OP3 and two mirror regions of the dorsal prefrontal cortex, thought to correspond to the human homologue of the premotor ear-eye field bilaterally and the inferior parietal lobule involved in proprioception, in the tinnitus group. Conclusions: These new findings support the view that acoustic trauma tinnitus could bear a proprioceptive contribution and that a permanent cognitive control is required to filter out this chronic phantom percept.

Relationship Between Audio-Vestibular Functional Tests and Inner Ear MRI in Meniere's Disease.

OBJECTIVES: Meniere's disease is an inner ear disorder generally attributed to an endolymphatic hydrops. Different electrophysiological tests and imaging techniques have been developed to improve endolymphatic hydrops diagnosis. The goal of our study was to compare the sensitivity and the specificity of delayed inner ear magnetic resonance imaging (MRI) after intravenous injection of gadolinium with extratympanic clicks electrocochleography (EcochG), phase shift of distortion product otoacoustic emissions (shift-DPOAEs), and cervical vestibular-evoked myogenic potentials (cVEMP) for the diagnosis of Meniere's disease. DESIGN: Forty-one patients, with a total of 50 affected ears, were included prospectively from April 2015 to April 2016 in our institution. Patients included had definite or possible Meniere's disease based on the latest American Academy of Otolaryngology-Head and Neck Surgery guidelines revised in 2015. All patients went through delayed inner ear MRI after intravenous injection of gadolinium (three dimension-fluid attenuated inversion recovery sequences), pure-tone audiometry, extratympanic clicks EcochG, shift-DPOAEs, and cVEMP on the same day. Endolymphatic hydrops was graded on MRI using the saccule to utricle ratio inversion defined as when the saccule appeared equal or larger than the utricle. RESULTS: Abnormal EcochG and shift-DPOAEs in patients with definite Meniere's disease (DMD) were found in 68 and 64.5%, respectively. The two methods were significantly associated in DMD group. In DMD group, 25.7% had a positive MRI. The correlation between MRI versus EcochG and MRI versus shift-DPOAEs was not significant. MRI hydrops detection was correlated with hearing loss. Finally, 22.9% of DMD group had positive cVEMP. CONCLUSIONS: EcochG and shift-DPOAEs were both well correlated with clinical criteria of Meniere's disease. Inner ear MRI showed hydrops when hearing loss was higher than 35 dB. The shift-DPOAEs presented the advantage of a rapid and easy measurement if DPOAEs could be recorded (i.e., hearing threshold <60dB). In contrast, EcochG can be performed regardless of hearing loss. In combination with shift-DPOAEs, it enhances the chances to confirm the diagnosis with a better confidence.

Tinnitus and Associated Handicaps in the French Mountain Artillery: Assessment by the Tinnitus Handicap Inventory.

INTRODUCTION: Tinnitus and associated handicap related to acoustic trauma sequelae have never been assessed in the French artillery. Although impulsive noise exposure to firearms and canons are thought to increase prevalence of tinnitus among soldiers, recent studies demonstrating this fact are missing. MATERIALS AND METHODS: Here, a representative sample of 389 soldiers from an operational mountain artillery regiment was surveyed. Soldiers personally concerned by tinnitus were invited to fill in a questionnaire. We assessed tinnitus and the associated handicap using a French translation of the Tinnitus Handicap Inventory (THI). Questions about attention/concentration problems, impaired speech hearing and understanding, sleep disorders, social and familial tension, irritability, depression, and tiredness as linked to tinnitus were the core of the questionnaire. RESULTS: Soldiers that completed the THI (n = 73, 19%) had a mean THI score of 18 ± 17, this mean score corresponded to a mild handicap. At this grade, tinnitus should be easily masked and should not interfere with daily activities. The percentage of soldiers concerned by tinnitus was slightly higher in the older age class, but there was no significant difference of THI scores between the different age classes. The most reported handicaps were attention/concentration problems, impaired speech hearing, and understanding. Among the THI fillers, eight soldiers (11%) had THI scores >36, indicating a moderate to severe handicap. CONCLUSION: Despite a mild tinnitus handicap, the percentage of people concerned by tinnitus in this regiment is higher (19%) than that in the estimated percentage of general population of European countries (about 10%). It should be of interest to replicate this type of study from other regiments and from other countries. Education and good fitting of hearing protection for prevention of acoustic trauma sequelae should still be encouraged.

Specific activation of operculum 3 (OP3) brain region during provoked tinnitus-related phantom auditory perceptions in humans.

The phantom sound perception mechanism by which a sound perception occurs without any external sound source is still enigmatic. According to our previous fMRI study, a small region in the parietal operculum 3 was hyperactivated as a function of tinnitus periodicity in subjects with acoustic trauma tinnitus sequelae. This region was localized in the vicinity of neural correlates of middle-ear tympano-ossicular chain movements due to pressure variations. Disturbed proprioceptors are known to trigger illusory perceptions; therefore, we hypothesized that a disturbance of middle-ear proprioceptors may originate phantom sound perceptions. We designed an fMRI study that aimed to stimulate middle-ear proprioceptors by repetitive vibrations using various rates of click trains. In this study, we report that exposure to specific rates of stimuli for a few minutes at comfortable intensity level in healthy subjects distinctly triggered transient tinnitus-like aftereffects. The fMRI neural correlates of the aftereffects were unequivocally localized in the same parietal region as in acoustic trauma tinnitus sufferers. Our results strongly suggest that a middle-ear kinesthetic/proprioceptive illusion exists at the origin of acoustic trauma tinnitus via a somatosensory pathway encompassing the trigeminal system.

Abnormal cortical sensorimotor activity during "Target" sound detection in subjects with acute acoustic trauma sequelae: an fMRI study.

The most common consequences of acute acoustic trauma (AAT) are hearing loss at frequencies above 3 kHz and tinnitus. In this study, we have used functional Magnetic Resonance Imaging (fMRI) to visualize neuronal activation patterns in military adults with AAT and various tinnitus sequelae during an auditory "oddball" attention task. AAT subjects displayed overactivities principally during reflex of target sound detection, in sensorimotor areas and in emotion-related areas such as the insula, anterior cingulate and prefrontal cortex, in premotor area, in cross-modal sensory associative areas, and, interestingly, in a region of the Rolandic operculum that has recently been shown to be involved in tympanic movements due to air pressure. We propose further investigations of this brain area and fine middle ear investigations, because our results might suggest a model in which AAT tinnitus may arise as a proprioceptive illusion caused by abnormal excitability of middle-ear muscle spindles possibly link with the acoustic reflex and associated with emotional and sensorimotor disturbances.

Cortical representation of tympanic membrane movements due to pressure variation: an fMRI study.

Middle ear sensory information has never been localized in the homunculus of the somatosensory cortex (S1). We investigated the somatosensory representation of the middle ear in 15 normal hearing subjects. We applied small air pressure variations to the tympanic membrane while performing a 3T-fMRI study. Unilateral stimulations of the right ear triggered bilateral activations in the caudal part of the postcentral gyrus in Brodmann area 43 (BA 43) and in the auditory associative areas 42 (BA 42) and 22 (BA 22). BA 43 has been found to be involved in activities accompanying oral intake and could be more largely involved in pressure activities in the oropharynx area. The tympanic membrane is indirectly related to the pharynx area through the action of tensor tympani, which is a Eustachian tube muscle. The Eustachian tube muscles have a role in pressure equalization in the middle ear and also have a role in the pharyngeal phase of swallowing. Activation of BA 42 and BA 22 could reflect activations associated with the bilateral acoustic reflex triggered prior to self-vocalization to adjust air pressure in the oropharynx during speech. We propose that BA 43, 42, and 22 are the cortical areas associated with middle ear function. We did not find representation of tympanic membrane movements due to pressure in S1, but its representation in the postcentral gyrus in BA 43 seems to suggest that at least part of this area conveys pure somatosensory information.

Prediction of soman-induced cerebral damage by distortion product otoacoustic emissions.

The organophosphorus nerve agent soman is an irreversible cholinesterase (ChE) inhibitor that can produce long-lasting seizures and seizure-related brain damage (SRBD) in which acetylcholine and glutamate are involved. Since these neurotransmitters play a key-role in the auditory function, it was hypothesized that a hearing test may be an efficient way for detecting the central effects of soman intoxication. In the present study, distortion product otoacoustic emissions (DPOAEs), a non-invasive audiometric method, were used in rats administered with soman (70 µg/kg). Four hours post-soman, DPOAE intensities were significantly decreased. They returned to baseline one day later. The amplitude of the temporary drop of the DPOAEs was well related to the severity of the intoxication. The greatest change was recorded in the rats that survived long-lasting convulsions, i.e. those that showed the highest ChE inhibition in brain and severe encephalopathy. Furthermore, the administration, immediately after soman, of a three-drug therapy composed of atropine sulfate, HI-6 and avizafone abolished the convulsions, the transient drop of DPOAEs at 4h and the occurrence of SRBD at 28 h without modifying brain ChE inhibition. This showed that DPOAE change was not directly related to soman-induced inhibition of cerebral ChE but rather to its neuropathological consequences. The present findings strongly suggest that DPOAEs represent a promising non-invasive tool to predict SRBD occurrence in nerve agent poisoning and to control the efficacy of a neuroprotective treatment.

Hearing status after an industrial explosion: experience of the AZF explosion, 21 September 2001, France.

OBJECTIVES: Following the explosion of a chemical plant in France, a study was conducted to analyse the relationship between hearing thresholds and distance from the explosion based on post- and pre-blast audiometric data, and to describe the functional symptoms and visits for hearing problems. METHODS: Audiometric tests with standard procedure of 511 workers of a company located near the explosion were proposed and conducted by the occupational medicine department after the explosion. Past occupational noise exposure, past medical history of ear problems, distance from the explosion, functional symptoms and visits for hearing problems following explosion and results of past audiometric tests if available were collected. Workers were classified as "exposed" or "less exposed" according to the distance from the explosion. Mean decibel threshold shifts for each ear were analysed by frequency with Student's t test and by multiple linear regression taking into account confounding factors. RESULTS: Of a total of 425 (83%) of the firm's workers who participated in the study, 49% had received an audiometric test before the explosion. Hearing shift between pre- and post-explosion audiograms was significantly greater for the "exposed" group than for the "less exposed" one at 2,000 and 4,000 Hz (P < 0.05, P < 0.001, respectively) and borderline at 6,000 Hz (P = 0.09) for the right ear and at 2,000 (P < 0.01), 6,000 and 8,000 Hz (P < 0.05) for the left ear. Among those of the "exposed" workers who reported any functional symptom following the explosion, 45% did not visit an ENT specialist despite these signs. CONCLUSIONS: The study demonstrated statistically significant hearing shift from 2,000 to 6,000 Hz in relation with distance from the explosion and showed that even when functional symptoms were present, people did not necessarily seek medical advice. Screening for hearing loss should be recommended for people most exposed to excess acoustic pressure, in order to offer them prevention advice.

Distortion product otoacoustic emissions as non-invasive biomarkers and predictors of soman-induced central neurotoxicity: a preliminary study.

The organophosphorus nerve agent soman is an irreversible cholinesterase (ChE) inhibitor that can produce long-lasting seizures and brain damage in which the neurotransmitters acetylcholine and glutamate are involved. These same neurotransmitters play key-roles in the auditory function. It was then assumed that exploring the hearing function may provide markers of the central events triggered by soman intoxication. In the present study, distortion product otoacoustic emissions (DPOAEs), a non-invasive audiometric method, were used to monitor cochlear functionality in rats administered with a moderate dose of soman (45 microg/kg). DPOAEs were investigated either 4h or 24h post-challenge. In parallel, the effects of soman on whole blood and brain ChE activity and on brain histology were also studied. The first main result is that DPOAE intensities were significantly decreased 4h post-soman and returned to baseline at 24h. The amplitude changes were well related to the severity of symptoms, with the greatest change being recorded in the rats that survived long-lasting convulsions. The second main result is that baseline DPOAEs recorded 8 days before soman appear to predict the severity of symptoms produced by the intoxication. Indeed, the lowest baseline DPOAEs corresponded to the occurrence of long-lasting convulsions and brain damage and to the greatest inhibition in central ChE. These results thus suggest that DPOAEs represent a promising non-invasive tool to assess and predict the central consequences of nerve agent poisoning. Further investigations will be carried out to assess the potential applications and the limits of this non-invasive method.

Susceptibility to tinnitus revealed at 2 kHz range by bilateral lower DPOAEs in normal hearing subjects with noise exposure.

We investigated potential markers of susceptibility to tinnitus in a group of normal hearing young pilots aged 25-35 years and with 8 +/- 5 years of aircraft noise exposure. 316 pilots were interviewed about their tinnitus status and were tested for hearing thresholds (audiograms) and distortion products otoacoustic emissions (DPOAE-grams). There was no subject with permanent tinnitus. 23% reported having occasionally perceived tinnitus after flight missions and 77% reported never having experienced tinnitus after flight missions. General discomfort in the ears to noise was higher in the occasional tinnitus group (15 vs. 6%). The major finding was that difference of susceptibility to tinnitus in normal hearing subjects exposed to noise on a daily basis seemed to be clearly related to lower DPOAEs, bilaterally, in the 1500- to 2800-kHz range. However, no difference could be observed between groups on audiograms at the 2-kHz frequency range. This study provided evidence of outer hair cell dysfunctions in normal hearing subjects exposed to noise and susceptible to tinnitus. Hypersensitivity to noise and decreased DPOAEs in a non-noise-specific frequency range support the idea of another alteration mechanism than noise itself. This point was discussed in the light of recent publications.

Otoacoustic emissions and persistent tinnitus after acute acoustic trauma.

OBJECTIVES: To follow up the auditory status of military personnel after an acute acoustic trauma and to identify the possible predictive value of hearing thresholds and otoacoustic emissions during the first 24 hours after the acoustic trauma. STUDY DESIGN: A group of 24 young military subjects, aged 22 +/- 2.3 years, without any otologic problem before the acoustic trauma, were examined at three time intervals after an accidental acoustic trauma caused by the discharge of a firearm: 24 hours, 72 hours, and 15 days. METHODS: Each subject was submitted to medical examination and to a questionnaire detailing the circumstances of the acoustic trauma. Pure tone audiometry was performed from 1 to 8 kHz per half octave. Transiently evoked otoacoustic emissions were recorded in the nonlinear mode at 80 dB pSPL, and distortion product otoacoustic emissions were recorded from 1 to 6 kHz, using a distortion product-gram type procedure, at 65/55 dB SPL, with f2/f1 = 1.22. Two groups of subjects were defined: group 1 (n = 8) represented subjects with short-lasting tinnitus (<72 h) and group 2 (n = 16) subjects with long-lasting tinnitus (>72 h). RESULTS: Hearing thresholds did not differ significantly between these two groups 24 hours after the acoustic trauma. However, otoacoustic emissions showed significantly lower amplitudes 24 hours after the acoustic trauma in subjects showing a longer lasting tinnitus. CONCLUSION: Otoacoustic emissions appear to be a better predictor of the persistence of tinnitus than hearing thresholds alone 24 hours after an acute acoustic trauma.

Hearing in military pilots: one-time audiometry in pilots of fighters, transports, and helicopters.

INTRODUCTION: Pilots are exposed to potentially harmful levels of noise, the actual consequences of which are still poorly documented. We have determined the audiometric profiles of pilots as a function of age and type of aircraft (i.e., fighter, transport, helicopter) and have searched for risk factors of deafness other than noise in a pilot population. METHODS: We examined 521 French military pilots ages 20-40 yr during their annual medical check-ups. Pilots were interviewed using a standardized questionnaire and data from tonal audiograms of both ears were collected. Hearing levels were compared between groups of age and aircraft category. RESULTS: Abnormal hearing levels in pilots were found essentially at high frequencies with a marked notch on audiograms at 6 kHz. Left ears had a significantly poorer performance compared with right ears. At a given age, transport pilots had, on average, better hearing at 8 kHz than other pilots, despite a higher number of flying hours. In addition to the 6 kHz notch, helicopter pilots showed a significant hearing loss at 3 kHz. Such an enlargement of the impaired frequency range can disturb speech communication. Prevalence of otitis media in childhood was significantly higher in pilots with abnormal hearing. DISCUSSION: Pilots flying fighter and helicopter aircraft are at a higher risk of hearing loss compared with pilots flying transport aircraft. Improvements in ear protection seem particularly needed for the left ear. Hearing losses can potentially compromise speech communication in helicopter pilots.

Moderate variations of mood/emotional states related to alterations in cochlear otoacoustic emissions and tinnitus onset in young normal hearing subjects exposed to gun impulse noise.

This study was designed to test whether under impulse noise exposure mood and emotional states could play a role in the onset of tinnitus and/or could modify cochlear sensitivity objectively measured with distortion product otoacoustic emissions (DPOAEs). The experimental design consisted in a short follow-up study of 54 young military subjects (20+/-2 years old), psychologically normal, with normal hearing, during two consecutive days of target practice rounds. Data collection included an abbreviated version of the profile of mood states (POMSs) inventory [Profile of Mood States, Educational and Industrial Testing Service, San Diego, 1971], questionnaires on tinnitus perception (previous history and after shooting) and DPOAEs measurements before and after shooting. Higher scores of tension-anxiety were found in subjects having previous history of tinnitus. Association between tinnitus previous history and tinnitus after shooting was found significant. Perception of tinnitus after target practice rounds was associated with significantly lower DPOAEs at 3 kHz. The most tense-anxious subjects were found to have DPOAEs decreases of 3.35+/-6 dB at 3 kHz after shooting. This study clearly shows that, in young healthy population, psychologically normal and with normal hearing, moderate variations in mood and emotional states were related to tinnitus onset and DPOAEs alterations. It is possible that stronger variations in mood and/or emotional condition would increase risks of tinnitus and alterations of cochlear sensitivity.

DPOAEs in young normal-hearing subjects with histories of otitis media: evidence of sub-clinical impairments.

To investigate the origin of the susceptibility to noise in subjects with histories of otitis media (OM), we assessed early sub-clinical impairments in normally hearing subjects with a history of OM using distortion product otoacoustic emissions (DPOAEs). DPOAEs of 213 normal-hearing subjects aged 18-24 years were obtained and comparisons of DPOAE levels in several groups as a function of OM past infections were tested by ANOVA. A main finding was that young normal-hearing subjects with a history of OM had significantly lower DPOAEs over all octaves tested compared to normal-hearing subjects without antecedent of OM. The mean difference was 3.5+/-1.1 dB in the 2-4 kHz zone, which was especially marked in subjects (n=21) that had undergone a myringotomy (6.6+/-1.5 dB) in the 4 kHz zone. The level of impairment seemed to depend on the severity of the past infection as characterised by the importance and the duration of the infectious effusions.

Ex vivo expansion marginally amplifies repopulating cells from baboon peripheral blood mobilized CD34+ cells.

The ability of ex vivo expansion to increase the long-term repopulating capacity of a graft is still unknown. One problem is the most reliable way to quantify transplantable cells. We addressed this point in a baboon model based on autologous transplantation of serial limiting doses of non-manipulated or ex vivo-expanded mobilized CD34+ cells and determined the threshold doses of non-manipulated and expanded cells which supported long-term multilineage engraftment. In the expansion group, CD34+ cells were cultured for 6 d with a combination of early acting cytokines (Flt3-ligand, stem cell factor, thrombopoietin and interleukin 3). Grafted cells were characterized by their surface antigens and biological properties [semisolid assays, long-term culture-initiating cells (LTC-IC) and non-obese diabetic severe combined immunodeficient reconstituting cells (SRC)]. Animals were followed for at least 12 months post transplantation. The expansion protocol yielded 12.3-fold, 16.9-fold, 3.7-fold, 3.5-fold and 2.2-fold increases in CD34+ cells, granulocyte-macrophage colony-forming units (CFU-GM), megakaryocyte CFU (CFU-MK), LTC-IC and SRC respectively. It induced a modest increase in the long term reconstitutive ability of the graft; the threshold value for long-term engraftment was 0.5 x 10(6)/kg CD34+ cells in the control group and 0.3 x 10(6)/kg CD34+ cells in the expansion group, although one animal in this latter group remained hypoplastic. Frequencies of SRC had a high predictive value of long-term engraftment (r > 0.80). The main advantage of the protocol was the acceleration of granulocyte recovery, achieved at the different doses tested. In conclusion, these experiments suggest that this ex vivo expansion protocol marginally amplifies long-term reconstituting cells.

Over-stimulation of the vestibular system and body balance.

The purpose of this study was to examine whether an over-stimulation of the vestibular system, induced by thousands of time saccadic head stimulations, affects the vestibular sensitivity, and consequently if such a phenomenon could contribute to the deterioration of postural stability observed after a long distance running exercise. Eighteen athletic subjects performed a 20.5 km over ground race with an average speed of 15 km x h(-1), corresponding roughly to 7,500 strides shocks with associated saccadic accelerations transmitted to the head. A preliminary validation of the exercise protocol was realized to confirm the effect of the sustained exercise on body balance by recording standard postural parameters. A visually perceived eye level (VPEL) task was used to indirectly assess otolithic sensitivity motionless or undergoing low centrifugation conditions, before and after exercise. Results obtained from body balance analysis confirmed a decreased postural stability illustrated by increased postural oscillations after the 20.5 km run. Under low centrifugation conditions, results showed a lowering of the VPEL with the increase of the gravito-inertial acceleration in accordance with the literature. However, no significant change in the VPEL after a sustained running exercise was observed. In conclusion, the vestibular sensitivity at the otolithic level does not seem to be altered by an intensive running exercise and then failed to play a key role in the post-exercise deterioration of postural stability.