Improving the Reliability of Tinnitus Screening in Laboratory Animals

Abstract

Behavioral screening remains a contentious issue for animal studies of tinnitus. Most paradigms base a positive tinnitus test on an animal’s natural tendency to respond to the “sound” of tinnitus as if it were an actual sound. As a result, animals with tinnitus are expected to display sound-conditioned behaviors when no sound is present or to miss gaps in background sounds because tinnitus “fills in the gap.” Reliable confirmation of the behavioral indications of tinnitus can be problematic because the reinforcement contingencies of conventional discrimination tasks break down an animal’s tendency to group tinnitus with sound. When responses in silence are rewarded, animals respond in silence regardless of their tinnitus status. When responses in silence are punished, animals stop responding. This study introduces stimulus classification as an alternative approach to tinnitus screening. Classification procedures train animals to respond to the common perceptual features that define a group of sounds (e.g., high pitch or narrow bandwidth). Our procedure trains animals to drink when they hear tinnitus and to suppress drinking when they hear other sounds. Animals with tinnitus are revealed by their tendency to drink in the presence of unreinforced probe sounds that share the perceptual features of the tinnitus classification. The advantages of this approach are illustrated by taking laboratory rats through a testing sequence that includes classification training, the experimental induction of tinnitus, and postinduction screening. Behavioral indications of tinnitus are interpreted and then verified by simulating a known tinnitus percept with objective sounds.

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MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 3: Brainstem involvement - frequency, presentation and outcome.

Related Articles

MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 3: Brainstem involvement - frequency, presentation and outcome.

J Neuroinflammation. 2016 Nov 1;13(1):281

Authors: Jarius S, Kleiter I, Ruprecht K, Asgari N, Pitarokoili K, Borisow N, Hümmert MW, Trebst C, Pache F, Winkelmann A, Beume LA, Ringelstein M, Stich O, Aktas O, Korporal-Kuhnke M, Schwarz A, Lukas C, Haas J, Fechner K, Buttmann M, Bellmann-Strobl J, Zimmermann H, Brandt AU, Franciotta D, Schanda K, Paul F, Reindl M, Wildemann B, in cooperation with the Neuromyelitis Optica Study Group (NEMOS)

Abstract
BACKGROUND: Myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) are present in a subset of aquaporin-4 (AQP4)-IgG-negative patients with optic neuritis (ON) and/or myelitis. Little is known so far about brainstem involvement in MOG-IgG-positive patients.
OBJECTIVE: To investigate the frequency, clinical and paraclinical features, course, outcome, and prognostic implications of brainstem involvement in MOG-IgG-positive ON and/or myelitis.
METHODS: Retrospective case study.
RESULTS: Among 50 patients with MOG-IgG-positive ON and/or myelitis, 15 (30 %) with a history of brainstem encephalitis were identified. All were negative for AQP4-IgG. Symptoms included respiratory insufficiency, intractable nausea and vomiting (INV), dysarthria, dysphagia, impaired cough reflex, oculomotor nerve palsy and diplopia, nystagmus, internuclear ophthalmoplegia (INO), facial nerve paresis, trigeminal hypesthesia/dysesthesia, vertigo, hearing loss, balance difficulties, and gait and limb ataxia; brainstem involvement was asymptomatic in three cases. Brainstem inflammation was already present at or very shortly after disease onset in 7/15 (47 %) patients. 16/21 (76.2 %) brainstem attacks were accompanied by acute myelitis and/or ON. Lesions were located in the pons (11/13), medulla oblongata (8/14), mesencephalon (cerebral peduncles; 2/14), and cerebellar peduncles (5/14), were adjacent to the fourth ventricle in 2/12, and periaqueductal in 1/12; some had concomitant diencephalic (2/13) or cerebellar lesions (1/14). MRI or laboratory signs of blood-brain barrier damage were present in 5/12. Cerebrospinal fluid pleocytosis was found in 11/14 cases, with neutrophils in 7/11 (3-34 % of all CSF white blood cells), and oligoclonal bands in 4/14. Attacks were preceded by acute infection or vaccination in 5/15 (33.3 %). A history of teratoma was noted in one case. The disease followed a relapsing course in 13/15 (87 %); the brainstem was involved more than once in 6. Immunosuppression was not always effective in preventing relapses. Interferon-beta was followed by new attacks in two patients. While one patient died from central hypoventilation, partial or complete recovery was achieved in the remainder following treatment with high-dose steroids and/or plasma exchange. Brainstem involvement was associated with a more aggressive general disease course (higher relapse rate, more myelitis attacks, more frequently supratentorial brain lesions, worse EDSS at last follow-up).
CONCLUSIONS: Brainstem involvement is present in around one third of MOG-IgG-positive patients with ON and/or myelitis. Clinical manifestations are diverse and may include symptoms typically seen in AQP4-IgG-positive neuromyelitis optica, such as INV and respiratory insufficiency, or in multiple sclerosis, such as INO. As MOG-IgG-positive brainstem encephalitis may take a serious or even fatal course, particular attention should be paid to signs or symptoms of additional brainstem involvement in patients presenting with MOG-IgG-positive ON and/or myelitis.

PMID: 27802825 [PubMed - in process]

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MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 3: Brainstem involvement - frequency, presentation and outcome.

Related Articles

MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 3: Brainstem involvement - frequency, presentation and outcome.

J Neuroinflammation. 2016 Nov 1;13(1):281

Authors: Jarius S, Kleiter I, Ruprecht K, Asgari N, Pitarokoili K, Borisow N, Hümmert MW, Trebst C, Pache F, Winkelmann A, Beume LA, Ringelstein M, Stich O, Aktas O, Korporal-Kuhnke M, Schwarz A, Lukas C, Haas J, Fechner K, Buttmann M, Bellmann-Strobl J, Zimmermann H, Brandt AU, Franciotta D, Schanda K, Paul F, Reindl M, Wildemann B, in cooperation with the Neuromyelitis Optica Study Group (NEMOS)

Abstract
BACKGROUND: Myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) are present in a subset of aquaporin-4 (AQP4)-IgG-negative patients with optic neuritis (ON) and/or myelitis. Little is known so far about brainstem involvement in MOG-IgG-positive patients.
OBJECTIVE: To investigate the frequency, clinical and paraclinical features, course, outcome, and prognostic implications of brainstem involvement in MOG-IgG-positive ON and/or myelitis.
METHODS: Retrospective case study.
RESULTS: Among 50 patients with MOG-IgG-positive ON and/or myelitis, 15 (30 %) with a history of brainstem encephalitis were identified. All were negative for AQP4-IgG. Symptoms included respiratory insufficiency, intractable nausea and vomiting (INV), dysarthria, dysphagia, impaired cough reflex, oculomotor nerve palsy and diplopia, nystagmus, internuclear ophthalmoplegia (INO), facial nerve paresis, trigeminal hypesthesia/dysesthesia, vertigo, hearing loss, balance difficulties, and gait and limb ataxia; brainstem involvement was asymptomatic in three cases. Brainstem inflammation was already present at or very shortly after disease onset in 7/15 (47 %) patients. 16/21 (76.2 %) brainstem attacks were accompanied by acute myelitis and/or ON. Lesions were located in the pons (11/13), medulla oblongata (8/14), mesencephalon (cerebral peduncles; 2/14), and cerebellar peduncles (5/14), were adjacent to the fourth ventricle in 2/12, and periaqueductal in 1/12; some had concomitant diencephalic (2/13) or cerebellar lesions (1/14). MRI or laboratory signs of blood-brain barrier damage were present in 5/12. Cerebrospinal fluid pleocytosis was found in 11/14 cases, with neutrophils in 7/11 (3-34 % of all CSF white blood cells), and oligoclonal bands in 4/14. Attacks were preceded by acute infection or vaccination in 5/15 (33.3 %). A history of teratoma was noted in one case. The disease followed a relapsing course in 13/15 (87 %); the brainstem was involved more than once in 6. Immunosuppression was not always effective in preventing relapses. Interferon-beta was followed by new attacks in two patients. While one patient died from central hypoventilation, partial or complete recovery was achieved in the remainder following treatment with high-dose steroids and/or plasma exchange. Brainstem involvement was associated with a more aggressive general disease course (higher relapse rate, more myelitis attacks, more frequently supratentorial brain lesions, worse EDSS at last follow-up).
CONCLUSIONS: Brainstem involvement is present in around one third of MOG-IgG-positive patients with ON and/or myelitis. Clinical manifestations are diverse and may include symptoms typically seen in AQP4-IgG-positive neuromyelitis optica, such as INV and respiratory insufficiency, or in multiple sclerosis, such as INO. As MOG-IgG-positive brainstem encephalitis may take a serious or even fatal course, particular attention should be paid to signs or symptoms of additional brainstem involvement in patients presenting with MOG-IgG-positive ON and/or myelitis.

PMID: 27802825 [PubMed - in process]

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Acoustic Analysis and Electroglottography in Elite Vocal Performers

Publication date: Available online 2 November 2016
Source:Journal of Voice
Author(s): Rocio Villafuerte-Gonzalez, Victor M. Valadez-Jimenez, Jose A. Sierra-Ramirez, Pablo Antonio Ysunza, Karen Chavarria-Villafuerte, Xochiquetzal Hernandez-Lopez
BackgroundAcoustic analysis of voice (AAV) and electroglottography (EGG) have been used for assessing vocal quality in patients with voice disorders. The effectiveness of these procedures for detecting mild disturbances in vocal quality in elite vocal performers has been controversial.ObjectiveTo compare acoustic parameters obtained by AAV and EGG before and after vocal training to determine the effectiveness of these procedures for detecting vocal improvements in elite vocal performers.Materials and MethodsThirty-three elite vocal performers were studied. The study group included 14 males and 19 females, ages 18–40 years, without a history of voice disorders. Acoustic parameters were obtained through AAV and EGG before and after vocal training using the Linklater method.ResultsNonsignificant differences (P > 0.05) were found between values of fundamental frequency (F0), shimmer, and jitter obtained by both procedures before vocal training. Mean F0 was similar after vocal training. Jitter percentage as measured by AAV showed nonsignificant differences (P > 0.05) before and after vocal training. Shimmer percentage as measured by AAV demonstrated a significant reduction (P < 0.05) after vocal training. As measured by EGG after vocal training, shimmer and jitter were significantly reduced (P < 0.05); open quotient was significantly increased (P < 0.05); and irregularity was significantly reduced (P < 0.05).ConclusionsAAV and EGG were effective for detecting improvements in vocal function after vocal training in male and female elite vocal performers undergoing vocal training. EGG demonstrated better efficacy for detecting improvements and provided additional parameters as compared to AAV.



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Formant Tuning and Feedback in the Male Passaggio

Publication date: Available online 2 November 2016
Source:Journal of Voice
Author(s): Wim G.J. Ritzerfeld, Donald G. Miller
It has been suggested that traversing the male (secondo) passaggio requires two important adjustments. When singing up the scale, first of all, the second harmonic (H2) needs to pass over the first formant (F1). After that, the timbre of the voice takes on a different, slightly “darker” quality. This is the pitch where, in singers' jargon, the voice reaches secondo passaggio. Above secondo passaggio, in the optimal arrangement, the second formant (F2) is tuned close to one of the higher harmonics, or, sometimes alternatively, the singer's formant cluster induces a dominant resonance in the approximate range of 2.4–3.4 kHz. These two adjustments together produce the typical sound of the classical male upper voice. In this study, we have investigated the choices individual singers make while negotiating the passaggio and the effect of feedback from the vocal tract to the voice source during this maneuver. Electroglottograph (EGG) and microphone signals were recorded of nine male singers (five tenors and four baritones) using VoceVista. Inverse filtering was performed on the microphone signals, using the Sopran/DeCap application, to reveal the shape of the glottal airflow pulses.



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Correlations Between Serum Apolipoprotein A-I and Formation of Vocal Cord Polyp

Publication date: Available online 2 November 2016
Source:Journal of Voice
Author(s): Hui-Ping Zhang, Rong Zhang
ObjectiveThis study aims to investigate the correlations between serum apolipoprotein A-I (ApoA-I) and the formation of vocal cord polyps (VCPs).Study DesignThis study used the nonmatched case–control study method.MethodsThe serum total cholesterol (TC), triglyceride, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, ApoA-I, apolipoprotein B (ApoB), and ApoA-I/ApoB levels of 89 VCP patients and 87 normal volunteers were compared. Additionally, such VCP-related factors as excessive vocal use, vocal abuse, smoking, drinking, and the size of VCPs were analyzed.ResultsThe two groups did not significantly differ with regard to triglyceride, low-density lipoprotein cholesterol, ApoB, and ApoA-I/ApoB levels (P > 0.05), whereas they did significantly differ with regard to TC, HDL-C, and ApoA-I levels (P < 0.05) according to independent t tests. Logistic regression analysis showed that excessive vocal use and vocal abuse were risk factors for VCPs (P < 0.05), with odds ratio values of 5.675 and 12.781, respectively. The ApoA-I level was negatively associated with VCPs (P < 0.05), with an odds ratio of 0.511; however, TC and HDL-C were not associated with the formation of VCPs (P > 0.05). The size of VCPs in females was negatively correlated with the serum ApoA-I level (r = −0.349, P = 0.032), whereas that in males was not (P > 0.05).ConclusionsAs the serum ApoA-I level was negatively correlated with the formation of VCPs, ApoA-I may reduce the risk of VCPs. These findings may facilitate the prevention and treatment of VCPs.



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Evaluation of Vocal Fold Motion Abnormalities: Are We All Seeing the Same Thing?

Publication date: Available online 2 November 2016
Source:Journal of Voice
Author(s): Lyndsay L. Madden, Clark A. Rosen
ObjectivesFlexible laryngoscopy is the principle tool for the evaluation of vocal fold motion. As of yet, no consistent, unified outcome metric has been developed for vocal fold paralysis/immobility research. The goal of this study was to evaluate vocal fold motion assessment (inter- and intra-rater reliability) among general otolaryngologists and fellowship-trained laryngologists.Study DesignProspective video perceptual analysis study.MethodsFlexible laryngoscopic examinations, with sound, of 15 unique patient cases (20 seconds each) were sent to 10 general otolaryngologists and 10 fellowship-trained laryngologists blinded to clinical history. Reviewers were given written definitions of vocal fold mobility and immobility and two video examples. The cases included bilateral vocal fold mobility (six), unilateral vocal fold immobility (five), and unilateral vocal fold hypomobility (four). Five examinations were repeated to determine intra-rater reliability. Participants were asked to judge if there was or there was no purposeful motion, as described by written definitions, for each vocal fold (800 tokens in total).ResultsTwenty reviewers (100%) replied. Both general otolaryngologists and fellowship-trained laryngologists had an overall inter-rater reliability of 95%. Difference in inter-rater reliability between the two groups of raters was negligible: 95% for general otolaryngologists and 97.5% for fellowship-trained laryngologists. There was no variability in intra-rater reliability within either rater group (99%).ConclusionIntra- and inter-rater agreement in determining whether the patient had purposeful vocal fold motion on flexible laryngoscopic examination was excellent in both groups. This study demonstrates that otolaryngologists can consistently and accurately judge the presence and the absence of vocal fold motion.



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