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1.
eNeuro ; 9(5)2022.
Article in English | MEDLINE | ID: mdl-36041828

ABSTRACT

Opsin-3 (Opn3, encephalopsin) was the first nonvisual opsin gene discovered in mammals. Since then, several Opn3 functions have been described, and in two cases (adipose tissue, smooth muscle) light sensing activity is implicated. In addition to peripheral tissues, Opn3 is robustly expressed within the central nervous system, for which it derives its name. Despite this expression, no studies have investigated developmental or adult CNS consequences of Opn3 loss-of-function. Here, the behavioral consequences of mice deficient in Opn3 were investigated. Opn3-deficient mice perform comparably to wild-type mice in measures of motor coordination, socialization, anxiety-like behavior, and various aspects of learning and memory. However, Opn3-deficient mice have an attenuated acoustic startle reflex (ASR) relative to littermates. This deficit is not because of changes in hearing sensitivity, although Opn3 was shown to be expressed in auditory and vestibular structures, including cochlear outer hair cells. Interestingly, the ASR was not acutely light-dependent and did not vary between daytime and nighttime trials, despite known functions of Opn3 in photoreception and circadian gene amplitude. Together, these results demonstrate the first role of Opn3 on behavior, although the role of this opsin in the CNS remains largely elusive.


Subject(s)
Reflex, Startle , Rod Opsins , Acoustic Stimulation , Animals , Mammals/metabolism , Mice , Opsins , Rod Opsins/genetics , Rod Opsins/metabolism
2.
Article in English | MEDLINE | ID: mdl-35954792

ABSTRACT

Addressing patients' religion and spirituality (R/S) needs has been associated with positive health outcomes. However, despite receiving extensive training in spiritual assessment and care, chaplaincy services are primarily confined to inpatient settings, with few studies occurring in outpatient settings. The study sought to understand mental health providers' views about what shaped provider and patient motivation to engage in R/S discussions and seek referrals to chaplaincy services. We conducted five one-hour focus group sessions with a total of 38 staff members and thematically analyzed the resulting session and field notes. We identified four themes concerning provider knowledge and attitudes about R/S and chaplaincy services: Staff Information Needs, Staff Motivation to Discuss R/S and Refer, Patient Motivation to Use Chaplaincy Services, and Chaplain Accessibility. The study findings suggest that providers in outpatient substance use treatment clinics in the Veterans Health Administration are receptive to learning about R/S care and the possibility of expanding chaplaincy services. However, staff have misconceptions about the roles and responsibilities of chaplains. Attitudes about and experiences with R/S discussions varied. Trust and confidence in the benefits of chaplaincy services may be improved among both providers and patients by increasing chaplains' accessibility and visibility within these outpatient settings.


Subject(s)
Spiritual Therapies , Substance-Related Disorders , Health Personnel , Humans , Outpatients , Spirituality , Substance-Related Disorders/psychology , Substance-Related Disorders/therapy
3.
Front Psychol ; 13: 937712, 2022.
Article in English | MEDLINE | ID: mdl-36814887

ABSTRACT

All brain processes that generate behaviour, apart from reflexes, operate with information that is in an "activated" state. This activated information, which is known as working memory (WM), is generated by the effect of attentional processes on incoming information or information previously stored in short-term or long-term memory (STM or LTM). Information in WM tends to remain the focus of attention; and WM, attention and STM together enable information to be available to mental processes and the behaviours that follow on from them. WM and attention underpin all flexible mental processes, such as solving problems, making choices, preparing for opportunities or threats that could be nearby, or simply finding the way home. Neither WM nor attention are necessarily conscious, and both may have evolved long before consciousness. WM and attention, with similar properties, are possessed by humans, archerfish, and other vertebrates; jumping spiders, honey bees, and other arthropods; and members of other clades, whose last common ancestor (LCA) is believed to have lived more than 600 million years ago. It has been reported that very similar genes control the development of vertebrate and arthropod brains, and were likely inherited from their LCA. Genes that control brain development are conserved because brains generate adaptive behaviour. However, the neural processes that generate behaviour operate with the activated information in WM, so WM and attention must have existed prior to the evolution of brains. It is proposed that WM and attention are widespread amongst animal species because they are phylogenetically conserved mechanisms that are essential to all mental processing, and were inherited from the LCA of vertebrates, arthropods, and some other animal clades.

4.
Pediatr Dev Pathol ; 24(4): 366-370, 2021.
Article in English | MEDLINE | ID: mdl-33729851

ABSTRACT

Post-hematopoietic stem cell transplant secondary solid neoplasms are uncommon and usually host-derived. We describe a 6-year-old female who developed a mixed donor-recipient origin mesenchymal stromal tumor-like lesion in the liver following an unrelated hematopoietic stem cell transplant complicated by severe graft-versus-host disease. This lesion arose early post-transplant in association with hepatic graft-versus-host disease. At 12 years post-transplant, the neoplasm has progressively shrunken in size and the patient remains well with no neoplasm-associated sequelae. This report characterizes a novel lesion of mixed origin post-transplant and offers unique insights into the contribution of bone marrow-derived cells to extra-medullary tissues.


Subject(s)
Hematopoietic Stem Cell Transplantation/adverse effects , Liver Neoplasms/etiology , Liver/pathology , Mesenchymal Stem Cells/pathology , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/therapy , Cell Proliferation , Child , Female , Graft vs Host Disease/complications , Humans , Liver Neoplasms/diagnosis , Liver Neoplasms/pathology , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/complications , Transplantation, Homologous
5.
Int J Pediatr Otorhinolaryngol ; 138: 110275, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32828018

ABSTRACT

OBJECTIVES: Determine whether a murine model of cytomegalovirus (CMV) and CMV- infected children show evidence of synaptopathy. STUDY DESIGN: Murine model of CMV infection and case series. SUBJECTS AND METHODS: C57 BL/6 mice were inoculated with murine-CMV (mCMV). Auditory function was assessed using Auditory Brainstem Response (ABR) and distortion product otoacoustic emission (DPOAE) testing. Temporal bones from mCMV-infected mice were used for both ribbon synapse and hair cell quantification. Four groups of children (non-CMV normal hearing, non-CMV hearing impaired, CMV normal hearing and CMV hearing impaired) underwent ABRs between 2014 and 2018. The outcomes included raw amplitude, wave I:V amplitude ratio, absolute latency, and interpeak latency. RESULTS: Mice at 8 weeks post mCMV infection had higher ABR and DPOAE (P < 0.05) thresholds and increased outer hair cell loss compared to uninfected mice and mCMV-infected mice at 4 and 6 weeks post infection, indicating progressive hearing loss. A reduction in the wave I amplitude and synaptic counts were noted earlier at 4 weeks in CMV-infected mice (P < 0.05). The human data indicated that the wave I:V amplitude ratio was lower on average in CMV-infected groups when compared to the uninfected cohorts. The wave I:V amplitude ratio for the click and 4k stimuli were not significantly different between the congenital CMV-infected and uninfected children with normal or with hearing loss. CONCLUSION: This study suggests mCMV infection results in a synaptopathy before hair cell damage. Additional studies need to be performed to determine whether this effect is also observed in CMV-infected children. LEVEL OF EVIDENCE: Animal studies and basic science- NA; human studies: level 4.


Subject(s)
Cytomegalovirus Infections , Cytomegalovirus , Animals , Auditory Threshold , Cochlea , Evoked Potentials, Auditory, Brain Stem , Mice , Otoacoustic Emissions, Spontaneous
6.
Curr Opin Otolaryngol Head Neck Surg ; 28(5): 281-285, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32833886

ABSTRACT

PURPOSE OF REVIEW: To review the principles of oncolytic virotherapy and summarize the recent preliminary evidence on the efficacy of oncolytic virotherapy for cholesteatoma (CHST) treatment in vitro in human CHST cells and in a gerbil CHST model. RECENT FINDINGS: The use of oncolytic virotherapy for nonmalignant lesions is innovative. In-vitro results showed that oncolytic herpes simplex virus 1 (oHSV) selectively targets and kills CHST cells. In a gerbil model of CHST, local oHSV injections were associated with a decrease in CHST volume and modulation of bony changes. SUMMARY: Surgical treatment options for CHST are limited by high morbidity and recidivism, emphasizing the need for developing treatment alternatives. Preliminary results support the potential therapeutic effect of oncolytic virotherapy on CHST, yet further research is needed to evaluate this novel approach.


Subject(s)
Cholesteatoma, Middle Ear/therapy , Oncolytic Virotherapy , Humans
7.
J Dermatol ; 47(8): 898-902, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32602142

ABSTRACT

Transmembrane tyrosine kinase receptors represent a fundamental mechanism for transducing extracellular signals into the activation of signaling cascades responsible for intercellular communication, embryogenesis and tissue integrity. The epidermal growth factor receptor (EGFR) is a canonical member of this family, regarded for its dysregulated function in various malignancies. Here, we describe a young female born prematurely with friable and immature skin who developed chronic diarrhea, recurrent gastrointestinal and respiratory infections, as well as an ichthyotic and inflammatory papulopustular rash accompanied by alopecia. Whole-exome sequencing revealed a constitutional homozygous variant in EGFR (NM_005228.3:c1283G>A; p.[G428D]), identified as a pathogenic loss-of-function variant in three patients with EGFR deficiency. These patients succumbed to early mortality; however, the proposita's condition has stabilized, despite only supportive interventions, with dermatological improvements and reduced frequency of infections at 8 years. This report provides a clinical phenotyping of the longest surviving individual with EGFR deficiency and substantiates our understanding of the natural history of this multisystemic dermatological disorder.


Subject(s)
ErbB Receptors , Neoplasms , ErbB Receptors/genetics , Female , Humans , Infant , Phenotype , Signal Transduction , Skin/metabolism
8.
Laryngoscope Investig Otolaryngol ; 4(5): 532-542, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31637298

ABSTRACT

OBJECTIVE: Determine if oncolytic herpes simplex virus (oHSV) can eradicate cholesteatoma (CHST) in a gerbil model. METHODS: An in vivo model of CHST was developed in Mongolian gerbils by combining Pseudomonas aeruginosa inoculation with double ligation of the external auditory canal (EAC). CHST size and bone thickness were measured using morphometric and volumetric quantification techniques via micro-computed tomography (micro-CT). The CHST induction and quantification techniques were then used in an additional group of 10 gerbils (n = 20 ears) to determine the within-group treatment efficacy of oHSV against CHST in vivo. Treated animals received either one, two, or three intrabullar injections of oHSV between 2 and 6 weeks postinduction of CHST. RESULTS: The P. aeruginosa inoculation plus double EAC ligation technique successfully induced a range of CHST growth in 100% of the ears in the model-development group. Osteolytic effects of CHST were observed in 6% of ears whereas osteoblastic effects were observed in 31% of ears. CHST volume decreased by 50% or more in 12 of the 20 ears in the oHSV-treatment groups. An apparent reversal of osteoblastic effects was also observed in three out of four ears 6 weeks following the third oHSV injection. CONCLUSIONS: P. aeruginosa inoculation plus double EAC ligation reliably induces CHST formation in gerbil. CT-based volumetric measures are significantly more accurate than single-slice morphometric area measures for quantification of CHST size. Treatment with oHSV appears to be efficacious for reducing CHST volume by as much as 77% with as few as one treatment. LEVEL OF EVIDENCE: NA.

9.
Subst Abus ; 40(4): 444-452, 2019.
Article in English | MEDLINE | ID: mdl-31206342

ABSTRACT

Background: Interprofessional training is increasing in focus within medical education. Although substance use treatment has long been interprofessional in nature, chaplaincy has been relatively absent in outpatient settings. Since 2013, the Veterans Health Administration has supported an Interprofessional Advanced Fellowship in Addiction Treatment (IAFAT), with 7 sites nationally recruiting across multiple health care disciplines. In the fall of 2017, Veteran Affairs Connecticut Healthcare System (VACHS) became the first such fellowship to expand its recruitment to include chaplain fellows. We seek to share rationale for recruiting chaplains, current curriculum and curricular needs, and the potential roles of chaplains in outpatient addiction treatment. Methods: Collaborating with the office of chaplaincy education, we describe the process of chaplain recruitment, incorporation into a new treatment setting, and supervision, and we report on the feasibility of this innovative training initiative. Results: During the first year, the chaplain fellow has developed and maintained a new clinical service in an outpatient substance use disorder (SUD) specialty care setting, delivering over 150 hours of group and individual treatment to veterans. He has provided 12 presentations to staff on the role of a chaplain and other related topics, as well as written an article on the topic of addiction for a clergy audience. Anecdotally, staff satisfaction has been high, and the current chaplain is helping to recruit for his replacement. Limitations: As a feasibility pilot project, there is no outcome and very limited quantitative data. Conclusions: Chaplain fellows can be successfully incorporated into outpatient SUD clinics with a noticeable degree of fellow, staff, and patient satisfaction.


Subject(s)
Alcoholism/rehabilitation , Clergy , Interdisciplinary Communication , Intersectoral Collaboration , Patient Care Team , Substance-Related Disorders/rehabilitation , United States Department of Veterans Affairs , Alcoholism/prevention & control , Alcoholism/psychology , Feasibility Studies , Pastoral Care , Patient Satisfaction , Spirituality , Substance-Related Disorders/prevention & control , Substance-Related Disorders/psychology , United States
10.
Int J Audiol ; 58(8): 484-496, 2019 08.
Article in English | MEDLINE | ID: mdl-31017499

ABSTRACT

Objective: To examine the auditory system of Brazilian gasoline station workers using an extensive audiological test battery. Design: This was a cross-sectional study. The audiological evaluation included a questionnaire, pure-tone audiometry, acoustic immittance tests, transient-evoked otoacoustic emissions (TEOAEs), distortion product otoacoustic emissions (DPOAEs), auditory brainstem response (ABR) and P300 auditory-evoked potentials. Study sample: A total of 77 Brazilian gasoline station workers were evaluated, and their results were compared with those of 36 participants who were not exposed to chemicals or noise at work. The gasoline station employees worked in 18 different gas stations, and the noise area measurements from all gas stations revealed time-weighted averages below 85 dBA. Results: Of the 77 gasoline station workers evaluated, 67.5% had audiometric results within the normal range, but 59.7% reported difficulties in communication in noisy places. Gasoline station workers showed significantly poorer results than non-exposed control participants in one or more conditions of each of the audiological tests used, except P300. Conclusions: The results suggest that the gasoline station workers have both peripheral and central auditory dysfunctions that could be partly explained by their exposure to gasoline.


Subject(s)
Auditory Pathways/physiopathology , Auditory Perception , Gasoline/adverse effects , Hearing Disorders/etiology , Hearing Loss, Noise-Induced/etiology , Hearing , Occupational Exposure/adverse effects , Adult , Aged , Audiometry, Pure-Tone , Auditory Threshold , Brazil , Cross-Sectional Studies , Event-Related Potentials, P300 , Evoked Potentials, Auditory, Brain Stem , Female , Hearing Disorders/diagnosis , Hearing Disorders/physiopathology , Hearing Disorders/psychology , Hearing Loss, Noise-Induced/diagnosis , Hearing Loss, Noise-Induced/physiopathology , Hearing Loss, Noise-Induced/psychology , Humans , Male , Middle Aged , Noise/adverse effects , Occupational Diseases/etiology , Occupational Diseases/physiopathology , Occupational Diseases/psychology , Occupational Health , Otoacoustic Emissions, Spontaneous , Risk Assessment , Risk Factors , Young Adult
11.
Otolaryngol Head Neck Surg ; 160(5): 891-893, 2019 05.
Article in English | MEDLINE | ID: mdl-30598045

ABSTRACT

Cholesteatomas (CHSTs) are congenital or acquired lesions of the temporal bone that are associated with significant morbidity. We hypothesized that an oncolytic herpes simplex virus (oHSV) could preferentially eradicate primary human CHST cells in vitro and that this virus will replicate selectively and efficiently in CHST cells when compared with control cells. In this work, primary human CHST cells were cultured from surgically collected tissue. Cholesteatomas and control cells were grown and infected by oncolytic oHSV. More than 80% CHST cells versus <5% control cells were killed by oHSV. The oHSV showed a significant enhanced cytotoxic effect against CHST cells in a time- and dose-dependent manner. Therefore, this novel therapy has promise as a future treatment to minimize the spread and recurrence of CHST.


Subject(s)
Cholesteatoma/pathology , Oncolytic Virotherapy , Oncolytic Viruses/physiology , Simplexvirus/physiology , Skull Neoplasms/pathology , Temporal Bone , Cell Culture Techniques , Humans
12.
Int J Audiol ; 56(12): 989-996, 2017 12.
Article in English | MEDLINE | ID: mdl-28783994

ABSTRACT

OBJECTIVE: To assess the utility of noise cancelation earphones (NCE) in audiometric evaluations. DESIGN: Degree of noise reduction of Bose QuietComfort 15 NCE was assessed through probe-microphone measures and sound-field audiometry. Occlusion effects from NCE were assessed for potential effects on bone-conduction thresholds. STUDY SAMPLE: Twenty participants were tested to determine average occlusion effect values during bone-conduction testing with and without NCE. Noise reduction values of the NCE were assessed on a single subject through probe-microphone measures and sound-field testing. RESULTS: NCE sufficiently reduced ambient noise to levels acceptable for air-conduction testing as well as for bone-conduction testing for most patients when adding minimal adjustment to acceptable levels as outlined by the ANSI S3.1-1999 standard. In addition, NCE did not create a clinically significant change in the occlusion effect for bone-conduction testing. CONCLUSION: NCE placed over insert earphones provide a sound pressure level at the tympanic membrane that is below ANSI standards for routine air-conduction testing and result in sufficient ambient noise reduction for bone-conduction testing with most patients. There is no clinically significant occlusion effect from NCE during routine bone-conduction audiometry. These findings support the utility of using NCE for offsite audiometric testing.


Subject(s)
Audiometry, Pure-Tone/instrumentation , Auditory Perception , Bone Conduction , Ear Protective Devices , Noise/prevention & control , Adult , Audiometry, Pure-Tone/methods , Auditory Threshold , Equipment Design , Female , Humans , Male , Noise/adverse effects , Young Adult
13.
Front Neurosci ; 10: 464, 2016.
Article in English | MEDLINE | ID: mdl-27826221

ABSTRACT

Objective: The objectives of this study were: (1) to determine if musicians have a better ability to detect frequency changes under quiet and noisy conditions; (2) to use the acoustic change complex (ACC), a type of electroencephalographic (EEG) response, to understand the neural substrates of musician vs. non-musician difference in frequency change detection abilities. Methods: Twenty-four young normal hearing listeners (12 musicians and 12 non-musicians) participated. All participants underwent psychoacoustic frequency detection tests with three types of stimuli: tones (base frequency at 160 Hz) containing frequency changes (Stim 1), tones containing frequency changes masked by low-level noise (Stim 2), and tones containing frequency changes masked by high-level noise (Stim 3). The EEG data were recorded using tones (base frequency at 160 and 1200 Hz, respectively) containing different magnitudes of frequency changes (0, 5, and 50% changes, respectively). The late-latency evoked potential evoked by the onset of the tones (onset LAEP or N1-P2 complex) and that evoked by the frequency change contained in the tone (the acoustic change complex or ACC or N1'-P2' complex) were analyzed. Results: Musicians significantly outperformed non-musicians in all stimulus conditions. The ACC and onset LAEP showed similarities and differences. Increasing the magnitude of frequency change resulted in increased ACC amplitudes. ACC measures were found to be significantly different between musicians (larger P2' amplitude) and non-musicians for the base frequency of 160 Hz but not 1200 Hz. Although the peak amplitude in the onset LAEP appeared to be larger and latency shorter in musicians than in non-musicians, the difference did not reach statistical significance. The amplitude of the onset LAEP is significantly correlated with that of the ACC for the base frequency of 160 Hz. Conclusion: The present study demonstrated that musicians do perform better than non-musicians in detecting frequency changes in quiet and noisy conditions. The ACC and onset LAEP may involve different but overlapping neural mechanisms. Significance: This is the first study using the ACC to examine music-training effects. The ACC measures provide an objective tool for documenting musical training effects on frequency detection.

14.
Am J Physiol Regul Integr Comp Physiol ; 310(7): R578-85, 2016 Apr 01.
Article in English | MEDLINE | ID: mdl-26791833

ABSTRACT

While it is well recognized that riboflavin accumulates in breast milk as an essential vitamin for neonates, transport mechanisms for its milk excretion are not well characterized. The multidrug efflux transporter ABCG2 in the apical membrane of milk-producing mammary epithelial cells (MECs) is involved with riboflavin excretion. However, it is not clear whether MECs possess other riboflavin transport systems, which may facilitate its basolateral uptake into MECs. We report here that transcripts encoding the second (SLC52A2) and third (SLC52A3) member of the recently discovered family of SLC52A riboflavin uptake transporters are expressed in milk fat globules from human breast milk. Furthermore, Slc52a2 and Slc52a3 mRNA are upregulated in the mouse mammary gland during lactation. Importantly, the induction ofSlc52a2, which was the major Slc52a riboflavin transporter in the lactating mammary gland, was also observed at the protein level. Subcellular localization studies showed that green fluorescent protein-tagged mouse SLC52A2 mainly localized to the cell membrane, with no preferential distribution to the apical or basolateral membrane in polarized kidney MDCK cells. These results strongly implicate a potential role for SLC52A2 in riboflavin uptake by milk-producing MECs, a critical step in the transfer of riboflavin into breast milk.


Subject(s)
Lactation/physiology , Mammary Glands, Animal/physiology , Membrane Transport Proteins/metabolism , Milk, Human/metabolism , Riboflavin/metabolism , Animals , Female , Mice , Mice, Inbred C57BL , Up-Regulation/physiology
15.
J Acoust Soc Am ; 136(3): 1212, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25190395

ABSTRACT

The electrical signal recorded at the round window was used to estimate the location of missing outer hair cells. The cochlear response was recorded to a low frequency tone embedded in high-pass filtered noise conditions. Cochlear damage was created by either overexposure to frequency-specific tones or laser light. In animals with continuous damage along the partition, the amplitude of the cochlear response increased as the high-pass cutoff frequency increased, eventually reaching a plateau. The cochlear distance at the onset of the plateau correlated with the anatomical onset of outer hair cell loss. A mathematical model replicated the physiologic data but was limited to cases with continuous hair cell loss in the middle and basal turns. The neural contribution to the cochlear response was determined by recording the response before and after application of Ouabain. Application of Ouabain eliminated or reduced auditory neural activity from approximately two turns of the cochlea. The amplitude of the cochlear response was reduced for moderate signal levels with a limited effect at higher levels, indicating that the cochlear response was dominated by outer hair cell currents at high signal levels and neural potentials at low to moderate signal levels.


Subject(s)
Cochlear Microphonic Potentials , Hair Cells, Auditory, Outer/pathology , Hearing Loss, Noise-Induced/pathology , Hearing Loss, Noise-Induced/physiopathology , Round Window, Ear/innervation , Animals , Audiometry, Pure-Tone , Auditory Threshold , Cochlear Microphonic Potentials/drug effects , Disease Models, Animal , Female , Gerbillinae , Hair Cells, Auditory, Outer/drug effects , Hearing Loss, Noise-Induced/etiology , Lasers , Models, Biological , Ouabain/pharmacology , Round Window, Ear/injuries
16.
Front Psychol ; 5: 697, 2014.
Article in English | MEDLINE | ID: mdl-25140159

ABSTRACT

This research is an investigation of whether consciousness-one's ongoing experience-influences one's behavior and, if so, how. Analysis of the components, structure, properties, and temporal sequences of consciousness has established that, (1) contrary to one's intuitive understanding, consciousness does not have an active, executive role in determining behavior; (2) consciousness does have a biological function; and (3) consciousness is solely information in various forms. Consciousness is associated with a flexible response mechanism (FRM) for decision-making, planning, and generally responding in nonautomatic ways. The FRM generates responses by manipulating information and, to function effectively, its data input must be restricted to task-relevant information. The properties of consciousness correspond to the various input requirements of the FRM; and when important information is missing from consciousness, functions of the FRM are adversely affected; both of which indicate that consciousness is the input data to the FRM. Qualitative and quantitative information (shape, size, location, etc.) are incorporated into the input data by a qualia array of colors, sounds, and so on, which makes the input conscious. This view of the biological function of consciousness provides an explanation why we have experiences; why we have emotional and other feelings, and why their loss is associated with poor decision-making; why blindsight patients do not spontaneously initiate responses to events in their blind field; why counter-habitual actions are only possible when the intended action is in mind; and the reason for inattentional blindness.

17.
J Acoust Soc Am ; 132(5): 3351-62, 2012 Nov.
Article in English | MEDLINE | ID: mdl-23145616

ABSTRACT

The cochlear microphonic was recorded in response to a 733 Hz tone embedded in noise that was high-pass filtered at 25 different frequencies. The amplitude of the cochlear microphonic increased as the high-pass cutoff frequency of the noise increased. The amplitude growth for a 60 dB SPL tone was steeper and saturated sooner than that of an 80 dB SPL tone. The growth for both signal levels, however, was not entirely cumulative with plateaus occurring at about 4 and 7 mm from the apex. A phenomenological model of the electrical potential in the cochlea that included a hair cell probability function and spiral geometry of the cochlea could account for both the slope of the growth functions and the plateau regions. This suggests that with high-pass-filtered noise, the cochlear microphonic recorded at the round window comes from the electric field generated at the source directed towards the electrode and not down the longitudinal axis of the cochlea.


Subject(s)
Cochlea/physiology , Cochlear Microphonic Potentials , Noise , Acoustic Stimulation , Animals , Audiometry , Auditory Threshold , Cochlea/anatomy & histology , Gerbillinae , Hair Cells, Auditory/physiology , Models, Biological
18.
J Acoust Soc Am ; 131(1): 337-52, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22280596

ABSTRACT

Future implementation of regenerative treatments for sensorineural hearing loss may be hindered by the lack of diagnostic tools that specify the target(s) within the cochlea and auditory nerve for delivery of therapeutic agents. Recent research has indicated that the amplitude of high-level compound action potentials (CAPs) is a good predictor of overall auditory nerve survival, but does not pinpoint the location of neural damage. A location-specific estimate of nerve pathology may be possible by using a masking paradigm and high-level CAPs to map auditory nerve firing density throughout the cochlea. This initial study in gerbil utilized a high-pass masking paradigm to determine normative ranges for CAP-derived neural firing density functions using broadband chirp stimuli and low-frequency tonebursts, and to determine if cochlear outer hair cell (OHC) pathology alters the distribution of neural firing in the cochlea. Neural firing distributions for moderate-intensity (60 dB pSPL) chirps were affected by OHC pathology whereas those derived with high-level (90 dB pSPL) chirps were not. These results suggest that CAP-derived neural firing distributions for high-level chirps may provide an estimate of auditory nerve survival that is independent of OHC pathology.


Subject(s)
Action Potentials/physiology , Cochlear Nerve/physiology , Noise , Perceptual Masking/physiology , Acoustic Stimulation , Action Potentials/drug effects , Animals , Auditory Threshold , Central Nervous System Agents/pharmacology , Cochlear Diseases/physiopathology , Cochlear Nerve/drug effects , Dose-Response Relationship, Drug , Gentamicins/pharmacology , Gerbillinae , Hair Cells, Auditory/physiology , Hearing Loss, Sensorineural/physiopathology , Neural Conduction/physiology , Reaction Time
19.
Ear Hear ; 31(1): 7-21, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19838117

ABSTRACT

OBJECTIVE: Advances in cochlear hair-cell regeneration, neural regeneration, and genetic therapy encourage continued development of diagnostic tests that can accurately specify the appropriate target within the cochlea and auditory nerve for delivery of therapeutic agents. In this study, we test the hypothesis that the morphology of the acoustically evoked compound action potential (CAP) may reflect the condition of the auditory nerve in individuals with sensorineural hearing loss. DESIGN: CAPs to tone burst stimuli at octave frequencies from 1 to 16 kHz were recorded at low- to high-stimulus levels from sedated Mongolian gerbils with partial lesions of the auditory nerve (n = 10). Distortion-product otoacoustic emissions were measured to ensure preservation of normal outer hair-cell function. CAPs were analyzed with conventional measures of N1 latency and amplitude and by fitting the CAPs with a mathematical model that includes a parameter (N) representing the number of nerve fibers contributing to the CAP and a parameter (f) representing the oscillation frequency of the CAP waveform. Nerve fiber density and percent normal nerve area were estimated from cross-sections of the auditory nerve bundle. RESULTS: Despite substantial lesions in the auditory nerve, CAP thresholds remained within normal or were only moderately elevated and were not correlated with histological measures of nerve fiber density and normal nerve area. At high-stimulus levels, the model parameter N was strongly correlated with nerve fiber density for three of the five test frequencies and with normal nerve area for all five test frequencies. Correlations between N1 amplitude measures at high-stimulus levels and our histological measures were also significant for the majority of test frequencies, but they were generally weaker than the correlations for the model parameter N. The model parameter f, at low- and high-stimulus levels, was also positively correlated with measures of normal nerve area. CONCLUSIONS: Consistent with previous findings, physiological measures of threshold were not correlated with partial lesions of the auditory nerve. The model parameter N at high-stimulus levels was strongly correlated with normal nerve area suggesting, that it is a good predictor of auditory nerve survival. The model parameter N also seemed to be a better predictor of the condition of the auditory nerve than the conventional measure of N1 amplitude. Because the model parameter f was correlated with normal nerve area at low- and high-stimulus levels, it may provide information on the functional status of the auditory nerve.


Subject(s)
Cell Survival/physiology , Cochlear Nerve/physiopathology , Hearing Loss, Sensorineural/physiopathology , Animals , Auditory Threshold/physiology , Cochlear Nerve/pathology , Gerbillinae , Hair Cells, Auditory/pathology , Hair Cells, Auditory/physiology , Hearing Loss, Sensorineural/therapy , Nerve Fibers/pathology , Nerve Fibers/physiology , Otoacoustic Emissions, Spontaneous/physiology
20.
Int J Pediatr Otorhinolaryngol ; 71(11): 1789-95, 2007 Nov.
Article in English | MEDLINE | ID: mdl-17870187

ABSTRACT

OBJECTIVE: The first purpose of this study was to compare transient evoked otoacoustic emissions (TEOAE) with distortion product otoacoustic emissions (DPOAE) to determine if they resulted in equivalent signal-to-noise ratios (SNRs) when used for hearing screening in a preschool population in a community setting. The second purpose was to determine if the OAE methods would result in equivalent pass/refer rates. The third purpose was to determine the agreement between the pass/refer rates from a tympanometric screening and the pass/refer rates from each OAE method. METHODS: Thirty-three preschool children ages 4 months to 4 years, 4 months were tested using DPOAE and TEOAE. The frequencies 800-4000Hz were compared. The tympanometric gradient was obtained from a tympanogram done on each ear. A multivariate statistic was used to compare the emission SNR from both methods. A chi(2) statistic was used to compare the pass/refer rates from both methods. The agreement between the pass/refer rates from the OAE screens and from the tympanometric gradient were compared. RESULTS: TEOAE and DPOAE SNRs were significantly different in the low frequency however, there were no significant differences found in the high frequencies. There were no significant pass/refer differences found between the methods at any frequency. When comparing the agreement between the OAE methods with the tympanometry, both methods produced nearly equivalent agreement with tympanometric gradient. However, the overall correspondence between OAE findings and tympanometry was not perfect. CONCLUSIONS: Both methods are effective and especially equivalent in the high frequencies and can be recommended for use in a preschool population in the field. Tympanometric gradient disagreed with both OAE screening results about 25% of the time. Finally, our study also found that higher refer rates can be expected when young (<3 years) preschool children are included in the screen.


Subject(s)
Acoustic Stimulation/methods , Hearing Disorders/diagnosis , Hearing Disorders/epidemiology , Mass Screening/instrumentation , Otoacoustic Emissions, Spontaneous/physiology , Acoustic Impedance Tests , Child, Preschool , Community Health Services/statistics & numerical data , Female , Humans , Infant , Male
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