Anatomical variability, multi-modal coordinate systems, and precision targeting in the marmoset brain.

Localising accurate brain regions needs careful evaluation in each experimental species due to their individual variability. However, the function and connectivity of brain areas is commonly studied using a single-subject cranial landmark-based stereotactic atlas in animal neuroscience. Here, we address this issue in a small primate, the common marmoset, which is increasingly widely used in systems neuroscience. We developed a non-invasive multi-modal neuroimaging-based targeting pipeline, which accounts for intersubject anatomical variability in cranial and cortical landmarks in marmosets. This methodology allowed creation of multi-modal templates (MarmosetRIKEN20) including head CT and brain MR images, embedded in coordinate systems of anterior and posterior commissures (AC-PC) and CIFTI grayordinates. We found that the horizontal plane of the stereotactic coordinate was significantly rotated in pitch relative to the AC-PC coordinate system (10 degrees, frontal downwards), and had a significant bias and uncertainty due to positioning procedures. We also found that many common cranial and brain landmarks (e.g., bregma, intraparietal sulcus) vary in location across subjects and are substantial relative to average marmoset cortical area dimensions. Combining the neuroimaging-based targeting pipeline with robot-guided surgery enabled proof-of-concept targeting of deep brain structures with an accuracy of 0.2 mm. Altogether, our findings demonstrate substantial intersubject variability in marmoset brain and cranial landmarks, implying that subject-specific neuroimaging-based localization is needed for precision targeting in marmosets. The population-based templates and atlases in grayordinates, created for the first time in marmoset monkeys, should help bridging between macroscale and microscale analyses.

[A Trial of Unified Management of Language Tasks Using a Tablet Device for Language Area Mapping].

Language tasks must be based on perioperative neuropsychological evaluation during intraoperative language area mapping for the resection of brain tumor near the language cortex under awake craniotomy. However, flexibility is needed during surgery, because actions during surgery must change based on neurological symptoms and the presence or absence of aphasia. Here, we developed software to assess patients' ability to complete language tasks during surgery by using a tablet device; these language tasks serve as indicators of changes in patient status. We examined its effectiveness through the use of the software. In this case, the patient was a 68-year-old female. Before the surgery, the patient exhibited transcortical sensory aphasia. However, 1 day before the surgery, she exhibited worsening of language symptoms. We prepared a language task on the tablet device based on the patient's ability to complete the task before the surgery. The patient's wakefulness baseline was different from that predicted before the surgery. However, we were able to modify the surgical plan by using the results of the language task on the tablet device. In addition, we were able to finish mapping in approximately 90 minutes.

Individual identity and affective valence in marmoset calls: in vivo brain imaging with vocal sound playback.

As with humans, vocal communication is an important social tool for nonhuman primates. Common marmosets (Callithrix jacchus) often produce whistle-like 'phee' calls when they are visually separated from conspecifics. The neural processes specific to phee call perception, however, are largely unknown, despite the possibility that these processes involve social information. Here, we examined behavioral and whole-brain mapping evidence regarding the detection of individual conspecific phee calls using an audio playback procedure. Phee calls evoked sound exploratory responses when the caller changed, indicating that marmosets can discriminate between caller identities. Positron emission tomography with [18F] fluorodeoxyglucose revealed that perception of phee calls from a single subject was associated with activity in the dorsolateral prefrontal, medial prefrontal, orbitofrontal cortices, and the amygdala. These findings suggest that these regions are implicated in cognitive and affective processing of salient social information. However, phee calls from multiple subjects induced brain activation in only some of these regions, such as the dorsolateral prefrontal cortex. We also found distinctive brain deactivation and functional connectivity associated with phee call perception depending on the caller change. According to changes in pupillary size, phee calls from a single subject induced a higher arousal level compared with those from multiple subjects. These results suggest that marmoset phee calls convey information about individual identity and affective valence depending on the consistency or variability of the caller. Based on the flexible perception of the call based on individual recognition, humans and marmosets may share some neural mechanisms underlying conspecific vocal perception.

Marmoset Serotonin 5-HT1A Receptor Mapping with a Biased Agonist PET Probe 18F-F13714: Comparison with an Antagonist Tracer 18F-MPPF in Awake and Anesthetized States.

BACKGROUND: In vivo mapping by positron emission tomography of the serotonin 1A receptors has been hindered by the lack of suitable agonist positron emission tomography probes. 18F-labeled F13714 is a recently developed biased agonist positron emission tomography probe that preferentially targets subpopulations of serotonin 1A receptors in their "active state," but its brain labeling pattern in nonhuman primate has not been described. In addition, a potential confound in the translatability of PET data between nonhuman animal and human arise from the use of anesthetics that may modify the binding profiles of target receptors. METHODS: Positron emission tomography scans were conducted in a cohort of common marmosets (n=4) using the serotonin 1A receptor biased agonist radiotracer, 18F-F13714, compared with a well-characterized 18F-labeled antagonist radiotracer, 18F-MPPF. Experiments on each animal were performed under both consciousness and isoflurane-anesthesia conditions. RESULTS: 18F-F13714 binding distribution in marmosets by positron emission tomography differs markedly from that of the 18F-MPPF. Whereas 18F-MPPF showed highest binding in hippocampus and amygdala, 18F-F13714 showed highest labeling in other regions, including insular and cingulate cortex, thalamus, raphe, caudate nucleus, and putamen. The binding potential values of 18F-F13714 were about one-third of those observed with 18F-MPPF, with marked individual- and region-specific differences under isoflurane-anesthetized vs conscious conditions. CONCLUSIONS: These findings highlight the importance of investigating the brain imaging of serotonin 1A receptors using agonist probes such as 18F-F13714, which may preferentially target subpopulations of serotonin 1A receptors in specific brain regions of nonhuman primate as a biased agonist.

Linkage between the midline cortical serotonergic system and social behavior traits: positron emission tomography studies of common marmosets.

Serotonin is known to play an important role not only in regulating emotional behaviors, but also in the formation of social behavior traits. To determine the location and serotonin function of brain areas involved in social behavior traits, we tested serotonin transporter (SERT) binding and neural activity linked with the social behaviors of common marmosets with positron emission tomography using [(11)C]-3-amino-4-(2-dimetylaminomethyl-phenylsulfanyl)-benzonitrile and [(18)F]fluorodeoxyglucose, respectively. Factor analysis of behavioral measures during a direct encounter between unfamiliar adult males identified three classes of social behavioral traits: (1) aggressive, (2) anxious, and (3) unfriendly (opposite of friendly). Voxel-based analysis revealed a significant association between SERT binding with the social behavioral traits in the midline cortical subregions. Aggressive and friendly traits are localized to the posterior cingulate cortex, and the anxious trait is localized to the anterior cingulate cortex. In addition, neural activity and functional connectivity of the posterior and anterior cingulate cortices appear to be altered depending on the social situation. These results suggest that the midline cortical serotonergic system is crucial in social behavior traits and its subregions are functionally segregated in socio-emotional processing.

Neuroregulatory Effects of Microcone Patch Stimulation on the Auricular Branch of the Vagus Nerve and the Prefrontal Cortex: A Feasibility Study.

Background: The primary purpose of this study was to preliminarily examine the effects of autonomic nervous system activity on the dorsolateral prefrontal cortex. Recent studies have examined approaches to modulating autonomic activity using invasive and non-invasive methods, but the effects of changes in autonomic activity during cognitive tasks on the dorsolateral prefrontal cortex have not been fully investigated. The purpose of this preliminary investigation was to examine changes in autonomic activity and blood oxygen saturation in the dorsolateral prefrontal cortex during reading tasks induced by vagus nerve stimulation using a microcone patch. Methods: A cohort of 40 typically developing adults was enrolled in this study. We carefully examined changes in autonomic nervous system activity and blood oxygen saturation in the dorsolateral prefrontal cortex during a reading task in two conditions: with and without microcone patch stimulation. Results: Significant changes in brain activation in the dorsolateral prefrontal cortext due to microcone patch stimulation were confirmed. In addition, hierarchical multiple regression analysis revealed specific changes in reading task-related blood oxygen saturation in the dorsolateral prefrontal region during microcone patch stimulation. Conclusions: It should be recognized that this study is a preliminary investigation and does not have immediate clinical applications. However, our results suggest that changes in autonomic nervous system activity induced by external vagal stimulation may affect activity in specific reading-related regions of the dorsolateral prefrontal cortex. Further research and evaluation are needed to fully understand the implications and potential applications of these findings.

Cortical adaptation of the night monkey to a nocturnal niche environment: a comparative non-invasive T1w/T2w myelin study.

Night monkeys (Aotus) are the only genus of monkeys within the Simian lineage that successfully occupy a nocturnal environmental niche. Their behavior is supported by their sensory organs' distinctive morphological features; however, little is known about their evolutionary adaptations in sensory regions of the cerebral cortex. Here, we investigate this question by exploring the cortical organization of night monkeys using high-resolution in-vivo brain MRI and comparative cortical-surface T1w/T2w myeloarchitectonic mapping. Our results show that the night monkey cerebral cortex has a qualitatively similar but quantitatively different pattern of cortical myelin compared to the diurnal macaque and marmoset monkeys. T1w/T2w myelin and its gradient allowed us to parcellate high myelin areas, including the middle temporal complex (MT +) and auditory cortex, and a low-myelin area, Brodmann area 7 (BA7) in the three species, despite species differences in cortical convolutions. Relative to the total cortical-surface area, those of MT + and the auditory cortex are significantly larger in night monkeys than diurnal monkeys, whereas area BA7 occupies a similar fraction of the cortical sheet in all three species. We propose that the selective expansion of sensory areas dedicated to visual motion and auditory processing in night monkeys may reflect cortical adaptations to a nocturnal environment.

Switching of the enzymatic activity synchronized with signal recognition by an artificial DNA receptor on a liposomal membrane.

We constructed a supramolecular system on a liposomal membrane that is capable of activating an enzyme via DNA hybridization. The design of the system was inspired by natural signal transduction systems, in which enzymes amplify external signals to control signal transduction pathways. The liposomal membrane, providing a platform for the system, was prepared by the self-assembly of an oligonucleotide lipid, a phospholipid and a cationic synthetic lipid. The enzyme was immobilized on the liposomal surface through electrostatic interactions. Selective recognition of DNA signals was achieved by hybridizing the DNA signals with the oligonucleotide lipid embedded in the liposome. The hybridized DNA signal was sent to the enzyme by a copper ion acting as a mediator species. The enzyme then amplified the event by the catalytic reaction to generate the output signal. In addition, our system demonstrated potential for the discrimination of single nucleotide polymorphisms.

Automated segmentation of an intensity calibration phantom in clinical CT images using a convolutional neural network.

PURPOSE: In quantitative computed tomography (CT), manual selection of the intensity calibration phantom's region of interest is necessary for calculating density (mg/cm3) from the radiodensity values (Hounsfield units: HU). However, as this manual process requires effort and time, the purposes of this study were to develop a system that applies a convolutional neural network (CNN) to automatically segment intensity calibration phantom regions in CT images and to test the system in a large cohort to evaluate its robustness. METHODS: This cross-sectional, retrospective study included 1040 cases (520 each from two institutions) in which an intensity calibration phantom (B-MAS200, Kyoto Kagaku, Kyoto, Japan) was used. A training dataset was created by manually segmenting the phantom regions for 40 cases (20 cases for each institution). The CNN model's segmentation accuracy was assessed with the Dice coefficient, and the average symmetric surface distance was assessed through fourfold cross-validation. Further, absolute difference of HU was compared between manually and automatically segmented regions. The system was tested on the remaining 1000 cases. For each institution, linear regression was applied to calculate the correlation coefficients between HU and phantom density. RESULTS: The source code and the model used for phantom segmentation can be accessed at https://github.com/keisuke-uemura/CT-Intensity-Calibration-Phantom-Segmentation . The median Dice coefficient was 0.977, and the median average symmetric surface distance was 0.116 mm. The median absolute difference of the segmented regions between manual and automated segmentation was 0.114 HU. For the test cases, the median correlation coefficients were 0.9998 and 0.999 for the two institutions, with a minimum value of 0.9863. CONCLUSION: The proposed CNN model successfully segmented the calibration phantom regions in CT images with excellent accuracy.

Low Immunogenicity and Immunosuppressive Properties of Human ESC- and iPSC-Derived Retinas.

ESC- and iPSC-derived retinal transplantation is a promising therapeutic approach for disease with end-stage retinal degeneration, such as retinitis pigmentosa and age-related macular degeneration. We previously showed medium- to long-term survival, maturation, and light response of transplanted human ESC- and iPSC-retina in mouse, rat, and monkey models of end-stage retinal degeneration. Because the use of patient hiPSC-derived retina with a disease-causing gene mutation is not appropriate for therapeutic use, allogeneic transplantation using retinal tissue/cells differentiated from a stocked hESC and iPSC line would be most practical. Here, we characterize the immunological properties of hESC- and iPSC-retina and present their three major advantages: (1) hESC- and iPSC-retina expressed low levels of human leukocyte antigen (HLA) class I and little HLA class II in vitro, (2) hESC- and iPSC-retina greatly suppressed immune activation of lymphocytes in co-culture, and (3) hESC- and iPSC-retina suppressed activated immune cells partially via transforming growth factor ß signaling. These results support the use of allogeneic hESC- and iPSC-retina in future clinical application.

Mapping of serotonin transporters by positron emission tomography with [11C]DASB in conscious common marmosets: comparison with rhesus monkeys.

The common marmoset (Callithrix jacchus) is unique among the primates in its small body size, reproductive efficacy, and characteristic social behavior, making it useful as an animal model in neuroscientific research. To assess the brain serotonergic systems, we investigated the binding of [(11)C]-3-amino-4-(2-dimetylaminomethyl-phenylsulfanyl)-benzonitrile ([(11)C]DASB) to brain serotonin transporter (SERT) in conscious common marmosets using positron emission tomography (PET), and compared with findings for rhesus monkeys. Both species showed globally similar distribution patterns of [(11)C]DASB uptake in the brain, with highest activity in the midline of the brain and lowest in the cerebellum, and higher activity in some subcortical regions than in surrounding cortex, while the common marmoset brain showed almost equal or rather higher binding potential (BP) values (BP(ND)) in cortical regions and hippocampus, and lower BP(ND) than the rhesus monkey brain in some subcortical regions. Test-retest reproducibility of BP(ND) at an interval of several months was high, indicating reliable and stable measurements of serotonin transporters in both species. These results suggest that SERT imaging by PET with [(11)C]DASB under conscious state is valuable for investigating the physiological serotonergic functions in common marmosets (182).

Developmental dysgraphia with profound hearing impairment: intervention by auditory methods enabled by cochlear implant.

Learning disability combined with hearing impairment (LDHI) is a poor prognostic factor for the language development of hearing impaired children after educational intervention. A typical example of a child with LDHI and effective interventions provided by cochlear implants are presented in this report. A case of congenital cytomegaloviral infection that showed dysgraphia as well as profound deafness was reported and an underlying visual processing problem diagnosed in the present case caused the patient's dysgraphia. The dysgraphia could be circumvented by the use of auditory memory fairly established by a cochlear implant.

Cochlear expression of a dominant-negative GJB2R75W construct delivered through the round window membrane in mice.

Development of a gene-delivery method to the inner ear is an essential step for studies of hearing function and gene therapy. Application of liposomes or adenoviral vectors onto the intact round window membrane (RWM) offers the possibility of atraumatic exogenous gene transfer. GJB2 encodes the gap junction protein Connexin26, which plays a crucial role in potassium recycling in the inner ear. The R75W allele of GJB is a well-characterized mutation that causes deafness at the DFNA3 through a dominant-negative mechanism of action. In this study, a plasmid vector, pGJB2(R75W)-eGFP, was lipocomplexed with N-[1-(2,3-Dioleoloxy)propyl]N,N,N-trimethylammonium methylsulfate: cholesterol and applied onto mouse RWM. At 3 days (3d) post-treatment, immunohistochemistry demonstrated GJB2(R75W)-eGFP transgene expression in the cochlea in: inner and outer pillar cells, outer hair cells, Claudius cells and, in the spiral limbus and ligament. Significant hearing loss was detected by auditory brainstem response testing after 1, 2 and 3d post-treatment; hearing levels returned to control levels at 5d post-treatment. These data confirm that GJB2(R75W) induces functional impairment in the mature cochlea through a dominant negative effect, and importantly, that RWM application of exogenous genes is a feasible method to test their impact on hearing.

Comprehension of abstract words among hearing impaired children.

INTRODUCTION: This study examines the ability and development in the comprehension of abstract words with hearing impaired children. The ability to understand abstract words is quite important for their academic learning and adaptation in their school life. Here, we qualitatively and quantitatively analyzed the development of abstract vocabulary in hearing impaired children using The Standardized Comprehension Test for Abstract Words (SCTAW). SUBJECTS AND METHODS: We examined 75 hearing impaired children (hearing aid users, 61; cochlear implant users, 14; 1st to 10th grade) and 188 children with normal hearing (1st to 6th grade) using the Picture Vocabulary Test (PVT) and SCTAW. RESULTS: The PVT and SCTAW results closely correlated (r=0.87). The SCTAW scores of the hearing impaired group were lower than those of their peers with normal hearing, but the scores improved as their school grade advanced. In particular, their abstract ability began to catch up from the fifth grade. The error trends of abstract vocabulary in the two groups did not significantly differ. CONCLUSIONS: The SCTAW was useful as an abstract lexical evaluation of hearing impaired children. The development of an abstract vocabulary did not qualitatively differ between children with or without a hearing impairment.

Using assessment of higher brain functions of children with GJB2-associated deafness and cochlear implants as a procedure to evaluate language development.

OBJECTIVE: While investigators have reported that patients with GJB2-associated deafness and cochlear implants have preferable language development, the mechanisms of this phenomenon remains unknown. The goal of the present study was to assess higher brain functions of patients with GJB2-related and GJB2-unrelated deafness as a method of evaluating language development. METHODS: Eight children with cochlear implants were subjected to genetic testing for GJB2 and underwent the Raven colored progressive matrices test, Rey's auditory verbal learning test, Rey's complex figure test, the standardized language test for aphasia, the picture vocabulary test, and the standardized comprehension test for abstract words. RESULTS: Three children were diagnosed with GJB2-related deafness, and five children were diagnosed with GJB2-unrelated deafness. All three GJB2-related cases demonstrated normal range higher brain functions and fair language development. By contrast, one GJB2-unrelated case showed a semantic disorder, another demonstrated a visual cognitive disorder with dyslexia, and another had attention deficit-hyperactivity disorder. CONCLUSIONS: Children with GJB2-unrelated deafness showed a high frequency of heterogeneous disorders that can affect proper language development. This difference between children with GJB2-related and GJB2-unrelated deafness may account for the improved language development in children with GJB2-related deafness and cochlear implants. Further, genetic diagnosis of the non-syndromic hearing loss represents a useful tool for the preoperative prediction of outcomes following a cochlear implant procedure.

Longitudinal formant analysis after cochlear implantation in school-aged children.

INTRODUCTION: The purpose of this investigation was to describe the correlation between vocal and hearing development by longitudinal analysis of sound spectrograms, as a basic system for evaluating progress in vocal development. SUBJECTS AND METHODS: Two school-aged children with prelingual deafness were evaluated diachronically to assess speech perception and speech intelligibility after cochlear implantation. One child had non-syndromic hearing impairment without any known neurological deficit except for hearing loss, while the other had hearing impairment accompanied by mild mental retardation and attention deficit disorder. Their voices were recorded for monthly follow-up after cochlear implantation; these were used for formant analysis and compared with their mother's voice, and alteration of the formant data was also compared with monosyllable speech perception. RESULTS: Formant analysis demonstrated high concordance was observed between monosyllable speech perception and speech intelligibility. F1-F2 forms of the patients more closely resembled those of their mothers after 1 year's follow-up. The time point at which speech development altered was very similar in both cases although the final outcomes were different. CONCLUSION: Fair improvement of articulation after cochlear implant was demonstrated by the F1-F2 gram analysis. This procedure can be used for data sharing and cooperation between medical and educational specialists.

Reduced neurotoxicity with combined treatment of high-dose methotrexate, cyclophosphamide, doxorubicin, vincristine and prednisolone (M-CHOP) and deferred radiotherapy for primary central nervous system lymphoma.

OBJECTIVE: Although high-dose methotrexate and whole-brain radiation therapy (WBRT) is the current standard for primary central nervous system lymphoma (PCNSL), it has a limited response rate and produces radiation-induced neurotoxicity. We report the effect of a combined treatment of high-dose methotrexate, cyclophosphamide, doxorubicin, vincristine and prednisolone (M-CHOP) for immunocompetent patients with PCNSL. METHODS: We analyzed 24 patients who had received M-CHOP administered in 28-day cycles with or without WBRT. The response rate to M-CHOP, overall survival (OS), and recurrence-free survival (RFS) were analyzed. RESULTS: Nine patients were treated with M-CHOP plus WBRT and 15 patients were treated with M-CHOP alone. Twenty-one patients achieved a complete response and three patients achieved a partial response to M-CHOP, for a 100% response rate. With a median follow-up of 70 months, the median OS and RFS were 33 and 13 months, respectively. The median OS for patients treated with M-CHOP plus WBRT and M-CHOP alone was 33 and 32 months, respectively. Of the 13 patients whose age was above 65 years, the median OS for the M-CHOP plus WBRT group (two patients) and the M-CHOP alone group (11 patients) was 14 and 32 months, respectively. Toxicities related to M-CHOP were mostly hematologic and generally mild to moderate. Two patients whose age was above 65 years in the M-CHOP plus WBRT group developed neurotoxicity. CONCLUSION: Combined treatment with M-CHOP was well tolerated and produced a high response rate. Deferring WBRT was associated with reduced neurotoxicity without worsening the prognosis, especially in elderly patients.

Evaluation of dopamine D2/D3 and serotonin 5-HT2A receptor occupancy for a novel antipsychotic, lurasidone, in conscious common marmosets using small-animal positron emission tomography.

RATIONALE: Lurasidone is a novel antipsychotic drug with potent binding affinity for dopamine D(2) and serotonin (5-hydroxytryptamine, 5-HT)(2A), 5-HT(7), and 5-HT(1A) receptors. Previous pharmacological studies have revealed that lurasidone exhibits a preferable profile (potent antipsychotic activity and lower incidence of catalepsy) to other antipsychotic drugs, although the contribution of receptor subtypes to this profile remains unclear. OBJECTIVES: To compare target engagements of lurasidone with those of an atypical antipsychotic, olanzapine, we performed evaluation of dopamine D(2)/D(3) and serotonin 5-HT(2A) receptor occupancy in vivo by positron emission tomography (PET) with conscious common marmosets. METHODS: We measured brain receptor occupancies in conscious common marmosets after oral administrations of lurasidone or olanzapine by PET with [(11)C]raclopride and [(11)C]R-(+)-α-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-piperidine methanol (MDL 100907) for D(2)/D(3) and 5-HT(2A) receptors, respectively. RESULTS: Increases in brain D(2)/D(3) receptor occupancies of both lurasidone and olanzapine, which reached >80 % at maximum, were observed in the striatum with significant correlations to plasma drug levels. However, lurasidone showed lower 5-HT(2A) receptor occupancy in the frontal cortex within the same dose range, while olanzapine showed broadly comparable 5-HT(2A) and D(2)/D(3) receptor occupancies. CONCLUSIONS: Compared with olanzapine, lurasidone preferentially binds to D(2)/D(3) receptors rather than 5-HT(2A) receptors in common marmosets. These results suggest that the contribution of in vivo 5-HT(2A) receptor blocking activity to the pharmacological profile of lurasidone might differ from olanzapine in terms of the low risk of extrapyramidal syndrome and efficacy against negative symptoms.

Recombinant human bone morphogenetic protein-2/atelocollagen composite as a new material for ossicular reconstruction.

Ossicular reconstruction is the rebuilding of the damaged middle ear. There are many different prosthesis and techniques used to reconstruct the middle ear ossicles. However, precision in the surgical procedures and prostheses used for ossiculoplasty are still imperfect. The objective of this study was to evaluate the potential of recombinant human bone morphogenetic protein-2 (rhBMP-2)/ atelocollagen composite for ossicular reconstruction implanted in the tympanic cavity of rat. The ossicles were extirpated by perforating the tympanic membranes of rats. rhBMP-2/atelocollagen composite was implanted as substitute of ossicles in intimate contact with the tympanic membrane. Composites were subjected to histological, immunohistochemical, and radiological examination. To evaluate the auditory function, auditory brainstem response (ABR) was measured. rhBMP-2/atelocollagen composites showed good stability and durability without any inflammatory reaction within the tympanic cavity. The process of new bone formation was similar to intramembranous ossification. They also demonstrated that the hearing ability was re-established by ABR threshold shifts. rhBMP-2/atelocollagen composite exhibited excellent potential for ossicular reconstruction, maintaining their vibratory function. This ossicular tissue engineering may be considered as a future therapeutic strategy for ossiculoplasty.

Auditory steady-state responses to multiple simultaneous stimuli in children with functional or sensorineural hearing loss.

The goal of our study was to identify the role of auditory steady-state responses for hearing assessment in patients with functional hearing loss. The study design was to compare auditory steady-state response thresholds and standard pure-tone audiometry thresholds between patients with functional or sensorineural hearing loss. Subjects comprised 16 patients (24 ears) with functional hearing loss and 17 patients (24 ears) with sensorineural hearing loss. Differences and correlations between auditory steady-state response thresholds and standard pure-tone audiometry thresholds at 500, 1,000, 2,000 and 4,000 Hz were evaluated. In children with functional hearing loss, pure-tone audiometry thresholds and auditory steady-state response thresholds were significantly different at all frequencies and were not significantly correlated. In patients with sensorineural hearing loss, pure-tone audiometry thresholds and auditory steady-state response thresholds did not differ significantly at any frequencies and were significantly correlated. Auditory steady-state responses may have principal role in the assessment of auditory brainstem acuity, particularly at low frequencies in patients with functional hearing loss.