Different time courses of maturation for learning and generalization following auditory training in children.

OBJECTIVE: We recently demonstrated that learning abilities among school-age children vary following frequency discrimination (FD) training, with some exhibiting mature adult-like learning while others performing poorly (non-adult-like learners). This study tested the hypothesis that children's post-training generalisation is related to their learning maturity. Additionally, it investigated how training duration influences children's generalisation, considering the observed decrease with increased training in adults. DESIGN: Generalisation to the untrained ear and untrained 2000 Hz frequency was assessed following single-session or nine-session 1000 Hz FD training, using an adaptive forced-choice procedure. Two additional groups served as controls for the untrained frequency. STUDY SAMPLE: Fifty-four children aged 7-9 years and 59 adults aged 18-30 years. RESULTS: (1) Only adult-like learners generalised their learning gains across frequency or ear, albeit less efficiently than adults; (2) As training duration increased children experienced reduced generalisation, similar to adults; (3) Children's performance in the untrained tasks correlated strongly with their trained task performance after the first training session. CONCLUSIONS: Auditory skill learning and its generalisation do not necessarily mature contemporaneously, although mature learning is a prerequisite for mature generalisation. Furthermore, in children, as in adults, more practice makes rather specific experts. These findings should be considered when designing training programs.

Non-memory subjective cognitive concerns predict incident motoric cognitive risk syndrome.

BACKGROUND AND PURPOSE: Motoric cognitive risk syndrome (MCR) is a predementia condition that combines slow gait and subjective cognitive concerns. As the earliest markers of MCR are relatively unknown, the role of subjective cognitive concerns was investigated to predict incident MCR in a well-characterized prospective cohort of non-demented older adults. METHODS: Non-demented MCR-free older adults (n = 476) from the Central Control of Mobility in Aging cohort completed gait, subjective cognition and neuropsychological assessment at baseline and follow-up. Subjective concerns were analyzed via responses to 12 items from three validated measures, the Late-Life Function and Disability Instrument - Disability Component, the Activities of Daily Living Prevention Instrument and the Geriatric Depression Scale, and were independent of items utilized to diagnose MCR. Cox proportional hazard models examined the association between cognitive concerns and incident MCR. RESULTS: After 2.36 ± 1.4 years, 28 participants developed MCR. Executive functioning (adjusted hazard ratio 2.458, 95% confidence interval 1.094-5.524, P = 0.029) and mental clarity concerns (adjusted hazard ratio 3.917, 95% confidence interval 1.690-9.077, P = 0.001) were associated with incident MCR, controlling for age, sex, education and gait speed. CONCLUSIONS: Subjective cognitive concerns in non-memory cognitive domains predict incident MCR. Although most MCR studies assess cognitive concerns about memory, our findings suggest the need to broaden the scope of subjective cognitive assessment to enhance the accuracy of diagnosis and prediction of future cognitive decline.

World Trade Center exposure, post-traumatic stress disorder, and subjective cognitive concerns in a cohort of rescue/recovery workers.

OBJECTIVE: To determine whether World Trade Center (WTC)-exposure intensity and post-traumatic stress disorder (PTSD) are associated with subjective cognitive change in rescue/recovery workers. METHOD: The population included 7875 rescue/recovery workers who completed a subjective cognition measure, the Cognitive Function Instrument (CFI), between 3/1/2018 and 2/28/2019 during routine monitoring, indicating whether they had experienced cognitive and functional difficulties in the past year. Higher scores indicated greater self-perceived cognitive change. Probable PTSD, depression, and alcohol abuse were evaluated by validated mental health screeners. Logistic regression assessed the associations of WTC exposure and current PTSD with top-quartile (≥2) CFI score, and of early post-9/11 PTSD with top-quartile CFI in a subpopulation (N = 6440). Models included demographics, smoking, depression, and alcohol abuse as covariates. RESULTS: Mean age at CFI completion was 56.7 ± 7.7 (range: 36-81). Participants with high-intensity WTC exposure had an increased likelihood of top-quartile CFI score (odds ratio[OR] vs. low exposure: 1.32, 95%CI: 1.07-1.64), controlling for covariates. Current and early PTSD were both associated with top-quartile CFI (OR: 3.25, 95%CI: 2.53-4.19 and OR: 1.56, 95%CI: 1.26-1.93) respectively. CONCLUSIONS: High-intensity WTC exposure was associated with self-reported cognitive change 17 years later in rescue/recovery workers, as was PTSD. Highly WTC-exposed subgroups may benefit from additional cognitive evaluation and monitoring of cognition over time.

Suppression of HIV infection in AZT-treated SCID-hu mice.

The SCID-hu mouse, engrafted with human hematolymphoid organs, is permissive for infection with the human immunodeficiency virus (HIV). This mouse model was used to test compounds for antiviral efficacy. Two weeks after infection with HIV, 100 percent (40/40) of SCID-hu mice were positive for HIV by the polymerase chain reaction. When first treated with 3'-azido-3'-deoxythymidine (AZT), none (0/17) were HIV-positive by this assay. However, AZT-treated SCID-hu mice did have a few infected cells; after AZT treatment was stopped, viral spread was detected by polymerase chain reaction in such mice. Thus, the SCID-hu mouse provides a means to directly compare new antiviral compounds with AZT and to further improve antiviral efficacy.

Long-Term Training-Induced Gains of an Auditory Skill in School-Age Children As Compared With Adults.

The few studies that compared auditory skill learning between children and adults found variable results, with only some children reaching adult-like thresholds following training. The present study aimed to assess auditory skill learning in children as compared with adults during single- and multisession training. It was of interest to ascertain whether children who do not reach adult-like performance following a single training session simply require additional training, or whether different mechanisms underlying skill learning need to reach maturity in order to become adult-like performers. Forty children (7-9 years) and 45 young adults (18-35 years) trained in a single session. Of them, 20 children and 24 adults continued training for eight additional sessions. Each session included six frequency discrimination thresholds at 1000 Hz using adaptive forced-choice procedure. Retention of the learning-gains was tested 6 to 8 months posttraining. Results showed that (a) over half of the children presented similar performance and time course of learning as the adults. These children had better nonverbal reasoning and working memory abilities than their non-adult-like peers. (b) The best predicting factor for the outcomes of multisession training was a child's performance following one training session. (c) Performance gains were retained for all children with the non-adult-like children further improving, 6 to 8 months posttraining. Results suggest that mature auditory skill learning can emerge before puberty, provided that task-related cognitive mechanisms and task-specific sensory processing are already mature. Short-term training is sufficient, however, to reflect the maturity of these mechanisms, allowing the prediction of the efficiency of a prolonged training for a given child.

Preserved verb generation priming in global amnesia.

In the verb generation task, participants are presented with nouns and generate for each one an appropriate verb. Raichle et al. (Cerebral Cortex, 1994, 4, 8-26) found that when participants generated verbs to repeated nouns, generation latencies were reduced and different patterns of brain activation were present. In order to examine whether verb generation priming is dependent or independent of declarative memory, verb generation priming was compared between 13 amnesic (seven with alcoholic Korsakoff's syndrome, six with other etiologies) and 19 control participants (10 with a history of alcoholism). Both amnesic and control participants became faster across blocks on repeated nouns and slowed when novel nouns were introduced. Priming was verb specific for both groups: it was equivalent whether generated to a repeated or a novel noun. Verb generation priming, therefore, can occur independently of declarative memory.

Bile duct adenoma. A study of 152 cases.

In order to determine the morphologic spectrum of bile duct adenoma (BDA), we reviewed the clinical, gross, and histopathological features of 152 cases. All BDA were asymptomatic nodules discovered incidentally during intra-abdominal surgery (103 cases) or at autopsy (49 cases). They were usually subcapsular, ranged in size from 1 to 20 mm (mean, 5.8 mm), and were well circumscribed but nonencapsulated. Histologically, BDA was composed of benign, noncystic ductules and variable degrees of inflammation and fibrosis. The immunophenotype of these ductules was similar to that of interlobular bile ducts. Follow-up of 38 of the surgically treated patients confirmed the benign behavior of this lesion. BDA should be distinguished from an adenocarcinoma by the absence, in the former, of nuclear hyperchromasia, mitotic activity, and vascular invasion. The absence of bile and cystic changes and lack of association with polycystic disease of the liver and kidneys are the main features distinguishing BDA from von Meyenburg complex. We believe that BDA is a reactive process to a focal injury rather than a true neoplasm or a developmental anomaly.

Clear cell carcinoid tumor of the gallbladder: another distinctive manifestation of von Hippel-Lindau disease.

We describe a morphologically distinctive carcinoid tumor of the gallbladder that occurred in a 38-year-old man with von Hippel-Lindau (VHL) disease. The carcinoid tumor was composed predominantly of lipid-containing clear cells arranged in nests and tubules with pagetoid spread into the biliary epithelium and was interpreted as metastatic renal cell carcinoma. The neoplastic cells showed diffuse immunoreactivity for chromogranin, synaptophysin, cytokeratins (cytokeratin 7 and AE1/AE3) and, unexpectedly, for inhibin, but were negative for monoclonal carcinoembryonic antigen, serotonin and a variety of peptide hormones. This clear cell carcinoid tumor of the gallbladder was histologically similar to the recently described clear cell endocrine pancreatic tumor associated with VHL. Four cases of the latter tumor, which were also inhibin positive showed, in addition, focal and variable reactivity for the pancreatic hormones. Two classical carcinoid tumors of the gallbladder, two renal cell carcinomas associated with VHL and 11 of 13 sporadic endocrine pancreatic tumors (not associated with VHL) did not show immunoreactivity for inhibin. Inhibin appears to be an immunohistochemical marker for gallbladder clear cell carcinoid and clear cell endocrine pancreatic tumors associated with VHL and is a useful tool to distinguish these tumors from metastatic renal cell carcinoma. However, the basis for the inhibin positivity in these endocrine tumors is unknown.

Epithelioid hemangioendothelioma of the liver: a clinicopathologic and follow-up study of 32 cases.

The clinical, morphologic, and follow-up findings in 32 patients with a hitherto rarely reported tumor of the liver are reported. The study comprised 20 women (62.5 per cent) and 12 men (37.5 per cent) ranging in age from 19 to 86 years (average, 49.65 years). The tumors were discovered incidentally in four patients (12.5 per cent). Four patients (12.5 per cent) had jaundice attributable to the tumors; one of these patients experienced liver failure. One patient presented with an acutely painful abdomen due to hemoperitoneum. The remaining patients had nonspecific complaints. Grossly, the tumors were often multiple and involved both lobes of the liver. They were generally white and firm to hard. Microscopically, the neoplastic cells infiltrated sinusoids and intrahepatic veins of all sizes. Two types of tumor cells were identified--dendritic and epithelioid. Tumor cells were also vasoformative and synthesized Factor VIII-related antigen. Nine patients survived five years or longer. Two of these patients were alive five years, two nine years, one 12 years, and one 15 years after the onset of disease. Three patients died seven, ten, and 28 years, respectively, after the initial diagnosis. This vascular tumor has distinctive morphologic features that allow differentiation from sclerosing carcinoma and angiosarcoma. Although the prognosis is much more favorable than that for angiosarcoma, extrahepatic metastases occurred in nine of the patients (28 per cent) in this series. The biologic behavior of the tumor may be related in part to its matrix, which may show inflammation, dense sclerosis, and calcification.

Talc in liver tissue of intravenous drug abusers with chronic hepatitis. A comparative study.

To determine the frequency of talc microcrystals in liver tissue of intravenous (IV) drug abusers and the significance of this finding, the authors reviewed, with light and polarizing microscopy, sections of liver tissue from 70 patients with chronic hepatitis and a history of active (45) or past (25) IV drug abuse. Birefringent crystalline particles consistent with talc were found in 44 cases (63%), 31 associated with active and 13 with past drug abuse. The microcrystals were situated predominantly in hypertrophied portal macrophages; there were no well-formed granulomas. Scanning electron microscopic and energy-dispersive spectrophotometry performed on eight of the positive cases showed the characteristic "flake-pastry" appearance and chemical composition (silicon and magnesium) of talc. For comparison, the authors similarly examined 70 cases of posttransfusion chronic hepatitis, all of which had negative findings for talc, and 70 cases of chronic hepatitis with no documented risk factors for viral hepatitis, of which two had positive findings for talc, even though IV drug abuse was denied by the two patients. The authors conclude that talc is frequently present in the liver of IV drug abusers and whenever encountered it strongly suggests IV drug abuse. Only two patients (1.4%) with a negative history also had talc.

Morphometric study of hepatic ultrastructure in alcoholic hepatitis. Veterans Administration Cooperative Study Group on Alcoholic Hepatitis.

We undertook a morphometric analysis of hepatocellular organelles in an attempt to correlate their changes with the clinical stages of patients with alcoholic hepatitis. Although hepatic ultrastructural alterations did not correlate with disease severity, we found significant differences between patient and control groups in the measured parameters of non-organelle cytoplasm, mitochondria, SER, RER, glycogen, and lipid.

Hemochromatosis (HFE) gene sequence analysis of formalin-fixed, paraffin-embedded liver biopsy specimens.

BACKGROUND: Hereditary hemochromatosis (HH) is a common disease predominantly characterized by mutations of the HFE gene. METHODS AND RESULTS: We investigated the utility of HFE gene sequence analysis in the diagnosis of HH in 61 prospectively accrued formalin-fixed, paraffin-embedded liver biopsy specimens with clinical or histologic features suggestive of HH. Mutations in codons 63 or 282 of the HFE gene were identified by direct sequencing; in 21 of these samples, quantitative hepatic iron testing was also performed. Changes characteristic of HH were present in 16 (26%) of the cases, and 54% of the cases showed HFE gene mutations. The most common alteration was homozygous mutation of codon 282 (11 cases, 18%), followed by the combined 63 + 282 heterozygous mutation (3 cases, 5%). Two cases (3%) showed biallelic mutation of codon 63. The other 28 cases (46%) showed no sequence abnormalities. Weak iron staining did not exclude HH; intense staining did not reliably predict HH. CONCLUSION: When HH is clinically and/or histologically suspected, HFE gene sequencing of formalin-fixed, paraffin-embedded liver biopsy specimens is a rapid and cost-effective approach to genotypic diagnosis of HH.

A brief medical necessity scale for mental disorders: reliability, validity, and clinical utility.

Managed care organizations (MCOs) use the concept of "medical necessity" to decide whether a prescribed treatment is warranted for a given medical condition. Because mental disorders lack the objective disease criteria common to medical illness, behavioral health administrators need a validated means to identify and quantify the severity of "medically important" aspects of mental disorders. The authors developed and tested a brief medical necessity scale for mental disorders in 205 patients presenting for initial evaluation. The scale had a factor structure with four subscales; good internal consistency, interrater reliability, and concurrent and predictive validity; and modest ability to identify patients requiring hospitalization and, in hospitalized patients, those requiring involuntary hospitalization. The authors propose use of the scale to better clarify decisions about level of care assignments and to better assess patient characteristics predictive of good outcome.

Multisensory speech perception of young children with profound hearing loss.

The contribution of a two-channel vibrotactile aid (Trill VTA 2/3, AVR Communications LTD) to the audiovisual perception of speech was evaluated in four young children with profound hearing loss using words and speech pattern contrasts. An intensive, hierarchical, and systematic training program was provided. The results show that the addition of the tactile (T) modality to the auditory and visual (A+V) modalities enhanced speech perception performance significantly on all tests. Specifically, at the end of the training sessions, the tactile supplementation increased word recognition scores in a 44-word, closed-set task by 12 percentage points; detection of consonant in final position by 50 percentage points; detection of sibilant in final position by 30 percentage points; and detection of voicing in final position by 25 percentage points. Significant learning over time was evident for all test materials, in all modalities. As expected, fastest learning (i.e., smallest time constants) was found for the AVT condition. The results of this study provide further evidence that sensory information provided by the tactile modality can enhance speech perception in young children.

The perception of phonologically significant contrasts using speech envelope cues.

The observation that many cochlear implantees demonstrate high levels of speech recognition, despite limited or distorted spectral information, has motivated research on the importance of temporal information for the perception of speech. The purpose of this study was to measure the recognition of speech contrasts via only the speech envelope before and after training. Test stimuli consisted of eight segmental and two suprasegmental contrasts of the Hebrew Speech Pattern Contrast test using a binary forced-choice paradigm. Multiplying the speech waveform with white noise eliminated spectral information. Results show that stress, intonation and manner of articulation were very well perceived using only temporal information, whereas voicing and place of articulation were perceived above chance levels. Results also show that vowels were more susceptible to the removal of spectral information than consonants. These findings help to better understand speech perception performance of hearing-impaired individuals, including cochlear implant users. They may also have practical implications for aural rehabilitation and sensory aids design for the Hebrew speaking population.

Identification of the relative onset time of a two-tone complex: auditory sensitivity or language based?

Categorical perception occurs when equal physical differences on a continuum sometimes cause no changes in the identification of a stimulus, while at other points on the same continuum, that difference causes an abrupt change in perception. One of the unresolved issues regarding this phenomenon is what determines categorical perception: a special speech mode or "natural" psychophysical boundaries. One way to answer this question is by investigating categorical perception with non-speech stimuli. An example is the identification of the relative onset of a two-tone complex (TOT) analogous to voice-onset time (VOT), the acoustic cue to voicing in initial position. Studies in English found similar category boundaries for TOT and VOT (at +20 ms) supporting the non-speech specific theory. The purpose of this study was to investigate TOT in Hebrew-speaking listeners whose language uses very different VOT values from those reported in English. Twenty Hebrew-speaking young adults participated in this study. Stimuli consisted of a two-tone complex that varied in the relative onset time of the lower tone from a lead of -50 ms to a lag of +50 ms in 10 ms steps. Results show that: (1) All subjects were able to identify the lag conditions from the simultaneous ones but only half of them were also able to identify the lead from the simultaneous ones. This was explained in terms of prominent pitch cues available when shifting from simultaneous to lagging stimuli. (2) Hebrew category boundaries (CBs) for TOT are shorter than those of VOT, and both are shorter than the respective English ones. Nonetheless, all CBs fell into the range of 10 to 30 ms. The data support the hypothesis that "natural" psychophysical boundaries determine categorical perception but behavioral measures may be influenced by speech.

Auditory backward masking and the effect of training in normal hearing adults.

Recent renewed interest in auditory backward masking has stemmed from studies of children with language impairments who were found to have significant, elevated thresholds for this paradigm, compared to normal cohorts. There are, however, many unresolved theoretical and procedural issues. The present study was conducted to investigate some of these issues. Specific purposes were: 1) To establish the differences between backward masking and simultaneous masking in normal hearing subjects; 2) To investigate the effect of listening conditions, i.e., monaural versus binaural; 3) To measure the effect of training on the performance of a backward masking paradigm; and 4) To measure generalization of the trained condition to untrained conditions. Two experiments were conducted: In experiment I, we compared the performance of 10 normal-hearing adult subjects for backward masking and simultaneous masking paradigms in both monaural and binaural modes of presentation. Stimuli consisted of a 1000 Hz pure-tone and bandpass masker (600-1400 Hz). Tone thresholds for backward masking were significantly lower than those of the simultaneous masking. The binaural mode of presentation yielded lower thresholds than those of the monaural mode only for the backward masking condition. A significantly large inter- and intra-subject variability was observed in the backward masking paradigm. Experiment II was conducted to measure the effects of training and generalization. Two groups of subjects were included: a trained group and a control group of six and eight normal hearing adults, respectively. The trained group received 10 sessions of backward masking training with feedback. The control group was tested only twice, with a 2-week interval between testing. Only the trained group showed a significant improvement in backward masking thresholds, which amounted to an average of 10.7 dB. No significant improvement was observed in the non-trained group. A nonsignificant trend of generalization occurred for the trained task to the untrained ear. No generalization was evident in the untrained condition (simultaneous masking). The data have important clinical and theoretical implications regarding the ability to train for auditory tasks in general, and for backward masking in particular.

Pitch discrimination: are professional musicians better than non-musicians?

Musicians are typically considered to exhibit exceptional auditory skills. Only few studies, however, have substantiated this in basic psychoacoustic tasks. The purpose of the present investigation was to expand our knowledge on basic auditory abilities of musicians compared to non-musicians. Specific goals were: (1) to compare frequency discrimination thresholds (difference limen for frequency [DLF]) of non-musical pure tones in controlled groups of professional musicians and non-musicians; (2) to relate DLF performance to musical background; and (3) to compare DLF thresholds obtained with two threshold estimation procedures: 2- and 3- interval forced choice procedures (2IFC and 3IFC). Subjects were 16 professional musicians and 14 non-musicians. DLFs were obtained for three frequencies (0.25, 1 and 1.5 kHz) using the 3IFC adaptive procedure, and for one frequency (1 kHz) also using the 2IFC. Three threshold estimates were obtained for each frequency, procedure and subject. The results of the present study support five major findings: (a) mean DLFs for musicians were approximately half the values of the non-musicians; (b) significant learning for both groups during the three threshold estimations; (c) classical musicians performed better than those with contemporary musical background; (d) performance was influenced by years of musical experience; and (e) both groups showed better DLF in a 2IFC paradigm compared to the 3IFC. These data highlight the importance of short-term training on an auditory task, auditory memory and factors related to musical background (such as musical genre and years of experience) on auditory performance.

A test of the overconfidence phenomenon using audio signals.

The existence of the overconfidence phenomenon was examined using a signal detection paradigm. Fifty-five participants were asked to decide whether they heard a signal or noise only, and to rate how certain they were of their decisions. The results confirmed the existence of overconfidence as well as the "hard-easy" effect.