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Sample records for neurodegenerative generalized auditory

  1. Pleasurable emotional response to music: a case of neurodegenerative generalized auditory agnosia.

    PubMed

    Matthews, Brandy R; Chang, Chiung-Chih; De May, Mary; Engstrom, John; Miller, Bruce L

    2009-06-01

    Recent functional neuroimaging studies implicate the network of mesolimbic structures known to be active in reward processing as the neural substrate of pleasure associated with listening to music. Psychoacoustic and lesion studies suggest that there is a widely distributed cortical network involved in processing discreet musical variables. Here we present the case of a young man with auditory agnosia as the consequence of cortical neurodegeneration who continues to experience pleasure when exposed to music. In a series of musical tasks, the subject was unable to accurately identify any of the perceptual components of music beyond simple pitch discrimination, including musical variables known to impact the perception of affect. The subject subsequently misidentified the musical character of personally familiar tunes presented experimentally, but continued to report that the activity of 'listening' to specific musical genres was an emotionally rewarding experience. The implications of this case for the evolving understanding of music perception, music misperception, music memory, and music-associated emotion are discussed.

  2. Pleasurable Emotional Response to Music: A Case of Neurodegenerative Generalized Auditory Agnosia

    PubMed Central

    Matthews, Brandy R.; Chang, Chiung-Chih; De May, Mary; Engstrom, John; Miller, Bruce L.

    2009-01-01

    Recent functional neuroimaging studies implicate the network of mesolimbic structures known to be active in reward processing as the neural substrate of pleasure associated with listening to music. Psychoacoustic and lesion studies suggest that there is a widely distributed cortical network involved in processing discreet musical variables. Here we present the case of a young man with auditory agnosia as the consequence of cortical neurodegeneration who continues to experience pleasure when exposed to music. In a series of musical tasks the subject was unable to accurately identify any of the perceptual components of music beyond simple pitch discrimination, including musical variables know to impact the perception of affect. The subject subsequently misidentified the musical character of personally familiar tunes presented experimentally, but continued to report the activity of “listening” to specific musical genres was an emotionally rewarding experience. The implications of this case for the evolving understanding of music perception, music misperception, music memory, and music-associated emotion are discussed. PMID:19253088

  3. Enhanced Generalization of Auditory Conditioned Fear in Juvenile Mice

    ERIC Educational Resources Information Center

    Ito, Wataru; Pan, Bing-Xing; Yang, Chao; Thakur, Siddarth; Morozov, Alexei

    2009-01-01

    Increased emotionality is a characteristic of human adolescence, but its animal models are limited. Here we report that generalization of auditory conditioned fear between a conditional stimulus (CS+) and a novel auditory stimulus is stronger in 4-5-wk-old mice (juveniles) than in their 9-10-wk-old counterparts (adults), whereas nonassociative…

  4. Enhanced Generalization of Auditory Conditioned Fear in Juvenile Mice

    ERIC Educational Resources Information Center

    Ito, Wataru; Pan, Bing-Xing; Yang, Chao; Thakur, Siddarth; Morozov, Alexei

    2009-01-01

    Increased emotionality is a characteristic of human adolescence, but its animal models are limited. Here we report that generalization of auditory conditioned fear between a conditional stimulus (CS+) and a novel auditory stimulus is stronger in 4-5-wk-old mice (juveniles) than in their 9-10-wk-old counterparts (adults), whereas nonassociative…

  5. Lack of Generalization of Auditory Learning in Typically Developing Children

    ERIC Educational Resources Information Center

    Halliday, Lorna F.; Taylor, Jenny L.; Millward, Kerri E.; Moore, David R.

    2012-01-01

    Purpose: To understand the components of auditory learning in typically developing children by assessing generalization across stimuli, across modalities (i.e., hearing, vision), and to higher level language tasks. Method: Eighty-six 8- to 10-year-old typically developing children were quasi-randomly assigned to 4 groups. Three of the groups…

  6. Lack of generalization of auditory learning in typically developing children.

    PubMed

    Halliday, Lorna F; Taylor, Jenny L; Millward, Kerri E; Moore, David R

    2012-02-01

    To understand the components of auditory learning in typically developing children by assessing generalization across stimuli, across modalities (i.e., hearing, vision), and to higher level language tasks. Eighty-six 8- to 10-year-old typically developing children were quasi-randomly assigned to 4 groups. Three of the groups received twelve 30-min training sessions on multiple standards using either an auditory frequency discrimination task (AFD group), auditory phonetic discrimination task (PD group), or visual frequency discrimination task (VFD group) over 4 weeks. The 4th group, which was the no-intervention control (NI) group, did not receive any training. Thresholds on all tasks (AFD, PD, and VFD) were assessed immediately before and after training, along with performance on a battery of language assessments. Relative to the other groups, both the AFD group and the PD group, but not the VFD group, showed significant learning on the stimuli upon which they were trained. However, in those instances where learning was observed, it did not generalize to the nontrained stimuli or to the language assessments. Nonspeech (AFD) or speech (PD) discrimination training can lead to auditory learning in typically developing children of this age range. However, this learning does not always generalize across stimuli or tasks, across modalities, or to higher level measures of language ability.

  7. Generalized model of the microwave auditory effect

    NASA Astrophysics Data System (ADS)

    Yitzhak, N. M.; Ruppin, R.; Hareuveny, R.

    2009-07-01

    A generalized theoretical model for evaluating the amplitudes of the sound waves generated in a spherical head model, which is irradiated by microwave pulses, is developed. The thermoelastic equation of motion is solved for a spherically symmetric heating pattern of arbitrary form. For previously treated heating patterns that are peaked at the sphere centre, the results reduce to those presented before. The generalized model is applied to the case in which the microwave absorption is concentrated near the sphere surface. It is found that, for equal average specific absorption rates, the sound intensity generated by a surface localized heating pattern is comparable to that generated by a heating pattern that is peaked at the centre. The dependence of the induced sound pressure on the shape of the microwave pulse is explored. Another theoretical extension, to the case of repeated pulses, is developed and applied to the interpretation of existing experimental data on the dependence of the human hearing effect threshold on the pulse repetition frequency.

  8. Generalized model of the microwave auditory effect.

    PubMed

    Yitzhak, N M; Ruppin, R; Hareuveny, R

    2009-07-07

    A generalized theoretical model for evaluating the amplitudes of the sound waves generated in a spherical head model, which is irradiated by microwave pulses, is developed. The thermoelastic equation of motion is solved for a spherically symmetric heating pattern of arbitrary form. For previously treated heating patterns that are peaked at the sphere centre, the results reduce to those presented before. The generalized model is applied to the case in which the microwave absorption is concentrated near the sphere surface. It is found that, for equal average specific absorption rates, the sound intensity generated by a surface localized heating pattern is comparable to that generated by a heating pattern that is peaked at the centre. The dependence of the induced sound pressure on the shape of the microwave pulse is explored. Another theoretical extension, to the case of repeated pulses, is developed and applied to the interpretation of existing experimental data on the dependence of the human hearing effect threshold on the pulse repetition frequency.

  9. Generalization lags behind learning on an auditory perceptual task.

    PubMed

    Wright, Beverly A; Wilson, Roselyn M; Sabin, Andrew T

    2010-09-01

    The generalization of learning from trained to untrained conditions is of great potential value because it markedly increases the efficacy of practice. In principle, generalization and the learning itself could arise from either the same or distinct neural changes. Here, we assessed these two possibilities in the realm of human perceptual learning by comparing the time course of improvement on a trained condition (learning) to that on an untrained condition (generalization) for an auditory temporal-interval discrimination task. While significant improvement on the trained condition occurred within 2 d, generalization to the untrained condition lagged behind, only emerging after 4 d. The different time courses for learning and generalization suggest that these two types of perceptual improvement can arise from at least partially distinct neural changes. The notably longer time course for generalization than learning demonstrates that increasing the duration of training can be an effective means to increase the number of conditions to which learning generalizes on perceptual tasks.

  10. Processing familiar and unfamiliar auditory stimuli during general anesthesia.

    PubMed

    Donker, A G; Phaf, R H; Porcelijn, T; Bonke, B

    1996-03-01

    We tested memory priming for auditory stimuli presented during general propofol-sufentanil anesthesia in 58 patients undergoing day-case arthroscopic surgery. Stimuli were presented via headphones and consisted of common facts (Group A, 29 patients), or familiar or unfamiliar full names of fictitious people (GRoup B, 29 patients). Group A was expected to give more correct answers to questions about the common facts than Group B, when tested postoperatively, and Group B to attribute more fame to presented names than Group A (famous names test). Because the process for learning new or unfamiliar stimuli (elaboration) in particular may be impaired under general anesthesia, more memory priming was expected for familiar than for unfamiliar material. No significant differences were demonstrated between the two groups in performance on common facts or in fame attributed to the names. The amount of memory priming, however, was positively related to one of two measures of preoperative anxiety.

  11. A Case of Generalized Auditory Agnosia with Unilateral Subcortical Brain Lesion

    PubMed Central

    Suh, Hyee; Kim, Soo Yeon; Kim, Sook Hee; Chang, Jae Hyeok; Shin, Yong Beom; Ko, Hyun-Yoon

    2012-01-01

    The mechanisms and functional anatomy underlying the early stages of speech perception are still not well understood. Auditory agnosia is a deficit of auditory object processing defined as a disability to recognize spoken languages and/or nonverbal environmental sounds and music despite adequate hearing while spontaneous speech, reading and writing are preserved. Usually, either the bilateral or unilateral temporal lobe, especially the transverse gyral lesions, are responsible for auditory agnosia. Subcortical lesions without cortical damage rarely causes auditory agnosia. We present a 73-year-old right-handed male with generalized auditory agnosia caused by a unilateral subcortical lesion. He was not able to repeat or dictate but to perform fluent and comprehensible speech. He could understand and read written words and phrases. His auditory brainstem evoked potential and audiometry were intact. This case suggested that the subcortical lesion involving unilateral acoustic radiation could cause generalized auditory agnosia. PMID:23342322

  12. A case of generalized auditory agnosia with unilateral subcortical brain lesion.

    PubMed

    Suh, Hyee; Shin, Yong-Il; Kim, Soo Yeon; Kim, Sook Hee; Chang, Jae Hyeok; Shin, Yong Beom; Ko, Hyun-Yoon

    2012-12-01

    The mechanisms and functional anatomy underlying the early stages of speech perception are still not well understood. Auditory agnosia is a deficit of auditory object processing defined as a disability to recognize spoken languages and/or nonverbal environmental sounds and music despite adequate hearing while spontaneous speech, reading and writing are preserved. Usually, either the bilateral or unilateral temporal lobe, especially the transverse gyral lesions, are responsible for auditory agnosia. Subcortical lesions without cortical damage rarely causes auditory agnosia. We present a 73-year-old right-handed male with generalized auditory agnosia caused by a unilateral subcortical lesion. He was not able to repeat or dictate but to perform fluent and comprehensible speech. He could understand and read written words and phrases. His auditory brainstem evoked potential and audiometry were intact. This case suggested that the subcortical lesion involving unilateral acoustic radiation could cause generalized auditory agnosia.

  13. Electrophysiological evidence for a general auditory prediction deficit in adults who stutter

    PubMed Central

    Daliri, Ayoub; Max, Ludo

    2015-01-01

    We previously found that stuttering individuals do not show the typical auditory modulation observed during speech planning in nonstuttering individuals. In this follow-up study, we further elucidate this difference by investigating whether stuttering speakers’ atypical auditory modulation is observed only when sensory predictions are based on movement planning or also when predictable auditory input is not a consequence of one’s own actions. We recorded 10 stuttering and 10 nonstuttering adults’ auditory evoked potentials in response to random probe tones delivered while anticipating either speaking aloud or hearing one’s own speech played back and in a control condition without auditory input (besides probe tones). N1 amplitude of nonstuttering speakers was reduced prior to both speaking and hearing versus the control condition. Stuttering speakers, however, showed no N1 amplitude reduction in either the speaking or hearing condition as compared with control. Thus, findings suggest that stuttering speakers have general auditory prediction difficulties. PMID:26335995

  14. Electrophysiological evidence for a general auditory prediction deficit in adults who stutter.

    PubMed

    Daliri, Ayoub; Max, Ludo

    2015-11-01

    We previously found that stuttering individuals do not show the typical auditory modulation observed during speech planning in nonstuttering individuals. In this follow-up study, we further elucidate this difference by investigating whether stuttering speakers' atypical auditory modulation is observed only when sensory predictions are based on movement planning or also when predictable auditory input is not a consequence of one's own actions. We recorded 10 stuttering and 10 nonstuttering adults' auditory evoked potentials in response to random probe tones delivered while anticipating either speaking aloud or hearing one's own speech played back and in a control condition without auditory input (besides probe tones). N1 amplitude of nonstuttering speakers was reduced prior to both speaking and hearing versus the control condition. Stuttering speakers, however, showed no N1 amplitude reduction in either the speaking or hearing condition as compared with control. Thus, findings suggest that stuttering speakers have general auditory prediction difficulties.

  15. General Auditory Processing, Speech Perception and Phonological Awareness Skills in Chinese-English Biliteracy

    ERIC Educational Resources Information Center

    Chung, Kevin K. H.; McBride-Chang, Catherine; Cheung, Him; Wong, Simpson W. L.

    2013-01-01

    This study focused on the associations of general auditory processing, speech perception, phonological awareness and word reading in Cantonese-speaking children from Hong Kong learning to read both Chinese (first language [L1]) and English (second language [L2]). Children in Grades 2--4 ("N" = 133) participated and were administered…

  16. General Auditory Processing, Speech Perception and Phonological Awareness Skills in Chinese-English Biliteracy

    ERIC Educational Resources Information Center

    Chung, Kevin K. H.; McBride-Chang, Catherine; Cheung, Him; Wong, Simpson W. L.

    2013-01-01

    This study focused on the associations of general auditory processing, speech perception, phonological awareness and word reading in Cantonese-speaking children from Hong Kong learning to read both Chinese (first language [L1]) and English (second language [L2]). Children in Grades 2--4 ("N" = 133) participated and were administered…

  17. Testing domain-general theories of perceptual awareness with auditory brain responses.

    PubMed

    Snyder, Joel S; Yerkes, Breanne D; Pitts, Michael A

    2015-06-01

    Past research has identified several candidate neural correlates of consciousness (NCCs) during visual perception. Recent research on auditory perception shows promise for establishing the generality of various NCCs across sensory modalities, as well as for revealing differences in how conscious processing unfolds in different sensory systems.

  18. Auditory evoked responses and learning and awareness during general anesthesia.

    PubMed

    Ghoneim, M M; Block, R I; Dhanaraj, V J; Todd, M M; Choi, W W; Brown, C K

    2000-02-01

    There is a major distinction between conscious and unconscious learning. Monitoring the mid-latency auditory evoked responses (AER) has been proposed as a measure to ascertain the adequacy of the hypnotic state during surgery. In the present study, we investigated the presence of explicit and implicit memories after anesthesia and examined the relationships of such memories to the AER. We studied 180 patients scheduled for elective surgical procedures. After a thiopental induction, one of four anesthetics were studied: Opioid bolus: 7.5 microg x kg(-1) fentanyl, 70% N2O, with 2.5 microg x kg(-1) supplements as needed (n=100); Opioid infusion: Alfentanil 50 microg x kg(-1) bolus, 1-1.5 microg x kg(-1) x min(-1) infusion, 70% N2O (n=40); Isoflurane 0.3%: Fentanyl 1 microg x kg(-1), 70% N2O, isoflurane 0.3% expired (n=16); Isoflurane 0.7%: Fentanyl 1 microg x kg(-1), 70% N2O, isoflurane 0.7% expired (n=23). AER were recorded before anesthesia, 5 min after surgical incision and then every 30 min until the end of surgery. A tape of either the story of the "Three Little Pigs" or the "Wizard of Oz" was played continuously between the recordings. Explicit memory was assessed postoperatively by tests of recall and recognition, and implicit memory was assessed by the frequency of story-related free associations to target words from the stories, which were solicited twice during a structured interview. Six patients showed explicit recall of intraoperative events: All received the opioid bolus regimen. About 7% of patients reported dreaming during anesthesia. The incidence of picking the correct story that had been presented during anesthesia averaged 49%, i.e., very close to chance level. Overall, priming occurred only at the second association tests for the opioid bolus regimen, for which the frequency of an association to the presented story among those not giving an association to the control story was 26%, which was double the frequency (13%) of an association to the

  19. Auditory startle reflex and startle reflex to somatosensory inputs in generalized dystonia.

    PubMed

    Kiziltan, Meral E; Gunduz, Aysegul; Apaydın, Hulya; Ertan, Sibel; Kiziltan, Gunes

    2015-09-01

    Startle reflex is a generalized defense reaction after unexpected auditory, visual, or tactile stimuli. Auditory startle reflex (ASR) and startle reflex to somatosensory inputs (SSS) have never been studied in generalized dystonia. Here, we aimed to study the characteristics and changes of ASR and SSS in this group. We have examined ASR and SSS in patients with generalized dystonia (n=11) and healthy subjects (n=25) under the same conditions. ASRs and SSSs were recorded over the orbicularis oculi (O.oc), sternocleidomastoid, biceps brachii (BB), and abductor pollicis brevis (APB) muscles after bilateral auditory stimulation and unilateral median nerve electrical stimulation at the wrist, respectively. Both ASR and SSS showed the same sequence of muscle activation in both groups. However, the presence rates over the APB and BB muscles after both modalities of stimuli were significantly higher in the generalized dystonia group. ASR did not habituate in the dystonia group. Both ASR and SSS are disinhibited, and both show a similar sequence of muscle recruitment in generalized dystonia. Higher probabilities over caudal muscles probably depend on the higher excitability of motor neurons secondary to central modulation. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  20. Auditory generalization gradients for response latency in the monkey1

    PubMed Central

    Moody, David B.; Stebbins, William C.; Iglauer, Carol

    1971-01-01

    Two monkeys were trained to press and hold a response key in the presence of a light and to release it at the onset of a pure tone. Initially, all responses with latencies shorter than 1 sec were reinforced without regard to the frequency of the pure tone, and the intensity of the pure tone that resulted in equal latencies at each frequency was determined. The second stage of the experiment consisted of discrimination training, during which releases to one pure-tone frequency (positive stimulus) were reinforced and releases to a second frequency (negative stimulus) were extinguished. Median latencies to the negative stimulus slowly increased as did the variability of the latency distribution for the negative stimulus. There was no evidence of a concurrent decrease in latencies to the positive stimulus indicative of behavioral contrast. The third part of the experiment consisted of determining maintained generalization gradients by increasing the number of nonreinforcement stimuli. The gradients that eventually resulted showed approximately equal latencies to all frequencies of the negative stimulus and shorter latencies to the positive stimulus frequency. PMID:5003971

  1. The Generalization of Auditory Accommodation to Altered Spectral Cues.

    PubMed

    Watson, Christopher J G; Carlile, Simon; Kelly, Heather; Balachandar, Kapilesh

    2017-09-14

    The capacity of healthy adult listeners to accommodate to altered spectral cues to the source locations of broadband sounds has now been well documented. In recent years we have demonstrated that the degree and speed of accommodation are improved by using an integrated sensory-motor training protocol under anechoic conditions. Here we demonstrate that the learning which underpins the localization performance gains during the accommodation process using anechoic broadband training stimuli generalize to environmentally relevant scenarios. As previously, alterations to monaural spectral cues were produced by fitting participants with custom-made outer ear molds, worn during waking hours. Following acute degradations in localization performance, participants then underwent daily sensory-motor training to improve localization accuracy using broadband noise stimuli over ten days. Participants not only demonstrated post-training improvements in localization accuracy for broadband noises presented in the same set of positions used during training, but also for stimuli presented in untrained locations, for monosyllabic speech sounds, and for stimuli presented in reverberant conditions. These findings shed further light on the neuroplastic capacity of healthy listeners, and represent the next step in the development of training programs for users of assistive listening devices which degrade localization acuity by distorting or bypassing monaural cues.

  2. Impairments of auditory scene analysis in Alzheimer's disease.

    PubMed

    Goll, Johanna C; Kim, Lois G; Ridgway, Gerard R; Hailstone, Julia C; Lehmann, Manja; Buckley, Aisling H; Crutch, Sebastian J; Warren, Jason D

    2012-01-01

    Parsing of sound sources in the auditory environment or 'auditory scene analysis' is a computationally demanding cognitive operation that is likely to be vulnerable to the neurodegenerative process in Alzheimer's disease. However, little information is available concerning auditory scene analysis in Alzheimer's disease. Here we undertook a detailed neuropsychological and neuroanatomical characterization of auditory scene analysis in a cohort of 21 patients with clinically typical Alzheimer's disease versus age-matched healthy control subjects. We designed a novel auditory dual stream paradigm based on synthetic sound sequences to assess two key generic operations in auditory scene analysis (object segregation and grouping) in relation to simpler auditory perceptual, task and general neuropsychological factors. In order to assess neuroanatomical associations of performance on auditory scene analysis tasks, structural brain magnetic resonance imaging data from the patient cohort were analysed using voxel-based morphometry. Compared with healthy controls, patients with Alzheimer's disease had impairments of auditory scene analysis, and segregation and grouping operations were comparably affected. Auditory scene analysis impairments in Alzheimer's disease were not wholly attributable to simple auditory perceptual or task factors; however, the between-group difference relative to healthy controls was attenuated after accounting for non-verbal (visuospatial) working memory capacity. These findings demonstrate that clinically typical Alzheimer's disease is associated with a generic deficit of auditory scene analysis. Neuroanatomical associations of auditory scene analysis performance were identified in posterior cortical areas including the posterior superior temporal lobes and posterior cingulate. This work suggests a basis for understanding a class of clinical symptoms in Alzheimer's disease and for delineating cognitive mechanisms that mediate auditory scene analysis

  3. Generalized learning of visual-to-auditory substitution in sighted individuals.

    PubMed

    Kim, Jung-Kyong; Zatorre, Robert J

    2008-11-25

    Visual-to-auditory substitution involves delivering information about the visual world using auditory input. Although the potential suitability of sound as visual substitution has previously been demonstrated, the basic mechanism behind crossmodal learning is largely unknown; particularly, the degree to which learning generalizes to new stimuli has not been formally tested. We examined learning processes involving the use of the image-to-sound conversion system developed by Meijer [Meijer, P., 1992. An experimental system for auditory image representations. IEEE Trans Biom Eng. 39 (2), 112-121.] that codes visual vertical and horizontal axes into frequency and time representations, respectively. Two behavioral experiments provided training to sighted individuals in a controlled environment. The first experiment explored the early learning stage, comparing performance of individuals who received short-term training and those who were only explicitly given the conversion rules. Both groups performed above chance, suggesting an intuitive understanding of the image-sound relationship; the lack of group difference indicates that this intuition could be acquired simply on the basis of explicit knowledge. The second experiment involved training over a three-week period using a larger variety of stimuli. Performance on both previously trained and novel items was examined over time. Performance on the familiar items was higher than on the novel items, but performance on the latter improved over time. While the lack of improvement with the familiar items suggests memory-based performance, the improvement with novel items demonstrated generalized learning, indicating abstraction of the conversion rules such that they could be applied to interpret auditory patterns coding new visual information. Such generalization could provide a basis for the substitution in a constantly changing visual environment.

  4. Vowel generalization and its relation to adaptation during perturbations of auditory feedback.

    PubMed

    Reilly, Kevin J; Pettibone, Chelsea

    2017-08-23

    Repeated perturbations of auditory feedback during vowel production elicit changes not only in the production of the perturbed vowel (adaptation) but also in the production of nearby vowels that were not perturbed (generalization). The finding that adaptation generalizes to other, non-perturbed vowels suggest that sensorimotor representations for vowels are not independent; instead the goals for producing any one vowel may depend in part on the goals for other vowels. The present study investigated the dependence or independence of vowel representations by evaluating adaptation and generalization in two groups of speakers exposed to auditory perturbations of their first formant (F1) during different vowels. The speakers in both groups who adapted to the perturbation exhibited generalization in two non-perturbed vowels that were produced under masking noise. Correlation testing was performed to evaluate the relations between adaptation and generalization as well as between the generalization in the two non-perturbed vowels. These tests identified significant coupling between the F1 changes of adjacent vowels but not non-adjacent vowels. The pattern of correlation findings indicates that generalization was due in part to feedforward representations that are partly shared across adjacent vowels, possibly to maintain their acoustic contrast. Copyright © 2016, Journal of Neurophysiology.

  5. Auditory rehabilitation of older people from the general population--the Leiden 85-plus study.

    PubMed Central

    Gussekloo, Jacobijn; de Bont, L E; von Faber, M; Eekhof, J A; de Laat, J A; Hulshof, J H; van Dongen, E; Westendorp, R G

    2003-01-01

    BACKGROUND: Very few older people with severe hearing loss use hearing aids to reduce the negative consequences of reduced hearing in daily functioning. AIM: Assessment of a screening test and a standardised auditory rehabilitation programme for older people from the general population with untreated severe hearing loss. DESIGN OF STUDY: Intervention study and qualitative exploration. SETTING: Leiden 85-Plus Study, a prospective population-based study of 85-year-old inhabitants of Leiden, the Netherlands. METHOD: Hearing loss was measured by pure-tone audiometry in 454 subjects aged 85 years. Subjects with hearing loss above 35 dB at 1, 2, and 4 kHz who did not use hearing aids were invited to participate in a standardised programme for auditory rehabilitation. In-depth interviews were held with participants to explore arguments for participating in this programme. RESULTS: Of the 367 participants with severe hearing loss (prevalence = 81%), 66% (241/367) did not use a hearing aid. Three out of four of these participants (n = 185) declined participation in the auditory rehabilitation programme. The most common reason given for not participating was the subjects' feeling that their current hearing loss did not warrant the use of a hearing aid. Subjects who participated in the programme were found to suffer from more severe hearing loss and experienced more hearing disability. Those who did not participate in the programme felt they could cope with their disabilities and considered a hearing aid unnecessary. CONCLUSION: Untreated hearing loss is prevalent among older people from the general population. The majority of older people decline auditory rehabilitation. For these people the use of a hearing aid is not perceived as necessary in order to function on a daily basis. Older people who have expected benefits from a hearing aid have already obtained them, marginalising the benefits of a rehabilitation (and screening) programme. PMID:14694666

  6. Increased Signal Complexity Improves the Breadth of Generalization in Auditory Perceptual Learning

    PubMed Central

    Brown, David J.; Proulx, Michael J.

    2013-01-01

    Perceptual learning can be specific to a trained stimulus or optimally generalized to novel stimuli with the breadth of generalization being imperative for how we structure perceptual training programs. Adapting an established auditory interval discrimination paradigm to utilise complex signals, we trained human adults on a standard interval for either 2, 4, or 10 days. We then tested the standard, alternate frequency, interval, and stereo input conditions to evaluate the rapidity of specific learning and breadth of generalization over the time course. In comparison with previous research using simple stimuli, the speed of perceptual learning and breadth of generalization were more rapid and greater in magnitude, including novel generalization to an alternate temporal interval within stimulus type. We also investigated the long term maintenance of learning and found that specific and generalized learning was maintained over 3 and 6 months. We discuss these findings regarding stimulus complexity in perceptual learning and how they can inform the development of effective training protocols. PMID:24349800

  7. Generalizing a neuropsychological model of visual categorization to auditory categorization of vowels.

    PubMed

    Maddox, W Todd; Molis, Michelle R; Diehl, Randy L

    2002-05-01

    Twelve male listeners categorized 54 synthetic vowel stimuli that varied in second and third formant frequency on a Bark scale into the American English vowel categories [see text]. A neuropsychologically plausible model of categorization in the visual domain, the Striatal Pattern Classifier (SPC; Ashby & Waldron, 1999), is generalized to the auditory domain and applied separately to the data from each observer. Performance of the SPC is compared with that of the successful Normal A Posteriori Probability model (NAPP; Nearey, 1990; Nearey & Hogan, 1986) of auditory categorization. A version of the SPC that assumed piece-wise linear response region partitions provided a better account of the data than the SPC that assumed linear partitions, and was indistinguishable from a version that assumed quadratic response region partitions. A version of the NAPP model that assumed nonlinear response regions was superior to the NAPP model with linear partitions. The best fitting SPC provided a good account of each observer's data but was outperformed by the best fitting NAPP model. Implications for bridging the gap between the domains of visual and auditory categorization are discussed.

  8. Generalization of sensory auditory learning to top-down skills in a randomized controlled trial.

    PubMed

    Murphy, Cristina B; Peres, Andressa K; Zachi, Elaine C; Ventura, Dora F; Pagan-Neves, Luciana; Wertzner, Haydee F; Schochat, Eliane

    2015-01-01

    Research has shown that auditory training improves auditory sensory skills; however, it is unclear whether this improvement is transferred to top-down skills, such as memory, attention, and language, and whether it depends on group characteristics in regard to memory and attention skills. The primary goal of this research was to investigate the generalization of learning from auditory sensory skills to top-down skills such as memory, attention, and language. We also aimed to compare whether this generalization process occurs in the same way among typically developing children and children with speech sound disorder. This study was a randomized controlled trial. Typically developing 7- to 12-yr-old children and children with speech sound disorder were separated into four groups: a trained control group (TDT; n = 10, age 9.6 ± 2.0 yr), a nontrained control group (TDNT; n = 11, age 8.2 ± 1.6 yr), a trained study group (SSDT; n = 10, age 7.7 ± 1.2 yr), and a nontrained study group (SSDNT; n = 8, age 8.6 ± 1.2 yr). Both trained groups underwent a computerized, nonverbal auditory training that focused on frequency discrimination, ordering, and backward-masking tasks. The training consisted of twelve 45 min sessions, once a week, for a total of 9 hr of training, approximately. Near-transfer (Gap-In-Noise [GIN] and Frequency Pattern Test) and far-transfer measures (auditory and visual sustained attention tests, phonological working memory and language tests) were applied before and after training. The results were analyzed using a 2 × 2 × 2 mixed-model analysis of variance with the group and training as the between-group variables and the period as the within-group variable. The significance threshold was p ≤ 0.05. There was a group × period × training interaction for GIN [F(1.35) = 7.18, p = 0.011], indicating a significant threshold reduction only for the TDT group (Tukey multiple comparisons). There was a significant group × period interaction [F(1.35) = 5

  9. Generalization of Auditory Sensory and Cognitive Learning in Typically Developing Children

    PubMed Central

    Murphy, Cristina F. B.; Moore, David R.; Schochat, Eliane

    2015-01-01

    Despite the well-established involvement of both sensory (“bottom-up”) and cognitive (“top-down”) processes in literacy, the extent to which auditory or cognitive (memory or attention) learning transfers to phonological and reading skills remains unclear. Most research has demonstrated learning of the trained task or even learning transfer to a closely related task. However, few studies have reported “far-transfer” to a different domain, such as the improvement of phonological and reading skills following auditory or cognitive training. This study assessed the effectiveness of auditory, memory or attention training on far-transfer measures involving phonological and reading skills in typically developing children. Mid-transfer was also assessed through untrained auditory, attention and memory tasks. Sixty 5- to 8-year-old children with normal hearing were quasi-randomly assigned to one of five training groups: attention group (AG), memory group (MG), auditory sensory group (SG), placebo group (PG; drawing, painting), and a control, untrained group (CG). Compliance, mid-transfer and far-transfer measures were evaluated before and after training. All trained groups received 12 x 45-min training sessions over 12 weeks. The CG did not receive any intervention. All trained groups, especially older children, exhibited significant learning of the trained task. On pre- to post-training measures (test-retest), most groups exhibited improvements on most tasks. There was significant mid-transfer for a visual digit span task, with highest span in the MG, relative to other groups. These results show that both sensory and cognitive (memory or attention) training can lead to learning in the trained task and to mid-transfer learning on a task (visual digit span) within the same domain as the trained tasks. However, learning did not transfer to measures of language (reading and phonological awareness), as the PG and CG improved as much as the other trained groups

  10. Generalization of Auditory Sensory and Cognitive Learning in Typically Developing Children.

    PubMed

    Murphy, Cristina F B; Moore, David R; Schochat, Eliane

    2015-01-01

    Despite the well-established involvement of both sensory ("bottom-up") and cognitive ("top-down") processes in literacy, the extent to which auditory or cognitive (memory or attention) learning transfers to phonological and reading skills remains unclear. Most research has demonstrated learning of the trained task or even learning transfer to a closely related task. However, few studies have reported "far-transfer" to a different domain, such as the improvement of phonological and reading skills following auditory or cognitive training. This study assessed the effectiveness of auditory, memory or attention training on far-transfer measures involving phonological and reading skills in typically developing children. Mid-transfer was also assessed through untrained auditory, attention and memory tasks. Sixty 5- to 8-year-old children with normal hearing were quasi-randomly assigned to one of five training groups: attention group (AG), memory group (MG), auditory sensory group (SG), placebo group (PG; drawing, painting), and a control, untrained group (CG). Compliance, mid-transfer and far-transfer measures were evaluated before and after training. All trained groups received 12 x 45-min training sessions over 12 weeks. The CG did not receive any intervention. All trained groups, especially older children, exhibited significant learning of the trained task. On pre- to post-training measures (test-retest), most groups exhibited improvements on most tasks. There was significant mid-transfer for a visual digit span task, with highest span in the MG, relative to other groups. These results show that both sensory and cognitive (memory or attention) training can lead to learning in the trained task and to mid-transfer learning on a task (visual digit span) within the same domain as the trained tasks. However, learning did not transfer to measures of language (reading and phonological awareness), as the PG and CG improved as much as the other trained groups. Further research

  11. Auditory stimuli as a contributor to consciousness while under general anesthesia.

    PubMed

    Thiele, Robert H; Knipper, Emily; Dunn, Lauren K; Nemergut, Edward C

    2013-05-01

    The incidence of intraoperative awareness under general anesthesia approaches 1% in high-risk patients. Anesthesiologists commonly utilize processed electroencephalograms (EEG) in order to monitor "depth" of anesthesia, the most common of which is the Bispectral Index (BIS). The B-aware and B-Unaware trials, which were designed to test the efficacy of the BIS monitor, noted an auditory component in 16 of 17 confirmed cases of intraoperative awareness. Implicit auditory memory formation has been documented under general anesthesia. Small studies have documented a significant effect of noise on BIS scores during monitored anesthesia care. Twenty-two patients undergoing general anesthesia received earplugs after the induction of anesthesia. Every ten minutes the earplugs were reinserted or removed. Noise levels were recorded every 0.125 s and both average and maximal BIS scores were recorded every minute. Non-parametric analysis of both populations (with and without earplugs) was performed. A mixed effects model with one degree of freedom (with and without earplugs) was generated to take into account the effect of anesthetic agents on BIS scores. 3009 min of data were recorded. The median and range (25-75%) BIS scores were 39 (29-46) and 39 (28-44) with and without earplugs in place, respectively. Earplugs were associated with lower BIS scores (p=0.0183). The mixed effects model confirmed this relationship (p<0.001). Subgroup analysis of BIS scores in which the potential for awareness existed (maximum BIS>60 in any one minute epoch) showed a 32% reduction in the incidence of maximal BIS scores exceeding 60 (p=0.0012). There was no relationship between ambient noise level and average maximal BIS score (R(2)=0.003). Our study suggests that earplugs may reduce the incidence of BIS scores >60 in patients undergoing total intravenous anesthesia and that auditory stimuli may affect EEG interpretation. Because of the low cost and safety of noise reduction, as well as the

  12. Concurrent sound segregation impairments in schizophrenia: The contribution of auditory-specific and general cognitive factors

    PubMed Central

    Ramage, Erin M.; Klimas, Nedka; Vogel, Sally J.; Vertinski, Mary; Yerkes, Breanne D.; Flores, Amanda; Sutton, Griffin P.; Ringdahl, Erik N.; Allen, Daniel N.; Snyder, Joel S.

    2015-01-01

    The present study sought to test whether perceptual segregation of concurrently played sounds is impaired in schizophrenia (SZ), whether impairment in sound segregation predicts difficulties with a real-world speech-in-noise task, and whether auditory-specific or general cognitive processing accounts for sound segregation problems. Participants with SZ and healthy controls (HCs) performed a mistuned harmonic segregation task during recording of event-related potentials (ERPs). Participants also performed a brief speech-in-noise task. Participants with SZ showed deficits in the mistuned harmonic task and the speech-in-noise task, compared to HCs. No deficit in SZ was found in the ERP component related to mistuned harmonic segregation at around 150 ms (the object-related negativity or ORN), but instead showed a deficit in processing at around 400 ms (the P4 response). However, regression analyses showed that indexes of education level and general cognitive function were the best predictors of sound segregation difficulties, suggesting non-auditory specific causes of concurrent sound segregation problems in SZ. PMID:26644302

  13. Concurrent sound segregation impairments in schizophrenia: The contribution of auditory-specific and general cognitive factors.

    PubMed

    Ramage, Erin M; Klimas, Nedka; Vogel, Sally J; Vertinski, Mary; Yerkes, Breanne D; Flores, Amanda; Sutton, Griffin P; Ringdahl, Erik N; Allen, Daniel N; Snyder, Joel S

    2016-01-01

    The present study sought to test whether perceptual segregation of concurrently played sounds is impaired in schizophrenia (SZ), whether impairment in sound segregation predicts difficulties with a real-world speech-in-noise task, and whether auditory-specific or general cognitive processing accounts for sound segregation problems. Participants with SZ and healthy controls (HCs) performed a mistuned harmonic segregation task during recording of event-related potentials (ERPs). Participants also performed a brief speech-in-noise task. Participants with SZ showed deficits in the mistuned harmonic task and the speech-in-noise task, compared to HCs. No deficit in SZ was found in the ERP component related to mistuned harmonic segregation at around 150ms (the object-related negativity or ORN), but instead showed a deficit in processing at around 400ms (the P4 response). However, regression analyses showed that indexes of education level and general cognitive function were the best predictors of sound segregation difficulties, suggesting non-auditory specific causes of concurrent sound segregation problems in SZ.

  14. Bat auditory cortex – model for general mammalian auditory computation or special design solution for active time perception?

    PubMed

    Kössl, Manfred; Hechavarria, Julio; Voss, Cornelia; Schaefer, Markus; Vater, Marianne

    2015-03-01

    Audition in bats serves passive orientation, alerting functions and communication as it does in other vertebrates. In addition, bats have evolved echolocation for orientation and prey detection and capture. This put a selective pressure on the auditory system in regard to echolocation-relevant temporal computation and frequency analysis. The present review attempts to evaluate in which respect the processing modules of bat auditory cortex (AC) are a model for typical mammalian AC function or are designed for echolocation-unique purposes. We conclude that, while cortical area arrangement and cortical frequency processing does not deviate greatly from that of other mammals, the echo delay time-sensitive dorsal cortex regions contain special designs for very powerful time perception. Different bat species have either a unique chronotopic cortex topography or a distributed salt-and-pepper representation of echo delay. The two designs seem to enable similar behavioural performance.

  15. Auditory agnosia.

    PubMed

    Slevc, L Robert; Shell, Alison R

    2015-01-01

    Auditory agnosia refers to impairments in sound perception and identification despite intact hearing, cognitive functioning, and language abilities (reading, writing, and speaking). Auditory agnosia can be general, affecting all types of sound perception, or can be (relatively) specific to a particular domain. Verbal auditory agnosia (also known as (pure) word deafness) refers to deficits specific to speech processing, environmental sound agnosia refers to difficulties confined to non-speech environmental sounds, and amusia refers to deficits confined to music. These deficits can be apperceptive, affecting basic perceptual processes, or associative, affecting the relation of a perceived auditory object to its meaning. This chapter discusses what is known about the behavioral symptoms and lesion correlates of these different types of auditory agnosia (focusing especially on verbal auditory agnosia), evidence for the role of a rapid temporal processing deficit in some aspects of auditory agnosia, and the few attempts to treat the perceptual deficits associated with auditory agnosia. A clear picture of auditory agnosia has been slow to emerge, hampered by the considerable heterogeneity in behavioral deficits, associated brain damage, and variable assessments across cases. Despite this lack of clarity, these striking deficits in complex sound processing continue to inform our understanding of auditory perception and cognition.

  16. General Auditory Processing, Chinese Tone Processing, English Phonemic Processing and English Reading Skill: A Comparison between Chinese-English and Korean-English Bilingual Children

    ERIC Educational Resources Information Center

    Wang, Min; Anderson, Alida; Cheng, Chenxi; Park, Yoonjung; Thomson, Jennifer

    2008-01-01

    In the present study, we investigated the relationship between general auditory processing, Chinese tone processing, English phonemic processing and English reading skill in a group of Chinese-English bilingual children with a tonal L1 and Korean-English counterparts with a non-tonal L1. We found that general auditory processing contributed to…

  17. Latency of auditory evoked potential monitoring the effects of general anesthetics on nerve fibers and synapses.

    PubMed

    Huang, Bowan; Liang, Feixue; Zhong, Lei; Lin, Minlin; Yang, Juan; Yan, Linqing; Xiao, Jinfan; Xiao, Zhongju

    2015-08-06

    Auditory evoked potential (AEP) is an effective index for the effects of general anesthetics. However, it's unknown if AEP can differentiate the effects of general anesthetics on nerve fibers and synapses. Presently, we investigated AEP latency and amplitude changes to different acoustic intensities during pentobarbital anesthesia. Latency more regularly changed than amplitude during anesthesia. AEP Latency monotonically decreased with acoustic intensity increase (i.e., latency-intensity curve) and could be fitted to an exponential decay equation, which showed two components, the theoretical minimum latency and stimulus-dependent delay. From the latency-intensity curves, the changes of these two components (∆L and ∆I) were extracted during anesthesia. ∆L and ∆I monitored the effect of pentobarbital on nerve fibers and synapses. Pentobarbital can induce anesthesia, and two side effects, hypoxemia and hypothermia. The hypoxemia was not related with ∆L and ∆I. However, ∆L was changed by the hypothermia, whereas ∆I was changed by the hypothermia and anesthesia. Therefore, we conclude that, AEP latency is superior to amplitude for the effects of general anesthetics, ∆L monitors the effect of hypothermia on nerve fibers, and ∆I monitors a combined effect of anesthesia and hypothermia on synapses. When eliminating the temperature factor, ∆I monitors the anesthesia effect on synapses.

  18. Assessment of Olfactory Function in MAPT-Associated Neurodegenerative Disease Reveals Odor-Identification Irreproducibility as a Non-Disease-Specific, General Characteristic of Olfactory Dysfunction

    PubMed Central

    Robowski, Piotr; Strongosky, Audrey; Narożańska, Ewa; Sitek, Emilia J.; Berdynski, Mariusz; Barcikowska, Maria; Baker, Matt C.; Rademakers, Rosa; Sławek, Jarosław; Klein, Christine; Hückelheim, Katja; Kasten, Meike; Wszolek, Zbigniew K.

    2016-01-01

    limitations of these tests used and the sample sizes, olfactory dysfunction appears to be associated with the inability to identify odors reliably and consistently, not with the loss of an ability to identify specific odors. Irreproducibility in odor identification appears to be a non-disease-specific, general feature of olfactory dysfunction that is accelerated or accentuated in neurodegenerative disease. It may reflect a fundamental organizational principle of the olfactory system, which is more “error-prone” than other sensory systems. PMID:27855167

  19. Assessment of Olfactory Function in MAPT-Associated Neurodegenerative Disease Reveals Odor-Identification Irreproducibility as a Non-Disease-Specific, General Characteristic of Olfactory Dysfunction.

    PubMed

    Markopoulou, Katerina; Chase, Bruce A; Robowski, Piotr; Strongosky, Audrey; Narożańska, Ewa; Sitek, Emilia J; Berdynski, Mariusz; Barcikowska, Maria; Baker, Matt C; Rademakers, Rosa; Sławek, Jarosław; Klein, Christine; Hückelheim, Katja; Kasten, Meike; Wszolek, Zbigniew K

    2016-01-01

    limitations of these tests used and the sample sizes, olfactory dysfunction appears to be associated with the inability to identify odors reliably and consistently, not with the loss of an ability to identify specific odors. Irreproducibility in odor identification appears to be a non-disease-specific, general feature of olfactory dysfunction that is accelerated or accentuated in neurodegenerative disease. It may reflect a fundamental organizational principle of the olfactory system, which is more "error-prone" than other sensory systems.

  20. Curcumin and neurodegenerative diseases

    PubMed Central

    Monroy, Adriana; Lithgow, Gordon J.; Alavez, Silvestre

    2013-01-01

    Over the last ten years curcumin has been reported to be effective against a wide variety of diseases and is characterized as having anti-carcinogenic, hepatoprotective, thrombosuppressive, cardioprotective, anti-arthritic, and anti-infectious properties. Recent studies performed in both vertebrate and invertebrate models have been conducted to determine whether curcumin was also neuroprotective. The efficacy of curcumin in several pre-clinical trials for neurodegenerative diseases has created considerable excitement mainly due to its lack of toxicity and low cost. This suggests that curcumin could be a worthy candidate for nutraceutical intervention. Since aging is a common risk factor for neurodegenerative diseases, it is possible that some compounds that target aging mechanisms could also prevent these kinds of diseases. One potential mechanism to explain several of the general health benefits associated with curcumin is that it may prevent aging-associated changes in cellular proteins that lead to protein insolubility and aggregation. This loss in protein homeostasis is associated with several age-related diseases. Recently, curcumin has been found to help maintain protein homeostasis and extend lifespan in the model invertebrate Caenorhabditis elegans. Here, we review the evidence from several animal models that curcumin improves healthspan by preventing or delaying the onset of various neurodegenerative diseases. PMID:23303664

  1. Categorical vowel perception enhances the effectiveness and generalization of auditory feedback in human-machine-interfaces.

    PubMed

    Larson, Eric; Terry, Howard P; Canevari, Margaux M; Stepp, Cara E

    2013-01-01

    Human-machine interface (HMI) designs offer the possibility of improving quality of life for patient populations as well as augmenting normal user function. Despite pragmatic benefits, utilizing auditory feedback for HMI control remains underutilized, in part due to observed limitations in effectiveness. The goal of this study was to determine the extent to which categorical speech perception could be used to improve an auditory HMI. Using surface electromyography, 24 healthy speakers of American English participated in 4 sessions to learn to control an HMI using auditory feedback (provided via vowel synthesis). Participants trained on 3 targets in sessions 1-3 and were tested on 3 novel targets in session 4. An "established categories with text cues" group of eight participants were trained and tested on auditory targets corresponding to standard American English vowels using auditory and text target cues. An "established categories without text cues" group of eight participants were trained and tested on the same targets using only auditory cuing of target vowel identity. A "new categories" group of eight participants were trained and tested on targets that corresponded to vowel-like sounds not part of American English. Analyses of user performance revealed significant effects of session and group (established categories groups and the new categories group), and a trend for an interaction between session and group. Results suggest that auditory feedback can be effectively used for HMI operation when paired with established categorical (native vowel) targets with an unambiguous cue.

  2. Musicians Show General Enhancement of Complex Sound Encoding and Better Inhibition of Irrelevant Auditory Change in Music: An ERP Study

    PubMed Central

    Kaganovich, Natalya; Kim, Jihyun; Herring, Caryn; Schumaker, Jennifer; MacPherson, Megan; Weber-Fox, Christine

    2012-01-01

    Using electrophysiology, we have examined two questions in relation to musical training – namely, whether it enhances sensory encoding of the human voice and whether it improves the ability to ignore irrelevant auditory change. Participants performed an auditory distraction task, in which they identified each sound as either short (350 ms) or long (550 ms) and ignored a change in sounds’ timbre. Sounds consisted of a male and a female voice saying a neutral sound [a], and of a cello and a French Horn playing an F3 note. In some blocks, musical sounds occurred on 80% of trials, while voice sounds on 20% of trials. In other blocks, the reverse was true. Participants heard naturally recorded sounds in half of experimental blocks and their spectrally-rotated versions in the other half. Regarding voice perception, we found that musicians had a larger N1 ERP component not only to vocal sounds but also to their never before heard spectrally-rotated versions. We, therefore, conclude that musical training is associated with a general improvement in the early neural encoding of complex sounds. Regarding the ability to ignore irrelevant auditory change, musicians’ accuracy tended to suffer less from the change in sounds’ timbre, especially when deviants were musical notes. This behavioral finding was accompanied by a marginally larger re-orienting negativity in musicians, suggesting that their advantage may lie in a more efficient disengagement of attention from the distracting auditory dimension. PMID:23301775

  3. A general population twin study of conduct problems and the auditory P300 waveform.

    PubMed

    Bertoletti, Eleonora; Michelini, Giorgia; Moruzzi, Sara; Ferrer, Giuseppina; Ferini-Strambi, Luigi; Stazi, Maria Antonietta; Ogliari, Anna; Battaglia, Marco

    2014-01-01

    Reduced amplitude of the P300 event-related potential has been consistently associated with a variety of externalising problems, including conduct disorder. The few available genetically-informative studies of these relationships, however, were conducted among adolescents/adults (i.e., at an age when conduct disorder has typically already become manifest). Among 200 general population twins with a mean age of 9 years (range 6-14 years), we studied the relationship between the P300 waveform elicited by an auditory oddball task and the DSM-oriented conduct problems scale of the Child Behavior Checklist 6-18. Conduct problems scores were negatively and significantly correlated (r = -0.19, p = 0.01) with P300 amplitude; correlations between P300 amplitude and the other DSM-oriented Child Behavior Checklist scales were non-significant, except for oppositional defiant problems (p = 0.01). We found moderate heritability estimates for both P300 amplitude (0.58, CI:0.37;0.73) and conduct problems (0.52, CI:0.25;0.70). Bivariate twin analyses indicated that the covariation between these two phenotypes can be explained by additive genetic factors only, with a genetic correlation of -0.33. An association between reduced P300 amplitude and conduct problems can be substantiated already in childhood, at an age that precedes the most typical onset of conduct disorder. This relationship appears to be genetic in nature. Reduced P300 amplitude can represent a valuable marker for conduct problems, and can contribute to the early identification of children at high-risk for conduct disorder.

  4. Meditation and neurodegenerative diseases.

    PubMed

    Newberg, Andrew B; Serruya, Mijail; Wintering, Nancy; Moss, Aleezé Sattar; Reibel, Diane; Monti, Daniel A

    2014-01-01

    Neurodegenerative diseases pose a significant problem for the healthcare system, doctors, and patients. With an aging population, more and more individuals are developing neurodegenerative diseases and there are few treatment options at the present time. Meditation techniques present an interesting potential adjuvant treatment for patients with neurodegenerative diseases and have the advantage of being inexpensive, and easy to teach and perform. There is increasing research evidence to support the application of meditation techniques to help improve cognition and memory in patients with neurodegenerative diseases. This review discusses the current data on meditation, memory, and attention, and the potential applications of meditation techniques in patients with neurodegenerative diseases.

  5. Generalized Selection-Based Auditory Matching and the Emergence of the Listener Component of Naming

    ERIC Educational Resources Information Center

    Speckman-Collins, JeanneMarie; Park, Hye-Suk Lee; Greer, Douglas

    2007-01-01

    We tested the effects of teaching an auditory match to sample repertoire on the emergence of the listener half of the verbal developmental cusp of Naming for 2-preschool students with language-based disabilities. The study was conducted in a special education CABAS[R] preschool. Neither of the students had selection or discrimination responses,…

  6. Musicians show general enhancement of complex sound encoding and better inhibition of irrelevant auditory change in music: an ERP study.

    PubMed

    Kaganovich, Natalya; Kim, Jihyun; Herring, Caryn; Schumaker, Jennifer; Macpherson, Megan; Weber-Fox, Christine

    2013-04-01

    Using electrophysiology, we have examined two questions in relation to musical training - namely, whether it enhances sensory encoding of the human voice and whether it improves the ability to ignore irrelevant auditory change. Participants performed an auditory distraction task, in which they identified each sound as either short (350 ms) or long (550 ms) and ignored a change in timbre of the sounds. Sounds consisted of a male and a female voice saying a neutral sound [a], and of a cello and a French Horn playing an F3 note. In some blocks, musical sounds occurred on 80% of trials, while voice sounds on 20% of trials. In other blocks, the reverse was true. Participants heard naturally recorded sounds in half of experimental blocks and their spectrally-rotated versions in the other half. Regarding voice perception, we found that musicians had a larger N1 event-related potential component not only to vocal sounds but also to their never before heard spectrally-rotated versions. We therefore conclude that musical training is associated with a general improvement in the early neural encoding of complex sounds. Regarding the ability to ignore irrelevant auditory change, musicians' accuracy tended to suffer less from the change in timbre of the sounds, especially when deviants were musical notes. This behavioral finding was accompanied by a marginally larger re-orienting negativity in musicians, suggesting that their advantage may lie in a more efficient disengagement of attention from the distracting auditory dimension. © 2013 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  7. Intensity dependence of auditory-evoked cortical potentials in fibromyalgia patients: a test of the generalized hypervigilance hypothesis.

    PubMed

    Carrillo-de-la-Peña, M T; Vallet, M; Pérez, M I; Gómez-Perretta, C

    2006-07-01

    On the basis of recent evidence concerning the amplification of incoming stimulation in fibromyalgia (FM) patients, it has been proposed that a generalized hypervigilance of painful and nonpainful sensations may be at the root of this disorder. So far, research into this issue has been inconclusive, possibly owing to the lack of agreement as to the operational definition of "generalized hypervigilance" and to the lack of robust objective measures characterizing the sensory style of FM patients. In this study, we recorded auditory-evoked potentials (AEPs) elicited by tones of increasing intensity (60, 70, 80, 90, and 105 dB) in 27 female FM patients and 25 healthy controls. Fibromyalgia patients presented shorter N1 and P2 latencies and a stronger intensity dependence of their AEPs. Both results suggest that FM patients may be hypervigilant to sensory stimuli, especially when very loud tones are used. The most noteworthy difference between patients and control subjects is at the highest stimulus intensity, for which far more patients maintained increased N1-P2 amplitudes in relation to the 90-dB tones. The larger AEP amplitudes to the 105-dB tones suggest that defects in an inhibitory system protecting against overstimulation may be a crucial factor in the pathophysiology of FM. Because a stronger loudness dependence of AEPs has been related to weak serotonergic transmission, it is hypothesized that for many FM patients deficient inhibition of the response to noxious and intense auditory stimuli may be due to a serotonergic deficit. The study of auditory-evoked potentials in response to tones of increasing intensity in FM patients may help to clarify the pathophysiology of this disorder, especially regarding the role of inhibition deficits involving serotonergic dysfunction, and may be a useful tool to guide the pharmacologic treatment of FM patients.

  8. Auditory Same/Different Concept Learning and Generalization in Black-Capped Chickadees (Poecile atricapillus)

    PubMed Central

    Hoeschele, Marisa; Cook, Robert G.; Guillette, Lauren M.; Hahn, Allison H.; Sturdy, Christopher B.

    2012-01-01

    Abstract concept learning was thought to be uniquely human, but has since been observed in many other species. Discriminating same from different is one abstract relation that has been studied frequently. In the current experiment, using operant conditioning, we tested whether black-capped chickadees (Poecile atricapillus) could discriminate sets of auditory stimuli based on whether all the sounds within a sequence were the same or different from one another. The chickadees were successful at solving this same/different relational task, and transferred their learning to same/different sequences involving novel combinations of training notes and novel notes within the range of pitches experienced during training. The chickadees showed limited transfer to pitches that was not used in training, suggesting that the processing of absolute pitch may constrain their relational performance. Our results indicate, for the first time, that black-capped chickadees readily form relational auditory same and different categories, adding to the list of perceptual, behavioural, and cognitive abilities that make this species an important comparative model for human language and cognition. PMID:23077660

  9. Epigenetic Changes in Neurodegenerative Diseases

    PubMed Central

    Kwon, Min Jee; Kim, Sunhong; Han, Myeong Hoon; Lee, Sung Bae

    2016-01-01

    Afflicted neurons in various neurodegenerative diseases generally display diverse and complex pathological features before catastrophic occurrence of massive neuronal loss at the late stages of the diseases. This complex nature of neuronal pathophysiology inevitably implicates systemwide changes in basic cellular activities such as transcriptional controls and signal cascades, and so on, as a cause. Recently, as one of these systemwide cellular changes associated with neurodegenerative diseases, epigenetic changes caused by protein toxicity have begun to be highlighted. Notably, recent advances in related techniques including next-generation sequencing (NGS) and mass spectrometry enable us to monitor changes in the post-translational modifications (PTMs) of histone proteins and to link these changes in histone PTMs to the specific transcriptional changes. Indeed, epigenetic alterations and consequent changes in neuronal transcriptome are now begun to be extensively studied in neurodegenerative diseases including Alzheimer’s disease (AD). In this review, we will discuss details of our current understandings on epigenetic changes associated with two representative neurodegenerative diseases [AD and polyglutamine (polyQ) diseases] and further discuss possible future development of pharmaceutical treatment of the diseases through modulating these epigenetic changes. PMID:27871175

  10. A general auditory bias for handling speaker variability in speech? Evidence in humans and songbirds

    PubMed Central

    Kriengwatana, Buddhamas; Escudero, Paola; Kerkhoven, Anne H.; Cate, Carel ten

    2015-01-01

    Different speakers produce the same speech sound differently, yet listeners are still able to reliably identify the speech sound. How listeners can adjust their perception to compensate for speaker differences in speech, and whether these compensatory processes are unique only to humans, is still not fully understood. In this study we compare the ability of humans and zebra finches to categorize vowels despite speaker variation in speech in order to test the hypothesis that accommodating speaker and gender differences in isolated vowels can be achieved without prior experience with speaker-related variability. Using a behavioral Go/No-go task and identical stimuli, we compared Australian English adults’ (naïve to Dutch) and zebra finches’ (naïve to human speech) ability to categorize / I/ and /ε/ vowels of an novel Dutch speaker after learning to discriminate those vowels from only one other speaker. Experiments 1 and 2 presented vowels of two speakers interspersed or blocked, respectively. Results demonstrate that categorization of vowels is possible without prior exposure to speaker-related variability in speech for zebra finches, and in non-native vowel categories for humans. Therefore, this study is the first to provide evidence for what might be a species-shared auditory bias that may supersede speaker-related information during vowel categorization. It additionally provides behavioral evidence contradicting a prior hypothesis that accommodation of speaker differences is achieved via the use of formant ratios. Therefore, investigations of alternative accounts of vowel normalization that incorporate the possibility of an auditory bias for disregarding inter-speaker variability are warranted. PMID:26379579

  11. Optogenetics for neurodegenerative diseases

    PubMed Central

    Vann, Kiara T; Xiong, Zhi-Gang

    2016-01-01

    Neurodegenerative diseases are devastating conditions that lead to progressive degeneration of neurons. Neurodegeneration may result in ataxia, dementia, and muscle atrophies, etc. Despite enormous research efforts that have been made, there is lack of effective therapeutic interventions for most of these diseases. Optogenetics is a recently developed novel technique that combines optics and genetics to modulate the activity of specific neurons. Optogenetics has been implemented in various studies including neuropsychiatric disorders and neurodegenerative diseases. This review focuses on the recent advance in using this technique for the studies of common neurodegenerative diseases. PMID:27186317

  12. Glutamate and Neurodegenerative Disease

    NASA Astrophysics Data System (ADS)

    Schaeffer, Eric; Duplantier, Allen

    As the main excitatory neurotransmitter in the mammalian central nervous system, glutamate is critically involved in most aspects of CNS function. Given this critical role, it is not surprising that glutamatergic dysfunction is associated with many CNS disorders. In this chapter, we review the literature that links aberrant glutamate neurotransmission with CNS pathology, with a focus on neurodegenerative diseases. The biology and pharmacology of the various glutamate receptor families are discussed, along with data which links these receptors with neurodegenerative conditions. In addition, we review progress that has been made in developing small molecule modulators of glutamate receptors and transporters, and describe how these compounds have helped us understand the complex pharmacology of glutamate in normal CNS function, as well as their potential for the treatment of neurodegenerative diseases.

  13. Auditory models for speech analysis

    NASA Astrophysics Data System (ADS)

    Maybury, Mark T.

    This paper reviews the psychophysical basis for auditory models and discusses their application to automatic speech recognition. First an overview of the human auditory system is presented, followed by a review of current knowledge gleaned from neurological and psychoacoustic experimentation. Next, a general framework describes established peripheral auditory models which are based on well-understood properties of the peripheral auditory system. This is followed by a discussion of current enhancements to that models to include nonlinearities and synchrony information as well as other higher auditory functions. Finally, the initial performance of auditory models in the task of speech recognition is examined and additional applications are mentioned.

  14. Microbiota and neurodegenerative diseases.

    PubMed

    Marizzoni, Moira; Provasi, Stefania; Cattaneo, Annamaria; Frisoni, Giovanni B

    2017-09-12

    Despite the extensive research carried out in the past decades, the current pathophysiological notions of neurodegenerative disease as well as effective treatments to reduce their progression are largely unknown. Alterations of the human microbiota, the plethora of different microscopic organisms that our body hosts, have been linked to neurodegenerative disease risk, onset and progression. This review summarizes the current knowledge on the possible role of microbiota in neurodegenerative disorders and briefly discusses strategies to restore microbiota homeostasis. Preclinical evidences and human cross-sectional studies posit the gut microbiota as a key actor in the Parkinson's disease onset and progression, reporting the presence of a specific gut microbiota profile in association with the modulation of disease and symptoms. Gut microbiota alterations have been correlated with brain disease and peripheral inflammation also in Alzheimer's patients. The interaction between the microbiota and the host is promising to answer clinical questions that have so far escaped clarification with the current pathophysiological notions of health and disease. However, human longitudinal studies starting in the earlier disease phases are needed to understand the causative relation between microbiota and the hallmarks of these neurodegenerative disorders and to develop innovative treatments aimed at preventing or slowing brain damages.

  15. [Cellular bases of neurodegenerative processes].

    PubMed

    Nieoullon, A

    1998-01-01

    Neurodegenerative processes are generally characterized by the long-lasting course of neuronal death and the selectivity of the neuronal population or brain structure involved in the lesion. This is the case for Alzheimer's, Parkinson's or Huntington's diseases, or amyotrophic lateral sclerosis (ALS). The reasons for such a specificity are largely unknown as are generally the mechanisms of the diseases. One common feature of these diseases, however, is that the neuronal death is thought to involve apoptosis, at least partly. Interestingly, apoptosis in the brain would involve specific gene products similar to that identified in the nematode c. elegans, partly corresponding in mammals to ICE-related compounds and Bcl2 protein. The involvement of calcium as well as of oxydative stress mechanisms in such neuronal death is to be fully proved but putative modulation by external signals (such as those provided through trophic factors or even neurotransmitters) represents an interesting way to validate the current hypothesis of neuronal death in neurodegenerative diseases in humans.

  16. Glutathione transferases and neurodegenerative diseases.

    PubMed

    Mazzetti, Anna Paola; Fiorile, Maria Carmela; Primavera, Alessandra; Lo Bello, Mario

    2015-03-01

    There is substantial agreement that the unbalance between oxidant and antioxidant species may affect the onset and/or the course of a number of common diseases including Parkinson's and Alzheimer's diseases. Many studies suggest a crucial role for oxidative stress in the first phase of aging, or in the pathogenesis of various diseases including neurological ones. Particularly, the role exerted by glutathione and glutathione-related enzymes (Glutathione Transferases) in the nervous system appears more relevant, this latter tissue being much more vulnerable to toxins and oxidative stress than other tissues such as liver, kidney or muscle. The present review addresses the question by focusing on the results obtained by specimens from patients or by in vitro studies using cells or animal models related to Parkinson's and Alzheimer's diseases. In general, there is an association between glutathione depletion and Parkinson's or Alzheimer's disease. In addition, a significant decrease of glutathione transferase activity in selected areas of brain and in ventricular cerebrospinal fluid was found. For some glutathione transferase genes there is also a correlation between polymorphisms and onset/outcome of neurodegenerative diseases. Thus, there is a general agreement about the protective effect exerted by glutathione and glutathione transferases but no clear answer about the mechanisms underlying this crucial role in the insurgence of neurodegenerative diseases.

  17. Glycoproteomics in Neurodegenerative Diseases

    PubMed Central

    Hwang, Hyejin; Zhang, Jianpeng; Chung, Kathryn A.; Leverenz, James B.; Zabetian, Cyrus P.; Peskind, Elaine R.; Jankovic, Joseph; Su, Zhen; Hancock, Aneeka M.; Pan, Catherine; Montine, Thomas J.; Pan, Sheng; Nutt, John; Albin, Roger; Gearing, Marla; Beyer, Richard P.; Shi, Min; Zhang, Jing

    2009-01-01

    Protein glycosylation regulates protein function and cellular distribution. Additionally, aberrant protein glycosylations have been recognized to play major roles in human disorders, including neurodegenerative diseases. Glycoproteomics, a branch of proteomics that catalogs and quantifies glycoproteins, provides a powerful means to systematically profile the glycopeptides or glycoproteins of a complex mixture that are highly enriched in body fluids, and therefore, carry great potential to be diagnostic and/or prognostic markers. Application of this mass spectrometry-based technology to the study of neurodegenerative disorders (e.g., Alzheimer's disease and Parkinson's disease) is relatively new, and is expected to provide insight into the biochemical pathogenesis of neurodegeneration, as well as biomarker discovery. In this review, we have summarized the current understanding of glycoproteins in biology and neurodegenerative disease, and have discussed existing proteomic technologies that are utilized to characterize glycoproteins. Some of the ongoing studies, where glycoproteins isolated from cerebrospinal fluid and human brain are being characterized in Parkinson's disease at different stages versus controls, are presented, along with future applications of targeted validation of brain specific glycoproteins in body fluids. PMID:19358229

  18. Inflammation in neurodegenerative diseases

    PubMed Central

    Amor, Sandra; Puentes, Fabiola; Baker, David; van der Valk, Paul

    2010-01-01

    Neurodegeneration, the slow and progressive dysfunction and loss of neurons and axons in the central nervous system, is the primary pathological feature of acute and chronic neurodegenerative conditions such as Alzheimer’s disease and Parkinson’s disease, neurotropic viral infections, stroke, paraneoplastic disorders, traumatic brain injury and multiple sclerosis. Despite different triggering events, a common feature is chronic immune activation, in particular of microglia, the resident macrophages of the central nervous system. Apart from the pathogenic role of immune responses, emerging evidence indicates that immune responses are also critical for neuroregeneration. Here, we review the impact of innate and adaptive immune responses on the central nervous system in autoimmune, viral and other neurodegenerative disorders, and discuss their contribution to either damage or repair. We also discuss potential therapies aimed at the immune responses within the central nervous system. A better understanding of the interaction between the immune and nervous systems will be crucial to either target pathogenic responses, or augment the beneficial effects of immune responses as a strategy to intervene in chronic neurodegenerative diseases. PMID:20561356

  19. Visual Hallucinations in the Psychosis Spectrum and Comparative Information From Neurodegenerative Disorders and Eye Disease

    PubMed Central

    Waters, Flavie; Collerton, Daniel; ffytche, Dominic H.; Jardri, Renaud; Pins, Delphine; Dudley, Robert; Blom, Jan Dirk; Mosimann, Urs Peter; Eperjesi, Frank; Ford, Stephen; Larøi, Frank

    2014-01-01

    Much of the research on visual hallucinations (VHs) has been conducted in the context of eye disease and neurodegenerative conditions, but little is known about these phenomena in psychiatric and nonclinical populations. The purpose of this article is to bring together current knowledge regarding VHs in the psychosis phenotype and contrast this data with the literature drawn from neurodegenerative disorders and eye disease. The evidence challenges the traditional views that VHs are atypical or uncommon in psychosis. The weighted mean for VHs is 27% in schizophrenia, 15% in affective psychosis, and 7.3% in the general community. VHs are linked to a more severe psychopathological profile and less favorable outcome in psychosis and neurodegenerative conditions. VHs typically co-occur with auditory hallucinations, suggesting a common etiological cause. VHs in psychosis are also remarkably complex, negative in content, and are interpreted to have personal relevance. The cognitive mechanisms of VHs in psychosis have rarely been investigated, but existing studies point to source-monitoring deficits and distortions in top-down mechanisms, although evidence for visual processing deficits, which feature strongly in the organic literature, is lacking. Brain imaging studies point to the activation of visual cortex during hallucinations on a background of structural and connectivity changes within wider brain networks. The relationship between VHs in psychosis, eye disease, and neurodegeneration remains unclear, although the pattern of similarities and differences described in this review suggests that comparative studies may have potentially important clinical and theoretical implications. PMID:24936084

  20. Effects of Ashwagandha (roots of Withania somnifera) on neurodegenerative diseases.

    PubMed

    Kuboyama, Tomoharu; Tohda, Chihiro; Komatsu, Katsuko

    2014-01-01

    Neurodegenerative diseases commonly induce irreversible destruction of central nervous system (CNS) neuronal networks, resulting in permanent functional impairments. Effective medications against neurodegenerative diseases are currently lacking. Ashwagandha (roots of Withania somnifera Dunal) is used in traditional Indian medicine (Ayurveda) for general debility, consumption, nervous exhaustion, insomnia, and loss of memory. In this review, we summarize various effects and mechanisms of Ashwagandha extracts and related compounds on in vitro and in vivo models of neurodegenerative diseases such as Alzheimer's disease and spinal cord injury.

  1. Ageing and neurodegenerative diseases.

    PubMed

    Hung, Chia-Wei; Chen, Yu-Chih; Hsieh, Wan-Ling; Chiou, Shih-Hwa; Kao, Chung-Lan

    2010-11-01

    Ageing, which all creatures must encounter, is a challenge to every living organism. In the human body, it is estimated that cell division and metabolism occurs exuberantly until about 25 years of age. Beyond this age, subsidiary products of metabolism and cell damage accumulate, and the phenotypes of ageing appear, causing disease formation. Among these age-related diseases, neurodegenerative diseases have drawn a lot of attention due to their irreversibility, lack of effective treatment, and accompanied social and economical burdens. In seeking to ameliorate ageing and age-related diseases, the search for anti-ageing drugs has been of much interest. Numerous studies have shown that the plant polyphenol, resveratrol (3,5,4'-trihydroxystilbene), extends the lifespan of several species, prevents age-related diseases, and possesses anti-inflammatory, and anti-cancer properties. The beneficial effects of resveratrol are believed to be associated with the activation of a longevity gene, SirT1. In this review, we discuss the pathogenesis of age-related neurodegenerative diseases including Alzheimer's disease, Parkinson's disease and cerebrovascular disease. The therapeutic potential of resveratrol, diet and the roles of stem cell therapy are discussed to provide a better understanding of the ageing mystery.

  2. Nanotechnology for neurodegenerative disorders.

    PubMed

    Re, Francesca; Gregori, Maria; Masserini, Massimo

    2012-09-01

    The efficacy, cellular uptake and specific transport of drugs and/or imaging agents to target organs, tissues and cells are common issues in the diagnosis and treatment of different disorders. In the case of neurodegenerative diseases, they represent complex problems, since brain targeting remains a still unsolved challenge in pharmacology, due to the presence of the blood-brain barrier, a tightly packed layer of endothelial cells that prevents unwanted substances to enter the brain. Engineered nanomaterials, objects with dimensions of 1-100 nm, are providing interesting biomedical tools potentially able to solve these problems, thanks to their physico-chemical features and to the possibility of multi-functionalization, allowing to confer them different features at the same time, including the ability to cross the blood-brain barrier. This review focuses on the state-of-the-art of nanomaterials suitable for therapy and diagnostic imaging of the most common neurodegenerative disorders, as well as for neuroprotection and neuronal tissue regeneration. Finally, their potential neurotoxicity is discussed, and future nanotechnological approaches are described. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Neuromodulation for neurodegenerative conditions.

    PubMed

    Tierney, Travis S; Vasudeva, Viren S; Weir, Sharada; Hayes, Michael T

    2013-01-01

    Pharmacological therapy has had limited success in the treatment of most major neurological diseases. This has motivated the development of a number of novel surgical approaches designed to ameliorate drug-induced side effects or pharmacoresistant symptoms. Deep brain stimulation (DBS) has been quite successful in controlling both the cardinal motor manifestation of Parkinson's disease and the side effects of prolonged levodopa therapy. This has encouraged the application of DBS technology to treat a number of other neurodegenerative conditions, including secondary dystonia associated with pantothenate kinase-associated neurodegeneration (PKAN, formerly Hallervorden-Spatz syndrome), chorea associated with Huntington's disease, and most recently, cognitive decline associated with Alzheimer's type dementia. We review the rationale, indications and outcomes of neuromodulation for selected neurodegenerative conditions. In addition to DBS, we discuss select small molecule and gene-based neuromodulatory approaches. Ongoing study of basic pathophysiological mechanisms may eventually allow directed primary prevention of some of these diseases, but until then, invasive neuromoduation will likely continue to play an ever-increasing role in the delivery of the most advanced care for patients with these debilitating conditions.

  4. Genetics of isolated auditory neuropathies.

    PubMed

    Del Castillo, Francisco J; Del Castillo, Ignacio

    2012-01-01

    Auditory neuropathies are disorders combining absent or abnormal auditory brainstem responses with preserved otoacoustic emissions and/or cochlear microphonics. These features indicate a normal function of cochlear outer hair cells. Thus, the primary lesion might be located in the inner hair cells, in the auditory nerve or in the intervening synapse. Auditory neuropathy is observed in up to 10 percent of deaf infants and children, either as part of some systemic neurodegenerative diseases or as an isolated entity. Research on the genetic causes of isolated auditory neuropathies has been remarkably successful in the last few years. Here we review the current knowledge on the structure, expression and function of the genes and proteins so far known to be involved in these disorders, as well as the clinical features that are associated with mutations in the different genes. This knowledge is permitting to classify isolated auditory neuropathies into etiologically homogeneous types, so providing clues for the better diagnosis, management and therapy of the affected subjects.

  5. Auditory Imagination.

    ERIC Educational Resources Information Center

    Croft, Martyn

    Auditory imagination is used in this paper to describe a number of issues and activities related to sound and having to do with listening, thinking, recalling, imagining, reshaping, creating, and uttering sounds and words. Examples of auditory imagination in religious and literary works are cited that indicate a belief in an imagined, expected, or…

  6. The hippocampus in neurodegenerative disease.

    PubMed

    Moodley, K K; Chan, D

    2014-01-01

    AD is the commonest neurodegenerative disorder resulting ultimately in dementia, a stage during which there is a loss of previously acquired intellectual skill and independent occupational and social function. Neurodegenerative changes within the hippocampus and an extended neuronal network involving the medial temporal and medial parietal lobe result in the archetypal memory impairment seen in Alzheimer's disease (AD). As attention focuses increasingly on early diagnosis and treatment of dementia, this understanding of the hippocampal involvement in AD has helped to develop diagnostic tools for use in early disease. However, hippocampal damage is also a common feature among non-AD neurodegenerative dementias. Neuroimaging techniques, in conjunction with behavioral and pathological techniques, can be used to determine the involvement of the hippocampus in AD and other neurodegenerative diseases.

  7. Proteomics of Human Neurodegenerative Diseases

    PubMed Central

    Zhang, Jing; Keene, C. Dirk; Pan, Catherine; Montine, Kathleen S.; Montine, Thomas J.

    2009-01-01

    The technology, experimental approaches, and bioinformatics that support proteomic research are evolving rapidly. The application of these new capabilities to the study of neurodegenerative diseases is providing insight into the biochemical pathogenesis of neurodegeneration as well as fueling major efforts in biomarker discovery. Here, we review the fundamentals of commonly used proteomic approaches and the outcomes of these investigations with autopsy and cerebrospinal fluid samples from patients with neurodegenerative diseases. PMID:18800015

  8. Auditory neglect.

    PubMed Central

    De Renzi, E; Gentilini, M; Barbieri, C

    1989-01-01

    Auditory neglect was investigated in normal controls and in patients with a recent unilateral hemispheric lesion, by requiring them to detect the interruptions that occurred in one ear in a sound delivered through earphones either mono-aurally or binaurally. Control patients accurately detected interruptions. One left brain damaged (LBD) patient missed only once in the ipsilateral ear while seven of the 30 right brain damaged (RBD) patients missed more than one signal in the monoaural test and nine patients did the same in the binaural test. Omissions were always more marked in the left ear and in the binaural test with a significant ear by test interaction. The lesion of these patients was in the parietal lobe (five patients) and the thalamus (four patients). The relation of auditory neglect to auditory extinction was investigated and found to be equivocal, in that there were seven RBD patients who showed extinction, but not neglect and, more importantly, two patients who exhibited the opposite pattern, thus challenging the view that extinction is a minor form of neglect. Also visual and auditory neglect were not consistently correlated, the former being present in nine RBD patients without auditory neglect and the latter in two RBD patients without visual neglect. The finding that in some RBD patients with auditory neglect omissions also occurred, though with less frequency, in the right ear, points to a right hemisphere participation in the deployment of attention not only to the contralateral, but also to the ipsilateral space. PMID:2732732

  9. Bile Acids in Neurodegenerative Disorders

    PubMed Central

    Ackerman, Hayley D.; Gerhard, Glenn S.

    2016-01-01

    Bile acids, a structurally related group of molecules derived from cholesterol, have a long history as therapeutic agents in medicine, from treatment for primarily ocular diseases in ancient Chinese medicine to modern day use as approved drugs for certain liver diseases. Despite evidence supporting a neuroprotective role in a diverse spectrum of age-related neurodegenerative disorders, including several small pilot clinical trials, little is known about their molecular mechanisms or their physiological roles in the nervous system. We review the data reported for their use as treatments for neurodegenerative diseases and their underlying molecular basis. While data from cellular and animal models and clinical trials support potential efficacy to treat a variety of neurodegenerative disorders, the relevant bile acids, their origin, and the precise molecular mechanism(s) by which they confer neuroprotection are not known delaying translation to the clinical setting. PMID:27920719

  10. Depressive symptoms in neurodegenerative diseases

    PubMed Central

    Baquero, Miquel; Martín, Nuria

    2015-01-01

    Depressive symptoms are very common in chronic conditions. This is true so for neurodegenerative diseases. A number of patients with cognitive decline and dementia due to Alzheimer’s disease and related conditions like Parkinson’s disease, Lewy body disease, vascular dementia, frontotemporal degeneration amongst other entities, experience depressive symptoms in greater or lesser grade at some point during the course of the illness. Depressive symptoms have a particular significance in neurological disorders, specially in neurodegenerative diseases, because brain, mind, behavior and mood relationship. A number of patients may develop depressive symptoms in early stages of the neurologic disease, occurring without clear presence of cognitive decline with only mild cognitive deterioration. Classically, depression constitutes a reliable diagnostic challenge in this setting. However, actually we can recognize and evaluate depressive, cognitive or motor symptoms of neurodegenerative disease in order to establish their clinical significance and to plan some therapeutic strategies. Depressive symptoms can appear also lately, when the neurodegenerative disease is fully developed. The presence of depression and other neuropsychiatric symptoms have a negative impact on the quality-of-life of patients and caregivers. Besides, patients with depressive symptoms also tend to further decrease function and reduce cognitive abilities and also uses to present more affected clinical status, compared with patients without depression. Depressive symptoms are treatable. Early detection of depressive symptoms is very important in patients with neurodegenerative disorders, in order to initiate the most adequate treatment. We review in this paper the main neurodegenerative diseases, focusing in depressive symptoms of each other entities and current recommendations of management and treatment. PMID:26301229

  11. Depressive symptoms in neurodegenerative diseases.

    PubMed

    Baquero, Miquel; Martín, Nuria

    2015-08-16

    Depressive symptoms are very common in chronic conditions. This is true so for neurodegenerative diseases. A number of patients with cognitive decline and dementia due to Alzheimer's disease and related conditions like Parkinson's disease, Lewy body disease, vascular dementia, frontotemporal degeneration amongst other entities, experience depressive symptoms in greater or lesser grade at some point during the course of the illness. Depressive symptoms have a particular significance in neurological disorders, specially in neurodegenerative diseases, because brain, mind, behavior and mood relationship. A number of patients may develop depressive symptoms in early stages of the neurologic disease, occurring without clear presence of cognitive decline with only mild cognitive deterioration. Classically, depression constitutes a reliable diagnostic challenge in this setting. However, actually we can recognize and evaluate depressive, cognitive or motor symptoms of neurodegenerative disease in order to establish their clinical significance and to plan some therapeutic strategies. Depressive symptoms can appear also lately, when the neurodegenerative disease is fully developed. The presence of depression and other neuropsychiatric symptoms have a negative impact on the quality-of-life of patients and caregivers. Besides, patients with depressive symptoms also tend to further decrease function and reduce cognitive abilities and also uses to present more affected clinical status, compared with patients without depression. Depressive symptoms are treatable. Early detection of depressive symptoms is very important in patients with neurodegenerative disorders, in order to initiate the most adequate treatment. We review in this paper the main neurodegenerative diseases, focusing in depressive symptoms of each other entities and current recommendations of management and treatment.

  12. Indian Herbs for the Treatment of Neurodegenerative Disease.

    PubMed

    Mannangatti, Padmanabhan; Naidu, Kamalakkannan Narasimha

    2016-01-01

    Ayurveda, an ancient system of medicine that is indigenous to India, is believed to be the world's oldest comprehensive health-care system and is now one of the most recognized and widely practiced disciplines of alternative medicine in the world. Medicinal herbs have been in use for treating diseases since ancient times in India. Ayurvedic therapies with medicinal herbs and herbomineral products generally provide relief without much adverse effects even after prolonged administration. Neurodegenerative disorders are a major cause of mortality and disability, and increasing life spans represent one of the key challenges of medical research. Ayurvedic medicine describes most neurodegenerative diseases and has defined a number of plants with therapeutic benefits for the treatment of neurodegenerative diseases having antioxidant activities. In this chapter, the role of four important Ayurvedic medicinal plants, viz., Withania somnifera (ashwagandha), Bacopa monnieri (brahmi), Centella asiatica (gotu kola), and Mucuna pruriens (velvet bean), on neurodegenerative diseases are discussed.

  13. The cytoskeleton in neurodegenerative diseases

    PubMed Central

    Cairns, Nigel J; Lee, Virginia M-Y; Trojanowski, John Q

    2009-01-01

    Abundant abnormal aggregates of cytoskeletal proteins are neuropathological signatures of many neurodegenerative diseases that are broadly classified by filamentous aggregates of neuronal intermediate filament (IF) proteins, or by inclusions containing the microtubule-associated protein (MAP) tau. The discovery of mutations in neuronal IF and tau genes firmly establishes the importance of neuronal IF proteins and tau in the pathogenesis of neurodegenerative diseases. Multiple IF gene mutations are pathogenic for Charcot–Marie–Tooth (CMT) disease and amyotrophic lateral sclerosis (ALS) — in addition to those in the copper/zinc superoxide dismutase-1 (SOD1) gene. Tau gene mutations are pathogenic for frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), and tau polymorphisms are genetic risk factors for sporadic progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Thus, IF and tau abnormalities are linked directly to the aetiology and pathogenesis of neurodegenerative diseases. In vitro and transgenic animal models are being used to demonstrate that different mutations impair protein function, promote tau fibrilization, or perturb tau gene splicing, leading to aberrant and distinct tau aggregates. For recognition of these disorders at neuropathological examination, immunohistochemistry is needed, and this may be combined with biochemistry and molecular genetics to properly determine the nosology of a particular case. As reviewed here, the identification of molecular genetic defects and biochemical alterations in cytoskeletal proteins of human neurodegenerative diseases has facilitated experimental studies and will promote the development of assays of molecules which inhibit abnormal neuronal IF and tau protein inclusions. PMID:15495240

  14. Auditory system

    NASA Technical Reports Server (NTRS)

    Ades, H. W.

    1973-01-01

    The physical correlations of hearing, i.e. the acoustic stimuli, are reported. The auditory system, consisting of external ear, middle ear, inner ear, organ of Corti, basilar membrane, hair cells, inner hair cells, outer hair cells, innervation of hair cells, and transducer mechanisms, is discussed. Both conductive and sensorineural hearing losses are also examined.

  15. Auditory system

    NASA Technical Reports Server (NTRS)

    Ades, H. W.

    1973-01-01

    The physical correlations of hearing, i.e. the acoustic stimuli, are reported. The auditory system, consisting of external ear, middle ear, inner ear, organ of Corti, basilar membrane, hair cells, inner hair cells, outer hair cells, innervation of hair cells, and transducer mechanisms, is discussed. Both conductive and sensorineural hearing losses are also examined.

  16. A generalized time-frequency subtraction method for robust speech enhancement based on wavelet filter banks modeling of human auditory system.

    PubMed

    Shao, Yu; Chang, Chip-Hong

    2007-08-01

    We present a new speech enhancement scheme for a single-microphone system to meet the demand for quality noise reduction algorithms capable of operating at a very low signal-to-noise ratio. A psychoacoustic model is incorporated into the generalized perceptual wavelet denoising method to reduce the residual noise and improve the intelligibility of speech. The proposed method is a generalized time-frequency subtraction algorithm, which advantageously exploits the wavelet multirate signal representation to preserve the critical transient information. Simultaneous masking and temporal masking of the human auditory system are modeled by the perceptual wavelet packet transform via the frequency and temporal localization of speech components. The wavelet coefficients are used to calculate the Bark spreading energy and temporal spreading energy, from which a time-frequency masking threshold is deduced to adaptively adjust the subtraction parameters of the proposed method. An unvoiced speech enhancement algorithm is also integrated into the system to improve the intelligibility of speech. Through rigorous objective and subjective evaluations, it is shown that the proposed speech enhancement system is capable of reducing noise with little speech degradation in adverse noise environments and the overall performance is superior to several competitive methods.

  17. Improving neural decoding in the central auditory system using bio-inspired spectro-temporal representations and a generalized bilinear model.

    PubMed

    Siahpoush, Shadi; Erfani, Yousof; Rode, Thilo; Lim, Hubert H; Rouat, Jean; Plourde, Eric

    2015-01-01

    We study the impact of different encoding models and spectro-temporal representations on the accuracy of Bayesian decoding of neural activity recorded from the central auditory system. Two encoding models, a generalized linear model (GLM) and a generalized bilinear model (GBM), are compared along with three different spectro-temporal representations of the input stimuli: a spectrogram and two bio-inspired representations, i.e. a gammatone filter bank (GFB) and a spikegram. Signal to noise ratios between the reconstructed and original representations are used to evaluate the decoding, or reconstruction accuracy. We experimentally show that the reconstruction accuracy is best with the spikegram representation and worst with the spectrogram representation and, furthermore, that using a GBM instead of a GLM significantly increases the reconstruction accuracy. In fact, our results show that the spikegram reconstruction accuracy with a GBM fitting yields an SNR that is 3.3 dB better than when using the standard decoding approach of reconstructing a spectrogram with GLM fitting.

  18. Developmental neuroplasticity and the origin of neurodegenerative diseases.

    PubMed

    Schaefers, Andrea T U; Teuchert-Noodt, Gertraud

    2016-12-01

    Neurodegenerative diseases like Alzheimer's and Parkinson's Disease, marked by characteristic protein aggregations, are more and more accepted to be synaptic disorders and to arise from a combination of genetic and environmental factors. In this review we propose our concept that neuroplasticity might constitute a link between early life challenges and neurodegeneration. After introducing the general principles of neuroplasticity, we show how adverse environmental stimuli during development impact adult neuroplasticity and might lead to neurodegenerative processes. There are significant overlaps between neurodevelopmental and neurodegenerative processes. Proteins that represent hallmarks of neurodegeneration are involved in plastic processes under physiological conditions. Brain regions - particularly the hippocampus - that retain life-long plastic capacities are the key targets of neurodegeneration. Neuroplasticity is highest in young age making the brain more susceptible to external influences than later in life. Impacts during critical periods have life-long consequences on neuroplasticity and structural self-organization and are known to be common risk factors for neurodegenerative diseases. Several lines of evidence support a link between developmental neuroplasticity and neurodegenerative processes later in life. A deeper insight into these processes is necessary to design strategies to mitigate or even prevent neurodegenerative pathologies.

  19. Incidental Auditory Category Learning

    PubMed Central

    Gabay, Yafit; Dick, Frederic K.; Zevin, Jason D.; Holt, Lori L.

    2015-01-01

    Very little is known about how auditory categories are learned incidentally, without instructions to search for category-diagnostic dimensions, overt category decisions, or experimenter-provided feedback. This is an important gap because learning in the natural environment does not arise from explicit feedback and there is evidence that the learning systems engaged by traditional tasks are distinct from those recruited by incidental category learning. We examined incidental auditory category learning with a novel paradigm, the Systematic Multimodal Associations Reaction Time (SMART) task, in which participants rapidly detect and report the appearance of a visual target in one of four possible screen locations. Although the overt task is rapid visual detection, a brief sequence of sounds precedes each visual target. These sounds are drawn from one of four distinct sound categories that predict the location of the upcoming visual target. These many-to-one auditory-to-visuomotor correspondences support incidental auditory category learning. Participants incidentally learn categories of complex acoustic exemplars and generalize this learning to novel exemplars and tasks. Further, learning is facilitated when category exemplar variability is more tightly coupled to the visuomotor associations than when the same stimulus variability is experienced across trials. We relate these findings to phonetic category learning. PMID:26010588

  20. Molecular diagnostics of neurodegenerative disorders.

    PubMed

    Agrawal, Megha; Biswas, Abhijit

    2015-01-01

    Molecular diagnostics provide a powerful method to detect and diagnose various neurological diseases such as Alzheimer's and Parkinson's disease. The confirmation of such diagnosis allows early detection and subsequent medical counseling that help specific patients to undergo clinically important drug trials. This provides a medical pathway to have better insight of neurogenesis and eventual cure of the neurodegenerative diseases. In this short review, we present recent advances in molecular diagnostics especially biomarkers and imaging spectroscopy for neurological diseases. We describe advances made in Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD), and finally present a perspective on the future directions to provide a framework for further developments and refinements of molecular diagnostics to combat neurodegenerative disorders.

  1. Reward processing in neurodegenerative disease.

    PubMed

    Perry, David C; Kramer, Joel H

    2015-02-01

    Representation of reward value involves a distributed network including cortical and subcortical structures. Because neurodegenerative illnesses target specific anatomic networks that partially overlap with the reward circuit, they would be predicted to have distinct impairments in reward processing. This review presents the existing evidence of reward processing changes in neurodegenerative diseases including mild cognitive impairment (MCI), Alzheimer's disease, frontotemporal dementia, amyotrophic lateral sclerosis (ALS), Parkinson's disease, and Huntington's disease, as well as in healthy aging. Carefully distinguishing the different aspects of reward processing (primary rewards, secondary rewards, reward-based learning, and reward-based decision-making) and using tasks that differentiate the stages of processing reward will lead to improved understanding of this fundamental process and clarify a contributing cause of behavioral change in these illnesses.

  2. Omental transplantation for neurodegenerative diseases

    PubMed Central

    Rafael, Hernando

    2014-01-01

    Up to date, almost all researchers consider that there is still no effective therapy for neurodegenerative diseases (NDDs) and therefore, these diseases are incurable. However, since May 1998, we know that a progressive ischemia in the medial temporal lobes and subcommissural regions can cause Alzheimer’s disease; because, in contrast to this, its revascularization by means of omental tissue can cure or improve this disease. Likewise we observed that the aging process, Huntington’s disease, Parkinson’s disease, and Amyotrophic lateral sclerosis; all of them are of ischemic origin caused by cerebral atherosclerosis, associated with vascular anomalies and/or environmental chemicals. On the contrary, an omental transplantation on the affected zone can stop and improve these diseases. For these reasons, I believe that NDDs, are wrongly classified as neurodegenerative disorders. PMID:25232510

  3. Primary Auditory Cortex Regulates Threat Memory Specificity

    ERIC Educational Resources Information Center

    Wigestrand, Mattis B.; Schiff, Hillary C.; Fyhn, Marianne; LeDoux, Joseph E.; Sears, Robert M.

    2017-01-01

    Distinguishing threatening from nonthreatening stimuli is essential for survival and stimulus generalization is a hallmark of anxiety disorders. While auditory threat learning produces long-lasting plasticity in primary auditory cortex (Au1), it is not clear whether such Au1 plasticity regulates memory specificity or generalization. We used…

  4. Primary Auditory Cortex Regulates Threat Memory Specificity

    ERIC Educational Resources Information Center

    Wigestrand, Mattis B.; Schiff, Hillary C.; Fyhn, Marianne; LeDoux, Joseph E.; Sears, Robert M.

    2017-01-01

    Distinguishing threatening from nonthreatening stimuli is essential for survival and stimulus generalization is a hallmark of anxiety disorders. While auditory threat learning produces long-lasting plasticity in primary auditory cortex (Au1), it is not clear whether such Au1 plasticity regulates memory specificity or generalization. We used…

  5. Essential Tremor: A Neurodegenerative Disease?

    PubMed Central

    Benito-León, Julián

    2014-01-01

    Background Essential tremor (ET) is one of the most common neurological disorders among adults, and is the most common of the many tremor disorders. It has classically been viewed as a benign monosymptomatic condition, yet over the past decade, a growing body of evidence indicates that ET is a progressive condition that is clinically heterogeneous, as it may be associated with a spectrum of clinical features, with both motor and non-motor elements. In this review, I will describe the most significant emerging milestones in research which, when taken together, suggest that ET is a neurodegenerative condition. Methods A PubMed search conducted in June 2014 crossing the terms “essential tremor” (ET) and “neurodegenerative” yielded 122 entries, 20 of which included the term “neurodegenerative” in the article title. This was supplemented by articles in the author's files that pertained to this topic. Results/Discussion There is an open and active dialogue in the medical community as to whether ET is a neurodegenerative disease, with considerable evidence in favor of this. Specifically, ET is a progressive disorder of aging associated with neuronal loss (reduction in Purkinje cells) as well as other post-mortem changes that occur in traditional neurodegenerative disorders. Along with this, advanced neuroimaging techniques are now demonstrating distinct structural changes, several of which are consistent with neuronal loss, in patients with ET. However, further longitudinal clinical and neuroimaging longitudinal studies to assess progression are required. PMID:25120943

  6. Metal imaging in neurodegenerative diseases

    PubMed Central

    Bourassa, Megan W.

    2014-01-01

    Metal ions are known to play an important role in many neurodegenerative diseases including Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and prion diseases. In these diseases, aberrant metal binding or improper regulation of redox active metal ions can induce oxidative stress by producing cytotoxic reactive oxygen species (ROS). Altered metal homeostasis is also frequently seen in the diseased state. As a result, the imaging of metals in intact biological cells and tissues has been very important for understanding the role of metals in neurodegenerative diseases. A wide range of imaging techniques have been utilized, including X-ray fluorescence microscopy (XFM), particle induced X-ray emission (PIXE), energy dispersive X-ray spectroscopy (EDS), laser ablation inductively coupled mass spectrometry (LA-ICP-MS), and secondary ion mass spectrometry (SIMS), all of which allow for the imaging of metals in biological specimens with high spatial resolution and detection sensitivity. These techniques represent unique tools for advancing the understanding of the disease mechanisms and for identifying possible targets for developing treatments. In this review, we will highlight the advances in neurodegenerative disease research facilitated by metal imaging techniques. PMID:22797194

  7. Auditory training improves auditory performance in cochlear implanted children.

    PubMed

    Roman, Stephane; Rochette, Françoise; Triglia, Jean-Michel; Schön, Daniele; Bigand, Emmanuel

    2016-07-01

    While the positive benefits of pediatric cochlear implantation on language perception skills are now proven, the heterogeneity of outcomes remains high. The understanding of this heterogeneity and possible strategies to minimize it is of utmost importance. Our scope here is to test the effects of an auditory training strategy, "sound in Hands", using playful tasks grounded on the theoretical and empirical findings of cognitive sciences. Indeed, several basic auditory operations, such as auditory scene analysis (ASA) are not trained in the usual therapeutic interventions in deaf children. However, as they constitute a fundamental basis in auditory cognition, their development should imply general benefit in auditory processing and in turn enhance speech perception. The purpose of the present study was to determine whether cochlear implanted children could improve auditory performances in trained tasks and whether they could develop a transfer of learning to a phonetic discrimination test. Nineteen prelingually unilateral cochlear implanted children without additional handicap (4-10 year-olds) were recruited. The four main auditory cognitive processing (identification, discrimination, ASA and auditory memory) were stimulated and trained in the Experimental Group (EG) using Sound in Hands. The EG followed 20 training weekly sessions of 30 min and the untrained group was the control group (CG). Two measures were taken for both groups: before training (T1) and after training (T2). EG showed a significant improvement in the identification, discrimination and auditory memory tasks. The improvement in the ASA task did not reach significance. CG did not show any significant improvement in any of the tasks assessed. Most importantly, improvement was visible in the phonetic discrimination test for EG only. Moreover, younger children benefited more from the auditory training program to develop their phonetic abilities compared to older children, supporting the idea that

  8. Personality and Social Cognition in Neurodegenerative Disease

    PubMed Central

    Shany-Ur, Tal; Rankin, Katherine P.

    2013-01-01

    Purpose of review Neurodegenerative diseases often cause focal damage to brain structures mediating social cognition and personality, resulting in altered interpersonal communication and behavior. We review recent research describing this phenomenon in various aspects of social cognition. Recent findings Corresponding to their pervasive social-emotional deficits, patients with frontotemporal dementia perform poorly on lab-based tasks including recognizing emotions, attending to salient information that guides social behavior, representing social knowledge, comprehending others’ mental states, and maintaining insight to their own difficulties. Together with poor executive and regulation mechanisms, these social cognition deficits ultimately impact behavior. Patients with logopenic and nonfluent primary progressive aphasia have some deficits recognizing emotional prosody, while those with the semantic variant show more widespread deficits in social comprehension. While Alzheimer’s disease patients perform poorly on some social cognition tasks, this typically reflects general cognitive impairment, and their real-life social functioning is less affected than in diseases targeting frontotemporal structures. Studies in motor diseases such as Parkinson’s suggest some degradation of emotion recognition and social comprehension which should be investigated further. Summary We summarize recent findings concerning perception and evaluation of socioemotional information, social knowledge storage and access, advanced information processing mechanisms, and behavioral response selection and regulation across various neurodegenerative diseases. PMID:22002077

  9. Autophagy, inflammation and neurodegenerative disease

    PubMed Central

    Alirezaei, Mehrdad; Kemball, Christopher C.; Whitton, J. Lindsay

    2010-01-01

    Autophagy is emerging as a central regulator of cellular health and disease and, in the central nervous system (CNS), this homeostatic process appears to influence synaptic growth and plasticity. Herein, we review the evidence that dysregulation of autophagy may contribute to several neurodegenerative diseases of the CNS. Up-regulation of autophagy may prevent, delay or ameliorate at least some of these disorders, and – based on recent findings from our laboratory – we speculate that this goal may be achieved using a safe, simple, and inexpensive approach. PMID:21138487

  10. Ubiquitin pathways in neurodegenerative disease

    PubMed Central

    Atkin, Graham; Paulson, Henry

    2014-01-01

    Control of proper protein synthesis, function, and turnover is essential for the health of all cells. In neurons these demands take on the additional importance of supporting and regulating the highly dynamic connections between neurons that are necessary for cognitive function, learning, and memory. Regulating multiple unique synaptic protein environments within a single neuron while maintaining cell health requires the highly regulated processes of ubiquitination and degradation of ubiquitinated proteins through the proteasome. In this review, we examine the effects of dysregulated ubiquitination and protein clearance on the handling of disease-associated proteins and neuronal health in the most common neurodegenerative diseases. PMID:25071440

  11. Neurodegenerative causes of death among retired National Football League players

    PubMed Central

    Hein, Misty J.; Baron, Sherry L.; Gersic, Christine M.

    2012-01-01

    Objective: To analyze neurodegenerative causes of death, specifically Alzheimer disease (AD), Parkinson disease, and amyotrophic lateral sclerosis (ALS), among a cohort of professional football players. Methods: This was a cohort mortality study of 3,439 National Football League players with at least 5 pension-credited playing seasons from 1959 to 1988. Vital status was ascertained through 2007. For analysis purposes, players were placed into 2 strata based on characteristics of position played: nonspeed players (linemen) and speed players (all other positions except punter/kicker). External comparisons with the US population used standardized mortality ratios (SMRs); internal comparisons between speed and nonspeed player positions used standardized rate ratios (SRRs). Results: Overall player mortality compared with that of the US population was reduced (SMR 0.53, 95% confidence interval [CI] 0.48−0.59). Neurodegenerative mortality was increased using both underlying cause of death rate files (SMR 2.83, 95% CI 1.36−5.21) and multiple cause of death (MCOD) rate files (SMR 3.26, 95% CI 1.90−5.22). Of the neurodegenerative causes, results were elevated (using MCOD rates) for both ALS (SMR 4.31, 95% CI 1.73−8.87) and AD (SMR 3.86, 95% CI 1.55−7.95). In internal analysis (using MCOD rates), higher neurodegenerative mortality was observed among players in speed positions compared with players in nonspeed positions (SRR 3.29, 95% CI 0.92−11.7). Conclusions: The neurodegenerative mortality of this cohort is 3 times higher than that of the general US population; that for 2 of the major neurodegenerative subcategories, AD and ALS, is 4 times higher. These results are consistent with recent studies that suggest an increased risk of neurodegenerative disease among football players. PMID:22955124

  12. Neurodegenerative causes of death among retired National Football League players.

    PubMed

    Lehman, Everett J; Hein, Misty J; Baron, Sherry L; Gersic, Christine M

    2012-11-06

    To analyze neurodegenerative causes of death, specifically Alzheimer disease (AD), Parkinson disease, and amyotrophic lateral sclerosis (ALS), among a cohort of professional football players. This was a cohort mortality study of 3,439 National Football League players with at least 5 pension-credited playing seasons from 1959 to 1988. Vital status was ascertained through 2007. For analysis purposes, players were placed into 2 strata based on characteristics of position played: nonspeed players (linemen) and speed players (all other positions except punter/kicker). External comparisons with the US population used standardized mortality ratios (SMRs); internal comparisons between speed and nonspeed player positions used standardized rate ratios (SRRs). Overall player mortality compared with that of the US population was reduced (SMR 0.53, 95% confidence interval [CI] 0.48-0.59). Neurodegenerative mortality was increased using both underlying cause of death rate files (SMR 2.83, 95% CI 1.36-5.21) and multiple cause of death (MCOD) rate files (SMR 3.26, 95% CI 1.90-5.22). Of the neurodegenerative causes, results were elevated (using MCOD rates) for both ALS (SMR 4.31, 95% CI 1.73-8.87) and AD (SMR 3.86, 95% CI 1.55-7.95). In internal analysis (using MCOD rates), higher neurodegenerative mortality was observed among players in speed positions compared with players in nonspeed positions (SRR 3.29, 95% CI 0.92-11.7). The neurodegenerative mortality of this cohort is 3 times higher than that of the general US population; that for 2 of the major neurodegenerative subcategories, AD and ALS, is 4 times higher. These results are consistent with recent studies that suggest an increased risk of neurodegenerative disease among football players.

  13. [Auditory fatigue].

    PubMed

    Sanjuán Juaristi, Julio; Sanjuán Martínez-Conde, Mar

    2015-01-01

    Given the relevance of possible hearing losses due to sound overloads and the short list of references of objective procedures for their study, we provide a technique that gives precise data about the audiometric profile and recruitment factor. Our objectives were to determine peripheral fatigue, through the cochlear microphonic response to sound pressure overload stimuli, as well as to measure recovery time, establishing parameters for differentiation with regard to current psychoacoustic and clinical studies. We used specific instruments for the study of cochlear microphonic response, plus a function generator that provided us with stimuli of different intensities and harmonic components. In Wistar rats, we first measured the normal microphonic response and then the effect of auditory fatigue on it. Using a 60dB pure tone acoustic stimulation, we obtained a microphonic response at 20dB. We then caused fatigue with 100dB of the same frequency, reaching a loss of approximately 11dB after 15minutes; after that, the deterioration slowed and did not exceed 15dB. By means of complex random tone maskers or white noise, no fatigue was caused to the sensory receptors, not even at levels of 100dB and over an hour of overstimulation. No fatigue was observed in terms of sensory receptors. Deterioration of peripheral perception through intense overstimulation may be due to biochemical changes of desensitisation due to exhaustion. Auditory fatigue in subjective clinical trials presumably affects supracochlear sections. The auditory fatigue tests found are not in line with those obtained subjectively in clinical and psychoacoustic trials. Copyright © 2013 Elsevier España, S.L.U. y Sociedad Española de Otorrinolaringología y Patología Cérvico-Facial. All rights reserved.

  14. Auditory Dysfunction in Patients with Cerebrovascular Disease

    PubMed Central

    2014-01-01

    Auditory dysfunction is a common clinical symptom that can induce profound effects on the quality of life of those affected. Cerebrovascular disease (CVD) is the most prevalent neurological disorder today, but it has generally been considered a rare cause of auditory dysfunction. However, a substantial proportion of patients with stroke might have auditory dysfunction that has been underestimated due to difficulties with evaluation. The present study reviews relationships between auditory dysfunction and types of CVD including cerebral infarction, intracerebral hemorrhage, subarachnoid hemorrhage, cerebrovascular malformation, moyamoya disease, and superficial siderosis. Recent advances in the etiology, anatomy, and strategies to diagnose and treat these conditions are described. The numbers of patients with CVD accompanied by auditory dysfunction will increase as the population ages. Cerebrovascular diseases often include the auditory system, resulting in various types of auditory dysfunctions, such as unilateral or bilateral deafness, cortical deafness, pure word deafness, auditory agnosia, and auditory hallucinations, some of which are subtle and can only be detected by precise psychoacoustic and electrophysiological testing. The contribution of CVD to auditory dysfunction needs to be understood because CVD can be fatal if overlooked. PMID:25401133

  15. Can rhythmic auditory cuing remediate language-related deficits in Parkinson's disease?

    PubMed

    Kotz, Sonja A; Gunter, Thomas C

    2015-03-01

    Neurodegenerative changes of the basal ganglia in idiopathic Parkinson's disease (IPD) lead to motor deficits as well as general cognitive decline. Given these impairments, the question arises as to whether motor and nonmotor deficits can be ameliorated similarly. We reason that a domain-general sensorimotor circuit involved in temporal processing may support the remediation of such deficits. Following findings that auditory cuing benefits gait kinematics, we explored whether reported language-processing deficits in IPD can also be remediated via auditory cuing. During continuous EEG measurement, an individual diagnosed with IPD heard two types of temporally predictable but metrically different auditory beat-based cues: a march, which metrically aligned with the speech accent structure, a waltz that did not metrically align, or no cue before listening to naturally spoken sentences that were either grammatically well formed or were semantically or syntactically incorrect. Results confirmed that only the cuing with a march led to improved computation of syntactic and semantic information. We infer that a marching rhythm may lead to a stronger engagement of the cerebello-thalamo-cortical circuit that compensates dysfunctional striato-cortical timing. Reinforcing temporal realignment, in turn, may lead to the timely processing of linguistic information embedded in the temporally variable speech signal. © 2014 New York Academy of Sciences.

  16. Visually Impaired Children with Progressive, Terminal Neurodegenerative Disorders.

    ERIC Educational Resources Information Center

    Koehler, W.; Loftin, M.

    1994-01-01

    This article presents general information on visually impaired children with progressive, terminal neurodegenerative disorders including implications for the classroom, specific techniques to help the child live and learn, and the development of multidisciplinary support systems including both professionals and family members. (DB)

  17. Genetic variants associated with neurodegenerative Alzheimer disease in natural models.

    PubMed

    Salazar, Claudia; Valdivia, Gonzalo; Ardiles, Álvaro O; Ewer, John; Palacios, Adrián G

    2016-02-26

    The use of transgenic models for the study of neurodegenerative diseases has made valuable contributions to the field. However, some important limitations, including protein overexpression and general systemic compensation for the missing genes, has caused researchers to seek natural models that show the main biomarkers of neurodegenerative diseases during aging. Here we review some of these models-most of them rodents, focusing especially on the genetic variations in biomarkers for Alzheimer diseases, in order to explain their relationships with variants associated with the occurrence of the disease in humans.

  18. Chameleon sequences in neurodegenerative diseases.

    PubMed

    Bahramali, Golnaz; Goliaei, Bahram; Minuchehr, Zarrin; Salari, Ali

    2016-03-25

    Chameleon sequences can adopt either alpha helix sheet or a coil conformation. Defining chameleon sequences in PDB (Protein Data Bank) may yield to an insight on defining peptides and proteins responsible in neurodegeneration. In this research, we benefitted from the large PDB and performed a sequence analysis on Chameleons, where we developed an algorithm to extract peptide segments with identical sequences, but different structures. In order to find new chameleon sequences, we extracted a set of 8315 non-redundant protein sequences from the PDB with an identity less than 25%. Our data was classified to "helix to strand (HE)", "helix to coil (HC)" and "strand to coil (CE)" alterations. We also analyzed the occurrence of singlet and doublet amino acids and the solvent accessibility in the chameleon sequences; we then sorted out the proteins with the most number of chameleon sequences and named them Chameleon Flexible Proteins (CFPs) in our dataset. Our data revealed that Gly, Val, Ile, Tyr and Phe, are the major amino acids in Chameleons. We also found that there are proteins such as Insulin Degrading Enzyme IDE and GTP-binding nuclear protein Ran (RAN) with the most number of chameleons (640 and 405 respectively). These proteins have known roles in neurodegenerative diseases. Therefore it can be inferred that other CFP's can serve as key proteins in neurodegeneration, and a study on them can shed light on curing and preventing neurodegenerative diseases.

  19. Chameleon sequences in neurodegenerative diseases

    SciTech Connect

    Bahramali, Golnaz; Goliaei, Bahram; Minuchehr, Zarrin; Salari, Ali

    2016-03-25

    Chameleon sequences can adopt either alpha helix sheet or a coil conformation. Defining chameleon sequences in PDB (Protein Data Bank) may yield to an insight on defining peptides and proteins responsible in neurodegeneration. In this research, we benefitted from the large PDB and performed a sequence analysis on Chameleons, where we developed an algorithm to extract peptide segments with identical sequences, but different structures. In order to find new chameleon sequences, we extracted a set of 8315 non-redundant protein sequences from the PDB with an identity less than 25%. Our data was classified to “helix to strand (HE)”, “helix to coil (HC)” and “strand to coil (CE)” alterations. We also analyzed the occurrence of singlet and doublet amino acids and the solvent accessibility in the chameleon sequences; we then sorted out the proteins with the most number of chameleon sequences and named them Chameleon Flexible Proteins (CFPs) in our dataset. Our data revealed that Gly, Val, Ile, Tyr and Phe, are the major amino acids in Chameleons. We also found that there are proteins such as Insulin Degrading Enzyme IDE and GTP-binding nuclear protein Ran (RAN) with the most number of chameleons (640 and 405 respectively). These proteins have known roles in neurodegenerative diseases. Therefore it can be inferred that other CFP's can serve as key proteins in neurodegeneration, and a study on them can shed light on curing and preventing neurodegenerative diseases.

  20. Oxidative Stress and Neurodegenerative Disorders

    PubMed Central

    Li, Jie; O, Wuliji; Li, Wei; Jiang, Zhi-Gang; Ghanbari, Hossein A.

    2013-01-01

    Living cells continually generate reactive oxygen species (ROS) through the respiratory chain during energetic metabolism. ROS at low or moderate concentration can play important physiological roles. However, an excessive amount of ROS under oxidative stress would be extremely deleterious. The central nervous system (CNS) is particularly vulnerable to oxidative stress due to its high oxygen consumption, weakly antioxidative systems and the terminal-differentiation characteristic of neurons. Thus, oxidative stress elicits various neurodegenerative diseases. In addition, chemotherapy could result in severe side effects on the CNS and peripheral nervous system (PNS) of cancer patients, and a growing body of evidence demonstrates the involvement of ROS in drug-induced neurotoxicities as well. Therefore, development of antioxidants as neuroprotective drugs is a potentially beneficial strategy for clinical therapy. In this review, we summarize the source, balance maintenance and physiologic functions of ROS, oxidative stress and its toxic mechanisms underlying a number of neurodegenerative diseases, and the possible involvement of ROS in chemotherapy-induced toxicity to the CNS and PNS. We ultimately assess the value for antioxidants as neuroprotective drugs and provide our comments on the unmet needs. PMID:24351827

  1. Parkin Regulation and Neurodegenerative Disorders

    PubMed Central

    Zhang, Cheng-Wu; Hang, Liting; Yao, Tso-Pang; Lim, Kah-Leong

    2016-01-01

    Parkin is a unique, multifunctional ubiquitin ligase whose various roles in the cell, particularly in neurons, are widely thought to be protective. The pivotal role that Parkin plays in maintaining neuronal survival is underscored by our current recognition that Parkin dysfunction represents not only a predominant cause of familial parkinsonism but also a formal risk factor for the more common, sporadic form of Parkinson’s disease (PD). Accordingly, keen research on Parkin over the past decade has led to an explosion of knowledge regarding its physiological roles and its relevance to PD. However, our understanding of Parkin is far from being complete. Indeed, surprises emerge from time to time that compel us to constantly update the paradigm of Parkin function. For example, we now know that Parkin’s function is not confined to mere housekeeping protein quality control (QC) roles but also includes mitochondrial homeostasis and stress-related signaling. Furthermore, emerging evidence also suggest a role for Parkin in several other major neurodegenerative diseases including Alzheimer’s disease (AD) and Amyotrophic Lateral Sclerosis (ALS). Yet, it remains truly amazing to note that a single enzyme could serve such multitude of functions and cellular roles. Clearly, its activity has to be tightly regulated. In this review, we shall discuss this and how dysregulated Parkin function may precipitate neuronal demise in various neurodegenerative disorders. PMID:26793099

  2. Tsallis statistics and neurodegenerative disorders

    NASA Astrophysics Data System (ADS)

    Iliopoulos, Aggelos C.; Tsolaki, Magdalini; Aifantis, Elias C.

    2016-08-01

    In this paper, we perform statistical analysis of time series deriving from four neurodegenerative disorders, namely epilepsy, amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), Huntington's disease (HD). The time series are concerned with electroencephalograms (EEGs) of healthy and epileptic states, as well as gait dynamics (in particular stride intervals) of the ALS, PD and HDs. We study data concerning one subject for each neurodegenerative disorder and one healthy control. The analysis is based on Tsallis non-extensive statistical mechanics and in particular on the estimation of Tsallis q-triplet, namely {qstat, qsen, qrel}. The deviation of Tsallis q-triplet from unity indicates non-Gaussian statistics and long-range dependencies for all time series considered. In addition, the results reveal the efficiency of Tsallis statistics in capturing differences in brain dynamics between healthy and epileptic states, as well as differences between ALS, PD, HDs from healthy control subjects. The results indicate that estimations of Tsallis q-indices could be used as possible biomarkers, along with others, for improving classification and prediction of epileptic seizures, as well as for studying the gait complex dynamics of various diseases providing new insights into severity, medications and fall risk, improving therapeutic interventions.

  3. Precision nanomedicine in neurodegenerative diseases.

    PubMed

    Goldsmith, Meir; Abramovitz, Lilach; Peer, Dan

    2014-03-25

    The treatment of neurodegenerative diseases remains a tremendous challenge due to the limited access of molecules across the blood-brain barrier, especially large molecules such as peptides and proteins. As a result, at most, a small percentage of a drug that is administered systemically will reach the central nervous system in its active form. Currently, research in the field focuses on developing safer and more effective approaches to deliver peptides and proteins into the central nervous system. Multiple strategies have been developed for this purpose. However, noninvasive approaches, such as nanostructured protein delivery carriers and intranasal administration, seem to be the most promising strategies for the treatment of chronic diseases, which require long-term interventions. These approaches are both target-specific and able to rapidly bypass the blood-brain barrier. In this Perspective, we detail some of these strategies and discuss some of the potential pitfalls and opportunities in this field. The next generation strategies will most likely be more cell-type-specific. Devising these strategies to target the brain may ultimately become a novel therapeutic modality to treat neurodegenerative diseases.

  4. The Cognitive Neuropsychology of Auditory Hallucinations: A Parallel Auditory Pathways Framework

    PubMed Central

    Badcock, Johanna C.

    2010-01-01

    Auditory hallucinations are generally defined as false perceptions. Recent developments in auditory neuroscience have rapidly increased our understanding of normal auditory perception revealing (partially) separate pathways for the identification (“what”) and localization (“where”) of auditory objects. The current review offers a reexamination of the nature of auditory hallucinations in schizophrenia using this object-based framework. First, the structural and functional organization of auditory what and where pathways is briefly described. Then, using recent functional neuroimaging data from healthy subjects and patients with schizophrenia, key phenomenological features of hallucinations are linked to abnormal processing both within and between these pathways. Finally, current cognitive explanations of hallucinations, based on intrusive cognitions and impaired source memory, are briefly outlined and set within this framework to provide an integrated cognitive neuropsychological model of auditory hallucinations. PMID:18835839

  5. The cognitive neuropsychology of auditory hallucinations: a parallel auditory pathways framework.

    PubMed

    Badcock, Johanna C

    2010-05-01

    Auditory hallucinations are generally defined as false perceptions. Recent developments in auditory neuroscience have rapidly increased our understanding of normal auditory perception revealing (partially) separate pathways for the identification ("what") and localization ("where") of auditory objects. The current review offers a reexamination of the nature of auditory hallucinations in schizophrenia using this object-based framework. First, the structural and functional organization of auditory what and where pathways is briefly described. Then, using recent functional neuroimaging data from healthy subjects and patients with schizophrenia, key phenomenological features of hallucinations are linked to abnormal processing both within and between these pathways. Finally, current cognitive explanations of hallucinations, based on intrusive cognitions and impaired source memory, are briefly outlined and set within this framework to provide an integrated cognitive neuropsychological model of auditory hallucinations.

  6. Auditory dysfunction in patients with Huntington's disease.

    PubMed

    Profant, Oliver; Roth, Jan; Bureš, Zbyněk; Balogová, Zuzana; Lišková, Irena; Betka, Jan; Syka, Josef

    2017-10-01

    Huntington's disease (HD) is an autosomal, dominantly inherited, neurodegenerative disease. The main clinical features are motor impairment, progressive cognitive deterioration and behavioral changes. The aim of our study was to find out whether patients with HD suffer from disorders of the auditory system. A group of 17 genetically verified patients (11 males, 6 females) with various stages of HD (examined by UHDRS - motor part and total functional capacity, MMSE for cognitive functions) underwent an audiological examination (high frequency pure tone audiometry, otoacoustic emissions, speech audiometry, speech audiometry in babble noise, auditory brainstem responses). Additionally, 5 patients underwent a more extensive audiological examination, focused on central auditory processing. The results were compared with a group of age-matched healthy volunteers. Our results show that HD patients have physiologic hearing thresholds, otoacoustic emissions and auditory brainstem responses; however, they display a significant decrease in speech understanding, especially under demanding conditions (speech in noise) compared to age-matched controls. Additional auditory tests also show deficits in sound source localization, based on temporal and intensity cues. We also observed a statistically significant correlation between the perception of speech in noise, and motoric and cognitive functions. However, a correlation between genetic predisposition (number of triplets) and function of inner ear was not found. We conclude that HD negatively influences the function of the central part of the auditory system at cortical and subcortical levels, altering predominantly speech processing and sound source lateralization. We have thoroughly characterized auditory pathology in patients with HD that suggests involvement of central auditory and cognitive areas. Copyright © 2017. Published by Elsevier B.V.

  7. Auditory sequence analysis and phonological skill.

    PubMed

    Grube, Manon; Kumar, Sukhbinder; Cooper, Freya E; Turton, Stuart; Griffiths, Timothy D

    2012-11-07

    This work tests the relationship between auditory and phonological skill in a non-selected cohort of 238 school students (age 11) with the specific hypothesis that sound-sequence analysis would be more relevant to phonological skill than the analysis of basic, single sounds. Auditory processing was assessed across the domains of pitch, time and timbre; a combination of six standard tests of literacy and language ability was used to assess phonological skill. A significant correlation between general auditory and phonological skill was demonstrated, plus a significant, specific correlation between measures of phonological skill and the auditory analysis of short sequences in pitch and time. The data support a limited but significant link between auditory and phonological ability with a specific role for sound-sequence analysis, and provide a possible new focus for auditory training strategies to aid language development in early adolescence.

  8. Auditory sequence analysis and phonological skill

    PubMed Central

    Grube, Manon; Kumar, Sukhbinder; Cooper, Freya E.; Turton, Stuart; Griffiths, Timothy D.

    2012-01-01

    This work tests the relationship between auditory and phonological skill in a non-selected cohort of 238 school students (age 11) with the specific hypothesis that sound-sequence analysis would be more relevant to phonological skill than the analysis of basic, single sounds. Auditory processing was assessed across the domains of pitch, time and timbre; a combination of six standard tests of literacy and language ability was used to assess phonological skill. A significant correlation between general auditory and phonological skill was demonstrated, plus a significant, specific correlation between measures of phonological skill and the auditory analysis of short sequences in pitch and time. The data support a limited but significant link between auditory and phonological ability with a specific role for sound-sequence analysis, and provide a possible new focus for auditory training strategies to aid language development in early adolescence. PMID:22951739

  9. Protein folding and misfolding in the neurodegenerative disorders: a review.

    PubMed

    Bolshette, N B; Thakur, K K; Bidkar, A P; Trandafir, C; Kumar, P; Gogoi, R

    2014-03-01

    Protein misfolding is an intrinsic aspect of normal folding within the complex cellular environment. Its effects are minimized in living system by the action of a range of protective mechanisms including molecular chaperones and quality control systems. According to the current growing research, protein misfolding is a recognized key feature of most neurodegenerative diseases. Extensive biochemical, neuropathological, and genetic evidence suggest that the cerebral accumulation of amyloid fibrils is the central event in the pathogenesis of neurodegenerative disorders. In the first part of this review we have discussed the general course of action of folding and misfolding of the proteins. Later part of this review gives an outline regarding the role of protein misfolding in the molecular and cellular mechanisms in the pathogenesis of Alzheimer's and Parkinson along with their treatment possibilities. Finally, we have mentioned about the recent findings in neurodegenerative diseases. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  10. The Use of Decoy Sentences to Measure Auditory Training Gains.

    ERIC Educational Resources Information Center

    Mapes, Frances M.; Moreau, Roberta

    1980-01-01

    To investigate students' ability to generalize auditory skills, precourse to postcourse measures were compared for an auditory training group (N=42) and a control group (N=7) on three auditory discimination measures: (1) the training sentences, (2) related but nontrained sentences (decoy sentences), and (3) a modified rhyme test. (Author/PHR)

  11. [Alzheimer's disease as neurodegenerative disorder].

    PubMed

    Zabłocka, Agnieszka

    2006-01-01

    Alzheimer's disease (AD) is a very common progressive neurodegenerative disorder. AD patients are affected by cognitive and memory deterioration. Cerebral degeneration, with selective neuronal death induced by extracellular amyloid deposits in the form of senile plaques and intracellular neurofibrillary tangles composed of helical paired tau protein, is the best-studied pathological event related to AD. Presenilins and apolipoprotein E are other neurotoxic agents involved in the pathogenesis of AD. A large body evidence has shown that permanent activation of glial cells in the brains of AD patients promotes the production of excessive quantities of free radicals, nitric oxide, and cytokines which could be detrimental to neuronal cells. Damage to the blood-brain barrier by inflammatory processes result in the influx of peripheral immune system cells and local immune reactions. Inhibition of ROS and NO overproduction as well as endogenic regulation of cytokine induction could be of therapeutic importance and delay neurodegeneration in AD.

  12. Thinking laterally about neurodegenerative proteinopathies

    PubMed Central

    Golde, Todd E.; Borchelt, David R.; Giasson, Benoit I.; Lewis, Jada

    2013-01-01

    Many neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and frontotemporal dementia, are proteinopathies that are associated with the aggregation and accumulation of misfolded proteins. While remarkable progress has been made in understanding the triggers of these conditions, several challenges have hampered the translation of preclinical therapies targeting pathways downstream of the initiating proteinopathies. Clinical trials in symptomatic patients using therapies directed toward initiating trigger events have met with little success, prompting concerns that such therapeutics may be of limited efficacy when used in advanced stages of the disease rather than as prophylactics. Herein, we discuss gaps in our understanding of the pathological processes downstream of the trigger and potential strategies to identify common features of the downstream degenerative cascade in multiple CNS proteinopathies, which could potentially lead to the development of common therapeutic targets for multiple disorders. PMID:23635781

  13. Estradiol and neurodegenerative oxidative stress.

    PubMed

    Nilsen, Jon

    2008-10-01

    Estradiol is a potent preventative against neurodegenerative disease, in part, by activating antioxidant defense systems scavenging reactive oxygen species, limiting mitochondrial protein damage, improving electron transport chain activity and reducing mitochondrial DNA damage. Estradiol also increases the activity of complex IV of the electron transport chain, improving mitochondrial respiration and ATP production under normal and stressful conditions. However, the high oxidative cellular environment present during neurodegeneration makes estradiol a poor agent for treatment of existing disease. Oxidative stress stimulates the production of the hydroperoxide-dependent hydroxylation of estradiol to the catecholestrogen metabolites, which can undergo reactive oxygen species producing redox cycling, setting up a self-generating toxic cascade offsetting any antioxidant/antiapoptotic effects generated by the parent estradiol. Additional disease-induced factors can further perpetuate this cycle. For example dysregulation of the catecholamine system could alter catechol-O-methyltransferase-catalyzed methylation, preventing removal of redox cycling catecholestrogens from the system enhancing pro-oxidant effects of estradiol.

  14. Neurodegenerative disorders and metabolic disease.

    PubMed

    Pierre, Germaine

    2013-08-01

    Most genetic causes of neurodegenerative disorders in childhood are due to neurometabolic disease. There are over 200 disorders, including aminoacidopathies, creatine disorders, mitochondrial cytopathies, peroxisomal disorders and lysosomal storage disorders. However, diagnosis can pose a challenge to the clinician when patients present with non-specific problems like epilepsy, developmental delay, autism, dystonia and ataxia. The variety of specialist tests involved can also be daunting. This review aims to give a practical approach to the investigation and diagnosis of neurometabolic disease from the neonatal period to late childhood while prioritising disorders where there are therapeutic options. In particular, patients who have a complex clinical picture of several neurological and non-neurological features should be investigated.

  15. Neurodegenerative diseases and oxidative stress.

    PubMed

    Emerit, J; Edeas, M; Bricaire, F

    2004-01-01

    Oxidative stress is now recognized as accountable for redox regulation involving reactive oxygen species (ROS) and reactive nitrogen species (RNS). Its role is pivotal for the modulation of critical cellular functions, notably for neurons astrocytes and microglia, such as apoptosis program activation, and ion transport, calcium mobilization, involved in excitotoxicity. Excitotoxicity and apoptosis are the two main causes of neuronal death. The role of mitochondria in apoptosis is crucial. Multiple apoptotic pathways emanate from the mitochondria. The respiratory chain of mitochondria that by oxidative phosphorylation, is the fount of cellular energy, i.e. ATP synthesis, is responsible for most of ROS and notably the first produced, superoxide anion (O(2)(;-)). Mitochondrial dysfunction, i.e. cell energy impairment, apoptosis and overproduction of ROS, is a final common pathogenic mechanism in aging and in neurodegenerative disease such as Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS). Nitric oxide (NO(;)), an RNS, which can be produced by three isoforms of NO-synthase in brain, plays a prominent role. The research on the genetics of inherited forms notably ALS, AD, PD, has improved our understanding of the pathobiology of the sporadic forms of neurodegenerative diseases or of aging of the brain. ROS and RNS, i.e. oxidative stress, are not the origin of neuronal death. The cascade of events that leads to neurons, death is complex. In addition to mitochondrial dysfunction (apoptosis), excitotoxicity, oxidative stress (inflammation), the mechanisms from gene to disease involve also protein misfolding leading to aggregates and proteasome dysfunction on ubiquinited material.

  16. Multisensory encoding improves auditory recognition.

    PubMed

    Moran, Zachary D; Bachman, Peter; Pham, Phillip; Cho, Seong Hah; Cannon, Tyrone D; Shams, Ladan

    2013-01-01

    Recent studies have challenged the long-held belief that recognition is unfailingly degraded by contextual differences between study and test items. In these studies, recognition of pictures presented in silence was better when during study or initial exposure the images were accompanied by a semantically congruent sound rather than silence. In the present study, we sought to examine the generalization of this phenomenon to auditory recognition and found a significant improvement in the recognition of auditory items when coupled with a congruent picture. We discuss these findings within the framework of the redintegration hypothesis of memory retrieval as well as Bayesian inference and learning.

  17. Amyloidosis in Retinal Neurodegenerative Diseases

    PubMed Central

    Masuzzo, Ambra; Dinet, Virginie; Cavanagh, Chelsea; Mascarelli, Frederic; Krantic, Slavica

    2016-01-01

    As a part of the central nervous system, the retina may reflect both physiological processes and abnormalities related to pathologies that affect the brain. Amyloidosis due to the accumulation of amyloid-beta (Aβ) was initially regarded as a specific and exclusive characteristic of neurodegenerative alterations seen in the brain of Alzheimer’s disease (AD) patients. More recently, it was discovered that amyloidosis-related alterations, similar to those seen in the brain of Alzheimer’s patients, also occur in the retina. Remarkably, these alterations were identified not only in primary retinal pathologies, such as age-related macular degeneration (AMD) and glaucoma, but also in the retinas of Alzheimer’s patients. In this review, we first briefly discuss the biogenesis of Aβ, a peptide involved in amyloidosis. We then discuss some pathological aspects (synaptic dysfunction, mitochondrial failure, glial activation, and vascular abnormalities) related to the neurotoxic effects of Aβ. We finally highlight common features shared by AD, AMD, and glaucoma in the context of Aβ amyloidosis and further discuss why the retina, due to the transparency of the eye, can be considered as a “window” to the brain. PMID:27551275

  18. Nanobiomaterials' applications in neurodegenerative diseases.

    PubMed

    Silva Adaya, Daniela; Aguirre-Cruz, Lucinda; Guevara, Jorge; Ortiz-Islas, Emma

    2017-02-01

    The blood-brain barrier is the interface between the blood and brain, impeding the passage of most circulating cells and molecules, protecting the latter from foreign substances, and maintaining central nervous system homeostasis. However, its restrictive nature constitutes an obstacle, preventing therapeutic drugs from entering the brain. Usually, a large systemic dose is required to achieve pharmacological therapeutic levels in the brain, leading to adverse effects in the body. As a consequence, various strategies are being developed to enhance the amount and concentration of therapeutic compounds in the brain. One such tool is nanotechnology, in which nanostructures that are 1-100 nm are designed to deliver drugs to the brain. In this review, we examine many nanotechnology-based approaches to the treatment of neurodegenerative diseases. The review begins with a brief history of nanotechnology, followed by a discussion of its definition, the properties of most reported nanomaterials, their biocompatibility, the mechanisms of cell-material interactions, and the current status of nanotechnology in treating Alzheimer's, Parkinson's diseases, and amyotrophic lateral sclerosis. Of all strategies to deliver drug to the brain that are used in nanotechnology, drug release systems are the most frequently reported.

  19. Uncommon neurodegenerative causes of dementia.

    PubMed

    Kurz, Alexander F

    2005-01-01

    A group of neurodegenerative diseases is outlined that affect cortical and subcortical areas of the brain. These diseases give rise to atypical forms of dementia and, unlike Alzheimer's disease (AD), are often associated with neurological symptoms. Clinical symptoms reflect the localization of the degenerative process rather than the nature of the underlying histopathology. Degeneration of the frontal and anterior temporal lobe presents initially with behavioral alterations, but later in the course, impairment of cognition and activities of daily living develops. Posterior cortical atrophy affects the parietal and occipital association cortices and causes complex visual disturbances. In corticobasal degeneration (CBD) the focus of pathology includes the frontoparietal cortex and several subcortical nuclei, causing symmetrical rigidity, bradykinesia, myoclonus and dystonia. Progressive supranuclear palsy (PSP) involves the frontal, temporal and parietal cortex as well as parts of the brain stem. Clinical features include a hypokinetic rigid syndrome with nuchal dystonia and vertical gaze palsy. Huntington's disease is a prototypical autosomal dominant disorder that affects the extrapyramidal system and causes choreatic movements in combination with personality changes and cognitive deterioration. Amyotrophic lateral sclerosis (ALS) with dementia is a neurodegeneration of the frontotemporal cortex and of the anterior horn of the spinal cord. Behavioral change similar to frontotemporal dementia (FTD) is paralleled or followed by the classic features of motor neuron disease.

  20. Neuronal Mitophagy in Neurodegenerative Diseases

    PubMed Central

    Martinez-Vicente, Marta

    2017-01-01

    Neuronal homeostasis depends on the proper functioning of different quality control systems. All intracellular components are subjected to continuous turnover through the coordinated synthesis, degradation and recycling of their constituent elements. Autophagy is the catabolic mechanism by which intracellular cytosolic components, including proteins, organelles, aggregates and any other intracellular materials, are delivered to lysosomes for degradation. Among the different types of selective autophagy described to date, the process of mitophagy involves the selective autophagic degradation of mitochondria. In this way, mitophagy is responsible for basal mitochondrial turnover, but can also be induced under certain physiological or pathogenic conditions to eliminate unwanted or damaged mitochondria. Dysfunctional cellular proteolytic systems have been linked extensively to neurodegenerative diseases (ND) like Alzheimer’s disease (AD), Parkinson’s disease (PD), or Huntington’s disease (HD), with autophagic failure being one of the main factors contributing to neuronal cell death in these diseases. Neurons are particularly vulnerable to autophagic impairment as well as to mitochondrial dysfunction, due mostly to their particular high energy dependence and to their post-mitotic nature. The accurate and proper degradation of dysfunctional mitochondria by mitophagy is essential for maintaining control over mitochondrial quality and quantity in neurons. In this report, I will review the role of mitophagy in neuronal homeostasis and the consequences of its dysfunction in ND. PMID:28337125

  1. Stem cell technology for neurodegenerative diseases.

    PubMed

    Lunn, J Simon; Sakowski, Stacey A; Hur, Junguk; Feldman, Eva L

    2011-09-01

    Over the past 20 years, stem cell technologies have become an increasingly attractive option to investigate and treat neurodegenerative diseases. In the current review, we discuss the process of extending basic stem cell research into translational therapies for patients suffering from neurodegenerative diseases. We begin with a discussion of the burden of these diseases on society, emphasizing the need for increased attention toward advancing stem cell therapies. We then explain the various types of stem cells utilized in neurodegenerative disease research, and outline important issues to consider in the transition of stem cell therapy from bench to bedside. Finally, we detail the current progress regarding the applications of stem cell therapies to specific neurodegenerative diseases, focusing on Parkinson disease, Huntington disease, Alzheimer disease, amyotrophic lateral sclerosis, and spinal muscular atrophy. With a greater understanding of the capacity of stem cell technologies, there is growing public hope that stem cell therapies will continue to progress into realistic and efficacious treatments for neurodegenerative diseases.

  2. Speech perception as complex auditory categorization

    NASA Astrophysics Data System (ADS)

    Holt, Lori L.

    2002-05-01

    Despite a long and rich history of categorization research in cognitive psychology, very little work has addressed the issue of complex auditory category formation. This is especially unfortunate because the general underlying cognitive and perceptual mechanisms that guide auditory category formation are of great importance to understanding speech perception. I will discuss a new methodological approach to examining complex auditory category formation that specifically addresses issues relevant to speech perception. This approach utilizes novel nonspeech sound stimuli to gain full experimental control over listeners' history of experience. As such, the course of learning is readily measurable. Results from this methodology indicate that the structure and formation of auditory categories are a function of the statistical input distributions of sound that listeners hear, aspects of the operating characteristics of the auditory system, and characteristics of the perceptual categorization system. These results have important implications for phonetic acquisition and speech perception.

  3. Sound naming in neurodegenerative disease.

    PubMed

    Chow, Maggie L; Brambati, Simona M; Gorno-Tempini, Maria Luisa; Miller, Bruce L; Johnson, Julene K

    2010-04-01

    Modern cognitive neuroscientific theories and empirical evidence suggest that brain structures involved in movement may be related to action-related semantic knowledge. To test this hypothesis, we examined the naming of environmental sounds in patients with corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP), two neurodegenerative diseases associated with cognitive and motor deficits. Subjects were presented with 56 environmental sounds: 28 sounds were of objects that required manipulation when producing the sound, and 28 sounds were of objects that required no manipulation. Subjects were asked to provide the name of the object that produced the sound and also complete a sound-picture matching condition. Subjects included 33 individuals from four groups: CBD/PSP, Alzheimer disease, frontotemporal dementia, and normal controls. We hypothesized that CBD/PSP patients would exhibit impaired naming performance compared with controls, but the impairment would be most apparent when naming sounds associated with actions. We also explored neural correlates of naming environmental sounds using voxel-based morphometry (VBM) of brain MRI. As expected, CBD/PSP patients scored lower on environmental sounds naming (p<0.007) compared with the controls. In particular, the CBD/PSP patients scored the lowest when naming sounds of manipulable objects (p<0.05), but did not show deficits in naming sounds of non-manipulable objects. VBM analysis across all groups showed that performance in naming sounds of manipulable objects correlated with atrophy in the left pre-motor region, extending from area six to the middle and superior frontal gyrus. These results indicate an association between impairment in the retrieval of action-related names and the motor system, and suggest that difficulty in naming manipulable sounds may be related to atrophy in the pre-motor cortex. Our results support the hypothesis that retrieval of action-related semantic knowledge involves motor

  4. Zinc homeostasis and neurodegenerative disorders

    PubMed Central

    Szewczyk, Bernadeta

    2013-01-01

    Zinc is an essential trace element, whose importance to the function of the central nervous system (CNS) is increasingly being appreciated. Alterations in zinc dyshomeostasis has been suggested as a key factor in the development of several neuropsychiatric disorders. In the CNS, zinc occurs in two forms: the first being tightly bound to proteins and, secondly, the free, cytoplasmic, or extracellular form found in presynaptic vesicles. Under normal conditions, zinc released from the synaptic vesicles modulates both ionotropic and metabotropic post-synaptic receptors. While under clinical conditions such as traumatic brain injury, stroke or epilepsy, the excess influx of zinc into neurons has been found to result in neurotoxicity and damage to postsynaptic neurons. On the other hand, a growing body of evidence suggests that a deficiency, rather than an excess, of zinc leads to an increased risk for the development of neurological disorders. Indeed, zinc deficiency has been shown to affect neurogenesis and increase neuronal apoptosis, which can lead to learning and memory deficits. Altered zinc homeostasis is also suggested as a risk factor for depression, Alzheimer's disease (AD), aging, and other neurodegenerative disorders. Under normal CNS physiology, homeostatic controls are put in place to avoid the accumulation of excess zinc or its deficiency. This cellular zinc homeostasis results from the actions of a coordinated regulation effected by different proteins involved in the uptake, excretion and intracellular storage/trafficking of zinc. These proteins include membranous transporters (ZnT and Zip) and metallothioneins (MT) which control intracellular zinc levels. Interestingly, alterations in ZnT and MT have been recently reported in both aging and AD. This paper provides an overview of both clinical and experimental evidence that implicates a dysfunction in zinc homeostasis in the pathophysiology of depression, AD, and aging. PMID:23882214

  5. Functional neuroanatomy of auditory scene analysis in Alzheimer's disease.

    PubMed

    Golden, Hannah L; Agustus, Jennifer L; Goll, Johanna C; Downey, Laura E; Mummery, Catherine J; Schott, Jonathan M; Crutch, Sebastian J; Warren, Jason D

    2015-01-01

    Auditory scene analysis is a demanding computational process that is performed automatically and efficiently by the healthy brain but vulnerable to the neurodegenerative pathology of Alzheimer's disease. Here we assessed the functional neuroanatomy of auditory scene analysis in Alzheimer's disease using the well-known 'cocktail party effect' as a model paradigm whereby stored templates for auditory objects (e.g., hearing one's spoken name) are used to segregate auditory 'foreground' and 'background'. Patients with typical amnestic Alzheimer's disease (n = 13) and age-matched healthy individuals (n = 17) underwent functional 3T-MRI using a sparse acquisition protocol with passive listening to auditory stimulus conditions comprising the participant's own name interleaved with or superimposed on multi-talker babble, and spectrally rotated (unrecognisable) analogues of these conditions. Name identification (conditions containing the participant's own name contrasted with spectrally rotated analogues) produced extensive bilateral activation involving superior temporal cortex in both the AD and healthy control groups, with no significant differences between groups. Auditory object segregation (conditions with interleaved name sounds contrasted with superimposed name sounds) produced activation of right posterior superior temporal cortex in both groups, again with no differences between groups. However, the cocktail party effect (interaction of own name identification with auditory object segregation processing) produced activation of right supramarginal gyrus in the AD group that was significantly enhanced compared with the healthy control group. The findings delineate an altered functional neuroanatomical profile of auditory scene analysis in Alzheimer's disease that may constitute a novel computational signature of this neurodegenerative pathology.

  6. Auditory Imagery: Empirical Findings

    ERIC Educational Resources Information Center

    Hubbard, Timothy L.

    2010-01-01

    The empirical literature on auditory imagery is reviewed. Data on (a) imagery for auditory features (pitch, timbre, loudness), (b) imagery for complex nonverbal auditory stimuli (musical contour, melody, harmony, tempo, notational audiation, environmental sounds), (c) imagery for verbal stimuli (speech, text, in dreams, interior monologue), (d)…

  7. Auditory Imagery: Empirical Findings

    ERIC Educational Resources Information Center

    Hubbard, Timothy L.

    2010-01-01

    The empirical literature on auditory imagery is reviewed. Data on (a) imagery for auditory features (pitch, timbre, loudness), (b) imagery for complex nonverbal auditory stimuli (musical contour, melody, harmony, tempo, notational audiation, environmental sounds), (c) imagery for verbal stimuli (speech, text, in dreams, interior monologue), (d)…

  8. Auditory Training for Central Auditory Processing Disorder

    PubMed Central

    Weihing, Jeffrey; Chermak, Gail D.; Musiek, Frank E.

    2015-01-01

    Auditory training (AT) is an important component of rehabilitation for patients with central auditory processing disorder (CAPD). The present article identifies and describes aspects of AT as they relate to applications in this population. A description of the types of auditory processes along with information on relevant AT protocols that can be used to address these specific deficits is included. Characteristics and principles of effective AT procedures also are detailed in light of research that reflects on their value. Finally, research investigating AT in populations who show CAPD or present with auditory complaints is reported. Although efficacy data in this area are still emerging, current findings support the use of AT for treatment of auditory difficulties. PMID:27587909

  9. Auditory Risk of Air Rifles

    PubMed Central

    Lankford, James E.; Meinke, Deanna K.; Flamme, Gregory A.; Finan, Donald S.; Stewart, Michael; Tasko, Stephen; Murphy, William J.

    2016-01-01

    Objective To characterize the impulse noise exposure and auditory risk for air rifle users for both youth and adults. Design Acoustic characteristics were examined and the auditory risk estimates were evaluated using contemporary damage-risk criteria for unprotected adult listeners and the 120-dB peak limit and LAeq75 exposure limit suggested by the World Health Organization (1999) for children. Study sample Impulses were generated by 9 pellet air rifles and 1 BB air rifle. Results None of the air rifles generated peak levels that exceeded the 140 dB peak limit for adults and 8 (80%) exceeded the 120 dB peak SPL limit for youth. In general, for both adults and youth there is minimal auditory risk when shooting less than 100 unprotected shots with pellet air rifles. Air rifles with suppressors were less hazardous than those without suppressors and the pellet air rifles with higher velocities were generally more hazardous than those with lower velocities. Conclusion To minimize auditory risk, youth should utilize air rifles with an integrated suppressor and lower velocity ratings. Air rifle shooters are advised to wear hearing protection whenever engaging in shooting activities in order to gain self-efficacy and model appropriate hearing health behaviors necessary for recreational firearm use. PMID:26840923

  10. Astroglial Vesicular Trafficking in Neurodegenerative Diseases.

    PubMed

    Zorec, Robert; Parpura, Vladimir; Verkhratsky, Alexei

    2017-03-01

    The neocortex represents one of the largest estates of the human brain. This structure comprises ~30-40 billions of neurones and even more of non-neuronal cells. Astrocytes, highly heterogeneous homoeostatic glial cells, are fundamental for housekeeping of the brain and contribute to information processing in neuronal networks. Gray matter astrocytes tightly enwrap synapses, contact blood vessels and, naturally, are also in contact with the extracellular space, where convection of fluid takes place. Thus astrocytes receive signals from several distinct extracellular domains and can get excited by numerous mechanisms, which regulate cytosolic concentration of second messengers, such as Ca(2+) and cAMP. Excited astrocytes often secrete diverse substances (generally referred to as gliosignalling molecules) that include classical neurotransmitters such as glutamate and ATP or neuromodulators such as D-serine or neuropeptides. Astrocytic secretion occurs through several mechanisms: by diffusion through membrane channels, by translocation via plasmalemmal transporters or by vesicular exocytosis. Vesicular release of gliosignalling molecules appears fundamentally similar to that operating in neurones, since it depends on the SNARE proteins-dependent merger of the vesicle membrane with the plasmalemma. However, the coupling between the stimulus and astroglial vesicular secretion is at least one order of magnitude slower than that in neurones. Here we review mechanisms of astrocytic excitability and the molecular, anatomical and physiological properties of vesicular apparatus mediating the release of gliosignalling molecules in health and in the neurodegenerative pathology.

  11. Neuroimaging Biomarkers of Neurodegenerative Diseases and Dementia

    PubMed Central

    Risacher, Shannon L.; Saykin, Andrew J.

    2014-01-01

    Neurodegenerative disorders leading to dementia are common diseases that affect many older and some young adults. Neuroimaging methods are important tools for assessing and monitoring pathological brain changes associated with progressive neurodegenerative conditions. In this review, the authors describe key findings from neuroimaging studies (magnetic resonance imaging and radionucleotide imaging) in neurodegenerative disorders, including Alzheimer’s disease (AD) and prodromal stages, familial and atypical AD syndromes, frontotemporal dementia, amyotrophic lateral sclerosis with and without dementia, Parkinson’s disease with and without dementia, dementia with Lewy bodies, Huntington’s disease, multiple sclerosis, HIV-associated neurocognitive disorder, and prion protein associated diseases (i.e., Creutzfeldt-Jakob disease). The authors focus on neuroimaging findings of in vivo pathology in these disorders, as well as the potential for neuroimaging to provide useful information for differential diagnosis of neurodegenerative disorders. PMID:24234359

  12. Epilepsy at the prodromal stages of neurodegenerative diseases.

    PubMed

    Cretin, Benjamin; Philippi, Nathalie; Dibitonto, Laure; Blanc, Frédéric

    2017-03-01

    This review provides a clinically grounded description of the links between epilepsy and early common neurodegenerative diseases (i.e. Alzheimer's disease, Lewy body disease, vascular cognitive impairment, fronto-temporal lobar degeneration). It shows that epilepsy does not only concern demented patients displaying convulsive seizures (whether focal or generalized) and obvious atrophy on brain imaging. On the contrary, unprovoked seizures and epilepsy - commonly involving the temporal lobe - are now reported at the prodromal stages of these diseases, when cognitive complaints are mild or even minimal and brain imaging inconstantly abnormal. Thus epilepsy must be considered as a part of the phenotypic spectrum at any stages of the neurodegenerative diseases. This must be kept in mind in everyday practice, and when defining these diseases with clinic-biological criteria. Such entanglement also explains the growing prevalence of elderly epileptic subjects and the need of a close collaboration between geriatricians, cognitivists and epileptologists.

  13. Olfaction in Neurologic and Neurodegenerative Diseases: A Literature Review

    PubMed Central

    Godoy, Maria Dantas Costa Lima; Voegels, Richard Louis; Pinna, Fábio de Rezende; Imamura, Rui; Farfel, José Marcelo

    2014-01-01

    Introduction Loss of smell is involved in various neurologic and neurodegenerative diseases, such as Parkinson disease and Alzheimer disease. However, the olfactory test is usually neglected by physicians at large. Objective The aim of this study was to review the current literature about the relationship between olfactory dysfunction and neurologic and neurodegenerative diseases. Data Synthesis Twenty-seven studies were selected for analysis, and the olfactory system, olfaction, and the association between the olfactory dysfunction and dementias were reviewed. Furthermore, is described an up to date in olfaction. Conclusion Otolaryngologist should remember the importance of olfaction evaluation in daily practice. Furthermore, neurologists and physicians in general should include olfactory tests in the screening of those at higher risk of dementia. PMID:25992176

  14. PET/SPECT imaging agents for neurodegenerative diseases

    PubMed Central

    Zhu, Lin; Ploessl, Karl; Kung, Hank F.

    2014-01-01

    Single photon emission computed tomography (SPECT) or positron emission computed tomography (PET) imaging agents for neurodegenerative disease have a significant impact on clinical diagnosis and patient care. The examples of Parkinson’s Disease (PD) and Alzheimer’s Disease (AD) imaging agents described in this paper provide a general view on how imaging agents, ie radioactive drugs, are selected, chemically prepared and applied in humans. Imaging the living human brain can provide unique information on the pathology and progression of neurodegenerative diseases, such as AD and PD. The imaging method will also facilitate preclinical and clinical trials of new drugs offering specific information related to drug binding sites in the brain. In the future, chemists will continue to play important roles in identifying specific targets, synthesizing target-specific probes for screening and ultimately testing them by in vitro and in vivo assays. PMID:24676152

  15. Auditory imagery: empirical findings.

    PubMed

    Hubbard, Timothy L

    2010-03-01

    The empirical literature on auditory imagery is reviewed. Data on (a) imagery for auditory features (pitch, timbre, loudness), (b) imagery for complex nonverbal auditory stimuli (musical contour, melody, harmony, tempo, notational audiation, environmental sounds), (c) imagery for verbal stimuli (speech, text, in dreams, interior monologue), (d) auditory imagery's relationship to perception and memory (detection, encoding, recall, mnemonic properties, phonological loop), and (e) individual differences in auditory imagery (in vividness, musical ability and experience, synesthesia, musical hallucinosis, schizophrenia, amusia) are considered. It is concluded that auditory imagery (a) preserves many structural and temporal properties of auditory stimuli, (b) can facilitate auditory discrimination but interfere with auditory detection, (c) involves many of the same brain areas as auditory perception, (d) is often but not necessarily influenced by subvocalization, (e) involves semantically interpreted information and expectancies, (f) involves depictive components and descriptive components, (g) can function as a mnemonic but is distinct from rehearsal, and (h) is related to musical ability and experience (although the mechanisms of that relationship are not clear).

  16. Auditory memory distortion for spoken prose.

    PubMed

    Hutchison, Joanna L; Hubbard, Timothy L; Ferrandino, Blaise; Brigante, Ryan; Wright, Jamie M; Rypma, Bart

    2012-11-01

    Observers often remember a scene as containing information that was not presented but that would have likely been located just beyond the observed boundaries of the scene. This effect is called boundary extension (BE; e.g., Intraub & Richardson, 1989). Previous studies have observed BE in memory for visual and haptic stimuli, and the present experiments examined whether BE occurred in memory for auditory stimuli (prose, music). Experiments 1 and 2 varied the amount of auditory content to be remembered. BE was not observed, but when auditory targets contained more content, boundary restriction (BR) occurred. Experiment 3 presented auditory stimuli with less content and BR also occurred. In Experiment 4, white noise was added to stimuli with less content to equalize the durations of auditory stimuli, and BR still occurred. Experiments 5 and 6 presented trained stories and popular music, and BR still occurred. This latter finding ruled out the hypothesis that the lack of BE in Experiments 1-4 reflected a lack of familiarity with the stimuli. Overall, memory for auditory content exhibited BR rather than BE, and this pattern was stronger if auditory stimuli contained more content. Implications for the understanding of general perceptual processing and directions for future research are discussed.

  17. Auditory Memory Distortion for Spoken Prose

    PubMed Central

    Hutchison, Joanna L.; Hubbard, Timothy L.; Ferrandino, Blaise; Brigante, Ryan; Wright, Jamie M.; Rypma, Bart

    2013-01-01

    Observers often remember a scene as containing information that was not presented but that would have likely been located just beyond the observed boundaries of the scene. This effect is called boundary extension (BE; e.g., Intraub & Richardson, 1989). Previous studies have observed BE in memory for visual and haptic stimuli, and the present experiments examined whether BE occurred in memory for auditory stimuli (prose, music). Experiments 1 and 2 varied the amount of auditory content to be remembered. BE was not observed, but when auditory targets contained more content, boundary restriction (BR) occurred. Experiment 3 presented auditory stimuli with less content and BR also occurred. In Experiment 4, white noise was added to stimuli with less content to equalize the durations of auditory stimuli, and BR still occurred. Experiments 5 and 6 presented trained stories and popular music, and BR still occurred. This latter finding ruled out the hypothesis that the lack of BE in Experiments 1–4 reflected a lack of familiarity with the stimuli. Overall, memory for auditory content exhibited BR rather than BE, and this pattern was stronger if auditory stimuli contained more content. Implications for the understanding of general perceptual processing and directions for future research are discussed. PMID:22612172

  18. Auditory Spatial Attention Representations in the Human Cerebral Cortex

    PubMed Central

    Kong, Lingqiang; Michalka, Samantha W.; Rosen, Maya L.; Sheremata, Summer L.; Swisher, Jascha D.; Shinn-Cunningham, Barbara G.; Somers, David C.

    2014-01-01

    Auditory spatial attention serves important functions in auditory source separation and selection. Although auditory spatial attention mechanisms have been generally investigated, the neural substrates encoding spatial information acted on by attention have not been identified in the human neocortex. We performed functional magnetic resonance imaging experiments to identify cortical regions that support auditory spatial attention and to test 2 hypotheses regarding the coding of auditory spatial attention: 1) auditory spatial attention might recruit the visuospatial maps of the intraparietal sulcus (IPS) to create multimodal spatial attention maps; 2) auditory spatial information might be encoded without explicit cortical maps. We mapped visuotopic IPS regions in individual subjects and measured auditory spatial attention effects within these regions of interest. Contrary to the multimodal map hypothesis, we observed that auditory spatial attentional modulations spared the visuotopic maps of IPS; the parietal regions activated by auditory attention lacked map structure. However, multivoxel pattern analysis revealed that the superior temporal gyrus and the supramarginal gyrus contained significant information about the direction of spatial attention. These findings support the hypothesis that auditory spatial information is coded without a cortical map representation. Our findings suggest that audiospatial and visuospatial attention utilize distinctly different spatial coding schemes. PMID:23180753

  19. Auditory spatial attention representations in the human cerebral cortex.

    PubMed

    Kong, Lingqiang; Michalka, Samantha W; Rosen, Maya L; Sheremata, Summer L; Swisher, Jascha D; Shinn-Cunningham, Barbara G; Somers, David C

    2014-03-01

    Auditory spatial attention serves important functions in auditory source separation and selection. Although auditory spatial attention mechanisms have been generally investigated, the neural substrates encoding spatial information acted on by attention have not been identified in the human neocortex. We performed functional magnetic resonance imaging experiments to identify cortical regions that support auditory spatial attention and to test 2 hypotheses regarding the coding of auditory spatial attention: 1) auditory spatial attention might recruit the visuospatial maps of the intraparietal sulcus (IPS) to create multimodal spatial attention maps; 2) auditory spatial information might be encoded without explicit cortical maps. We mapped visuotopic IPS regions in individual subjects and measured auditory spatial attention effects within these regions of interest. Contrary to the multimodal map hypothesis, we observed that auditory spatial attentional modulations spared the visuotopic maps of IPS; the parietal regions activated by auditory attention lacked map structure. However, multivoxel pattern analysis revealed that the superior temporal gyrus and the supramarginal gyrus contained significant information about the direction of spatial attention. These findings support the hypothesis that auditory spatial information is coded without a cortical map representation. Our findings suggest that audiospatial and visuospatial attention utilize distinctly different spatial coding schemes.

  20. Microbial Immuno-Communication in Neurodegenerative Diseases

    PubMed Central

    Main, Bevan S.; Minter, Myles R.

    2017-01-01

    Neuro-inflammation is a critical process by which the brain coordinates chemokine-regulated cellular recruitment, cytokine release, and cell-mediated removal of pathogenic material to protect against infection or brain injury. Dysregulation of this immune response is involved in multiple neurodegenerative disorders, however the precise contribution of neuro-inflammation to the exacerbation and progression of these diseases remains unclear. Evidence now suggests that commensal micro-organisms populating the host and their metabolites, collectively termed the microbiome, regulate innate immunity by influencing peripheral immune cell populations, and modulating microglial phenotype. Recent preclinical studies now demonstrate that perturbations in the host microbiome can induce alterations in pathological phenotypes associated with numerous neurodegenerative diseases. How perturbations in the host microbiome and subsequently altered peripheral immune status are communicated to the brain to influence neuro-inflammatory processes in these neurodegenerative disease settings is far from understood. This review provides insight into the regulation of neuro-inflammatory processes by the host microbiome in the context of neurodegenerative disease and highlights the potential importance of the blood-brain barrier and blood-cerebrospinal fluid-brain barrier, functioning as “immune barriers,” to communicate host immune status to the brain. Understanding the mechanisms by which the commensal microbiome communicates with the brain to influence neuro-inflammatory processes will be critical in the development of microbially-targeted therapeutics in the potential treatment of neurodegenerative disorders. PMID:28386215

  1. Genetically modified pig models for neurodegenerative disorders.

    PubMed

    Holm, Ida E; Alstrup, Aage Kristian Olsen; Luo, Yonglun

    2016-01-01

    Increasing incidence of neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease has become one of the most challenging health issues in ageing humans. One approach to combat this is to generate genetically modified animal models of neurodegenerative disorders for studying pathogenesis, prognosis, diagnosis, treatment, and prevention. Owing to the genetic, anatomic, physiologic, pathologic, and neurologic similarities between pigs and humans, genetically modified pig models of neurodegenerative disorders have been attractive large animal models to bridge the gap of preclinical investigations between rodents and humans. In this review, we provide a neuroanatomical overview in pigs and summarize and discuss the generation of genetically modified pig models of neurodegenerative disorders including Alzheimer's diseases, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, spinal muscular atrophy, and ataxia-telangiectasia. We also highlight how non-invasive bioimaging technologies such as positron emission tomography (PET), computer tomography (CT), and magnetic resonance imaging (MRI), and behavioural testing have been applied to characterize neurodegenerative pig models. We further propose a multiplex genome editing and preterm recloning (MAP) approach by using the rapid growth of the ground-breaking precision genome editing technology CRISPR/Cas9 and somatic cell nuclear transfer (SCNT). With this approach, we hope to shorten the temporal requirement in generating multiple transgenic pigs, increase the survival rate of founder pigs, and generate genetically modified pigs that will more closely resemble the disease-causing mutations and recapitulate pathological features of human conditions. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  2. Abnormalities of Mitochondrial Dynamics in Neurodegenerative Diseases.

    PubMed

    Gao, Ju; Wang, Luwen; Liu, Jingyi; Xie, Fei; Su, Bo; Wang, Xinglong

    2017-04-05

    Neurodegenerative diseases are incurable and devastating neurological disorders characterized by the progressive loss of the structure and function of neurons in the central nervous system or peripheral nervous system. Mitochondria, organelles found in most eukaryotic cells, are essential for neuronal survival and are involved in a number of neuronal functions. Mitochondrial dysfunction has long been demonstrated as a common prominent early pathological feature of a variety of common neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). Mitochondria are highly dynamic organelles that undergo continuous fusion, fission, and transport, the processes of which not only control mitochondrial morphology and number but also regulate mitochondrial function and location. The importance of mitochondrial dynamics in the pathogenesis of neurodegenerative diseases has been increasingly unraveled after the identification of several key fusion and fission regulators such as Drp1, OPA1, and mitofusins. In this review, after a brief discussion of molecular mechanisms regulating mitochondrial fusion, fission, distribution, and trafficking, as well as the important role of mitochondrial dynamics for neuronal function, we review previous and the most recent studies about mitochondrial dynamic abnormalities observed in various major neurodegenerative diseases and discuss the possibility of targeting mitochondrial dynamics as a likely novel therapeutic strategy for neurodegenerative diseases.

  3. Mitochondrial Medicine for Aging and Neurodegenerative Diseases

    PubMed Central

    2011-01-01

    Mitochondria are key cytoplasmic organelles, responsible for generating cellular energy, regulating intracellular calcium levels, altering the reduction-oxidation potential of cells, and regulating cell death. Increasing evidence suggests that mitochondria play a central role in aging and in neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and Freidriech ataxia. Further, several lines of evidence suggest that mitochondrial dysfunction is an early event in most late-onset neurodegenerative diseases. Biochemical and animal model studies of inherited neurodegenerative diseases have revealed that mutant proteins of these diseases are associated with mitochondria. Mutant proteins are reported to block the transport of nuclear-encoded mitochondrial proteins to mitochondria, interact with mitochondrial proteins and disrupt the electron transport chain, induce free radicals, cause mitochondrial dysfunction, and, ultimately, damage neurons. This article discusses critical issues of mitochondria causing dysfunction in aging and neurodegenerative diseases, and discusses the potential of developing mitochondrial medicine, particularly mitochondrially targeted antioxidants, to treat aging and neurodegenerative diseases. PMID:18566920

  4. Cerebral correlates of psychotic syndromes in neurodegenerative diseases

    PubMed Central

    Jellinger, Kurt A

    2012-01-01

    Abstract Psychosis has been recognized as a common feature in neurodegenerative diseases and a core feature of dementia that worsens most clinical courses. It includes hallucinations, delusions including paranoia, aggressive behaviour, apathy and other psychotic phenomena that occur in a wide range of degenerative disorders including Alzheimer’s disease, synucleinopathies (Parkinson’s disease, dementia with Lewy bodies), Huntington’s disease, frontotemporal degenerations, motoneuron and prion diseases. Many of these psychiatric manifestations may be early expressions of cognitive impairment, but often there is a dissociation between psychotic/behavioural symptoms and the rather linear decline in cognitive function, suggesting independent pathophysiological mechanisms. Strictly neuropathological explanations are likely to be insufficient to explain them, and a large group of heterogeneous factors (environmental, neurochemical changes, genetic factors, etc.) may influence their pathogenesis. Clinico-pathological evaluation of behavioural and psychotic symptoms (PS) in the setting of neurodegenerative and dementing disorders presents a significant challenge for modern neurosciences. Recognition and understanding of these manifestations may lead to the development of more effective preventive and therapeutic options that can serve to delay long-term progression of these devastating disorders and improve the patients’ quality of life. A better understanding of the pathophysiology and distinctive pathological features underlying the development of PS in neurodegenerative diseases may provide important insights into psychotic processes in general. PMID:21418522

  5. Protein aggregate spreading in neurodegenerative diseases: Problems and perspectives

    PubMed Central

    Lee, Seung-Jae; Lim, Hee-Sun; Masliah, Eliezer; Lee, He-Jin

    2014-01-01

    Progressive accumulation of specific protein aggregates is a defining feature of many major neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, fronto-temporal dementia, Huntington’s disease, and Creutzfeldt–Jakob disease (CJD). Findings from several recent studies have suggested that aggregation-prone proteins, such as tau, α-synuclein, polyglutamine-containing proteins, and amyloid-β, can spread to other cells and brain regions, a phenomenon considered unique to prion disorders, such as CJD and bovine spongiform encephalopathy. Cell-to-cell propagation of protein aggregates may be the general underlying principle for progressive deterioration of neurodegenerative diseases. This may also have significant implications in cell replacement therapies, as evidenced by the propagation of α-synuclein aggregates from host to grafted cells in long-term transplants in Parkinson’s patients. Here, we review recent progress in protein aggregate propagation in experimental model systems and discuss outstanding questions and future perspectives. Understanding the mechanisms of this pathological spreading may open the way to unique opportunities for development of diagnostic techniques and novel therapies for protein misfolding-associated neurodegenerative diseases. PMID:21624403

  6. Role of iron in neurodegenerative diseases.

    PubMed

    Li, Kai; Reichmann, Heinz

    2016-04-01

    Currently, we still lack effective measures to modify disease progression in neurodegenerative diseases. Iron-containing proteins play an essential role in many fundamental biological processes in the central nervous system. In addition, iron is a redox-active ion and can induce oxidative stress in the cell. Although the causes and pathology hallmarks of different neurodegenerative diseases vary, iron dyshomeostasis, oxidative stress and mitochondrial injury constitute a common pathway to cell death in several neurodegenerative diseases. MRI is capable of depicting iron content in the brain, and serves as a potential biomarker for early and differential diagnosis, tracking disease progression and evaluating the effectiveness of neuroprotective therapy. Iron chelators have shown their efficacy against neurodegeneration in a series of animal models, and been applied in several clinical trials. In this review, we summarize recent developments on iron dyshomeostasis in Parkinson's disease, Alzheimer's disease, Friedreich ataxia, and Huntington's disease.

  7. Advanced magnetic resonance imaging of neurodegenerative diseases.

    PubMed

    Agosta, Federica; Galantucci, Sebastiano; Filippi, Massimo

    2017-01-01

    Magnetic resonance imaging (MRI) is playing an increasingly important role in the study of neurodegenerative diseases, delineating the structural and functional alterations determined by these conditions. Advanced MRI techniques are of special interest for their potential to characterize the signature of each neurodegenerative condition and aid both the diagnostic process and the monitoring of disease progression. This aspect will become crucial when disease-modifying (personalized) therapies will be established. MRI techniques are very diverse and go from the visual inspection of MRI scans to more complex approaches, such as manual and automatic volume measurements, diffusion tensor MRI, and functional MRI. All these techniques allow us to investigate the different features of neurodegeneration. In this review, we summarize the most recent advances concerning the use of MRI in some of the most important neurodegenerative conditions, putting an emphasis on the advanced techniques.

  8. Metal attenuating therapies in neurodegenerative disease.

    PubMed

    Mot, Alexandra I; Wedd, Anthony G; Sinclair, Layla; Brown, David R; Collins, Steven J; Brazier, Marcus W

    2011-12-01

    The clinical and pathological spectrum of neurodegenerative diseases is diverse, although common to many of these disorders is the accumulation of misfolded proteins, with oxidative stress thought to be an important contributing mechanism to neuronal damage. As a corollary, transition metal ion dyshomeostasis appears to play a key pathogenic role in a number of these maladies, including the most common of neurodegenerative diseases. In this review, studies spanning a wide variety of neurodegenerative disorders are presented with their involvement of transition metals compared and contrasted, including more detailed treatise in relation to Alzheimer's disease, Parkinson's disease and prion diseases. For each of these diseases, a discussion of the evolving scientific rationale for the development of therapies aimed at ameliorating the detrimental effects of transition metal dysregulation, including results from various human trials, is then provided.

  9. [Immunotherapy targeting misfolded proteins in neurodegenerative disease].

    PubMed

    Kanemaru, Kazutomi

    2013-04-01

    Aberrant protein aggregation is closely linked to the molecular pathogeneses of most neurodegenerative diseases. The major components of pathological aggregates have been characterized in various neurodegenerative diseases; for example, amyloid β-protein and phosphorylated tau in Alzheimer's disease, α-synuclein in Parkinson's disease, SOD1 or TDP-43 in amyotrophic lateral sclerosis, and huntingtin in Huntington's disease. These misfolded protein aggregates play a vital role in disease initiation and progression, and they have recently been shown to have prion-like spreading or seeded aggregation properties. Immunotherapy with specific monoclonal antibodies is a promising approach to clear misfolded protein aggregates and treat various neurodegenerative diseases; it is planned for use in clinical trials in the near future.

  10. The impact of obesity on neurodegenerative diseases.

    PubMed

    Mazon, Janaína Niero; de Mello, Aline Haas; Ferreira, Gabriela Kozuchovski; Rezin, Gislaine Tezza

    2017-08-01

    Neurodegenerative diseases are a growing health concern. The increasing incidences of these disorders have a great impact on the patients' quality of life. Although the mechanisms of neurodegenerative diseases are still far from being clarified, several studies look for new discoveries about their pathophysiology and prevention. Furthermore, evidence has shown a strong correlation between obesity and the development of Alzheimer's disease (AD) and Parkinson's disease (PD). Metabolic changes caused by overweight are related to damage to the central nervous system (CNS), which can lead to neural death, either by apoptosis or cell necrosis, as well as alter the synaptic plasticity of the neuron. This review aims to show the association between neurodegenerative diseases, focusing on AD and PD, and metabolic alterations. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Decision-making cognition in neurodegenerative diseases.

    PubMed

    Gleichgerrcht, Ezequiel; Ibáñez, Agustín; Roca, María; Torralva, Teresa; Manes, Facundo

    2010-11-01

    A large proportion of human social neuroscience research has focused on the issue of decision-making. Impaired decision-making is a symptomatic feature of a number of neurodegenerative diseases, but the nature of these decision-making deficits depends on the particular disease. Thus, examining the qualitative differences in decision-making impairments associated with different neurodegenerative diseases could provide valuable information regarding the underlying neural basis of decision-making. Nevertheless, few comparative reports of decision-making across patient groups exist. In this Review, we examine the neuroanatomical substrates of decision-making in relation to the neuropathological changes that occur in Alzheimer disease, frontotemporal dementia, Parkinson disease and Huntington disease. We then examine the main findings from studies of decision-making in these neurodegenerative diseases. Finally, we suggest a number of recommendations that future studies could adopt to aid our understanding of decision-making cognition.

  12. Connected Speech in Neurodegenerative Language Disorders: A Review

    PubMed Central

    Boschi, Veronica; Catricalà, Eleonora; Consonni, Monica; Chesi, Cristiano; Moro, Andrea; Cappa, Stefano F.

    2017-01-01

    Language assessment has a crucial role in the clinical diagnosis of several neurodegenerative diseases. The analysis of extended speech production is a precious source of information encompassing the phonetic, phonological, lexico-semantic, morpho-syntactic, and pragmatic levels of language organization. The knowledge about the distinctive linguistic variables identifying language deficits associated to different neurodegenerative diseases has progressively improved in the last years. However, the heterogeneity of such variables and of the way they are measured and classified limits any generalization and makes the comparison among studies difficult. Here we present an exhaustive review of the studies focusing on the linguistic variables derived from the analysis of connected speech samples, with the aim of characterizing the language disorders of the most prevalent neurodegenerative diseases, including primary progressive aphasia, Alzheimer's disease, movement disorders, and amyotrophic lateral sclerosis. A total of 61 studies have been included, considering only those reporting group analysis and comparisons with a group of healthy persons. This review first analyzes the differences in the tasks used to elicit connected speech, namely picture description, story narration, and interview, considering the possible different contributions to the assessment of different linguistic domains. This is followed by an analysis of the terminologies and of the methods of measurements of the variables, indicating the need for harmonization and standardization. The final section reviews the linguistic domains affected by each different neurodegenerative disease, indicating the variables most consistently impaired at each level and suggesting the key variables helping in the differential diagnosis among diseases. While a large amount of valuable information is already available, the review highlights the need of further work, including the development of automated methods, to

  13. Connected Speech in Neurodegenerative Language Disorders: A Review.

    PubMed

    Boschi, Veronica; Catricalà, Eleonora; Consonni, Monica; Chesi, Cristiano; Moro, Andrea; Cappa, Stefano F

    2017-01-01

    Language assessment has a crucial role in the clinical diagnosis of several neurodegenerative diseases. The analysis of extended speech production is a precious source of information encompassing the phonetic, phonological, lexico-semantic, morpho-syntactic, and pragmatic levels of language organization. The knowledge about the distinctive linguistic variables identifying language deficits associated to different neurodegenerative diseases has progressively improved in the last years. However, the heterogeneity of such variables and of the way they are measured and classified limits any generalization and makes the comparison among studies difficult. Here we present an exhaustive review of the studies focusing on the linguistic variables derived from the analysis of connected speech samples, with the aim of characterizing the language disorders of the most prevalent neurodegenerative diseases, including primary progressive aphasia, Alzheimer's disease, movement disorders, and amyotrophic lateral sclerosis. A total of 61 studies have been included, considering only those reporting group analysis and comparisons with a group of healthy persons. This review first analyzes the differences in the tasks used to elicit connected speech, namely picture description, story narration, and interview, considering the possible different contributions to the assessment of different linguistic domains. This is followed by an analysis of the terminologies and of the methods of measurements of the variables, indicating the need for harmonization and standardization. The final section reviews the linguistic domains affected by each different neurodegenerative disease, indicating the variables most consistently impaired at each level and suggesting the key variables helping in the differential diagnosis among diseases. While a large amount of valuable information is already available, the review highlights the need of further work, including the development of automated methods, to

  14. Amylin at the interface between metabolic and neurodegenerative disorders

    PubMed Central

    Lutz, Thomas A.; Meyer, Urs

    2015-01-01

    The pancreatic peptide amylin is best known for its role as a satiation hormone in the control of food intake and as the major component of islet amyloid deposits in the pancreatic islets of patients with type 2 diabetes mellitus (T2DM). Epidemiological studies have established a clear association between metabolic and neurodegenerative disorders in general, and between T2DM and Alzheimer's disease (AD) in particular. Here, we discuss that amylin may be an important player acting at the interface between these metabolic and neurodegenerative disorders. Abnormal amylin production is a hallmark peripheral pathology both in the early (pre-diabetic) and late phases of T2DM, where hyperamylinemic (early phase) and hypoamylinemic (late phase) conditions coincide with hyper- and hypo-insulinemia, respectively. Moreover, there are notable biochemical similarities between amylin and β-amyloids (Aβ), which are both prone to amyloid plaque formation and to cytotoxic effects. Amylin's propensity to form amyloid plaques is not restricted to pancreatic islet cells, but readily extends to the CNS, where it has been found to co-localize with Aβ plaques in at least a subset of AD patients. Hence, amylin may constitute a “second amyloid” in neurodegenerative disorders such as AD. We further argue that hyperamylinemic conditions may be more relevant for the early processes of amyloid formation in the CNS, whereas hypoamylinemic conditions may be more strongly associated with late stages of central amyloid pathologies. Advancing our understanding of these temporal relationships may help to establish amylin-based interventions in the treatment of AD and other neurodegenerative disorders with metabolic comorbidities. PMID:26136651

  15. Transient human auditory cortex activation during volitional attention shifting.

    PubMed

    Uhlig, Christian Harm; Gutschalk, Alexander

    2017-01-01

    While strong activation of auditory cortex is generally found for exogenous orienting of attention, endogenous, intra-modal shifting of auditory attention has not yet been demonstrated to evoke transient activation of the auditory cortex. Here, we used fMRI to test if endogenous shifting of attention is also associated with transient activation of the auditory cortex. In contrast to previous studies, attention shifts were completely self-initiated and not cued by transient auditory or visual stimuli. Stimuli were two dichotic, continuous streams of tones, whose perceptual grouping was not ambiguous. Participants were instructed to continuously focus on one of the streams and switch between the two after a while, indicating the time and direction of each attentional shift by pressing one of two response buttons. The BOLD response around the time of the button presses revealed robust activation of the auditory cortex, along with activation of a distributed task network. To test if the transient auditory cortex activation was specifically related to auditory orienting, a self-paced motor task was added, where participants were instructed to ignore the auditory stimulation while they pressed the response buttons in alternation and at a similar pace. Results showed that attentional orienting produced stronger activity in auditory cortex, but auditory cortex activation was also observed for button presses without focused attention to the auditory stimulus. The response related to attention shifting was stronger contralateral to the side where attention was shifted to. Contralateral-dominant activation was also observed in dorsal parietal cortex areas, confirming previous observations for auditory attention shifting in studies that used auditory cues.

  16. Transient human auditory cortex activation during volitional attention shifting

    PubMed Central

    Uhlig, Christian Harm; Gutschalk, Alexander

    2017-01-01

    While strong activation of auditory cortex is generally found for exogenous orienting of attention, endogenous, intra-modal shifting of auditory attention has not yet been demonstrated to evoke transient activation of the auditory cortex. Here, we used fMRI to test if endogenous shifting of attention is also associated with transient activation of the auditory cortex. In contrast to previous studies, attention shifts were completely self-initiated and not cued by transient auditory or visual stimuli. Stimuli were two dichotic, continuous streams of tones, whose perceptual grouping was not ambiguous. Participants were instructed to continuously focus on one of the streams and switch between the two after a while, indicating the time and direction of each attentional shift by pressing one of two response buttons. The BOLD response around the time of the button presses revealed robust activation of the auditory cortex, along with activation of a distributed task network. To test if the transient auditory cortex activation was specifically related to auditory orienting, a self-paced motor task was added, where participants were instructed to ignore the auditory stimulation while they pressed the response buttons in alternation and at a similar pace. Results showed that attentional orienting produced stronger activity in auditory cortex, but auditory cortex activation was also observed for button presses without focused attention to the auditory stimulus. The response related to attention shifting was stronger contralateral to the side where attention was shifted to. Contralateral-dominant activation was also observed in dorsal parietal cortex areas, confirming previous observations for auditory attention shifting in studies that used auditory cues. PMID:28273110

  17. Epigenetics-Based Therapeutics for Neurodegenerative Disorders

    PubMed Central

    Xu, Zihui; Li, He; Jin, Peng

    2013-01-01

    Epigenetic regulation, such as DNA methylation and histone modification, is implicated in the aberrant changes in gene expression that occur during the progression of neurodegeneration. Many epigenetics-based drugs have been developed recently for the treatment of some neurodegenerative disorders, including Alzheimer’s, Parkinson’s, and Huntington’s diseases. Here we review recent studies that highlight the role of epigenetic modifications in neurodegeneration, among them DNA methylation and demethylation and histone acetylation and deacetylation; we also explore the possibility of using epigenetics-based therapeutics to treat neurodegenerative disorders. PMID:23526405

  18. The Ontario Neurodegenerative Disease Research Initiative (ONDRI).

    PubMed

    Farhan, Sali M K; Bartha, Robert; Black, Sandra E; Corbett, Dale; Finger, Elizabeth; Freedman, Morris; Greenberg, Barry; Grimes, David A; Hegele, Robert A; Hudson, Chris; Kleinstiver, Peter W; Lang, Anthony E; Masellis, Mario; McIlroy, William E; McLaughlin, Paula M; Montero-Odasso, Manuel; Munoz, David G; Munoz, Douglas P; Strother, Stephen; Swartz, Richard H; Symons, Sean; Tartaglia, Maria Carmela; Zinman, Lorne; Strong, Michael J

    2017-03-01

    Because individuals develop dementia as a manifestation of neurodegenerative or neurovascular disorder, there is a need to develop reliable approaches to their identification. We are undertaking an observational study (Ontario Neurodegenerative Disease Research Initiative [ONDRI]) that includes genomics, neuroimaging, and assessments of cognition as well as language, speech, gait, retinal imaging, and eye tracking. Disorders studied include Alzheimer's disease, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson's disease, and vascular cognitive impairment. Data from ONDRI will be collected into the Brain-CODE database to facilitate correlative analysis. ONDRI will provide a repertoire of endophenotyped individuals that will be a unique, publicly available resource.

  19. Effects of an Auditory Lateralization Training in Children Suspected to Central Auditory Processing Disorder

    PubMed Central

    Lotfi, Yones; Moosavi, Abdollah; Bakhshi, Enayatollah; Sadjedi, Hamed

    2016-01-01

    Background and Objectives Central auditory processing disorder [(C)APD] refers to a deficit in auditory stimuli processing in nervous system that is not due to higher-order language or cognitive factors. One of the problems in children with (C)APD is spatial difficulties which have been overlooked despite their significance. Localization is an auditory ability to detect sound sources in space and can help to differentiate between the desired speech from other simultaneous sound sources. Aim of this research was investigating effects of an auditory lateralization training on speech perception in presence of noise/competing signals in children suspected to (C)APD. Subjects and Methods In this analytical interventional study, 60 children suspected to (C)APD were selected based on multiple auditory processing assessment subtests. They were randomly divided into two groups: control (mean age 9.07) and training groups (mean age 9.00). Training program consisted of detection and pointing to sound sources delivered with interaural time differences under headphones for 12 formal sessions (6 weeks). Spatial word recognition score (WRS) and monaural selective auditory attention test (mSAAT) were used to follow the auditory lateralization training effects. Results This study showed that in the training group, mSAAT score and spatial WRS in noise (p value≤0.001) improved significantly after the auditory lateralization training. Conclusions We used auditory lateralization training for 6 weeks and showed that auditory lateralization can improve speech understanding in noise significantly. The generalization of this results needs further researches. PMID:27626084

  20. Increased cognitive functioning in symptomatic Huntington's disease as revealed by behavioral and event-related potential indices of auditory sensory memory and attention.

    PubMed

    Beste, Christian; Saft, Carsten; Güntürkün, Onur; Falkenstein, Michael

    2008-11-05

    Cognitive functions are thought to deteriorate globally in late stages of various neurodegenerative disorders. Here we describe that this general assumption is not justified and fails in Huntington's disease (HD). Presymptomatic gene mutation carriers (pHDs) and healthy controls performed worse compared with symptomatic HDs in an auditory signal detection task. During task performance, behavioral data and event-related potentials (ERPs) [i.e., MMN (mismatch negativity), P3a, and RON (reorienting negativity)] were recorded. Not only behavioral performance but also neurophysiological correlates of auditory sensory memory and attentional reorientation indicate enhanced performance occurring primal in late stages of a neurodegenerative disorder. Increased activity of the NMDA-receptor system, an assumed pathogenic mechanism in HD, might facilitate signal propagation at striatal level that enables more efficient task execution through a winner-take-all process. The results challenge the view that late stage neurodegeneration is necessarily related to a global decline in cognitive abilities in HD. In contrast, selectively enhanced cognitive functioning can emerge together with otherwise impaired cognitive functioning.

  1. Induced pluripotent stem cells and neurodegenerative diseases.

    PubMed

    Chen, Chao; Xiao, Shi-Fu

    2011-04-01

    Neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease and Amyotrophic Lateral Sclerosis, are characterized by idiopathic neuron loss in different regions of the central nervous system, which contributes to the relevant dysfunctions in the patients. The application of cell replacement therapy using human embryonic stem (hES) cells, though having attracted much attention, has been hampered by the intrinsic ethical problems. It has been demonstrated that adult somatic cells can be reprogrammed into the embryonic state, called induced pluripotent stem (iPS) cells. It is soon realized that iPS cells may be an alternative source for cell replacement therapy, because it raises no ethical problems and using patient-specific iPS cells for autologous transplantation will not lead to immunological rejection. What's more, certain types of neurons derived from patient-specific iPS cells may display disease-relevant phenotypes. Thus, patient-specific iPS cells can provide a unique opportunity to directly investigate the pathological properties of relevant neural cells in individual patient, and to study the vulnerability of neural cells to pathogenic factors in vitro, which may help reveal the pathogenesis of many neurodegenerative diseases. In this review, the recent development in cellular treatment of neurodegenerative diseases using iPS cells was summarized, and the potential value of iPS cells in the modeling of neurodegenerative disease was discussed.

  2. DNA methylation, a hand behind neurodegenerative diseases

    PubMed Central

    Lu, Haoyang; Liu, Xinzhou; Deng, Yulin; Qing, Hong

    2013-01-01

    Epigenetic alterations represent a sort of functional modifications related to the genome that are not responsible for changes in the nucleotide sequence. DNA methylation is one of such epigenetic modifications that have been studied intensively for the past several decades. The transfer of a methyl group to the 5 position of a cytosine is the key feature of DNA methylation. A simple change as such can be caused by a variety of factors, which can be the cause of many serious diseases including several neurodegenerative diseases. In this review, we have reviewed and summarized recent progress regarding DNA methylation in four major neurodegenerative diseases: Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). The studies of these four major neurodegenerative diseases conclude the strong suggestion of the important role DNA methylation plays in these diseases. However, each of these diseases has not yet been understood completely as details in some areas remain unclear, and will be investigated in future studies. We hope this review can provide new insights into the understanding of neurodegenerative diseases from the epigenetic perspective. PMID:24367332

  3. Disulfide Bonding in Neurodegenerative Misfolding Diseases

    PubMed Central

    2013-01-01

    In recent years an increasing number of neurodegenerative diseases has been linked to the misfolding of a specific protein and its subsequent accumulation into aggregated species, often toxic to the cell. Of all the factors that affect the behavior of these proteins, disulfide bonds are likely to be important, being very conserved in protein sequences and being the enzymes devoted to their formation among the most conserved machineries in mammals. Their crucial role in the folding and in the function of a big fraction of the human proteome is well established. The role of disulfide bonding in preventing and managing protein misfolding and aggregation is currently under investigation. New insights into their involvement in neurodegenerative diseases, their effect on the process of protein misfolding and aggregation, and into the role of the cellular machineries devoted to disulfide bond formation in neurodegenerative diseases are emerging. These studies mark a step forward in the comprehension of the biological base of neurodegenerative disorders and highlight the numerous questions that still remain open. PMID:23983694

  4. Microglia-Mediated Inflammation and Neurodegenerative Disease.

    PubMed

    Xu, Ling; He, Dan; Bai, Ying

    2016-12-01

    Microglia are the main effectors in the inflammatory process of the central nervous system. As the first line of defense, microglia play an important role in the inflammatory reaction. When there is pathogen invasion or cell debris, microglia will be activated rapidly and remove it, while releasing the inflammatory cytokines to mediate inflammatory reaction. Activated microglia were found surrounding lesions of various neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, muscular amyotrophic lateral sclerosis, and multiple sclerosis. Microglia, the effectors of neuronal degeneration and necrosis, are involved in the removal of necrotic neurons. But over activated microglia may accelerate the process of some neurodegenerative diseases. Activated microglia can release cytotoxic factor and cytokines. Some of them may cause further damage to neuron, and some of them can regulate inflammatory cells to gather to the lesion. Microglia-mediated inflammation was considered to be the possible mechanism for the occurrence or deterioration of neurodegenerative diseases. Therefore, inhibiting the activity of microglia appropriately may be an effective way for the treatment of neurodegenerative diseases.

  5. Supporting communication for patients with neurodegenerative disease.

    PubMed

    Fried-Oken, Melanie; Mooney, Aimee; Peters, Betts

    2015-01-01

    Communication supports, referred to as augmentative and alternative communication (AAC), are an integral part of medical speech-language pathology practice, yet many providers remain unfamiliar with assessment and intervention principles. For patients with complex communication impairments secondary to neurodegenerative disease, AAC services differ depending on whether their condition primarily affects speech and motor skills (ALS), language (primary progressive aphasia) or cognition (Alzheimer's disease). This review discusses symptom management for these three conditions, identifying behavioral strategies, low- and high-tech solutions for implementation during the natural course of disease. These AAC principles apply to all neurodegenerative diseases in which common symptoms appear. To present AAC interventions for patients with neurodegenerative diseases affecting speech, motor, language and cognitive domains. Three themes emerge: (1) timing of intervention: early referral, regular re-evaluations and continual treatment are essential; (2) communication partners must be included from the onset to establish AAC acceptance and use; and (3) strategies will change over time and use multiple modalities to capitalize on patients' strengths. AAC should be standard practice for adults with neurodegenerative disease. Patients can maintain effective, functional communication with AAC supports. Individualized communication systems can be implemented ensuring patients remain active participants in daily activities.

  6. Walking the tightrope: proteostasis and neurodegenerative disease.

    PubMed

    Yerbury, Justin J; Ooi, Lezanne; Dillin, Andrew; Saunders, Darren N; Hatters, Danny M; Beart, Philip M; Cashman, Neil R; Wilson, Mark R; Ecroyd, Heath

    2016-05-01

    A characteristic of many neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), is the aggregation of specific proteins into protein inclusions and/or plaques in degenerating brains. While much of the aggregated protein consists of disease specific proteins, such as amyloid-β, α-synuclein, or superoxide dismutase1 (SOD1), many other proteins are known to aggregate in these disorders. Although the role of protein aggregates in the pathogenesis of neurodegenerative diseases remains unknown, the ubiquitous association of misfolded and aggregated proteins indicates that significant dysfunction in protein homeostasis (proteostasis) occurs in these diseases. Proteostasis is the concept that the integrity of the proteome is in fine balance and requires proteins in a specific conformation, concentration, and location to be functional. In this review, we discuss the role of specific mechanisms, both inside and outside cells, which maintain proteostasis, including molecular chaperones, protein degradation pathways, and the active formation of inclusions, in neurodegenerative diseases associated with protein aggregation. A characteristic of many neurodegenerative diseases is the aggregation of specific proteins, which alone provides strong evidence that protein homeostasis is disrupted in these disease states. Proteostasis is the maintenance of the proteome in the correct conformation, concentration, and location by functional pathways such as molecular chaperones and protein degradation machinery. Here, we discuss the potential roles of quality control pathways, both inside and outside cells, in the loss of proteostasis during aging and disease. © 2016 International Society for Neurochemistry.

  7. Genetic manipulation for inherited neurodegenerative diseases: myth or reality?

    PubMed Central

    Yu-Wai-Man, Patrick

    2016-01-01

    Rare genetic diseases affect about 7% of the general population and over 7000 distinct clinical syndromes have been described with the majority being due to single gene defects. This review will provide a critical overview of genetic strategies that are being pioneered to halt or reverse disease progression in inherited neurodegenerative diseases. This field of research covers a vast area and only the most promising treatment paradigms will be discussed with a particular focus on inherited eye diseases, which have paved the way for innovative gene therapy paradigms, and mitochondrial diseases, which are currently generating a lot of debate centred on the bioethics of germline manipulation. PMID:27002113

  8. Auditory and visual memory in musicians and nonmusicians

    PubMed Central

    Evans, Karla K.; Horowitz, Todd S.; Wolfe, Jeremy M.

    2014-01-01

    Numerous studies have shown that musicians outperform nonmusicians on a variety of tasks. Here we provide the first evidence that musicians have superior auditory recognition memory for both musical and nonmusical stimuli, compared to nonmusicians. However, this advantage did not generalize to the visual domain. Previously, we showed that auditory recognition memory is inferior to visual recognition memory. Would this be true even for trained musicians? We compared auditory and visual memory in musicians and nonmusicians using familiar music, spoken English, and visual objects. For both groups, memory for the auditory stimuli was inferior to memory for the visual objects. Thus, although considerable musical training is associated with better musical and nonmusical auditory memory, it does not increase the ability to remember sounds to the levels found with visual stimuli. This suggests a fundamental capacity difference between auditory and visual recognition memory, with a persistent advantage for the visual domain. PMID:21374094

  9. An immunocytochemical mapping of somatostatin in the cat auditory cortex.

    PubMed

    Martín, F; Coveñas, R; Narváez, J A; Tramu, G

    2003-10-01

    Using an indirect immunoperoxidase technique, the localization of somatostatin-28 (1-12)-like immunoreactive fibers and cell bodies in the auditory cortex of the cat (anterior, primary, secondary, temporal, ventral, ventroposterior, posterior and dorsoposterior auditory fields) was studied. In general, the distribution of SOM-ir structures is widespread in the auditory cortex of the feline. A high density of immunoreactive fibers as well as a low density of cell bodies containing somatostatin were observed in all the layers of the eight above-mentioned auditory fields. These data indicate that somatostatin-28 (1-12) could act as a neurotransmitter and/or a neuromodulator in the auditory cortex of the cat. The origin of the SOM-ir fibers in the auditory cortex of the cat, as well as the issue of whether the cell bodies containing somatostatin-28 (1-12) are local or projecting neurons is discussed.

  10. The auditory brainstem is a barometer of rapid auditory learning.

    PubMed

    Skoe, E; Krizman, J; Spitzer, E; Kraus, N

    2013-07-23

    To capture patterns in the environment, neurons in the auditory brainstem rapidly alter their firing based on the statistical properties of the soundscape. How this neural sensitivity relates to behavior is unclear. We tackled this question by combining neural and behavioral measures of statistical learning, a general-purpose learning mechanism governing many complex behaviors including language acquisition. We recorded complex auditory brainstem responses (cABRs) while human adults implicitly learned to segment patterns embedded in an uninterrupted sound sequence based on their statistical characteristics. The brainstem's sensitivity to statistical structure was measured as the change in the cABR between a patterned and a pseudo-randomized sequence composed from the same set of sounds but differing in their sound-to-sound probabilities. Using this methodology, we provide the first demonstration that behavioral-indices of rapid learning relate to individual differences in brainstem physiology. We found that neural sensitivity to statistical structure manifested along a continuum, from adaptation to enhancement, where cABR enhancement (patterned>pseudo-random) tracked with greater rapid statistical learning than adaptation. Short- and long-term auditory experiences (days to years) are known to promote brainstem plasticity and here we provide a conceptual advance by showing that the brainstem is also integral to rapid learning occurring over minutes. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  11. Fine-grained auditory discrimination: factor structures.

    PubMed

    Elliott, L L; Hammer, M A

    1993-04-01

    This research tested the hypothesis that as children's language development matures, factor-analytic structural changes occur that are associated with measurements of fine-grained auditory discrimination, receptive vocabulary, receptive language, speech production, and three performance subtests of the WISC-R. Among 6- to 7-year-old children, the percent of total variance attributed to the factor defined by fine-grained auditory discrimination measures was approximately 43% for children who were intellectually impaired (Experiment 2), 27% for youngsters who had language-learning problems, and 16% for regularly progressing children (Experiment 1). The WISC-R subtest scores, generally, did not load on the auditory discrimination factor. The difference in variance explained by the auditory discrimination factor was interpreted as representing greater relative importance of auditory discrimination among children with less-well-developed language competencies than among children with more mature language skills. This interpretation was strengthened by the finding of no distinct auditory discrimination factor for 8- to 11-year-old children who were either regularly progressing or language-disabled even though the language/speech factor at this age closely resembled that found among younger children. Results were consonant with Ackerman's (1987) model, suggesting that task-specific variance associated with tasks that remain resource-dependent may diminish after practice and experience.

  12. Glial Cell Contributions to Auditory Brainstem Development

    PubMed Central

    Cramer, Karina S.; Rubel, Edwin W

    2016-01-01

    Glial cells, previously thought to have generally supporting roles in the central nervous system, are emerging as essential contributors to multiple aspects of neuronal circuit function and development. This review focuses on the contributions of glial cells to the development of auditory pathways in the brainstem. These pathways display specialized synapses and an unusually high degree of precision in circuitry that enables sound source localization. The development of these pathways thus requires highly coordinated molecular and cellular mechanisms. Several classes of glial cells, including astrocytes, oligodendrocytes and microglia, have now been explored in these circuits in both avian and mammalian brainstems. Distinct populations of astrocytes are found over the course of auditory brainstem maturation. Early appearing astrocytes are associated with spatial compartments in the avian auditory brainstem. Factors from late appearing astrocytes promote synaptogenesis and dendritic maturation, and astrocytes remain integral parts of specialized auditory synapses. Oligodendrocytes play a unique role in both birds and mammals in highly regulated myelination essential for proper timing to decipher interaural cues. Microglia arise early in brainstem development and may contribute to maturation of auditory pathways. Together these studies demonstrate the importance of non-neuronal cells in the assembly of specialized auditory brainstem circuits. PMID:27818624

  13. Auditory-motor learning influences auditory memory for music.

    PubMed

    Brown, Rachel M; Palmer, Caroline

    2012-05-01

    In two experiments, we investigated how auditory-motor learning influences performers' memory for music. Skilled pianists learned novel melodies in four conditions: auditory only (listening), motor only (performing without sound), strongly coupled auditory-motor (normal performance), and weakly coupled auditory-motor (performing along with auditory recordings). Pianists' recognition of the learned melodies was better following auditory-only or auditory-motor (weakly coupled and strongly coupled) learning than following motor-only learning, and better following strongly coupled auditory-motor learning than following auditory-only learning. Auditory and motor imagery abilities modulated the learning effects: Pianists with high auditory imagery scores had better recognition following motor-only learning, suggesting that auditory imagery compensated for missing auditory feedback at the learning stage. Experiment 2 replicated the findings of Experiment 1 with melodies that contained greater variation in acoustic features. Melodies that were slower and less variable in tempo and intensity were remembered better following weakly coupled auditory-motor learning. These findings suggest that motor learning can aid performers' auditory recognition of music beyond auditory learning alone, and that motor learning is influenced by individual abilities in mental imagery and by variation in acoustic features.

  14. Task- and Talker-Specific Gains in Auditory Training

    ERIC Educational Resources Information Center

    Barcroft, Joe; Spehar, Brent; Tye-Murray, Nancy; Sommers, Mitchell

    2016-01-01

    Purpose: This investigation focused on generalization of outcomes for auditory training by examining the effects of task and/or talker overlap between training and at test. Method: Adults with hearing loss completed 12 hr of meaning-oriented auditory training and were placed in a group that trained on either multiple talkers or a single talker. A…

  15. Task- and Talker-Specific Gains in Auditory Training

    ERIC Educational Resources Information Center

    Barcroft, Joe; Spehar, Brent; Tye-Murray, Nancy; Sommers, Mitchell

    2016-01-01

    Purpose: This investigation focused on generalization of outcomes for auditory training by examining the effects of task and/or talker overlap between training and at test. Method: Adults with hearing loss completed 12 hr of meaning-oriented auditory training and were placed in a group that trained on either multiple talkers or a single talker. A…

  16. Reading and subcortical auditory function.

    PubMed

    Banai, Karen; Hornickel, Jane; Skoe, Erika; Nicol, Trent; Zecker, Steven; Kraus, Nina

    2009-11-01

    Although it is largely agreed that phonological processing deficits are a major cause of poor reading, the neural origins of phonological processing are not well understood. We now show, for the first time, that phonological decoding, measured with a test of single-nonword reading, is significantly correlated with the timing of subcortical auditory processing and also, to a lesser extent, with the robustness of subcortical representation of the harmonic content of speech, but not with pitch encoding. The relationships we observe between reading and subcortical processing fall along a continuum, with poor readers at one end and good readers at the other. These data suggest that reading skill may depend on the integrity of subcortical auditory mechanisms and are consistent with the idea that subcortical representation of the acoustic features of speech may play a role in normal reading as well as in the development of reading disorders. These data establish a significant link between subcortical auditory function and reading, thereby contributing to the understanding of the biological bases of reading. At a more general level, these findings are among the first to establish a direct relationship between subcortical sensory function and a specific cognitive skill (reading). We argue that this relationship between cortical and subcortical function could be shaped during development by the corticofugal pathway and that this cortical-subcortical link could contribute to the phonological processing deficits experienced by poor readers.

  17. 19 CFR 10.121 - Visual or auditory materials of an educational, scientific, or cultural character.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Visual or auditory materials of an educational... RATE, ETC. General Provisions Visual Or Auditory Materials § 10.121 Visual or auditory materials of an... such articles a document issued by the U.S. Information Agency certifying that it has determined that...

  18. Oligonucleotide-based therapy for neurodegenerative diseases.

    PubMed

    Magen, Iddo; Hornstein, Eran

    2014-10-10

    Molecular genetics insight into the pathogenesis of several neurodegenerative diseases, such as Alzheimer׳s disease, Parkinson׳s disease, Huntington׳s disease and amyotrophic lateral sclerosis, encourages direct interference with the activity of neurotoxic genes or the molecular activation of neuroprotective pathways. Oligonucleotide-based therapies are recently emerging as an efficient strategy for drug development and these can be employed as new treatments of neurodegenerative states. Here we review advances in this field in recent years which suggest an encouraging assessment that oligonucleotide technologies for targeting of RNAs will enable the development of new therapies and will contribute to preservation of brain integrity. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Chronic traumatic encephalopathy and other neurodegenerative proteinopathies.

    PubMed

    Tartaglia, Maria Carmela; Hazrati, Lili-Naz; Davis, Karen D; Green, Robin E A; Wennberg, Richard; Mikulis, David; Ezerins, Leo J; Keightley, Michelle; Tator, Charles

    2014-01-01

    "Chronic traumatic encephalopathy" (CTE) is described as a slowly progressive neurodegenerative disease believed to result from multiple concussions. Traditionally, concussions were considered benign events and although most people recover fully, about 10% develop a post-concussive syndrome with persisting neurological, cognitive and neuropsychiatric symptoms. CTE was once thought to be unique to boxers, but it has now been observed in many different athletes having suffered multiple concussions as well as in military personal after repeated blast injuries. Much remains unknown about the development of CTE but its pathological substrate is usually tau, similar to that seen in Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD). The aim of this "perspective" is to compare and contrast clinical and pathological CTE with the other neurodegenerative proteinopathies and highlight that there is an urgent need for understanding the relationship between concussion and the development of CTE as it may provide a window into the development of a proteinopathy and thus new avenues for treatment.

  20. Resveratrol: A Focus on Several Neurodegenerative Diseases

    PubMed Central

    Tellone, Ester; Galtieri, Antonio; Russo, Annamaria; Giardina, Bruno; Ficarra, Silvana

    2015-01-01

    Molecules of the plant world are proving their effectiveness in countering, slowing down, and regressing many diseases. The resveratrol for its intrinsic properties related to its stilbene structure has been proven to be a universal panacea, especially for a wide range of neurodegenerative diseases. This paper evaluates (in vivo and in vitro) the various molecular targets of this peculiar polyphenol and its ability to effectively counter several neurodegenerative disorders such as Parkinson's, Alzheimer's, and Huntington's diseases and amyotrophic lateral sclerosis. What emerges is that, in the deep heterogeneity of the pathologies evaluated, resveratrol through a convergence on the protein targets is able to give therapeutic responses in neuronal cells deeply diversified not only in morphological structure but especially in their function performed in the anatomical district to which they belong. PMID:26180587

  1. Effects of Panax ginseng in Neurodegenerative Diseases

    PubMed Central

    Cho, Ik-Hyun

    2012-01-01

    Ginseng, the root of the Panax ginseng, has been a popular and widely-used traditional herbal medicine in Korea, China, and Japan for thousands of years. Now it has become popular as a functional health food and is used globally as a natural medicine. Evidence is accumulating in the literature on the physiological and pharmacological effects of P. ginseng on neurodegenerative diseases. Possible ginseng- or ginsenosides-mediated neuroprotective mechanisms mainly involve maintaining homeostasis, and anti-inflammatory, anti-oxidant, anti-apoptotic, and immune-stimulatory activities. This review considers publications dealing with the various actions of P. ginseng that are indicative of possible neurotherapeutic efficacies in neurodegenerative diseases and neurological disorders such as Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, and amyotrophic lateral sclerosis and multiple sclerosis. PMID:23717136

  2. Brain drug delivery systems for neurodegenerative disorders.

    PubMed

    Garbayo, E; Ansorena, E; Blanco-Prieto, M J

    2012-09-01

    Neurodegenerative disorders (NDs) are rapidly increasing as population ages. However, successful treatments for NDs have so far been limited and drug delivery to the brain remains one of the major challenges to overcome. There has recently been growing interest in the development of drug delivery systems (DDS) for local or systemic brain administration. DDS are able to improve the pharmacological and therapeutic properties of conventional drugs and reduce their side effects. The present review provides a concise overview of the recent advances made in the field of brain drug delivery for treating neurodegenerative disorders. Examples include polymeric micro and nanoparticles, lipidic nanoparticles, pegylated liposomes, microemulsions and nanogels that have been tested in experimental models of Parkinson's, Alzheimer's and Huntington's disease. Overall, the results reviewed here show that DDS have great potential for NDs treatment.

  3. [Link between aluminum neurotoxicity and neurodegenerative disorders].

    PubMed

    Kawahara, Masahiro

    2016-07-01

    Aluminum is an old element that has been known for a long time, but some of its properties are only now being discovered. Although environmentally abundant, aluminum is not essential for life; in fact, because of its specific chemical properties, aluminum inhibits more than 200 biologically important functions and exerts various adverse effects in plants, animals, and humans. Aluminum is a widely recognized neurotoxin. It has been suggested that there is a relationship between exposure to aluminum and neurodegenerative diseases, including dialysis encephalopathy, amyotrophic lateral sclerosis and parkinsonism dementia in the Kii Peninsula and Guam, as well as Alzheimer' s disease: however, this claim remains to be verified. In this chapter, we review the detailed characteristics of aluminum neurotoxicity and the link between Alzheimer' s disease and other neurodegenerative diseases, based on recent findings on metal-metal interactions and the functions of metalloproteins in synapses.

  4. Neurodegenerative disorders--4th annual SMi conference.

    PubMed

    Phillips, Tom

    2004-08-01

    The prevalence of neurodegenerative diseases in the Western World and Japan is predicted to increase sharply as a consequence of the rapidly aging population. To discuss the development of therapeutics in this increasingly important field, the 2-day Neurodegenerative Disorders SMi meeting once again brought together delegates from both large pharmaceutical companies and smaller technology and analysis companies. The majority of presentations focused on Alzheimer's disease, one of the gravest of such conditions that affects approximately half of all people aged 90 years, and on Parkinson's disease. As well as disclosing new therapeutic targets and preclinical and clinical data for drugs in development, several presentations discussed the development of surrogate markers and imaging techniques to monitor disease progression and therapeutic efficacy.

  5. Neurodegenerative disorders and nanoformulated drug development

    PubMed Central

    Nowacek, Ari; Kosloski, Lisa M; Gendelman, Howard E

    2009-01-01

    Degenerative and inflammatory diseases of the CNS include, but are not limited to, Alzheimer’s and Parkinson’s disease, amyotrophic lateral sclerosis, stroke, multiple sclerosis and HIV-1-associated neurocognitive disorders. These are common, debilitating and, unfortunately, hold few therapeutic options. In recent years, the application of nanotechnologies as commonly used or developing medicines has served to improve pharmacokinetics and drug delivery specifically to CNS-diseased areas. In addition, nanomedical advances are leading to therapies that target CNS pathobiology and as such, can interrupt disordered protein aggregation, deliver functional neuroprotective proteins and alter the oxidant state of affected neural tissues. This article focuses on the pathobiology of common neurodegenerative disorders with a view towards how nanomedicine may be used to improve the clinical course of neurodegenerative disorders. PMID:19572820

  6. Mechanisms of Protein Seeding in Neurodegenerative Diseases

    PubMed Central

    Walker, Lary C.; Diamond, Marc I.; Duff, Karen E.; Hyman, Bradley T.

    2013-01-01

    Most age-associated neurodegenerative diseases involve the aggregation of specific proteins within the nervous system. In Alzheimer’s disease, the insidious pathogenic process begins many years before the symptoms emerge, and the lesions that characterize the disease – senile plaques and neurofibrillary tangles – ramify systematically through the brain. We review evidence that the β-amyloid and tau proteins, which aggregate to form senile plaques and neurofibrillary tangles, respectively, are induced to misfold and self-assemble by a process of templated conformational change that amplifies a toxic species. Recent data also indicate that the spread of these lesions from one site to another is mediated by the cellular uptake, transport and release of endogenous seeds formed by the cognate proteins. This simple pathogenic principle suggests that the formation, trafficking and metabolism of pathogenic protein seeds are promising therapeutic targets for Alzheimer’s disease and other neurodegenerative disorders. PMID:23599928

  7. Multimodal comparative studies of neurodegenerative diseases.

    PubMed

    Grossman, Murray

    2013-01-01

    Here we provide a brief description of our program to improve diagnostic accuracy in cases with phenotypically similar presentations that are due to distinct histopathologic abnormalities. We propose a staged approach to diagnosis, beginning with a screening assessment of specific, quantitative neuropsychological measures, and followed by assessments of imaging and biofluid biomarkers. Our goal is to determine the specific histopathologic abnormalities contributing to an individual's neurodegenerative condition.

  8. Synthetic prions and other human neurodegenerative proteinopathies.

    PubMed

    Le, Nhat Tran Thanh; Narkiewicz, Joanna; Aulić, Suzana; Salzano, Giulia; Tran, Hoa Thanh; Scaini, Denis; Moda, Fabio; Giachin, Gabriele; Legname, Giuseppe

    2015-09-02

    Transmissible spongiform encephalopathies (TSE) are a heterogeneous group of neurodegenerative disorders. The common feature of these diseases is the pathological conversion of the normal cellular prion protein (PrP(C)) into a β-structure-rich conformer-termed PrP(Sc). The latter can induce a self-perpetuating process leading to amplification and spreading of pathological protein assemblies. Much evidence suggests that PrP(Sc) itself is able to recruit and misfold PrP(C) into the pathological conformation. Recent data have shown that recombinant PrP(C) can be misfolded in vitro and the resulting synthetic conformers are able to induce the conversion of PrP(C) into PrP(Sc)in vivo. In this review we describe the state-of-the-art of the body of literature in this field. In addition, we describe a cell-based assay to test synthetic prions in cells, providing further evidence that synthetic amyloids are able to template conversion of PrP into prion inclusions. Studying prions might help to understand the pathological mechanisms governing other neurodegenerative diseases. Aggregation and deposition of misfolded proteins is a common feature of several neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and other disorders. Although the proteins implicated in each of these diseases differ, they share a common prion mechanism. Recombinant proteins are able to aggregate in vitro into β-rich amyloid fibrils, sharing some features of the aggregates found in the brain. Several studies have reported that intracerebral inoculation of synthetic aggregates lead to unique pathology, which spread progressively to distal brain regions and reduced survival time in animals. Here, we review the prion-like features of different proteins involved in neurodegenerative disorders, such as α-synuclein, superoxide dismutase-1, amyloid-β and tau.

  9. Autophagy and apoptosis dysfunction in neurodegenerative disorders.

    PubMed

    Ghavami, Saeid; Shojaei, Shahla; Yeganeh, Behzad; Ande, Sudharsana R; Jangamreddy, Jaganmohan R; Mehrpour, Maryam; Christoffersson, Jonas; Chaabane, Wiem; Moghadam, Adel Rezaei; Kashani, Hessam H; Hashemi, Mohammad; Owji, Ali A; Łos, Marek J

    2014-01-01

    Autophagy and apoptosis are basic physiologic processes contributing to the maintenance of cellular homeostasis. Autophagy encompasses pathways that target long-lived cytosolic proteins and damaged organelles. It involves a sequential set of events including double membrane formation, elongation, vesicle maturation and finally delivery of the targeted materials to the lysosome. Apoptotic cell death is best described through its morphology. It is characterized by cell rounding, membrane blebbing, cytoskeletal collapse, cytoplasmic condensation, and fragmentation, nuclear pyknosis, chromatin condensation/fragmentation, and formation of membrane-enveloped apoptotic bodies, that are rapidly phagocytosed by macrophages or neighboring cells. Neurodegenerative disorders are becoming increasingly prevalent, especially in the Western societies, with larger percentage of members living to an older age. They have to be seen not only as a health problem, but since they are care-intensive, they also carry a significant economic burden. Deregulation of autophagy plays a pivotal role in the etiology and/or progress of many of these diseases. Herein, we briefly review the latest findings that indicate the involvement of autophagy in neurodegenerative diseases. We provide a brief introduction to autophagy and apoptosis pathways focusing on the role of mitochondria and lysosomes. We then briefly highlight pathophysiology of common neurodegenerative disorders like Alzheimer's diseases, Parkinson's disease, Huntington's disease and Amyotrophic lateral sclerosis. Then, we describe functions of autophagy and apoptosis in brain homeostasis, especially in the context of the aforementioned disorders. Finally, we discuss different ways that autophagy and apoptosis modulation may be employed for therapeutic intervention during the maintenance of neurodegenerative disorders.

  10. Aptamer and its applications in neurodegenerative diseases.

    PubMed

    Qu, Jing; Yu, Shuqing; Zheng, Yuan; Zheng, Yan; Yang, Hui; Zhang, Jianliang

    2017-02-01

    Aptamers are small single-stranded DNA or RNA oligonucleotide fragments or small peptides, which can bind to targets by high affinity and specificity. Because aptamers are specific, non-immunogenic and non-toxic, they are ideal materials for clinical applications. Neurodegenerative disorders are ravaging the lives of patients. Even though the mechanism of these diseases is still elusive, they are mainly characterized by the accumulation of misfolded proteins in the central nervous system. So it is essential to develop potential measures to slow down or prevent the onset of these diseases. With the advancements of the technologies, aptamers have opened up new areas in this research field. Aptamers could bind with these related target proteins to interrupt their accumulation, subsequently blocking or preventing the process of neurodegenerative diseases. This review presents recent advances in the aptamer generation and its merits and limitations, with emphasis on its applications in neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, transmissible spongiform encephalopathy, Huntington's disease and multiple sclerosis.

  11. Chronic neurodegenerative consequences of traumatic brain injury.

    PubMed

    Chauhan, Neelima B

    2014-01-01

    Traumatic brain injury (TBI) is a serious public health concern and a major cause of death and disability worldwide. Each year, an estimated 1.7 million Americans sustain TBI of which ~52,000 people die, ~275,000 people are hospitalized and 1,365,000 people are treated as emergency outpatients. Currently there are ~5.3 million Americans living with TBI. TBI is more of a disease process than of an event that is associated with immediate and long-term sensomotor, psychological and cognitive impairments. TBI is the best known established epigenetic risk factor for later development of neurodegenerative diseases and dementia. People sustaining TBI are ~4 times more likely to develop dementia at a later stage than people without TBI. Single brain injury is linked to later development of symptoms resembling Alzheimer's disease while repetitive brain injuries are linked to later development of chronic traumatic encephalopathy (CTE) and/or Dementia Pugilistica (DP). Furthermore, genetic background of ß-amyloid precursor protein (APP), Apolipoprotein E (ApoE), presenilin (PS) and neprilysin (NEP) genes is associated with exacerbation of neurodegenerative process after TBI. This review encompasses acute effects and chronic neurodegenerative consequences after TBI.

  12. Role of FET proteins in neurodegenerative disorders

    PubMed Central

    Svetoni, Francesca; Frisone, Paola; Paronetto, Maria Paola

    2016-01-01

    ABSTRACT Neurodegenerative disorders such as Alzheimer disease (AD), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), Parkinson disease (PD), Huntington's disease (HD), and multiple sclerosis (MS) affect different neuronal cells, and have a variable age of onset, clinical symptoms, and pathological features. Despite the great progress in understanding the etiology of these disorders, the underlying mechanisms remain largely unclear. Among the processes affected in neurodegenerative diseases, alteration in RNA metabolism is emerging as a crucial player. RNA-binding proteins (RBPs) are involved at all stages of RNA metabolism and display a broad range of functions, including modulation of mRNA transcription, splicing, editing, export, stability, translation and localization and miRNA biogenesis, thus enormously impacting regulation of gene expression. On the other hand, aberrant regulation of RBP expression or activity can contribute to disease onset and progression. Recent reports identified mutations causative of neurological disorders in the genes encoding a family of RBPs named FET (FUS/TLS, EWS and TAF15). This review summarizes recent works documenting the involvement of FET proteins in the pathology of ALS, FTLD, essential tremor (ET) and other neurodegenerative diseases. Moreover, clinical implications of recent advances in FET research are critically discussed. PMID:27415968

  13. Insulin resistance and gray matter volume in neurodegenerative disease.

    PubMed

    Morris, J K; Vidoni, E D; Perea, R D; Rada, R; Johnson, D K; Lyons, K; Pahwa, R; Burns, J M; Honea, R A

    2014-06-13

    The goal of this study was to compare insulin resistance in aging and aging-related neurodegenerative diseases, and to determine the relationship between insulin resistance and gray matter volume (GMV) in each cohort using an unbiased, voxel-based approach. Insulin resistance was estimated in apparently healthy elderly control (HC, n=21) and neurodegenerative disease (Alzheimer's disease (AD), n=20; Parkinson's disease (PD), n=22) groups using Homeostasis Model Assessment of Insulin Resistance 2 (HOMA2) and intravenous glucose tolerance test (IVGTT). HOMA2 and GMV were assessed within groups through General Linear Model multiple regression. We found that HOMA2 was increased in both AD and PD compared to the HC group (HC vs. AD, p=0.002, HC vs. PD, p=0.003), although only AD subjects exhibited increased fasting glucose (p=0.005). Furthermore, our voxel-based morphometry analysis revealed that HOMA2 was related to GMV in all cohorts in a region-specific manner (p<0.001, uncorrected). Significant relationships were observed in the medial prefrontal cortex (HC), medial temporal regions (AD), and parietal regions (PD). Finally, the directionality of the relationship between HOMA2 and GMV was disease-specific. Both HC and AD subjects exhibited negative relationships between HOMA2 and brain volume (increased HOMA2 associated with decreased brain volume), while a positive relationship was observed in PD. This cross-sectional study suggests that insulin resistance is increased in neurodegenerative disease, and that individuals with AD appear to have more severe metabolic dysfunction than individuals with PD or PD dementia.

  14. Towards Clinical Application of Neurotrophic Factors to the Auditory Nerve; Assessment of Safety and Efficacy by a Systematic Review of Neurotrophic Treatments in Humans

    PubMed Central

    Bezdjian, Aren; Kraaijenga, Véronique J. C.; Ramekers, Dyan; Versnel, Huib; Thomeer, Hans G. X. M.; Klis, Sjaak F. L.; Grolman, Wilko

    2016-01-01

    Animal studies have evidenced protection of the auditory nerve by exogenous neurotrophic factors. In order to assess clinical applicability of neurotrophic treatment of the auditory nerve, the safety and efficacy of neurotrophic therapies in various human disorders were systematically reviewed. Outcomes of our literature search included disorder, neurotrophic factor, administration route, therapeutic outcome, and adverse event. From 2103 articles retrieved, 20 randomized controlled trials including 3974 patients were selected. Amyotrophic lateral sclerosis (53%) was the most frequently reported indication for neurotrophic therapy followed by diabetic polyneuropathy (28%). Ciliary neurotrophic factor (50%), nerve growth factor (24%) and insulin-like growth factor (21%) were most often used. Injection site reaction was a frequently occurring adverse event (61%) followed by asthenia (24%) and gastrointestinal disturbances (20%). Eighteen out of 20 trials deemed neurotrophic therapy to be safe, and six out of 17 studies concluded the neurotrophic therapy to be effective. Positive outcomes were generally small or contradicted by other studies. Most non-neurodegenerative diseases treated by targeted deliveries of neurotrophic factors were considered safe and effective. Hence, since local delivery to the cochlea is feasible, translation from animal studies to human trials in treating auditory nerve degeneration seems promising. PMID:27898033

  15. Subcortical Modulation in Auditory Processing and Auditory Hallucinations

    PubMed Central

    Ikuta, Toshikazu; DeRosse, Pamela; Argyelan, Miklos; Karlsgodt, Katherine H.; Kingsley, Peter B.; Szeszko, Philip R.; Malhotra, Anil K.

    2015-01-01

    Hearing perception in individuals with auditory hallucinations has not been well studied. Auditory hallucinations have previously been shown to involve primary auditory cortex activation. This activation suggests that auditory hallucinations activate the terminal of the auditory pathway as if auditory signals are submitted from the cochlea, and that a hallucinatory event is therefore perceived as hearing. The primary auditory cortex is stimulated by some unknown source that is outside of the auditory pathway. The current study aimed to assess the outcomes of stimulating the primary auditory cortex through the auditory pathway in individuals who have experienced auditory hallucinations. Sixteen patients with schizophrenia underwent functional magnetic resonance imaging (fMRI) sessions, as well as hallucination assessments. During the fMRI session, auditory stimuli were presented in one-second intervals at times when scanner noise was absent. Participants listened to auditory stimuli of sine waves (SW) (4 kHz-5.5 kHz), English words (EW), and acoustically reversed English words (arEW) in a block design fashion. The arEW were employed to deliver the sound of a human voice with minimal linguistic components. Patients’ auditory hallucination severity was assessed by the auditory hallucination item of the Brief Psychiatric Rating Scale (BPRS). During perception of arEW when compared with perception of SW, bilateral activation of the globus pallidus correlated with severity of auditory hallucinations. EW when compared with arEW did not correlate with auditory hallucination severity. Our findings suggest that the sensitivity of the globus pallidus to the human voice is associated with the severity of auditory hallucination. PMID:26275927

  16. Auditory processing deficits in reading disabled adults.

    PubMed

    Amitay, Sygal; Ahissar, Meray; Nelken, Israel

    2002-09-01

    The nature of the auditory processing deficit of disabled readers is still an unresolved issue. The quest for a fundamental, nonlinguistic, perceptual impairment has been dominated by the hypothesis that the difficulty lies in processing sequences of stimuli at presentation rates of tens of milliseconds. The present study examined this hypothesis using tasks that require processing of a wide range of stimulus time constants. About a third of the sampled population of disabled readers (classified as "poor auditory processors") had difficulties in most of the tasks tested: detection of frequency differences, detection of tones in narrowband noise, detection of amplitude modulation, detection of the direction of sound sources moving in virtual space, and perception of the lateralized position of tones based on their interaural phase differences. Nevertheless, across-channel integration was intact in these poor auditory processors since comodulation masking release was not reduced. Furthermore, phase locking was presumably intact since binaural masking level differences were normal. In a further examination of temporal processing, participants were asked to discriminate two tones at various intervals where the frequency difference was ten times each individual's frequency just noticeable difference (JND). Under these conditions, poor auditory processors showed no specific difficulty at brief intervals, contrary to predictions under a fast temporal processing deficit assumption. The complementary subgroup of disabled readers who were not poor auditory processors showed some difficulty in this condition when compared with their direct controls. However, they had no difficulty on auditory tasks such as amplitude modulation detection, which presumably taps processing of similar time scales. These two subgroups of disabled readers had similar reading performance but those with a generally poor auditory performance scored lower on some cognitive tests. Taken together, these

  17. Auditory Spatial Layout

    NASA Technical Reports Server (NTRS)

    Wightman, Frederic L.; Jenison, Rick

    1995-01-01

    All auditory sensory information is packaged in a pair of acoustical pressure waveforms, one at each ear. While there is obvious structure in these waveforms, that structure (temporal and spectral patterns) bears no simple relationship to the structure of the environmental objects that produced them. The properties of auditory objects and their layout in space must be derived completely from higher level processing of the peripheral input. This chapter begins with a discussion of the peculiarities of acoustical stimuli and how they are received by the human auditory system. A distinction is made between the ambient sound field and the effective stimulus to differentiate the perceptual distinctions among various simple classes of sound sources (ambient field) from the known perceptual consequences of the linear transformations of the sound wave from source to receiver (effective stimulus). Next, the definition of an auditory object is dealt with, specifically the question of how the various components of a sound stream become segregated into distinct auditory objects. The remainder of the chapter focuses on issues related to the spatial layout of auditory objects, both stationary and moving.

  18. Comparison of auditory-vocal interactions across multiple types of vocalizations in marmoset auditory cortex

    PubMed Central

    Wang, Xiaoqin

    2013-01-01

    Auditory-vocal interaction, the modulation of auditory sensory responses during vocal production, is an important but poorly understood neurophysiological phenomenon in nonhuman primates. This sensory-motor processing has important behavioral implications for self-monitoring during vocal production as well as feedback-mediated vocal control for both animals and humans. Previous studies in marmosets have shown that a large portion of neurons in the auditory cortex are suppressed during self-produced vocalization but have primarily focused on a single type of isolation vocalization. The present study expands previous analyses to compare auditory-vocal interaction of cortical responses between different types of vocalizations. We recorded neurons from the auditory cortex of unrestrained marmoset monkeys with implanted electrode arrays and showed that auditory-vocal interactions generalize across vocalization types. We found the following: 1) Vocal suppression and excitation are a general phenomenon, occurring for all four major vocalization types. 2) Within individual neurons, suppression was the more general response, occurring for multiple vocalization types, while excitation tended to be more specific to a single vocalization type. 3) A subset of neurons changed their responses between different types of vocalization, most often from strong suppression or excitation for one vocalization to unresponsive for another, and only rarely from suppression to excitation. 4) Differences in neural responses between vocalization types were weakly correlated with passive response properties, measured by playbacks of acoustic stimuli including recorded vocalizations. These results indicate that vocalization-induced modulation of the auditory cortex is a general phenomenon applicable to all vocalization types, but variations within individual neurons suggest possible vocalization-specific coding. PMID:23274315

  19. Mode-locking neurodynamics predict human auditory brainstem responses to musical intervals.

    PubMed

    Lerud, Karl D; Almonte, Felix V; Kim, Ji Chul; Large, Edward W

    2014-02-01

    The auditory nervous system is highly nonlinear. Some nonlinear responses arise through active processes in the cochlea, while others may arise in neural populations of the cochlear nucleus, inferior colliculus and higher auditory areas. In humans, auditory brainstem recordings reveal nonlinear population responses to combinations of pure tones, and to musical intervals composed of complex tones. Yet the biophysical origin of central auditory nonlinearities, their signal processing properties, and their relationship to auditory perception remain largely unknown. Both stimulus components and nonlinear resonances are well represented in auditory brainstem nuclei due to neural phase-locking. Recently mode-locking, a generalization of phase-locking that implies an intrinsically nonlinear processing of sound, has been observed in mammalian auditory brainstem nuclei. Here we show that a canonical model of mode-locked neural oscillation predicts the complex nonlinear population responses to musical intervals that have been observed in the human brainstem. The model makes predictions about auditory signal processing and perception that are different from traditional delay-based models, and may provide insight into the nature of auditory population responses. We anticipate that the application of dynamical systems analysis will provide the starting point for generic models of auditory population dynamics, and lead to a deeper understanding of nonlinear auditory signal processing possibly arising in excitatory-inhibitory networks of the central auditory nervous system. This approach has the potential to link neural dynamics with the perception of pitch, music, and speech, and lead to dynamical models of auditory system development.

  20. Riboflavin Responsive Mitochondrial Dysfunction in Neurodegenerative Diseases.

    PubMed

    Udhayabanu, Tamilarasan; Manole, Andreea; Rajeshwari, Mohan; Varalakshmi, Perumal; Houlden, Henry; Ashokkumar, Balasubramaniem

    2017-05-05

    Mitochondria are the repository for various metabolites involved in diverse energy-generating processes, like the TCA cycle, oxidative phosphorylation, and metabolism of amino acids, fatty acids, and nucleotides, which rely significantly on flavoenzymes, such as oxidases, reductases, and dehydrogenases. Flavoenzymes are functionally dependent on biologically active flavin adenine dinucleotide (FAD) or flavin mononucleotide (FMN), which are derived from the dietary component riboflavin, a water soluble vitamin. Riboflavin regulates the structure and function of flavoenzymes through its cofactors FMN and FAD and, thus, protects the cells from oxidative stress and apoptosis. Hence, it is not surprising that any disturbance in riboflavin metabolism and absorption of this vitamin may have consequences on cellular FAD and FMN levels, resulting in mitochondrial dysfunction by reduced energy levels, leading to riboflavin associated disorders, like cataracts, neurodegenerative and cardiovascular diseases, etc. Furthermore, mutations in either nuclear or mitochondrial DNA encoding for flavoenzymes and flavin transporters significantly contribute to the development of various neurological disorders. Moreover, recent studies have evidenced that riboflavin supplementation remarkably improved the clinical symptoms, as well as the biochemical abnormalities, in patients with neuronopathies, like Brown-Vialetto-Van-Laere syndrome (BVVLS) and Fazio-Londe disease. This review presents an updated outlook on the cellular and molecular mechanisms of neurodegenerative disorders in which riboflavin deficiency leads to dysfunction in mitochondrial energy metabolism, and also highlights the significance of riboflavin supplementation in aforementioned disease conditions. Thus, the outcome of this critical assessment may exemplify a new avenue to enhance the understanding of possible mechanisms in the progression of neurodegenerative diseases and may provide new rational approaches of disease

  1. Auditory hallucinations induced by trazodone

    PubMed Central

    Shiotsuki, Ippei; Terao, Takeshi; Ishii, Nobuyoshi; Hatano, Koji

    2014-01-01

    A 26-year-old female outpatient presenting with a depressive state suffered from auditory hallucinations at night. Her auditory hallucinations did not respond to blonanserin or paliperidone, but partially responded to risperidone. In view of the possibility that her auditory hallucinations began after starting trazodone, trazodone was discontinued, leading to a complete resolution of her auditory hallucinations. Furthermore, even after risperidone was decreased and discontinued, her auditory hallucinations did not recur. These findings suggest that trazodone may induce auditory hallucinations in some susceptible patients. PMID:24700048

  2. Auditory hallucinations induced by trazodone.

    PubMed

    Shiotsuki, Ippei; Terao, Takeshi; Ishii, Nobuyoshi; Hatano, Koji

    2014-04-03

    A 26-year-old female outpatient presenting with a depressive state suffered from auditory hallucinations at night. Her auditory hallucinations did not respond to blonanserin or paliperidone, but partially responded to risperidone. In view of the possibility that her auditory hallucinations began after starting trazodone, trazodone was discontinued, leading to a complete resolution of her auditory hallucinations. Furthermore, even after risperidone was decreased and discontinued, her auditory hallucinations did not recur. These findings suggest that trazodone may induce auditory hallucinations in some susceptible patients.

  3. Are Auditory Percepts Determined by Experience?

    PubMed Central

    Monson, Brian B.; Han, Shui’Er; Purves, Dale

    2013-01-01

    Audition–what listeners hear–is generally studied in terms of the physical properties of sound stimuli and physiological properties of the auditory system. Based on recent work in vision, we here consider an alternative perspective that sensory percepts are based on past experience. In this framework, basic auditory qualities (e.g., loudness and pitch) are based on the frequency of occurrence of stimulus patterns in natural acoustic stimuli. To explore this concept of audition, we examined five well-documented psychophysical functions. The frequency of occurrence of acoustic patterns in a database of natural sound stimuli (speech) predicts some qualitative aspects of these functions, but with substantial quantitative discrepancies. This approach may offer a rationale for auditory phenomena that are difficult to explain in terms of the physical attributes of the stimuli as such. PMID:23667666

  4. Applied research in auditory data representation

    NASA Astrophysics Data System (ADS)

    Frysinger, Steve P.

    1990-08-01

    A class of data displays, characterized generally as Auditory Data Representation, is described and motivated. This type of data representation takes advantage of the tremendous pattern recognition capability of the human auditory channel. Audible displays offer an alternative means of conveying quantitative data to the analyst to facilitate information extraction, and are successfully used alone and in conjunction with visual displays. The Auditory Data Representation literature is reviewed, along with elements of the allied fields of investigation, Psychoacoustics and Musical Perception. A methodology for applied research in this field, based upon the well-developed discipline of psychophysics, is elaborated using a recent experiment as a case study. This method permits objective estimation of a data representation technique by comparing it to alternative displays for the pattern recognition task at hand. The psychophysical threshold of signal to noise level, for constant pattern recognition performance, is the measure of display effectiveness.

  5. Are auditory percepts determined by experience?

    PubMed

    Monson, Brian B; Han, Shui'Er; Purves, Dale

    2013-01-01

    Audition--what listeners hear--is generally studied in terms of the physical properties of sound stimuli and physiological properties of the auditory system. Based on recent work in vision, we here consider an alternative perspective that sensory percepts are based on past experience. In this framework, basic auditory qualities (e.g., loudness and pitch) are based on the frequency of occurrence of stimulus patterns in natural acoustic stimuli. To explore this concept of audition, we examined five well-documented psychophysical functions. The frequency of occurrence of acoustic patterns in a database of natural sound stimuli (speech) predicts some qualitative aspects of these functions, but with substantial quantitative discrepancies. This approach may offer a rationale for auditory phenomena that are difficult to explain in terms of the physical attributes of the stimuli as such.

  6. Exposures to fine particulate matter (PM2.5) and ozone above USA standards are associated with auditory brainstem dysmorphology and abnormal auditory brainstem evoked potentials in healthy young dogs.

    PubMed

    Calderón-Garcidueñas, Lilian; González-González, Luis O; Kulesza, Randy J; Fech, Tatiana M; Pérez-Guillé, Gabriela; Luna, Miguel Angel Jiménez-Bravo; Soriano-Rosales, Rosa Eugenia; Solorio, Edelmira; Miramontes-Higuera, José de Jesús; Gómez-Maqueo Chew, Aline; Bernal-Morúa, Alexia F; Mukherjee, Partha S; Torres-Jardón, Ricardo; Mills, Paul C; Wilson, Wayne J; Pérez-Guillé, Beatriz; D'Angiulli, Amedeo

    2017-10-01

    Delayed central conduction times in the auditory brainstem have been observed in Mexico City (MC) healthy children exposed to fine particulate matter (PM2.5) and ozone (O3) above the current United States Environmental Protection Agency (US-EPA) standards. MC children have α synuclein brainstem accumulation and medial superior olivary complex (MSO) dysmorphology. The present study used a dog model to investigate the potential effects of air pollution on the function and morphology of the auditory brainstem. Twenty-four dogs living in clean air v MC, average age 37.1 ± 26.3 months, underwent brainstem auditory evoked potential (BAEP) measurements. Eight dogs (4 MC, 4 Controls) were analysed for auditory brainstem morphology and histopathology. MC dogs showed ventral cochlear nuclei hypotrophy and MSO dysmorphology with a significant decrease in cell body size, decreased neuronal packing density with regions in the nucleus devoid of neurons and marked gliosis. MC dogs showed significant delayed BAEP absolute wave I, III and V latencies compared to controls. MC dogs show auditory nuclei dysmorphology and BAEPs consistent with an alteration of the generator sites of the auditory brainstem response waveform. This study puts forward the usefulness of BAEPs to study auditory brainstem neurodegenerative changes associated with air pollution in dogs. Recognition of the role of non-invasive BAEPs in urban dogs is warranted to elucidate novel neurodegenerative pathways link to air pollution and a promising early diagnostic strategy for Alzheimer's Disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. 40 Hz auditory steady state response to linguistic features of stimuli during auditory hallucinations.

    PubMed

    Ying, Jun; Yan, Zheng; Gao, Xiao-rong

    2013-10-01

    The auditory steady state response (ASSR) may reflect activity from different regions of the brain, depending on the modulation frequency used. In general, responses induced by low rates (≤40 Hz) emanate mostly from central structures of the brain, and responses from high rates (≥80 Hz) emanate mostly from the peripheral auditory nerve or brainstem structures. Besides, it was reported that the gamma band ASSR (30-90 Hz) played an important role in working memory, speech understanding and recognition. This paper investigated the 40 Hz ASSR evoked by modulated speech and reversed speech. The speech was Chinese phrase voice, and the noise-like reversed speech was obtained by temporally reversing the speech. Both auditory stimuli were modulated with a frequency of 40 Hz. Ten healthy subjects and 5 patients with hallucination symptom participated in the experiment. Results showed reduction in left auditory cortex response when healthy subjects listened to the reversed speech compared with the speech. In contrast, when the patients who experienced auditory hallucinations listened to the reversed speech, the auditory cortex of left hemispheric responded more actively. The ASSR results were consistent with the behavior results of patients. Therefore, the gamma band ASSR is expected to be helpful for rapid and objective diagnosis of hallucination in clinic.

  8. The Diagnosis and Understanding of Apraxia of Speech: Why Including Neurodegenerative Etiologies May Be Important

    ERIC Educational Resources Information Center

    Duffy, Joseph R.; Josephs, Keith A.

    2012-01-01

    Purpose: To discuss apraxia of speech (AOS) as it occurs in neurodegenerative disease (progressive AOS [PAOS]) and how its careful study may contribute to general concepts of AOS and help refine its diagnostic criteria. Method: The article summarizes our current understanding of the clinical features and neuroanatomical and pathologic correlates…

  9. Proactive Strategies for Managing the Behavior of Children with Neurodegenerative Diseases and Visual Impairment.

    ERIC Educational Resources Information Center

    Loftin, M. M.; Koehler, W. S.

    1998-01-01

    Presents proactive strategies to help educators deal with challenging behaviors of children with visual impairments and neurodegenerative diseases. Strategies are provided for general noncompliance, difficulty with changed or novel routines, difficulty maintaining physical movement, significant variations in affect, and intense tantrums and other…

  10. The Diagnosis and Understanding of Apraxia of Speech: Why Including Neurodegenerative Etiologies May Be Important

    ERIC Educational Resources Information Center

    Duffy, Joseph R.; Josephs, Keith A.

    2012-01-01

    Purpose: To discuss apraxia of speech (AOS) as it occurs in neurodegenerative disease (progressive AOS [PAOS]) and how its careful study may contribute to general concepts of AOS and help refine its diagnostic criteria. Method: The article summarizes our current understanding of the clinical features and neuroanatomical and pathologic correlates…

  11. Inflammation in neurodegenerative diseases--an update.

    PubMed

    Amor, Sandra; Peferoen, Laura A N; Vogel, Daphne Y S; Breur, Marjolein; van der Valk, Paul; Baker, David; van Noort, Johannes M

    2014-06-01

    Neurodegeneration, the progressive dysfunction and loss of neurons in the central nervous system (CNS), is the major cause of cognitive and motor dysfunction. While neuronal degeneration is well-known in Alzheimer's and Parkinson's diseases, it is also observed in neurotrophic infections, traumatic brain and spinal cord injury, stroke, neoplastic disorders, prion diseases, multiple sclerosis and amyotrophic lateral sclerosis, as well as neuropsychiatric disorders and genetic disorders. A common link between these diseases is chronic activation of innate immune responses including those mediated by microglia, the resident CNS macrophages. Such activation can trigger neurotoxic pathways leading to progressive degeneration. Yet, microglia are also crucial for controlling inflammatory processes, and repair and regeneration. The adaptive immune response is implicated in neurodegenerative diseases contributing to tissue damage, but also plays important roles in resolving inflammation and mediating neuroprotection and repair. The growing awareness that the immune system is inextricably involved in mediating damage as well as regeneration and repair in neurodegenerative disorders, has prompted novel approaches to modulate the immune system, although it remains whether these approaches can be used in humans. Additional factors in humans include ageing and exposure to environmental factors such as systemic infections that provide additional clues that may be human specific and therefore difficult to translate from animal models. Nevertheless, a better understanding of how immune responses are involved in neuronal damage and regeneration, as reviewed here, will be essential to develop effective therapies to improve quality of life, and mitigate the personal, economic and social impact of these diseases.

  12. In vitro imaging techniques in neurodegenerative diseases.

    PubMed

    Långström, Bengt; Andrén, Per E; Lindhe, Orjan; Svedberg, Marie; Hall, Håkan

    2007-01-01

    Neurodegeneration induces various changes in the brain, changes that may be investigated using neuroimaging techniques. The in vivo techniques are useful for the visualization of major changes, and the progressing abnormalities may also be followed longitudinally. However, to study and quantify minor abnormalities, neuroimaging of postmortem brain tissue is used. These in vitro methods are complementary to the in vivo techniques and contribute to the knowledge of pathophysiology and etiology of the neurodegenerative diseases. In vitro radioligand autoradiography has given great insight in the involvement of different neuronal receptor systems in these diseases. Data on the dopamine and cholinergic systems in neurodegeneration are discussed in this review. Also, the amyloid plaques are studied using in vitro radioligand autoradiography. Using one of the newer methods, imaging matrix-assisted laser desorption ionization mass spectrometry, the distribution of a large number of peptides and proteins may be detected in vitro on brain cryosections. In this overview, we describe in vitro imaging techniques in the neurodegenerative diseases as a complement to in vivo positron emission tomography and single photon emission computed tomography imaging.

  13. Chronic traumatic encephalopathy and other neurodegenerative proteinopathies

    PubMed Central

    Tartaglia, Maria Carmela; Hazrati, Lili-Naz; Davis, Karen D.; Green, Robin E. A.; Wennberg, Richard; Mikulis, David; Ezerins, Leo J.; Keightley, Michelle; Tator, Charles

    2014-01-01

    “Chronic traumatic encephalopathy” (CTE) is described as a slowly progressive neurodegenerative disease believed to result from multiple concussions. Traditionally, concussions were considered benign events and although most people recover fully, about 10% develop a post-concussive syndrome with persisting neurological, cognitive and neuropsychiatric symptoms. CTE was once thought to be unique to boxers, but it has now been observed in many different athletes having suffered multiple concussions as well as in military personal after repeated blast injuries. Much remains unknown about the development of CTE but its pathological substrate is usually tau, similar to that seen in Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD). The aim of this “perspective” is to compare and contrast clinical and pathological CTE with the other neurodegenerative proteinopathies and highlight that there is an urgent need for understanding the relationship between concussion and the development of CTE as it may provide a window into the development of a proteinopathy and thus new avenues for treatment. PMID:24550810

  14. [The role of thiamine in neurodegenerative diseases].

    PubMed

    Bubko, Irena; Gruber, Beata M; Anuszewska, Elżbieta L

    2015-09-21

    Vitamin B1 (thiamine) plays an important role in metabolism. It is indispensable for normal growth and development of the organism. Thiamine has a favourable impact on a number of systems, including the digestive, cardiovascular and nervous systems. It also stimulates the brain and improves the psycho-emotional state. Hence it is often called the vitamin of "reassurance of the spirit". Thiamine is a water-soluble vitamin. It can be present in the free form as thiamine or as its phosphate esters: mono-, di- or triphosphate. The main source of thiamine as an exogenous vitamin is certain foodstuffs, but trace amounts can be synthesised by microorganisms of the large intestine. The recommended daily intake of thiamine is about 2.0 mg. Since vitamin B1 has no ability to accumulate in the organism, manifestations of its deficiency begin to appear very quickly. The chronic state of thiamine deficiency, to a large extent, because of its function, contributes to the development of neurodegenerative diseases. It was proved that supporting vitamin B1 therapy not only constitutes neuroprotection but can also have a favourable impact on advanced neurodegenerative diseases. This article presents the current state of knowledge as regards the effects of thiamine exerted through this vitamin in a number of diseases such as Parkinson's disease, Alzheimer's disease, Wernicke's encephalopathy or Wernicke-Korsakoff syndrome and Huntington's disease.

  15. Diffusion-MRI in neurodegenerative disorders.

    PubMed

    Goveas, Joseph; O'Dwyer, Laurence; Mascalchi, Mario; Cosottini, Mirco; Diciotti, Stefano; De Santis, Silvia; Passamonti, Luca; Tessa, Carlo; Toschi, Nicola; Giannelli, Marco

    2015-09-01

    The ability to image the whole brain through ever more subtle and specific methods/contrasts has come to play a key role in understanding the basis of brain abnormalities in several diseases. In magnetic resonance imaging (MRI), "diffusion" (i.e. the random, thermally-induced displacements of water molecules over time) represents an extraordinarily sensitive contrast mechanism, and the exquisite structural detail it affords has proven useful in a vast number of clinical as well as research applications. Since diffusion-MRI is a truly quantitative imaging technique, the indices it provides can serve as potential imaging biomarkers which could allow early detection of pathological alterations as well as tracking and possibly predicting subtle changes in follow-up examinations and clinical trials. Accordingly, diffusion-MRI has proven useful in obtaining information to better understand the microstructural changes and neurophysiological mechanisms underlying various neurodegenerative disorders. In this review article, we summarize and explore the main applications, findings, perspectives as well as challenges and future research of diffusion-MRI in various neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease and degenerative ataxias.

  16. The role of copper in neurodegenerative disease.

    PubMed

    Waggoner, D J; Bartnikas, T B; Gitlin, J D

    1999-08-01

    Copper is an essential trace metal which plays a fundamental role in the biochemistry of the human nervous system. Menkes disease and Wilson disease are inherited disorders of copper metabolism and the dramatic neurodegenerative phenotypes of these two diseases underscore the essential nature of copper in nervous system development as well as the toxicity of this metal when neuronal copper homeostasis is perturbed. Ceruloplasmin contains 95% of the copper found in human plasma and inherited loss of this essential ferroxidase is associated with progressive neurodegeneration of the retina and basal ganglia. Gain-of-function mutations in the cytosolic copper enzyme superoxide dismutase result in the motor neuron degeneration of amyotrophic lateral sclerosis and current evidence suggests a direct pathogenic role for copper in this process. Recent studies have also implicated copper in the pathogenesis of neuronal injury in Alzheimer's disease and the prion-mediated encephalopathies, suggesting that further elucidation of the mechanisms of copper trafficking and metabolism within the nervous system will be of direct relevance to our understanding of the pathophysiology and treatment of neurodegenerative disease.

  17. Polyphenols: Multipotent Therapeutic Agents in Neurodegenerative Diseases

    PubMed Central

    Bhullar, Khushwant S.; Rupasinghe, H. P. Vasantha

    2013-01-01

    Aging leads to numerous transitions in brain physiology including synaptic dysfunction and disturbances in cognition and memory. With a few clinically relevant drugs, a substantial portion of aging population at risk for age-related neurodegenerative disorders require nutritional intervention. Dietary intake of polyphenols is known to attenuate oxidative stress and reduce the risk for related neurodegenerative diseases such as Alzheimer's disease (AD), stroke, multiple sclerosis (MS), Parkinson's disease (PD), and Huntington's disease (HD). Polyphenols exhibit strong potential to address the etiology of neurological disorders as they attenuate their complex physiology by modulating several therapeutic targets at once. Firstly, we review the advances in the therapeutic role of polyphenols in cell and animal models of AD, PD, MS, and HD and activation of drug targets for controlling pathological manifestations. Secondly, we present principle pathways in which polyphenol intake translates into therapeutic outcomes. In particular, signaling pathways like PPAR, Nrf2, STAT, HIF, and MAPK along with modulation of immune response by polyphenols are discussed. Although current polyphenol researches have limited impact on clinical practice, they have strong evidence and testable hypothesis to contribute clinical advances and drug discovery towards age-related neurological disorders. PMID:23840922

  18. Biology of Mitochondria in Neurodegenerative Diseases

    PubMed Central

    Martin, Lee J.

    2012-01-01

    Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) are the most common human adult-onset neurodegenerative diseases. They are characterized by prominent age-related neurodegeneration in selectively vulnerable neural systems. Some forms of AD, PD, and ALS are inherited, and genes causing these diseases have been identified. Nevertheless, the mechanisms of the neuronal degeneration in these familial diseases, and in the more common idiopathic (sporadic) diseases, are unresolved. Genetic, biochemical, and morphological analyses of human AD, PD, and ALS, as well as their cell and animal models, reveal that mitochondria could have roles in this neurodegeneration. The varied functions and properties of mitochondria might render subsets of selectively vulnerable neurons intrinsically susceptible to cellular aging and stress and the overlying genetic variations. In AD, alterations in enzymes involved in oxidative phosphorylation, oxidative damage, and mitochondrial binding of Aβ and amyloid precursor protein have been reported. In PD, mutations in mitochondrial proteins have been identified and mitochondrial DNA mutations have been found in neurons in the substantia nigra. In ALS, changes occur in mitochondrial respiratory chain enzymes and mitochondrial programmed cell death proteins. Transgenic mouse models of human neurodegenerative disease are beginning to reveal possible principles governing the biology of selective neuronal vulnerability that implicate mitochondria and the mitochondrial permeability transition pore. This chapter reviews several aspects of mitochondrial biology and how mitochondrial pathobiology might contribute to the mechanisms of neurodegeneration in AD, PD, and ALS. PMID:22482456

  19. HDL and Cognition in Neurodegenerative Disorders

    PubMed Central

    Hottman, David A.; Chernick, Dustin; Cheng, Shaowu; Wang, Zhe; Li, Ling

    2014-01-01

    High-density lipoproteins (HDL) are a heterogeneous group of lipoproteins composed of various lipids and proteins. HDL is formed both in the systemic circulation and in the brain. In addition to being a crucial player in the reverse cholesterol transport pathway, HDL possesses a wide range of other functions including anti-oxidation, anti-inflammation, pro-endothelial function, anti-thrombosis, and modulation of immune function. It has been firmly established that high plasma levels of HDL protect against cardiovascular disease. Accumulating evidence indicates that the beneficial role of HDL extends to many other systems including the central nervous system. Cognition is a complex brain function that includes all aspects of perception, thought, and memory. Cognitive function often declines during aging and this decline manifests as cognitive impairment/dementia in age-related and progressive neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. A growing concern is that no effective therapy is currently available to prevent or treat these devastating diseases. Emerging evidence suggests that HDL may play a pivotal role in preserving cognitive function under normal and pathological conditions. This review attempts to summarize recent genetic, clinical and experimental evidence for the impact of HDL on cognition in aging and in neurodegenerative disorders as well as the potential of HDL-enhancing approaches to improve cognitive function. PMID:25131449

  20. Engineering enhanced protein disaggregases for neurodegenerative disease

    PubMed Central

    Jackrel, Meredith E; Shorter, James

    2015-01-01

    Abstract Protein misfolding and aggregation underpin several fatal neurodegenerative diseases, including Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD). There are no treatments that directly antagonize the protein-misfolding events that cause these disorders. Agents that reverse protein misfolding and restore proteins to native form and function could simultaneously eliminate any deleterious loss-of-function or toxic gain-of-function caused by misfolded conformers. Moreover, a disruptive technology of this nature would eliminate self-templating conformers that spread pathology and catalyze formation of toxic, soluble oligomers. Here, we highlight our efforts to engineer Hsp104, a protein disaggregase from yeast, to more effectively disaggregate misfolded proteins connected with PD, ALS, and FTD. Remarkably subtle modifications of Hsp104 primary sequence yielded large gains in protective activity against deleterious α-synuclein, TDP-43, FUS, and TAF15 misfolding. Unusually, in many cases loss of amino acid identity at select positions in Hsp104 rather than specific mutation conferred a robust therapeutic gain-of-function. Nevertheless, the misfolding and toxicity of EWSR1, an RNA-binding protein with a prion-like domain linked to ALS and FTD, could not be buffered by potentiated Hsp104 variants, indicating that further amelioration of disaggregase activity or sharpening of substrate specificity is warranted. We suggest that neuroprotection is achievable for diverse neurodegenerative conditions via surprisingly subtle structural modifications of existing chaperones. PMID:25738979

  1. TRPM2, calcium and neurodegenerative diseases

    PubMed Central

    Xie, Yu-Feng; MacDonald, John F; Jackson, Michael F

    2010-01-01

    NMDA receptor overactivation triggers intracellular Ca2+ dysregulation, which has long been thought to be critical for initiating excitotoxic cell death cascades associated with stroke and neurodegenerative disease. The inability of NMDA receptor antagonists to afford neuroprotection in clinical stroke trials has led to a re-evaluation of excitotoxic models of cell death and has focused research efforts towards identifying additional Ca2+ influx pathways. Recent studies indicate that TRPM2, a member of the TRPM subfamily of Ca2+-permeant, non-selective cation channel, plays an important role in mediating cellular responses to a wide range of stimuli that, under certain situations, can induce cell death. These include reactive oxygen and nitrogen species, tumour necrosis factor as well as soluble oli-gomers of amyloid beta. However, the molecular basis of TRPM2 channel involvement in these processes is not fully understood. In this review, we summarize recent studies about the regulation of TRPM2, its interaction with calcium and the possible implications for neurodegenerative diseases. PMID:21383889

  2. Statistical Approaches to Longitudinal Data Analysis in Neurodegenerative Diseases: Huntington's Disease as a Model.

    PubMed

    Garcia, Tanya P; Marder, Karen

    2017-02-01

    Understanding the overall progression of neurodegenerative diseases is critical to the timing of therapeutic interventions and design of effective clinical trials. Disease progression can be assessed with longitudinal study designs in which outcomes are measured repeatedly over time and are assessed with respect to risk factors, either measured repeatedly or at baseline. Longitudinal data allows researchers to assess temporal disease aspects, but the analysis is complicated by complex correlation structures, irregularly spaced visits, missing data, and mixtures of time-varying and static covariate effects. We review modern statistical methods designed for these challenges. Among all methods, the mixed effect model most flexibly accommodates the challenges and is preferred by the FDA for observational and clinical studies. Examples from Huntington's disease studies are used for clarification, but the methods apply to neurodegenerative diseases in general, particularly as the identification of prodromal forms of neurodegenerative disease through sensitive biomarkers is increasing.

  3. Central auditory imperception.

    PubMed

    Snow, J B; Rintelmann, W F; Miller, J M; Konkle, D F

    1977-09-01

    The development of clinically applicable techniques for the evaluation of hearing impairment caused by lesions of the central auditory pathways has increased clinical interest in the anatomy and physiology of these pathways. A conceptualization of present understanding of the anatomy and physiology of the central auditory pathways is presented. Clinical tests based on reduction of redundancy of the speech message, degradation of speech and binaural interations are presented. Specifically performance-intensity functions, filtered speech tests, competing message tests and time-compressed speech tests are presented with the emphasis on our experience with time-compressed speech tests. With proper use of these tests not only can central auditory impairments by detected, but brain stem lesions can be distinguished from cortical lesions.

  4. The Drosophila Auditory System

    PubMed Central

    Boekhoff-Falk, Grace; Eberl, Daniel F.

    2013-01-01

    Development of a functional auditory system in Drosophila requires specification and differentiation of the chordotonal sensilla of Johnston’s organ (JO) in the antenna, correct axonal targeting to the antennal mechanosensory and motor center (AMMC) in the brain, and synaptic connections to neurons in the downstream circuit. Chordotonal development in JO is functionally complicated by structural, molecular and functional diversity that is not yet fully understood, and construction of the auditory neural circuitry is only beginning to unfold. Here we describe our current understanding of developmental and molecular mechanisms that generate the exquisite functions of the Drosophila auditory system, emphasizing recent progress and highlighting important new questions arising from research on this remarkable sensory system. PMID:24719289

  5. Genetic manipulation for inherited neurodegenerative diseases: myth or reality?

    PubMed

    Yu-Wai-Man, Patrick

    2016-10-01

    Rare genetic diseases affect about 7% of the general population and over 7000 distinct clinical syndromes have been described with the majority being due to single gene defects. This review will provide a critical overview of genetic strategies that are being pioneered to halt or reverse disease progression in inherited neurodegenerative diseases. This field of research covers a vast area and only the most promising treatment paradigms will be discussed with a particular focus on inherited eye diseases, which have paved the way for innovative gene therapy paradigms, and mitochondrial diseases, which are currently generating a lot of debate centred on the bioethics of germline manipulation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  6. Auditory hedonic phenotypes in dementia: A behavioural and neuroanatomical analysis.

    PubMed

    Fletcher, Phillip D; Downey, Laura E; Golden, Hannah L; Clark, Camilla N; Slattery, Catherine F; Paterson, Ross W; Schott, Jonathan M; Rohrer, Jonathan D; Rossor, Martin N; Warren, Jason D

    2015-06-01

    Patients with dementia may exhibit abnormally altered liking for environmental sounds and music but such altered auditory hedonic responses have not been studied systematically. Here we addressed this issue in a cohort of 73 patients representing major canonical dementia syndromes (behavioural variant frontotemporal dementia (bvFTD), semantic dementia (SD), progressive nonfluent aphasia (PNFA) amnestic Alzheimer's disease (AD)) using a semi-structured caregiver behavioural questionnaire and voxel-based morphometry (VBM) of patients' brain MR images. Behavioural responses signalling abnormal aversion to environmental sounds, aversion to music or heightened pleasure in music ('musicophilia') occurred in around half of the cohort but showed clear syndromic and genetic segregation, occurring in most patients with bvFTD but infrequently in PNFA and more commonly in association with MAPT than C9orf72 mutations. Aversion to sounds was the exclusive auditory phenotype in AD whereas more complex phenotypes including musicophilia were common in bvFTD and SD. Auditory hedonic alterations correlated with grey matter loss in a common, distributed, right-lateralised network including antero-mesial temporal lobe, insula, anterior cingulate and nucleus accumbens. Our findings suggest that abnormalities of auditory hedonic processing are a significant issue in common dementias. Sounds may constitute a novel probe of brain mechanisms for emotional salience coding that are targeted by neurodegenerative disease. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Bigger Brains or Bigger Nuclei? Regulating the Size of Auditory Structures in Birds

    PubMed Central

    Kubke, M. Fabiana; Massoglia, Dino P.; Carr, Catherine E.

    2012-01-01

    Increases in the size of the neuronal structures that mediate specific behaviors are believed to be related to enhanced computational performance. It is not clear, however, what developmental and evolutionary mechanisms mediate these changes, nor whether an increase in the size of a given neuronal population is a general mechanism to achieve enhanced computational ability. We addressed the issue of size by analyzing the variation in the relative number of cells of auditory structures in auditory specialists and generalists. We show that bird species with different auditory specializations exhibit variation in the relative size of their hindbrain auditory nuclei. In the barn owl, an auditory specialist, the hind-brain auditory nuclei involved in the computation of sound location show hyperplasia. This hyperplasia was also found in songbirds, but not in non-auditory specialists. The hyperplasia of auditory nuclei was also not seen in birds with large body weight suggesting that the total number of cells is selected for in auditory specialists. In barn owls, differences observed in the relative size of the auditory nuclei might be attributed to modifications in neurogenesis and cell death. Thus, hyperplasia of circuits used for auditory computation accompanies auditory specialization in different orders of birds. PMID:14726625

  8. Bigger brains or bigger nuclei? Regulating the size of auditory structures in birds.

    PubMed

    Kubke, M Fabiana; Massoglia, Dino P; Carr, Catherine E

    2004-01-01

    Increases in the size of the neuronal structures that mediate specific behaviors are believed to be related to enhanced computational performance. It is not clear, however, what developmental and evolutionary mechanisms mediate these changes, nor whether an increase in the size of a given neuronal population is a general mechanism to achieve enhanced computational ability. We addressed the issue of size by analyzing the variation in the relative number of cells of auditory structures in auditory specialists and generalists. We show that bird species with different auditory specializations exhibit variation in the relative size of their hindbrain auditory nuclei. In the barn owl, an auditory specialist, the hindbrain auditory nuclei involved in the computation of sound location show hyperplasia. This hyperplasia was also found in songbirds, but not in non-auditory specialists. The hyperplasia of auditory nuclei was also not seen in birds with large body weight suggesting that the total number of cells is selected for in auditory specialists. In barn owls, differences observed in the relative size of the auditory nuclei might be attributed to modifications in neurogenesis and cell death. Thus, hyperplasia of circuits used for auditory computation accompanies auditory specialization in different orders of birds.

  9. Protection and regrowth of the auditory nerve after deafness: neurotrophins, antioxidants and depolarization are effective in vivo.

    PubMed

    Miller, Josef M; Miller, Amy L; Yamagata, Takahiko; Bredberg, Goran; Altschuler, Richard A

    2002-01-01

    neurotrophins and cocktails of factors can also enhance survival of the deafferented nerve, and some can also initiate a regrowth of degenerated peripheral processes of the nerve into the region of the destroyed sensory epitheliae. Recently, we have shown that this rescue can occur with delayed intervention, after degeneration of some neurons has begun, more closely mimicking the human clinical situation. Finally, we have shown that interventions with antioxidants may also be effective in preventing pathophysiological changes of the auditory nerve following deafness. These studies in the auditory periphery support the 'neurotrophic factor hypothesis' as proposed as a general mechanism underlying neurodegenerative and age-related pathology of the central nervous system. Additional animal studies can yield a rational scientific basis to justify human trials, with a goal to maintain auditory cell survival and initiate and direct fiber growth to the next generation of prosthesis. Intimate contact between electrode and a dense population of auditory neurons should greatly enhance the benefits of these devices for the profoundly deaf.

  10. Antisense oligonucleotides in therapy for neurodegenerative disorders.

    PubMed

    Evers, Melvin M; Toonen, Lodewijk J A; van Roon-Mom, Willeke M C

    2015-06-29

    Antisense oligonucleotides are synthetic single stranded strings of nucleic acids that bind to RNA and thereby alter or reduce expression of the target RNA. They can not only reduce expression of mutant proteins by breakdown of the targeted transcript, but also restore protein expression or modify proteins through interference with pre-mRNA splicing. There has been a recent revival of interest in the use of antisense oligonucleotides to treat several neurodegenerative disorders using different approaches to prevent disease onset or halt disease progression and the first clinical trials for spinal muscular atrophy and amyotrophic lateral sclerosis showing promising results. For these trials, intrathecal delivery is being used but direct infusion into the brain ventricles and several methods of passing the blood brain barrier after peripheral administration are also under investigation.

  11. Neuroinflammation in Neurodegenerative Disorders-a Review.

    PubMed

    Schain, Martin; Kreisl, William Charles

    2017-03-01

    The potential for positron emission tomography (PET) to detect neuroinflammation in vivo has sparked a remarkable interest in various disciplines of neuroscience. Early PET radioligands, such as [(11)C]PK(R)-11195 for the 18-kDa translocator protein (TSPO) and [(11)C]L-deprenyl for monoamine oxidase B, have been used in studies designed to clarify the role of neuroinflammation in a variety of psychiatric and neurological disorders. Recent years have witnessed the development of several second-generation PET radioligands for TSPO and radioligands to measure endogenous targets that are active in various stages of the inflammatory cascade, such as cyclooxygenase and arachidonic acid. Here, we discuss some of the biomarkers for neuroinflammation that are available for quantification with PET, as well as recent findings from studies where neuroinflammation has been assessed in neurodegenerative disorders. In addition, we highlight the challenges to accurate interpretation of PET studies of neuroinflammation.

  12. Epigenetic mechanisms in neurodevelopmental and neurodegenerative disease

    PubMed Central

    Jakovcevski, Mira; Akbarian, Schahram

    2013-01-01

    The exploration of brain epigenomes, which consist of various types of DNA methylation and covalent histone modifications, is providing new and unprecedented insights into the mechanisms of normal neural development, neurological disease and aging. Traditionally, chromatin defects in brain were considered static lesions of early development that occurred in the context of rare genetic syndromes but it is now clear that mutations and maladaptations of the epigenetic machinery cover a much wider continuum, including adult-onset neurodegenerative disease. Here, we describe how recent advances in neuroepigenetics have contributed to an improved mechanistic understanding of developmental and degenerative brain disorders, as well as how they could influence the development of future therapies for these conditions. PMID:22869198

  13. Spongiform neurodegenerative disease in a Persian kitten.

    PubMed

    Salvadori, Claudia; Lossi, Laura; Arispici, Mario; Cantile, Carlo

    2007-06-01

    A congenital encephalopathy with spongiform degeneration and prominent neuronal apoptosis was observed in a 4-month-old Persian male cat with a history of depressed mental status and ataxia. On clinical examination, signs included right head tilt, ventroflexion of the head and neck, and tetraparesis. Histological examination of the central nervous system revealed multifocal, bilateral and symmetrical vacuolar degeneration of the neuropil, mainly involving the cerebellar and vestibular nuclei area, the caudal colliculi, the mesencephalic nuclei, the tegmental area and the deeper layer of the cerebral cortex. Accumulation of phosphorylated neurofilaments was detected in neuronal perikarya of the deep cortical layers, hippocampus and thalamus. Numerous pyknotic and apoptotic neurons were also observed in the cerebral cortex. These neuropathological changes differ from those observed in previous reports of spongiform degeneration of the grey matter in cats and were suggestive of a congenital neurodegenerative disease.

  14. A Potential Alternative against Neurodegenerative Diseases: Phytodrugs.

    PubMed

    Pérez-Hernández, Jesús; Zaldívar-Machorro, Víctor Javier; Villanueva-Porras, David; Vega-Ávila, Elisa; Chavarría, Anahí

    2016-01-01

    Neurodegenerative diseases (ND) primarily affect the neurons in the human brain secondary to oxidative stress and neuroinflammation. ND are more common and have a disproportionate impact on countries with longer life expectancies and represent the fourth highest source of overall disease burden in the high-income countries. A large majority of the medicinal plant compounds, such as polyphenols, alkaloids, and terpenes, have therapeutic properties. Polyphenols are the most common active compounds in herbs and vegetables consumed by man. The biological bioactivity of polyphenols against neurodegeneration is mainly due to its antioxidant, anti-inflammatory, and antiamyloidogenic effects. Multiple scientific studies support the use of herbal medicine in the treatment of ND; however, relevant aspects are still pending to explore such as metabolic analysis, pharmacokinetics, and brain bioavailability.

  15. A Potential Alternative against Neurodegenerative Diseases: Phytodrugs

    PubMed Central

    Pérez-Hernández, Jesús; Zaldívar-Machorro, Víctor Javier; Villanueva-Porras, David; Vega-Ávila, Elisa; Chavarría, Anahí

    2016-01-01

    Neurodegenerative diseases (ND) primarily affect the neurons in the human brain secondary to oxidative stress and neuroinflammation. ND are more common and have a disproportionate impact on countries with longer life expectancies and represent the fourth highest source of overall disease burden in the high-income countries. A large majority of the medicinal plant compounds, such as polyphenols, alkaloids, and terpenes, have therapeutic properties. Polyphenols are the most common active compounds in herbs and vegetables consumed by man. The biological bioactivity of polyphenols against neurodegeneration is mainly due to its antioxidant, anti-inflammatory, and antiamyloidogenic effects. Multiple scientific studies support the use of herbal medicine in the treatment of ND; however, relevant aspects are still pending to explore such as metabolic analysis, pharmacokinetics, and brain bioavailability. PMID:26881043

  16. Tau as a biomarker of neurodegenerative diseases

    PubMed Central

    Schraen-Maschke, Susanna; Sergeant, Nicolas; Dhaenens, Claire-Marie; Bombois, Stephanie; Deramecourt, Vincent; Caillet-Boudin, Marie-Laure; Pasquier, Florence; Maurage, Claude-Alain; Sablonniere, Bernard; Vanmechelen, Eugeen; Buee, Luc

    2008-01-01

    Summary The microtubule associated protein Tau is mainly expressed in neurons of the central nervous system and is crucial in axonal maintenance and axonal transport. The rationale for Tau as a biomarker of neurodegenerative diseases is that it is a major component of abnormal intraneuronal aggregates observed in numerous of these diseases named Tauopathies, including Alzheimer’s disease. The molecular diversity of Tau is very useful when analysing it in the brain or in the peripheral fluids. Immunohistochemical and biochemical characterisation of Tau aggregates in the brain allows the post-mortem classification and differential diagnosis of Tauopathies. As peripheral biomarker of Alzheimer’s disease in the cerebrospinal fluid, Tau proteins are now validated for diagnosis and predictive purposes. For the future, the detailed characterization of Tau in brain and in peripheral fluids will lead to novel promising biomarkers for differential diagnosis of dementia and monitoring of therapeutics. PMID:20477391

  17. Ketogenic Diet in Neuromuscular and Neurodegenerative Diseases

    PubMed Central

    Damiani, Ernesto; Bosco, Gerardo

    2014-01-01

    An increasing number of data demonstrate the utility of ketogenic diets in a variety of metabolic diseases as obesity, metabolic syndrome, and diabetes. In regard to neurological disorders, ketogenic diet is recognized as an effective treatment for pharmacoresistant epilepsy but emerging data suggests that ketogenic diet could be also useful in amyotrophic lateral sclerosis, Alzheimer, Parkinson's disease, and some mitochondriopathies. Although these diseases have different pathogenesis and features, there are some common mechanisms that could explain the effects of ketogenic diets. These mechanisms are to provide an efficient source of energy for the treatment of certain types of neurodegenerative diseases characterized by focal brain hypometabolism; to decrease the oxidative damage associated with various kinds of metabolic stress; to increase the mitochondrial biogenesis pathways; and to take advantage of the capacity of ketones to bypass the defect in complex I activity implicated in some neurological diseases. These mechanisms will be discussed in this review. PMID:25101284

  18. Auditory target detection in reverberation

    NASA Astrophysics Data System (ADS)

    Zurek, Patrick M.; Freyman, Richard L.; Balakrishnan, Uma

    2004-04-01

    Measurements and theoretical predictions of auditory target detection in simulated reverberant conditions are reported. The target signals were pulsed 13-octave bands of noise and the masker signal was a continuous wideband noise. Target and masker signals were passed through a software simulation of a reverberant room with a rigid sphere modeling a listener's head. The location of the target was fixed while the location of the masker was varied in the simulated room. Degree of reverberation was controlled by varying the uniform acoustic absorption of the simulated room's surfaces. The resulting target and masker signals were presented to the listeners over headphones in monaural-left, monaural-right, or binaural listening modes. Changes in detection performance in the monaural listening modes were largely predictable from the changes in target-to-masker ratio in the target band, but with a few dB of extra masking in reverberation. Binaural detection performance was generally well predicted by applying Durlach's [in Foundations of Modern Auditory Theory (Academic, New York, 1972)] equalization-cancellation theory to the direct-plus-reverberant ear signals. Predictions in all cases were based on a statistical description of room acoustics and on acoustic diffraction by a sphere. The success of these detection models in the present well-controlled reverberant conditions suggests that they can be used to incorporate listening mode and source location as factors in speech-intelligibility predictions.

  19. Integration of auditory and vibrotactile stimuli: Effects of frequency

    PubMed Central

    Wilson, E. Courtenay; Reed, Charlotte M.; Braida, Louis D.

    2010-01-01

    Perceptual integration of vibrotactile and auditory sinusoidal tone pulses was studied in detection experiments as a function of stimulation frequency. Vibrotactile stimuli were delivered through a single channel vibrator to the left middle fingertip. Auditory stimuli were presented diotically through headphones in a background of 50 dB sound pressure level broadband noise. Detection performance for combined auditory-tactile presentations was measured using stimulus levels that yielded 63% to 77% correct unimodal performance. In Experiment 1, the vibrotactile stimulus was 250 Hz and the auditory stimulus varied between 125 and 2000 Hz. In Experiment 2, the auditory stimulus was 250 Hz and the tactile stimulus varied between 50 and 400 Hz. In Experiment 3, the auditory and tactile stimuli were always equal in frequency and ranged from 50 to 400 Hz. The highest rates of detection for the combined-modality stimulus were obtained when stimulating frequencies in the two modalities were equal or closely spaced (and within the Pacinian range). Combined-modality detection for closely spaced frequencies was generally consistent with an algebraic sum model of perceptual integration; wider-frequency spacings were generally better fit by a Pythagorean sum model. Thus, perceptual integration of auditory and tactile stimuli at near-threshold levels appears to depend both on absolute frequency and relative frequency of stimulation within each modality. PMID:21117754

  20. [The Map of Auditory Function].

    PubMed

    Fujimoto, So; Komura, Yutaka

    2017-04-01

    Brodmann areas 41 and 42 are located in the superior temporal gyrus and regarded as auditory cortices. The fundamental function in audition is frequency analysis; however, the findings on tonotopy maps of the human auditory cortex were not unified until recently when they were compared to the findings on inputs and outputs of the monkey auditory cortex. The auditory cortex shows plasticity after conditioned learning and surgery of cochlear implant. It is also involved in speech perception, music appreciation, and auditory hallucination in schizophrenia through interactions with other brain areas, such as the thalamus, frontal cortex, and limbic systems.

  1. Auditory Fusion in Children.

    ERIC Educational Resources Information Center

    Davis, Sylvia M.; McCroskey, Robert L.

    1980-01-01

    Focuses on auditory fusion (defined in terms of a listerner's ability to distinguish paired acoustic events from single acoustic events) in 3- to 12-year-old children. The subjects listened to 270 pairs of tones controlled for frequency, intensity, and duration. (CM)

  2. Modelling auditory attention.

    PubMed

    Kaya, Emine Merve; Elhilali, Mounya

    2017-02-19

    Sounds in everyday life seldom appear in isolation. Both humans and machines are constantly flooded with a cacophony of sounds that need to be sorted through and scoured for relevant information-a phenomenon referred to as the 'cocktail party problem'. A key component in parsing acoustic scenes is the role of attention, which mediates perception and behaviour by focusing both sensory and cognitive resources on pertinent information in the stimulus space. The current article provides a review of modelling studies of auditory attention. The review highlights how the term attention refers to a multitude of behavioural and cognitive processes that can shape sensory processing. Attention can be modulated by 'bottom-up' sensory-driven factors, as well as 'top-down' task-specific goals, expectations and learned schemas. Essentially, it acts as a selection process or processes that focus both sensory and cognitive resources on the most relevant events in the soundscape; with relevance being dictated by the stimulus itself (e.g. a loud explosion) or by a task at hand (e.g. listen to announcements in a busy airport). Recent computational models of auditory attention provide key insights into its role in facilitating perception in cluttered auditory scenes.This article is part of the themed issue 'Auditory and visual scene analysis'.

  3. Modelling auditory attention

    PubMed Central

    Kaya, Emine Merve

    2017-01-01

    Sounds in everyday life seldom appear in isolation. Both humans and machines are constantly flooded with a cacophony of sounds that need to be sorted through and scoured for relevant information—a phenomenon referred to as the ‘cocktail party problem’. A key component in parsing acoustic scenes is the role of attention, which mediates perception and behaviour by focusing both sensory and cognitive resources on pertinent information in the stimulus space. The current article provides a review of modelling studies of auditory attention. The review highlights how the term attention refers to a multitude of behavioural and cognitive processes that can shape sensory processing. Attention can be modulated by ‘bottom-up’ sensory-driven factors, as well as ‘top-down’ task-specific goals, expectations and learned schemas. Essentially, it acts as a selection process or processes that focus both sensory and cognitive resources on the most relevant events in the soundscape; with relevance being dictated by the stimulus itself (e.g. a loud explosion) or by a task at hand (e.g. listen to announcements in a busy airport). Recent computational models of auditory attention provide key insights into its role in facilitating perception in cluttered auditory scenes. This article is part of the themed issue ‘Auditory and visual scene analysis’. PMID:28044012

  4. Attention Modulates the Auditory Cortical Processing of Spatial and Category Cues in Naturalistic Auditory Scenes.

    PubMed

    Renvall, Hanna; Staeren, Noël; Barz, Claudia S; Ley, Anke; Formisano, Elia

    2016-01-01

    This combined fMRI and MEG study investigated brain activations during listening and attending to natural auditory scenes. We first recorded, using in-ear microphones, vocal non-speech sounds, and environmental sounds that were mixed to construct auditory scenes containing two concurrent sound streams. During the brain measurements, subjects attended to one of the streams while spatial acoustic information of the scene was either preserved (stereophonic sounds) or removed (monophonic sounds). Compared to monophonic sounds, stereophonic sounds evoked larger blood-oxygenation-level-dependent (BOLD) fMRI responses in the bilateral posterior superior temporal areas, independent of which stimulus attribute the subject was attending to. This finding is consistent with the functional role of these regions in the (automatic) processing of auditory spatial cues. Additionally, significant differences in the cortical activation patterns depending on the target of attention were observed. Bilateral planum temporale and inferior frontal gyrus were preferentially activated when attending to stereophonic environmental sounds, whereas when subjects attended to stereophonic voice sounds, the BOLD responses were larger at the bilateral middle superior temporal gyrus and sulcus, previously reported to show voice sensitivity. In contrast, the time-resolved MEG responses were stronger for mono- than stereophonic sounds in the bilateral auditory cortices at ~360 ms after the stimulus onset when attending to the voice excerpts within the combined sounds. The observed effects suggest that during the segregation of auditory objects from the auditory background, spatial sound cues together with other relevant temporal and spectral cues are processed in an attention-dependent manner at the cortical locations generally involved in sound recognition. More synchronous neuronal activation during monophonic than stereophonic sound processing, as well as (local) neuronal inhibitory mechanisms in

  5. Attention Modulates the Auditory Cortical Processing of Spatial and Category Cues in Naturalistic Auditory Scenes

    PubMed Central

    Renvall, Hanna; Staeren, Noël; Barz, Claudia S.; Ley, Anke; Formisano, Elia

    2016-01-01

    This combined fMRI and MEG study investigated brain activations during listening and attending to natural auditory scenes. We first recorded, using in-ear microphones, vocal non-speech sounds, and environmental sounds that were mixed to construct auditory scenes containing two concurrent sound streams. During the brain measurements, subjects attended to one of the streams while spatial acoustic information of the scene was either preserved (stereophonic sounds) or removed (monophonic sounds). Compared to monophonic sounds, stereophonic sounds evoked larger blood-oxygenation-level-dependent (BOLD) fMRI responses in the bilateral posterior superior temporal areas, independent of which stimulus attribute the subject was attending to. This finding is consistent with the functional role of these regions in the (automatic) processing of auditory spatial cues. Additionally, significant differences in the cortical activation patterns depending on the target of attention were observed. Bilateral planum temporale and inferior frontal gyrus were preferentially activated when attending to stereophonic environmental sounds, whereas when subjects attended to stereophonic voice sounds, the BOLD responses were larger at the bilateral middle superior temporal gyrus and sulcus, previously reported to show voice sensitivity. In contrast, the time-resolved MEG responses were stronger for mono- than stereophonic sounds in the bilateral auditory cortices at ~360 ms after the stimulus onset when attending to the voice excerpts within the combined sounds. The observed effects suggest that during the segregation of auditory objects from the auditory background, spatial sound cues together with other relevant temporal and spectral cues are processed in an attention-dependent manner at the cortical locations generally involved in sound recognition. More synchronous neuronal activation during monophonic than stereophonic sound processing, as well as (local) neuronal inhibitory mechanisms in

  6. Auditory abnormalities in autism: toward functional distinctions among findings.

    PubMed

    Kellerman, Gabriella R; Fan, Jin; Gorman, Jack M

    2005-09-01

    Recently, findings on a wide range of auditory abnormalities among individuals with autism have been reported. To date, functional distinctions among these varied findings are poorly established. Such distinctions should be of interest to clinicians and researchers alike given their potential therapeutic and experimental applications. This review suggests three general trends among these findings as a starting point for future analyses. First, studies of auditory perception of linguistic and social auditory stimuli among individuals with autism generally have found impaired perception versus normal controls. Such findings may correlate with impaired language and communication skills and social isolation observed among individuals with autism. Second, studies of auditory perception of pitch and music among individuals with autism generally have found enhanced perception versus normal controls. These findings may correlate with the restrictive and highly focused behaviors observed among individuals with autism. Third, findings on the auditory perception of non-linguistic, non-musical stimuli among autism patients resist any generalized conclusions. Ultimately, as some researchers have already suggested, the distinction between impaired global processing and enhanced local processing may prove useful in making sense of apparently discordant findings on auditory abnormalities among individuals with autism.

  7. A somatic mutation in erythro-myeloid progenitors causes neurodegenerative disease.

    PubMed

    Mass, Elvira; Jacome-Galarza, Christian E; Blank, Thomas; Lazarov, Tomi; Durham, Benjamin H; Ozkaya, Neval; Pastore, Alessandro; Schwabenland, Marius; Chung, Young Rock; Rosenblum, Marc K; Prinz, Marco; Abdel-Wahab, Omar; Geissmann, Frederic

    2017-09-21

    The pathophysiology of neurodegenerative diseases is poorly understood and there are few therapeutic options. Neurodegenerative diseases are characterized by progressive neuronal dysfunction and loss, and chronic glial activation. Whether microglial activation, which is generally viewed as a secondary process, is harmful or protective in neurodegeneration remains unclear. Late-onset neurodegenerative disease observed in patients with histiocytoses, which are clonal myeloid diseases associated with somatic mutations in the RAS-MEK-ERK pathway such as BRAF(V600E), suggests a possible role of somatic mutations in myeloid cells in neurodegeneration. Yet the expression of BRAF(V600E) in the haematopoietic stem cell lineage causes leukaemic and tumoural diseases but not neurodegenerative disease. Microglia belong to a lineage of adult tissue-resident myeloid cells that develop during organogenesis from yolk-sac erythro-myeloid progenitors (EMPs) distinct from haematopoietic stem cells. We therefore hypothesized that a somatic BRAF(V600E) mutation in the EMP lineage may cause neurodegeneration. Here we show that mosaic expression of BRAF(V600E) in mouse EMPs results in clonal expansion of tissue-resident macrophages and a severe late-onset neurodegenerative disorder. This is associated with accumulation of ERK-activated amoeboid microglia in mice, and is also observed in human patients with histiocytoses. In the mouse model, neurobehavioural signs, astrogliosis, deposition of amyloid precursor protein, synaptic loss and neuronal death were driven by ERK-activated microglia and were preventable by BRAF inhibition. These results identify the fetal precursors of tissue-resident macrophages as a potential cell-of-origin for histiocytoses and demonstrate that a somatic mutation in the EMP lineage in mice can drive late-onset neurodegeneration. Moreover, these data identify activation of the MAP kinase pathway in microglia as a cause of neurodegeneration and this offers

  8. A basic study on universal design of auditory signals in automobiles.

    PubMed

    Yamauchi, Katsuya; Choi, Jong-dae; Maiguma, Ryo; Takada, Masayuki; Iwamiya, Shin-ichiro

    2004-11-01

    In this paper, the impression of various kinds of auditory signals currently used in automobiles and a comprehensive evaluation were measured by a semantic differential method. The desirable acoustic characteristic was examined for each type of auditory signal. Sharp sounds with dominant high-frequency components were not suitable for auditory signals in automobiles. This trend is expedient for the aged whose auditory sensitivity in the high frequency region is lower. When intermittent sounds were used, a longer OFF time was suitable. Generally, "dull (not sharp)" and "calm" sounds were appropriate for auditory signals. Furthermore, the comparison between the frequency spectrum of interior noise in automobiles and that of suitable sounds for various auditory signals indicates that the suitable sounds are not easily masked. The suitable auditory signals for various purposes is a good solution from the viewpoint of universal design.

  9. Processing of spatial sounds in human auditory cortex during visual, discrimination and 2-back tasks

    PubMed Central

    Rinne, Teemu; Ala-Salomäki, Heidi; Stecker, G. Christopher; Pätynen, Jukka; Lokki, Tapio

    2014-01-01

    Previous imaging studies on the brain mechanisms of spatial hearing have mainly focused on sounds varying in the horizontal plane. In this study, we compared activations in human auditory cortex (AC) and adjacent inferior parietal lobule (IPL) to sounds varying in horizontal location, distance, or space (i.e., different rooms). In order to investigate both stimulus-dependent and task-dependent activations, these sounds were presented during visual discrimination, auditory discrimination, and auditory 2-back memory tasks. Consistent with previous studies, activations in AC were modulated by the auditory tasks. During both auditory and visual tasks, activations in AC were stronger to sounds varying in horizontal location than along other feature dimensions. However, in IPL, this enhancement was detected only during auditory tasks. Based on these results, we argue that IPL is not primarily involved in stimulus-level spatial analysis but that it may represent such information for more general processing when relevant to an active auditory task. PMID:25120423

  10. The Role of Copper in Neurodegenerative Disease

    NASA Astrophysics Data System (ADS)

    Rose, Francis M.

    My research concerns the fundamental atomistic mechanisms of neurodegenerative diseases and the methodologies by which they may be discerned. This thesis consists of three primary parts. The introductory material is the raison d'etre for this work and a critical overview of the specific physics, mathematics and algorithms used in this research. The methods are presented along with specific details in order to facilitate future replication and enhancement. With the groundwork of mechanisms and methods out of the way, we then explore a nouveau atomistic mechanism describing the onset of Parkinson's disease, a disease that has been closely linked to misfolded metalloproteins. Further exploration of neurodegeneration takes place in the following chapter, where a remedial approach to Alzheimer's disease via a simulated chelation of a metalloprotein is undertaken. Altogether, the methods and techniques applied here allow for simulated exploration of both the atomistic mechanisms of neurodegeneration and their potential remediation strategies. The beginning portion of the research efforts explore protein misfolding dynamics in the presence a copper ion. Misfolding of the human alpha-synuclein (aS) protein has been implicated as a central constituent in neurodegenerative disease. In Parkinson's disease (PD) in particular, aS is thought to be the causative participant when found concentrated into neuritic plaques. Here we propose a scenario involving the metal ion Cu2+ as the protein misfolding initiator of fibrillized aS, the chief component of neuritic plaques. From experimental results we know these misfolded proteins have a rich beta--sheet signature, a marker that we reproduce with our simulated model. This model identifies a process of structural modifications to a natively unfolded alpha-synuclein resulting in a partially folded intermediate with a well defined nucleation site. It serves as a precursor to the fully misfolded protein. Understanding the nucleation

  11. Comparative Incidence of Conformational, Neurodegenerative Disorders

    PubMed Central

    de Pedro-Cuesta, Jesús; Rábano, Alberto; Martínez-Martín, Pablo; Ruiz-Tovar, María; Alcalde-Cabero, Enrique; Almazán-Isla, Javier; Avellanal, Fuencisla; Calero, Miguel

    2015-01-01

    Background The purpose of this study was to identify incidence and survival patterns in conformational neurodegenerative disorders (CNDDs). Methods We identified 2563 reports on the incidence of eight conditions representing sporadic, acquired and genetic, protein-associated, i.e., conformational, NDD groups and age-related macular degeneration (AMD). We selected 245 papers for full-text examination and application of quality criteria. Additionally, data-collection was completed with detailed information from British, Swedish, and Spanish registries on Creutzfeldt-Jakob disease (CJD) forms, amyotrophic lateral sclerosis (ALS), and sporadic rapidly progressing neurodegenerative dementia (sRPNDd). For each condition, age-specific incidence curves, age-adjusted figures, and reported or calculated median survival were plotted and examined. Findings Based on 51 valid reported and seven new incidence data sets, nine out of eleven conditions shared specific features. Age-adjusted incidence per million person-years increased from ≤1.5 for sRPNDd, different CJD forms and Huntington's disease (HD), to 1589 and 2589 for AMD and Alzheimer's disease (AD) respectively. Age-specific profiles varied from (a) symmetrical, inverted V-shaped curves for low incidences to (b) those increasing with age for late-life sporadic CNDDs and for sRPNDd, with (c) a suggested, intermediate, non-symmetrical inverted V-shape for fronto-temporal dementia and Parkinson's disease. Frequently, peak age-specific incidences from 20–24 to ≥90 years increased with age at onset and survival. Distinct patterns were seen: for HD, with a low incidence, levelling off at middle age, and long median survival, 20 years; and for sRPNDd which displayed the lowest incidence, increasing with age, and a short median disease duration. Interpretation These results call for a unified population view of NDDs, with an age-at-onset-related pattern for acquired and sporadic CNDDs. The pattern linking age at onset to

  12. Auditory risk estimates for youth target shooting

    PubMed Central

    Meinke, Deanna K.; Murphy, William J.; Finan, Donald S.; Lankford, James E.; Flamme, Gregory A.; Stewart, Michael; Soendergaard, Jacob; Jerome, Trevor W.

    2015-01-01

    Objective To characterize the impulse noise exposure and auditory risk for youth recreational firearm users engaged in outdoor target shooting events. The youth shooting positions are typically standing or sitting at a table, which places the firearm closer to the ground or reflective surface when compared to adult shooters. Design Acoustic characteristics were examined and the auditory risk estimates were evaluated using contemporary damage-risk criteria for unprotected adult listeners and the 120-dB peak limit suggested by the World Health Organization (1999) for children. Study sample Impulses were generated by 26 firearm/ammunition configurations representing rifles, shotguns, and pistols used by youth. Measurements were obtained relative to a youth shooter’s left ear. Results All firearms generated peak levels that exceeded the 120 dB peak limit suggested by the WHO for children. In general, shooting from the seated position over a tabletop increases the peak levels, LAeq8 and reduces the unprotected maximum permissible exposures (MPEs) for both rifles and pistols. Pistols pose the greatest auditory risk when fired over a tabletop. Conclusion Youth should utilize smaller caliber weapons, preferably from the standing position, and always wear hearing protection whenever engaging in shooting activities to reduce the risk for auditory damage. PMID:24564688

  13. Multivariate sensitivity to voice during auditory categorization.

    PubMed

    Lee, Yune Sang; Peelle, Jonathan E; Kraemer, David; Lloyd, Samuel; Granger, Richard

    2015-09-01

    Past neuroimaging studies have documented discrete regions of human temporal cortex that are more strongly activated by conspecific voice sounds than by nonvoice sounds. However, the mechanisms underlying this voice sensitivity remain unclear. In the present functional MRI study, we took a novel approach to examining voice sensitivity, in which we applied a signal detection paradigm to the assessment of multivariate pattern classification among several living and nonliving categories of auditory stimuli. Within this framework, voice sensitivity can be interpreted as a distinct neural representation of brain activity that correctly distinguishes human vocalizations from other auditory object categories. Across a series of auditory categorization tests, we found that bilateral superior and middle temporal cortex consistently exhibited robust sensitivity to human vocal sounds. Although the strongest categorization was in distinguishing human voice from other categories, subsets of these regions were also able to distinguish reliably between nonhuman categories, suggesting a general role in auditory object categorization. Our findings complement the current evidence of cortical sensitivity to human vocal sounds by revealing that the greatest sensitivity during categorization tasks is devoted to distinguishing voice from nonvoice categories within human temporal cortex.

  14. Multivariate sensitivity to voice during auditory categorization

    PubMed Central

    Peelle, Jonathan E.; Kraemer, David; Lloyd, Samuel; Granger, Richard

    2015-01-01

    Past neuroimaging studies have documented discrete regions of human temporal cortex that are more strongly activated by conspecific voice sounds than by nonvoice sounds. However, the mechanisms underlying this voice sensitivity remain unclear. In the present functional MRI study, we took a novel approach to examining voice sensitivity, in which we applied a signal detection paradigm to the assessment of multivariate pattern classification among several living and nonliving categories of auditory stimuli. Within this framework, voice sensitivity can be interpreted as a distinct neural representation of brain activity that correctly distinguishes human vocalizations from other auditory object categories. Across a series of auditory categorization tests, we found that bilateral superior and middle temporal cortex consistently exhibited robust sensitivity to human vocal sounds. Although the strongest categorization was in distinguishing human voice from other categories, subsets of these regions were also able to distinguish reliably between nonhuman categories, suggesting a general role in auditory object categorization. Our findings complement the current evidence of cortical sensitivity to human vocal sounds by revealing that the greatest sensitivity during categorization tasks is devoted to distinguishing voice from nonvoice categories within human temporal cortex. PMID:26245316

  15. Automated auditory recognition training and testing

    PubMed Central

    Gess, Austen; Schneider, David M.; Vyas, Akshat; Woolley, Sarah M. N.

    2011-01-01

    Laboratory training and testing of auditory recognition skills in animals is important for understanding animal communication systems that depend on auditory cues. Songbirds are commonly studied because of their exceptional ability to learn complex vocalizations. In recent years, mounting interest in the perceptual abilities of songbirds has increased the demand for laboratory behavioural training and testing paradigms. Here, we describe and demonstrate the success of a method for auditory discrimination experiments, including all the necessary hardware, training procedures and freely-available, versatile software. The system can run several behavioural training and testing paradigms, including operant (go-nogo, stimulus preference, and two-alternative forced choice) and classical conditioning tasks. The software and some hardware components can be used with any laboratory animal that learns and responds to sensory cues. The peripheral hardware and training procedures are designed for use with songbirds and auditory stimuli. Using the go-nogo paradigm of the training system, we show that adult zebra finches learn to recognize and correctly classify individual female calls and male songs. We also show that learning the task generalizes to new stimulus classes; birds that learned the task with calls subsequently learned to recognize songs faster than did birds that learned the task and songs at the same time. PMID:21857717

  16. Auditory pathways: anatomy and physiology.

    PubMed

    Pickles, James O

    2015-01-01

    This chapter outlines the anatomy and physiology of the auditory pathways. After a brief analysis of the external, middle ears, and cochlea, the responses of auditory nerve fibers are described. The central nervous system is analyzed in more detail. A scheme is provided to help understand the complex and multiple auditory pathways running through the brainstem. The multiple pathways are based on the need to preserve accurate timing while extracting complex spectral patterns in the auditory input. The auditory nerve fibers branch to give two pathways, a ventral sound-localizing stream, and a dorsal mainly pattern recognition stream, which innervate the different divisions of the cochlear nucleus. The outputs of the two streams, with their two types of analysis, are progressively combined in the inferior colliculus and onwards, to produce the representation of what can be called the "auditory objects" in the external world. The progressive extraction of critical features in the auditory stimulus in the different levels of the central auditory system, from cochlear nucleus to auditory cortex, is described. In addition, the auditory centrifugal system, running from cortex in multiple stages to the organ of Corti of the cochlea, is described. © 2015 Elsevier B.V. All rights reserved.

  17. Development of the auditory system.

    PubMed

    Litovsky, Ruth

    2015-01-01

    Auditory development involves changes in the peripheral and central nervous system along the auditory pathways, and these occur naturally, and in response to stimulation. Human development occurs along a trajectory that can last decades, and is studied using behavioral psychophysics, as well as physiologic measurements with neural imaging. The auditory system constructs a perceptual space that takes information from objects and groups, segregates sounds, and provides meaning and access to communication tools such as language. Auditory signals are processed in a series of analysis stages, from peripheral to central. Coding of information has been studied for features of sound, including frequency, intensity, loudness, and location, in quiet and in the presence of maskers. In the latter case, the ability of the auditory system to perform an analysis of the scene becomes highly relevant. While some basic abilities are well developed at birth, there is a clear prolonged maturation of auditory development well into the teenage years. Maturation involves auditory pathways. However, non-auditory changes (attention, memory, cognition) play an important role in auditory development. The ability of the auditory system to adapt in response to novel stimuli is a key feature of development throughout the nervous system, known as neural plasticity.

  18. Animal models for auditory streaming.

    PubMed

    Itatani, Naoya; Klump, Georg M

    2017-02-19

    Sounds in the natural environment need to be assigned to acoustic sources to evaluate complex auditory scenes. Separating sources will affect the analysis of auditory features of sounds. As the benefits of assigning sounds to specific sources accrue to all species communicating acoustically, the ability for auditory scene analysis is widespread among different animals. Animal studies allow for a deeper insight into the neuronal mechanisms underlying auditory scene analysis. Here, we will review the paradigms applied in the study of auditory scene analysis and streaming of sequential sounds in animal models. We will compare the psychophysical results from the animal studies to the evidence obtained in human psychophysics of auditory streaming, i.e. in a task commonly used for measuring the capability for auditory scene analysis. Furthermore, the neuronal correlates of auditory streaming will be reviewed in different animal models and the observations of the neurons' response measures will be related to perception. The across-species comparison will reveal whether similar demands in the analysis of acoustic scenes have resulted in similar perceptual and neuronal processing mechanisms in the wide range of species being capable of auditory scene analysis.This article is part of the themed issue 'Auditory and visual scene analysis'.

  19. Development of the auditory system

    PubMed Central

    Litovsky, Ruth

    2015-01-01

    Auditory development involves changes in the peripheral and central nervous system along the auditory pathways, and these occur naturally, and in response to stimulation. Human development occurs along a trajectory that can last decades, and is studied using behavioral psychophysics, as well as physiologic measurements with neural imaging. The auditory system constructs a perceptual space that takes information from objects and groups, segregates sounds, and provides meaning and access to communication tools such as language. Auditory signals are processed in a series of analysis stages, from peripheral to central. Coding of information has been studied for features of sound, including frequency, intensity, loudness, and location, in quiet and in the presence of maskers. In the latter case, the ability of the auditory system to perform an analysis of the scene becomes highly relevant. While some basic abilities are well developed at birth, there is a clear prolonged maturation of auditory development well into the teenage years. Maturation involves auditory pathways. However, non-auditory changes (attention, memory, cognition) play an important role in auditory development. The ability of the auditory system to adapt in response to novel stimuli is a key feature of development throughout the nervous system, known as neural plasticity. PMID:25726262

  20. Localized Cell and Drug Delivery for Auditory Prostheses

    PubMed Central

    Hendricks, Jeffrey L.; Chikar, Jennifer A.; Crumling, Mark A.; Raphael, Yehoash; Martin, David C.

    2011-01-01

    Localized cell and drug delivery to the cochlea and central auditory pathway can improve the safety and performance of implanted auditory prostheses (APs). While generally successful, these devices have a number of limitations and adverse effects including limited tonal and dynamic ranges, channel interactions, unwanted stimulation of non-auditory nerves, immune rejection, and infections including meningitis. Many of these limitations are associated with the tissue reactions to implanted auditory prosthetic devices and the gradual degeneration of the auditory system following deafness. Strategies to reduce the insertion trauma, degeneration of target neurons, fibrous and bony tissue encapsulation, and immune activation can improve the viability of tissue required for AP function as well as improve the resolution of stimulation for reduced channel interaction and improved place-pitch and level discrimination. Many pharmaceutical compounds have been identified that promote the viability of auditory tissue and prevent inflammation and infection. Cell delivery and gene therapy have provided promising results for treating hearing loss and reversing degeneration. Currently, many clinical and experimental methods can produce extremely localized and sustained drug delivery to address AP limitations. These methods provide better control over drug concentrations while eliminating the adverse effects of systemic delivery. Many of these drug delivery techniques can be integrated into modern auditory prosthetic devices to optimize the tissue response to the implanted device and reduce the risk of infection or rejection. Together, these methods and pharmaceutical agents can be used to optimize the tissue-device interface for improved AP safety and effectiveness. PMID:18573323

  1. Spatial processing in the auditory cortex of the macaque monkey

    NASA Astrophysics Data System (ADS)

    Recanzone, Gregg H.

    2000-10-01

    The patterns of cortico-cortical and cortico-thalamic connections of auditory cortical areas in the rhesus monkey have led to the hypothesis that acoustic information is processed in series and in parallel in the primate auditory cortex. Recent physiological experiments in the behaving monkey indicate that the response properties of neurons in different cortical areas are both functionally distinct from each other, which is indicative of parallel processing, and functionally similar to each other, which is indicative of serial processing. Thus, auditory cortical processing may be similar to the serial and parallel "what" and "where" processing by the primate visual cortex. If "where" information is serially processed in the primate auditory cortex, neurons in cortical areas along this pathway should have progressively better spatial tuning properties. This prediction is supported by recent experiments that have shown that neurons in the caudomedial field have better spatial tuning properties than neurons in the primary auditory cortex. Neurons in the caudomedial field are also better than primary auditory cortex neurons at predicting the sound localization ability across different stimulus frequencies and bandwidths in both azimuth and elevation. These data support the hypothesis that the primate auditory cortex processes acoustic information in a serial and parallel manner and suggest that this may be a general cortical mechanism for sensory perception.

  2. Music Lessons Improve Auditory Perceptual and Cognitive Performance in Deaf Children

    PubMed Central

    Rochette, Françoise; Moussard, Aline; Bigand, Emmanuel

    2014-01-01

    Despite advanced technologies in auditory rehabilitation of profound deafness, deaf children often exhibit delayed cognitive and linguistic development and auditory training remains a crucial element of their education. In the present cross-sectional study, we assess whether music would be a relevant tool for deaf children rehabilitation. In normal-hearing children, music lessons have been shown to improve cognitive and linguistic-related abilities, such as phonetic discrimination and reading. We compared auditory perception, auditory cognition, and phonetic discrimination between 14 profoundly deaf children who completed weekly music lessons for a period of 1.5–4 years and 14 deaf children who did not receive musical instruction. Children were assessed on perceptual and cognitive auditory tasks using environmental sounds: discrimination, identification, auditory scene analysis, auditory working memory. Transfer to the linguistic domain was tested with a phonetic discrimination task. Musically trained children showed better performance in auditory scene analysis, auditory working memory and phonetic discrimination tasks, and multiple regressions showed that success on these tasks was at least partly driven by music lessons. We propose that musical education contributes to development of general processes such as auditory attention and perception, which, in turn, facilitate auditory-related cognitive and linguistic processes. PMID:25071518

  3. Music lessons improve auditory perceptual and cognitive performance in deaf children.

    PubMed

    Rochette, Françoise; Moussard, Aline; Bigand, Emmanuel

    2014-01-01

    Despite advanced technologies in auditory rehabilitation of profound deafness, deaf children often exhibit delayed cognitive and linguistic development and auditory training remains a crucial element of their education. In the present cross-sectional study, we assess whether music would be a relevant tool for deaf children rehabilitation. In normal-hearing children, music lessons have been shown to improve cognitive and linguistic-related abilities, such as phonetic discrimination and reading. We compared auditory perception, auditory cognition, and phonetic discrimination between 14 profoundly deaf children who completed weekly music lessons for a period of 1.5-4 years and 14 deaf children who did not receive musical instruction. Children were assessed on perceptual and cognitive auditory tasks using environmental sounds: discrimination, identification, auditory scene analysis, auditory working memory. Transfer to the linguistic domain was tested with a phonetic discrimination task. Musically trained children showed better performance in auditory scene analysis, auditory working memory and phonetic discrimination tasks, and multiple regressions showed that success on these tasks was at least partly driven by music lessons. We propose that musical education contributes to development of general processes such as auditory attention and perception, which, in turn, facilitate auditory-related cognitive and linguistic processes.

  4. Exosomes, an Unmasked Culprit in Neurodegenerative Diseases

    PubMed Central

    Soria, Federico N.; Pampliega, Olatz; Bourdenx, Mathieu; Meissner, Wassilios G.; Bezard, Erwan; Dehay, Benjamin

    2017-01-01

    Exosomes are extracellular nanovesicles (30–100 nm) generated from endosomal membranes and known to be released by all cell lineages of the Central Nervous System (CNS). They constitute important vesicles for the secretion and transport of multilevel information, including signaling, toxic, and regulatory molecules. Initially thought to have a function merely in waste disposal, the involvement of exosomes in neuronal development, maintenance, and regeneration through its paracrine and endocrine signaling functions has drawn particular attention in recent years. These vesicles, being involved in the clearance and cell-to-cell spreading of toxic molecules, have been naturally implicated in aging, and in several neurodegenerative diseases associated with pathological conversion of proteins, as well as in the transport of other disease-associated molecules, such as nucleic acids or pro-inflammatory cytokines. Our understanding of such unique form of communication may provide not only answers about (patho)physiological processes in the brain, but can also offer means to exploit these vesicles as vehicles for the delivery of biologically relevant molecules or as tools to monitor brain diseases in a non-invasive way. A promising field in expansion, the study of exosomes and related extracellular vesicles has just commenced to unveil their potential as therapeutic tools for brain disorders as well as biomarkers of disease state. PMID:28197068

  5. Cerebral Toxocariasis: Silent Progression to Neurodegenerative Disorders?

    PubMed Central

    Holland, Celia V.; Loxton, Karen; Barghouth, Ursula

    2015-01-01

    SUMMARY Toxocara canis and T. cati are highly prevalent nematode infections of the intestines of dogs and cats. In paratenic hosts, larvae do not mature in the intestine but instead migrate through the somatic tissues and organs of the body. The presence of these migrating larvae can contribute to pathology. Toxocara larvae can invade the brains of humans, and while case descriptions of cerebral toxocariasis are historically rare, improved diagnosis and greater awareness have contributed to increased detection. Despite this, cerebral or neurological toxocariasis (NT) remains a poorly understood phenomenon. Furthermore, our understanding of cognitive deficits due to toxocariasis in human populations remains particularly deficient. Recent data describe an enhanced expression of biomarkers associated with brain injury, such as GFAP, AβPP, transforming growth factor β1 (TGF-β1), NF-L, S100B, tTG, and p-tau, in mice receiving even low doses of Toxocara ova. Finally, this review outlines a hypothesis to explore the relationship between the presence of T. canis larvae in the brain and the progression of Alzheimer's disease (AD) due to enhanced AD-associated neurodegenerative biomarker expression. PMID:26062575

  6. Cerebral Toxocariasis: Silent Progression to Neurodegenerative Disorders?

    PubMed

    Fan, Chia-Kwung; Holland, Celia V; Loxton, Karen; Barghouth, Ursula

    2015-07-01

    Toxocara canis and T. cati are highly prevalent nematode infections of the intestines of dogs and cats. In paratenic hosts, larvae do not mature in the intestine but instead migrate through the somatic tissues and organs of the body. The presence of these migrating larvae can contribute to pathology. Toxocara larvae can invade the brains of humans, and while case descriptions of cerebral toxocariasis are historically rare, improved diagnosis and greater awareness have contributed to increased detection. Despite this, cerebral or neurological toxocariasis (NT) remains a poorly understood phenomenon. Furthermore, our understanding of cognitive deficits due to toxocariasis in human populations remains particularly deficient. Recent data describe an enhanced expression of biomarkers associated with brain injury, such as GFAP, AβPP, transforming growth factor β1 (TGF-β1), NF-L, S100B, tTG, and p-tau, in mice receiving even low doses of Toxocara ova. Finally, this review outlines a hypothesis to explore the relationship between the presence of T. canis larvae in the brain and the progression of Alzheimer's disease (AD) due to enhanced AD-associated neurodegenerative biomarker expression.

  7. Effects of natural antioxidants in neurodegenerative disease.

    PubMed

    Albarracin, Sonia Luz; Stab, Ben; Casas, Zulma; Sutachan, Jhon Jairo; Samudio, Ismael; Gonzalez, Janneth; Gonzalo, Luis; Capani, Francisco; Morales, Ludis; Barreto, George E

    2012-01-01

    Polyphenols are secondary metabolites with antioxidant properties and are abundant in the diet. Fruits, vegetables, herbs, and various drinks (tea, wine, and juices) are all sources of these molecules. Despite their abundance, investigations into the benefits of polyphenols in human health have only recently begun. Phenolic compounds have received increasing interest because of numerous epidemiological studies. These studies have suggested associations between the consumption of polyphenol-rich aliments and the prevention of chronic diseases, such as cancer, cardiovascular diseases, and neurodegenerative diseases. More specifically, in the last 10 years literature on the neuroprotective effects of a polyphenol-rich diet has grown considerably. It has been demonstrated, in various cell culture and animal models, that these metabolites are able to protect neuronal cells by attenuating oxidative stress and damage. However, it remains unclear as to how these compounds reach the brain, what concentrations are necessary, and what biologically active forms are needed to exert beneficial effects. Therefore, further research is needed to identify the molecular pathways and intracellular targets responsible for polyphenol's neuroprotective effects. The aim of this paper is to present various well-known dietary polyphenols and their mechanisms of neuroprotection with an emphasis on Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis.

  8. Mapping Neurodegenerative Disease Onset and Progression.

    PubMed

    Seeley, William W

    2017-03-13

    Brain networks have been of long-standing interest to neurodegeneration researchers, including but not limited to investigators focusing on conventional prion diseases, which are known to propagate along neural pathways. Tools for human network mapping, however, remained inadequate, limiting our understanding of human brain network architecture and preventing clinical research applications. Until recently, neuropathological studies were the only viable approach to mapping disease onset and progression in humans but required large autopsy cohorts and laborious methods for whole-brain sectioning and staining. Despite important advantages, postmortem studies cannot address in vivo, physiological, or longitudinal questions and have limited potential to explore early-stage disease except for the most common disorders. Emerging in vivo network-based neuroimaging strategies have begun to address these issues, providing data that complement the neuropathological tradition. Overall, findings to date highlight several fundamental principles of neurodegenerative disease anatomy and pathogenesis, as well as some enduring mysteries. These principles and mysteries provide a road map for future research.

  9. Folic acid, neurodegenerative and neuropsychiatric disease.

    PubMed

    Kronenberg, Golo; Colla, Michael; Endres, Matthias

    2009-04-01

    Folic acid plays an important role in neuroplasticity and in the maintenance of neuronal integrity. Folate is a co-factor in one-carbon metabolism during which it promotes the regeneration of methionine from homocysteine, a highly reactive sulfur-containing amino acid. Methionine may then be converted to S-adenosylmethionine (SAM), the principal methyl donor in most biosynthetic methylation reactions. On the cellular level, folate deficiency and hyperhomocysteinemia exert multiple detrimental effects. These include induction of DNA damage, uracil misincorporation into DNA and altered patterns of DNA methylation. Low folate status and elevated homocysteine increase the generation of reactive oxygen species and contribute to excitotoxicity and mitochondrial dysfunction which may lead to apoptosis. Strong epidemiological and experimental evidence links derangements of one-carbon metabolism to vascular, neurodegenerative and neuropsychiatric disease, including most prominently cerebral ischemia, Alzheimer's dementia and depression. Although firm evidence from controlled clinical trials is largely lacking, B-vitamin supplementation and homocysteine reduction may have a role especially in the primary prevention of stroke and dementia as well as as an adjunct to antidepressant pharmacotherapy.

  10. Expression of Nrf2 in Neurodegenerative Diseases

    PubMed Central

    Ramsey, Chenere P.; Glass, Charles A.; Montgomery, Marshall B.; Lindl, Kathryn A.; Ritson, Gillian P.; Chia, Luis A.; Hamilton, Ronald L.; Chu, Charleen T.; Jordan-Sciutto, Kelly L.

    2008-01-01

    In response to oxidative stress, the nuclear factor E2-related factor 2 (Nrf2) transcription factor translocates from the cytoplasm into the nucleus and transactivates expression of genes with antioxidant activity. Despite this cellular mechanism, oxidative damage is abundant in Alzheimer and Parkinson disease (AD and PD). To investigate mechanisms by which Nrf2 activity may be aberrant or insufficient in neurodegenerative conditions, we assessed Nrf2 localization in affected brain regions of AD, Lewy body variant of AD (LBVAD), and PD. By immunohistochemistry, Nrf2 is expressed in both the nucleus and the cytoplasm of neurons in normal hippocampi with predominant expression in the nucleus. In AD and LBVAD, Nrf2 was predominantly cytoplasmic in hippocampal neurons and was not a major component of beta amyloid plaques or neurofibrillary tangles. By immunoblotting, we observed a significant decrease in nuclear Nrf2 levels in AD cases. In contrast, Nrf2 was strongly nuclear in PD nigral neurons but cytoplasmic in substantia nigra of normal, AD, and LBVAD cases. These findings suggest that Nrf2-mediated transcription is not induced in neurons in AD despite the presence of oxidative stress. In PD, nuclear localization of Nrf2 is strongly induced, but this response may be insufficient to protect neurons from degeneration. PMID:17204939

  11. Metabolic Vulnerability in the Neurodegenerative Disease Glaucoma

    PubMed Central

    Inman, Denise M.; Harun-Or-Rashid, Mohammad

    2017-01-01

    Axons can be several orders of magnitude longer than neural somas, presenting logistical difficulties in cargo trafficking and structural maintenance. Keeping the axon compartment well supplied with energy also presents a considerable challenge; even seemingly subtle modifications of metabolism can result in functional deficits and degeneration. Axons require a great deal of energy, up to 70% of all energy used by a neuron, just to maintain the resting membrane potential. Axonal energy, in the form of ATP, is generated primarily through oxidative phosphorylation in the mitochondria. In addition, glial cells contribute metabolic intermediates to axons at moments of high activity or according to need. Recent evidence suggests energy disruption is an early contributor to pathology in a wide variety of neurodegenerative disorders characterized by axonopathy. However, the degree to which the energy disruption is intrinsic to the axon vs. associated glia is not clear. This paper will review the role of energy availability and utilization in axon degeneration in glaucoma, a chronic axonopathy of the retinal projection. PMID:28424571

  12. Role of apolipoprotein E in neurodegenerative diseases

    PubMed Central

    Giau, Vo Van; Bagyinszky, Eva; An, Seong Soo A; Kim, Sang Yun

    2015-01-01

    Apolipoprotein E (APOE) is a lipid-transport protein abundantly expressed in most neurons in the central nervous system. APOE-dependent alterations of the endocytic pathway can affect different functions. APOE binds to cell-surface receptors to deliver lipids and to the hydrophobic amyloid-β peptide, regulating amyloid-β aggregations and clearances in the brain. Several APOE isoforms with major structural differences were discovered and shown to influence the brain lipid transport, glucose metabolism, neuronal signaling, neuroinflammation, and mitochondrial function. This review will summarize the updated research progress on APOE functions and its role in Alzheimer’s disease, Parkinson’s disease, cardiovascular diseases, multiple sclerosis, type 2 diabetes mellitus, Type III hyperlipoproteinemia, vascular dementia, and ischemic stroke. Understanding the mutations in APOE, their structural properties, and their isoforms is important to determine its role in various diseases and to advance the development of therapeutic strategies. Targeting APOE may be a potential approach for diagnosis, risk assessment, prevention, and treatment of various neurodegenerative and cardiovascular diseases in humans. PMID:26213471

  13. Exosomes, an Unmasked Culprit in Neurodegenerative Diseases.

    PubMed

    Soria, Federico N; Pampliega, Olatz; Bourdenx, Mathieu; Meissner, Wassilios G; Bezard, Erwan; Dehay, Benjamin

    2017-01-01

    Exosomes are extracellular nanovesicles (30-100 nm) generated from endosomal membranes and known to be released by all cell lineages of the Central Nervous System (CNS). They constitute important vesicles for the secretion and transport of multilevel information, including signaling, toxic, and regulatory molecules. Initially thought to have a function merely in waste disposal, the involvement of exosomes in neuronal development, maintenance, and regeneration through its paracrine and endocrine signaling functions has drawn particular attention in recent years. These vesicles, being involved in the clearance and cell-to-cell spreading of toxic molecules, have been naturally implicated in aging, and in several neurodegenerative diseases associated with pathological conversion of proteins, as well as in the transport of other disease-associated molecules, such as nucleic acids or pro-inflammatory cytokines. Our understanding of such unique form of communication may provide not only answers about (patho)physiological processes in the brain, but can also offer means to exploit these vesicles as vehicles for the delivery of biologically relevant molecules or as tools to monitor brain diseases in a non-invasive way. A promising field in expansion, the study of exosomes and related extracellular vesicles has just commenced to unveil their potential as therapeutic tools for brain disorders as well as biomarkers of disease state.

  14. Structural anatomy of empathy in neurodegenerative disease

    PubMed Central

    Rankin, Katherine P.; Gorno-Tempini, Maria Luisa; Allison, Stephen C.; Stanley, Christine M.; Glenn, Shenly; Weiner, Michael W.; Miller, Bruce L.

    2008-01-01

    Empathy is a complex social behaviour mediated by a network of brain structures. Recently, several functional imaging studies have investigated the neural basis of empathy, but few corroborative human lesion studies exist. Severe empathy loss is a common feature of frontotemporal lobar degeneration (FTLD), and is also seen in other neurodegenerative diseases. In this study, the neuroanatomic basis of empathy was investigated in 123 patients with FTLD, Alzheimer's disease, corticobasal degeneration and progressive supranuclear palsy using the Interpersonal Reactivity Index (IRI). IRI Empathic Concern and Perspective taking scores were correlated with structural MRI brain volume using voxel-based morphometry. Voxels in the right temporal pole, the right fusiform gyrus, the right caudate and right subcallosal gyrus correlated significantly with total empathy score (P < 0.05 after whole-brain correction for multiple comparisons). Empathy score correlated positively with the volume of right temporal structures in semantic dementia, and with subcallosal gyrus volume in frontotemporal dementia. These findings are consistent with previous research suggesting that a primarily right frontotemporal network of brain regions is involved in emotion processing, and highlights the roles of the right temporal pole and inferior frontal/striatal regions in regulating complex social interactions. This is the first large-scale lesion study to investigate the neural basis of empathy using correlational analytic methods. The results suggest that the right anterior temporal and medial frontal regions are essential for real-life empathic behaviour. PMID:17008334

  15. Health benefits of methylxanthines in neurodegenerative diseases.

    PubMed

    Oñatibia-Astibia, Ainhoa; Franco, Rafael; Martínez-Pinilla, Eva

    2017-01-11

    Methylxanthines (MTXs) are consumed by almost everybody in almost every area of the world. Caffeine, theophylline and theobromine are the most well-known members of this family of compounds; they are present, inter alia, in coffee, tea, cacao, yerba mate and cola drinks. MTXs are readily absorbed in the gastrointestinal tract and are able to penetrate into the central nervous system, where they exert significant psychostimulant actions, which are more evident in acute intake. Coffee has been paradigmatic, as its use was forbidden in many diseases, however, this negative view has radically changed; evidence shows that MTXs display health benefits in diseases involving cell death in the nervous system. This paper reviews data that appraise the preventive and even therapeutic potential of MTXs in a variety of neurodegenerative diseases. Future perspectives include the use of MTXs to advance the understanding the pathophysiology of, inter alia, Alzheimer's disease (AD) and Parkinson's disease (PD), and the use of the methylxanthine chemical moiety as a basis for the development of new and more efficacious drugs.

  16. Human DNA methylomes of neurodegenerative diseases show common epigenomic patterns.

    PubMed

    Sanchez-Mut, J V; Heyn, H; Vidal, E; Moran, S; Sayols, S; Delgado-Morales, R; Schultz, M D; Ansoleaga, B; Garcia-Esparcia, P; Pons-Espinal, M; de Lagran, M M; Dopazo, J; Rabano, A; Avila, J; Dierssen, M; Lott, I; Ferrer, I; Ecker, J R; Esteller, M

    2016-01-19

    Different neurodegenerative disorders often show similar lesions, such as the presence of amyloid plaques, TAU-neurotangles and synuclein inclusions. The genetically inherited forms are rare, so we wondered whether shared epigenetic aberrations, such as those affecting DNA methylation, might also exist. The studied samples were gray matter samples from the prefrontal cortex of control and neurodegenerative disease-associated cases. We performed the DNA methylation analyses of Alzheimer's disease, dementia with Lewy bodies, Parkinson's disease and Alzheimer-like neurodegenerative profile associated with Down's syndrome samples. The DNA methylation landscapes obtained show that neurodegenerative diseases share similar aberrant CpG methylation shifts targeting a defined gene set. Our findings suggest that neurodegenerative disorders might have similar pathogenetic mechanisms that subsequently evolve into different clinical entities. The identified aberrant DNA methylation changes can be used as biomarkers of the disorders and as potential new targets for the development of new therapies.

  17. Human DNA methylomes of neurodegenerative diseases show common epigenomic patterns

    PubMed Central

    Sanchez-Mut, J V; Heyn, H; Vidal, E; Moran, S; Sayols, S; Delgado-Morales, R; Schultz, M D; Ansoleaga, B; Garcia-Esparcia, P; Pons-Espinal, M; de Lagran, M M; Dopazo, J; Rabano, A; Avila, J; Dierssen, M; Lott, I; Ferrer, I; Ecker, J R; Esteller, M

    2016-01-01

    Different neurodegenerative disorders often show similar lesions, such as the presence of amyloid plaques, TAU-neurotangles and synuclein inclusions. The genetically inherited forms are rare, so we wondered whether shared epigenetic aberrations, such as those affecting DNA methylation, might also exist. The studied samples were gray matter samples from the prefrontal cortex of control and neurodegenerative disease-associated cases. We performed the DNA methylation analyses of Alzheimer's disease, dementia with Lewy bodies, Parkinson's disease and Alzheimer-like neurodegenerative profile associated with Down's syndrome samples. The DNA methylation landscapes obtained show that neurodegenerative diseases share similar aberrant CpG methylation shifts targeting a defined gene set. Our findings suggest that neurodegenerative disorders might have similar pathogenetic mechanisms that subsequently evolve into different clinical entities. The identified aberrant DNA methylation changes can be used as biomarkers of the disorders and as potential new targets for the development of new therapies. PMID:26784972

  18. Autophagy of mitochondria: a promising therapeutic target for neurodegenerative disease.

    PubMed

    Kamat, Pradip K; Kalani, Anuradha; Kyles, Philip; Tyagi, Suresh C; Tyagi, Neetu

    2014-11-01

    The autophagic process is the only known mechanism for mitochondrial turnover and it has been speculated that dysfunction of autophagy may result in mitochondrial error and cellular stress. Emerging investigations have provided new understanding of how autophagy of mitochondria (also known as mitophagy) is associated with cellular oxidative stress and its impact on neurodegeneration. This impaired autophagic function may be considered as a possible mechanism in the pathogenesis of several neurodegenerative disorders including Parkinson's disease, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington disease. It can be suggested that autophagy dysfunction along with oxidative stress is considered main events in neurodegenerative disorders. New therapeutic approaches have now begun to target mitochondria as a potential drug target. This review discusses evidence supporting the notion that oxidative stress and autophagy are intimately associated with neurodegenerative disease pathogenesis. This review also explores new approaches that can prevent mitochondrial dysfunction, improve neurodegenerative etiology, and also offer possible cures to the aforementioned neurodegenerative diseases.

  19. Auditory Learning. Dimensions in Early Learning Series.

    ERIC Educational Resources Information Center

    Zigmond, Naomi K.; Cicci, Regina

    The monograph discusses the psycho-physiological operations for processing of auditory information, the structure and function of the ear, the development of auditory processes from fetal responses through discrimination, language comprehension, auditory memory, and auditory processes related to written language. Disorders of auditory learning…

  20. Auditory Processing Disorders. Revised. Technical Assistance Paper.

    ERIC Educational Resources Information Center

    Florida State Dept. of Education, Tallahassee. Bureau of Instructional Support and Community Services.

    Designed to assist audiologists in the educational setting in responding to frequently asked questions concerning audiological auditory processing disorder (APD) evaluations, this paper addresses: (1) auditory processes; (2) auditory processing skills; (3) characteristics of auditory processing disorders; (4) causes of auditory overload; (5) why…

  1. Auditory Learning. Dimensions in Early Learning Series.

    ERIC Educational Resources Information Center

    Zigmond, Naomi K.; Cicci, Regina

    The monograph discusses the psycho-physiological operations for processing of auditory information, the structure and function of the ear, the development of auditory processes from fetal responses through discrimination, language comprehension, auditory memory, and auditory processes related to written language. Disorders of auditory learning…

  2. Incorporating Auditory Models in Speech/Audio Applications

    NASA Astrophysics Data System (ADS)

    Krishnamoorthi, Harish

    2011-12-01

    Following the success in incorporating perceptual models in audio coding algorithms, their application in other speech/audio processing systems is expanding. In general, all perceptual speech/audio processing algorithms involve minimization of an objective function that directly/indirectly incorporates properties of human perception. This dissertation primarily investigates the problems associated with directly embedding an auditory model in the objective function formulation and proposes possible solutions to overcome high complexity issues for use in real-time speech/audio algorithms. Specific problems addressed in this dissertation include: 1) the development of approximate but computationally efficient auditory model implementations that are consistent with the principles of psychoacoustics, 2) the development of a mapping scheme that allows synthesizing a time/frequency domain representation from its equivalent auditory model output. The first problem is aimed at addressing the high computational complexity involved in solving perceptual objective functions that require repeated application of auditory model for evaluation of different candidate solutions. In this dissertation, a frequency pruning and a detector pruning algorithm is developed that efficiently implements the various auditory model stages. The performance of the pruned model is compared to that of the original auditory model for different types of test signals in the SQAM database. Experimental results indicate only a 4-7% relative error in loudness while attaining up to 80-90 % reduction in computational complexity. Similarly, a hybrid algorithm is developed specifically for use with sinusoidal signals and employs the proposed auditory pattern combining technique together with a look-up table to store representative auditory patterns. The second problem obtains an estimate of the auditory representation that minimizes a perceptual objective function and transforms the auditory pattern back to

  3. Visual enhancement of auditory beat perception across auditory interference levels.

    PubMed

    Su, Yi-Huang

    2014-10-01

    This study dealt with audiovisual rhythm perception involving an observed movement. Two experiments investigated whether a visual beat conveyed by a bouncing human point-light figure facilitated beat perception of concurrent auditory rhythms, and whether this enhancement followed a profile of multisensory integration. In Experiment 1, participants listened to three repetitions of a metrically simple rhythm and detected a perturbation in the third repetition. The rhythm was presented alone or with a visual beat in phase to it. Both conditions were presented with or without an auditory interference sequence at four increasing tempi, which served to progressively weaken the beat of the auditory rhythm. In Experiment 2, participants tapped to a regular auditory beat in the same combinations of visual beat and auditory interference. Results showed that the visual beat improved the perception of (Experiment 1) and the synchronization to (Experiment 2) the auditory rhythms. Moreover, in both experiments, visual enhancement was greater when the performance in the unisensory (auditory) conditions was poorer, consistent with the principle of inverse effectiveness. The relative multisensory gain increased as auditory performance deteriorated, except in one intermediate level. Together these results demonstrate that rhythmic visual movement aids auditory rhythm perception, which may be subserved by a perceptually integrated audiovisual beat that couples the internal motor system. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Central auditory disorders: toward a neuropsychology of auditory objects

    PubMed Central

    Goll, Johanna C.; Crutch, Sebastian J.; Warren, Jason D.

    2012-01-01

    Purpose of review Analysis of the auditory environment, source identification and vocal communication all require efficient brain mechanisms for disambiguating, representing and understanding complex natural sounds as ‘auditory objects’. Failure of these mechanisms leads to a diverse spectrum of clinical deficits. Here we review current evidence concerning the phenomenology, mechanisms and brain substrates of auditory agnosias and related disorders of auditory object processing. Recent findings Analysis of lesions causing auditory object deficits has revealed certain broad anatomical correlations: deficient parsing of the auditory scene is associated with lesions involving the parieto-temporal junction, while selective disorders of sound recognition occur with more anterior temporal lobe or extra-temporal damage. Distributed neural networks have been increasingly implicated in the pathogenesis of such disorders as developmental dyslexia, congenital amusia and tinnitus. Auditory category deficits may arise from defective interaction of spectrotemporal encoding and executive and mnestic processes. Dedicated brain mechanisms are likely to process specialised sound objects such as voices and melodies. Summary Emerging empirical evidence suggests a clinically relevant, hierarchical and fractionated neuropsychological model of auditory object processing that provides a framework for understanding auditory agnosias and makes specific predictions to direct future work. PMID:20975559

  5. Complex Auditory Signals

    DTIC Science & Technology

    1988-09-01

    Journal of the Acoustical Society of America, 56, 1835-1847. Sachs, M. B., and Young, E.ID. (1979). Encoding of steady-state vowels in the auditory nerve...amplitude to the amplitude of that component of the standard in decibels . If the signal amplitude is one-eighth the amplitude of the com- ponent of the...Isolated pure tone appears to have little to do with how we recognize differences between vowels or broadband consonants. The simplicity of

  6. Early hominin auditory capacities.

    PubMed

    Quam, Rolf; Martínez, Ignacio; Rosa, Manuel; Bonmatí, Alejandro; Lorenzo, Carlos; de Ruiter, Darryl J; Moggi-Cecchi, Jacopo; Conde Valverde, Mercedes; Jarabo, Pilar; Menter, Colin G; Thackeray, J Francis; Arsuaga, Juan Luis

    2015-09-01

    Studies of sensory capacities in past life forms have offered new insights into their adaptations and lifeways. Audition is particularly amenable to study in fossils because it is strongly related to physical properties that can be approached through their skeletal structures. We have studied the anatomy of the outer and middle ear in the early hominin taxa Australopithecus africanus and Paranthropus robustus and estimated their auditory capacities. Compared with chimpanzees, the early hominin taxa are derived toward modern humans in their slightly shorter and wider external auditory canal, smaller tympanic membrane, and lower malleus/incus lever ratio, but they remain primitive in the small size of their stapes footplate. Compared with chimpanzees, both early hominin taxa show a heightened sensitivity to frequencies between 1.5 and 3.5 kHz and an occupied band of maximum sensitivity that is shifted toward slightly higher frequencies. The results have implications for sensory ecology and communication, and suggest that the early hominin auditory pattern may have facilitated an increased emphasis on short-range vocal communication in open habitats.

  7. Early hominin auditory capacities

    PubMed Central

    Quam, Rolf; Martínez, Ignacio; Rosa, Manuel; Bonmatí, Alejandro; Lorenzo, Carlos; de Ruiter, Darryl J.; Moggi-Cecchi, Jacopo; Conde Valverde, Mercedes; Jarabo, Pilar; Menter, Colin G.; Thackeray, J. Francis; Arsuaga, Juan Luis

    2015-01-01

    Studies of sensory capacities in past life forms have offered new insights into their adaptations and lifeways. Audition is particularly amenable to study in fossils because it is strongly related to physical properties that can be approached through their skeletal structures. We have studied the anatomy of the outer and middle ear in the early hominin taxa Australopithecus africanus and Paranthropus robustus and estimated their auditory capacities. Compared with chimpanzees, the early hominin taxa are derived toward modern humans in their slightly shorter and wider external auditory canal, smaller tympanic membrane, and lower malleus/incus lever ratio, but they remain primitive in the small size of their stapes footplate. Compared with chimpanzees, both early hominin taxa show a heightened sensitivity to frequencies between 1.5 and 3.5 kHz and an occupied band of maximum sensitivity that is shifted toward slightly higher frequencies. The results have implications for sensory ecology and communication, and suggest that the early hominin auditory pattern may have facilitated an increased emphasis on short-range vocal communication in open habitats. PMID:26601261

  8. High School Football and Late-Life Risk of Neurodegenerative Syndromes, 1956-1970.

    PubMed

    Janssen, Pieter H H; Mandrekar, Jay; Mielke, Michelle M; Ahlskog, J Eric; Boeve, Bradley F; Josephs, Keith; Savica, Rodolfo

    2017-01-01

    To assess whether athletes who played American varsity high school football between 1956 and 1970 have an increased risk of neurodegenerative diseases later in life. We identified all male varsity football players between 1956 and 1970 in the public high schools of Rochester, Minnesota, and non-football-playing male varsity swimmers, wrestlers, and basketball players. Using the medical records linkage system of the Rochester Epidemiology Project, we ascertained the incidence of late-life neurodegenerative diseases: dementia, parkinsonism, and amyotrophic lateral sclerosis. We also recorded medical record-documented head trauma during high school years. We identified 296 varsity football players and 190 athletes engaging in other sports. Football players had an increased risk of medically documented head trauma, especially if they played football for more than 1 year. Compared with nonfootball athletes, football players did not have an increased risk of neurodegenerative disease overall or of the individual conditions of dementia, parkinsonism, and amyotrophic lateral sclerosis. In this community-based study, varsity high school football players from 1956 to 1970 did not have an increased risk of neurodegenerative diseases compared with athletes engaged in other varsity sports. This was from an era when there was a generally nihilistic view of concussion dangers, less protective equipment, and no prohibition of spearing (head-first tackling). However, the size and strength of players from previous eras may not be comparable with that of current high school athletes. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  9. Auditory interfaces: The human perceiver

    NASA Technical Reports Server (NTRS)

    Colburn, H. Steven

    1991-01-01

    A brief introduction to the basic auditory abilities of the human perceiver with particular attention toward issues that may be important for the design of auditory interfaces is presented. The importance of appropriate auditory inputs to observers with normal hearing is probably related to the role of hearing as an omnidirectional, early warning system and to its role as the primary vehicle for communication of strong personal feelings.

  10. High Content Screening in Neurodegenerative Diseases

    PubMed Central

    Jain, Shushant; van Kesteren, Ronald E.; Heutink, Peter

    2012-01-01

    The functional annotation of genomes, construction of molecular networks and novel drug target identification, are important challenges that need to be addressed as a matter of great urgency1-4. Multiple complementary 'omics' approaches have provided clues as to the genetic risk factors and pathogenic mechanisms underlying numerous neurodegenerative diseases, but most findings still require functional validation5. For example, a recent genome wide association study for Parkinson's Disease (PD), identified many new loci as risk factors for the disease, but the underlying causative variant(s) or pathogenic mechanism is not known6, 7. As each associated region can contain several genes, the functional evaluation of each of the genes on phenotypes associated with the disease, using traditional cell biology techniques would take too long. There is also a need to understand the molecular networks that link genetic mutations to the phenotypes they cause. It is expected that disease phenotypes are the result of multiple interactions that have been disrupted. Reconstruction of these networks using traditional molecular methods would be time consuming. Moreover, network predictions from independent studies of individual components, the reductionism approach, will probably underestimate the network complexity8. This underestimation could, in part, explain the low success rate of drug approval due to undesirable or toxic side effects. Gaining a network perspective of disease related pathways using HT/HC cellular screening approaches, and identifying key nodes within these pathways, could lead to the identification of targets that are more suited for therapeutic intervention. High-throughput screening (HTS) is an ideal methodology to address these issues9-12. but traditional methods were one dimensional whole-well cell assays, that used simplistic readouts for complex biological processes. They were unable to simultaneously quantify the many phenotypes observed in

  11. Brainstem: Neglected Locus in Neurodegenerative Diseases

    PubMed Central

    Grinberg, Lea Tenenholz; Rueb, Udo; Heinsen, Helmut

    2011-01-01

    The most frequent neurodegenerative diseases (NDs) are Alzheimer’s disease (AD), Parkinson’s disease (PD), and frontotemporal lobar degeneration associated with protein TDP-43 (FTLD–TDP). Neuropathologically, NDs are characterized by abnormal intracellular and extra-cellular protein deposits and by disease-specific neuronal death. Practically all terminal stages of NDs are clinically associated with dementia. Therefore, major attention was directed to protein deposits and neuron loss in supratentorial (telencephalic) brain regions in the course of NDs. This was also true for PD, although the pathological hallmark of PD is degeneration of pigmented neurons of the brainstem’s substantia nigra (SN). However, PD pathophysiology was explained by dopamine depletion in the telencephalic basal ganglia due to insufficiency and degeneration of the projection neurons located in SN. In a similar line of argumentation AD- and FTLD-related clinical deficits were exclusively explained by supratentorial allo- and neo-cortical laminar neuronal necrosis. Recent comprehensive studies in AD and PD early stages found considerable and unexpected involvement of brainstem nuclei, which could have the potential to profoundly change our present concepts on origin, spread, and early clinical diagnosis of these diseases. In contrast with PD and AD, few studies addressed brainstem involvement in the course of the different types of FTLD–TDP. Some of the results, including ours, disclosed a higher and more widespread pathology than anticipated. The present review will focus mainly on the impact of brainstem changes during the course of the most frequent NDs including PD, AD, and FTLD–TDP, with special emphasis on the need for more comprehensive research on FTLDs. PMID:21808630

  12. Subcortical processing in auditory communication.

    PubMed

    Pannese, Alessia; Grandjean, Didier; Frühholz, Sascha

    2015-10-01

    The voice is a rich source of information, which the human brain has evolved to decode and interpret. Empirical observations have shown that the human auditory system is especially sensitive to the human voice, and that activity within the voice-sensitive regions of the primary and secondary auditory cortex is modulated by the emotional quality of the vocal signal, and may therefore subserve, with frontal regions, the cognitive ability to correctly identify the speaker's affective state. So far, the network involved in the processing of vocal affect has been mainly characterised at the cortical level. However, anatomical and functional evidence suggests that acoustic information relevant to the affective quality of the auditory signal might be processed prior to the auditory cortex. Here we review the animal and human literature on the main subcortical structures along the auditory pathway, and propose a model whereby the distinction between different types of vocal affect in auditory communication begins at very early stages of auditory processing, and relies on the analysis of individual acoustic features of the sound signal. We further suggest that this early feature-based decoding occurs at a subcortical level along the ascending auditory pathway, and provides a preliminary coarse (but fast) characterisation of the affective quality of the auditory signal before the more refined (but slower) cortical processing is completed.

  13. Selective adaptation to "oddball" sounds by the human auditory system.

    PubMed

    Simpson, Andrew J R; Harper, Nicol S; Reiss, Joshua D; McAlpine, David

    2014-01-29

    Adaptation to both common and rare sounds has been independently reported in neurophysiological studies using probabilistic stimulus paradigms in small mammals. However, the apparent sensitivity of the mammalian auditory system to the statistics of incoming sound has not yet been generalized to task-related human auditory perception. Here, we show that human listeners selectively adapt to novel sounds within scenes unfolding over minutes. Listeners' performance in an auditory discrimination task remains steady for the most common elements within the scene but, after the first minute, performance improves for distinct and rare (oddball) sound elements, at the expense of rare sounds that are relatively less distinct. Our data provide the first evidence of enhanced coding of oddball sounds in a human auditory discrimination task and suggest the existence of an adaptive mechanism that tracks the long-term statistics of sounds and deploys coding resources accordingly.

  14. Renin-angiotensin system gene expression and neurodegenerative diseases.

    PubMed

    Goldstein, Benjamin; Speth, Robert C; Trivedi, Malav

    2016-07-01

    Single nucleotide polymorphisms and altered gene expression of components of the renin-angiotensin system (RAS) are associated with neurodegenerative diseases. Drugs that interact with the RAS have been shown to affect the course of neurodegenerative disease, suggesting that abnormalities in the RAS may contribute to neurodegenerative disease. A meta-analysis of genome-wide association studies and gene expression data for 14 RAS-related proteins was carried out for five neurodegenerative diseases: Alzheimer's disease, Parkinson's disease, narcolepsy, amyotrophic lateral sclerosis and multiple sclerosis. No single nucleotide polymorphisms in any of the 14 RAS-related protein genes were significantly associated with the five neurodegenerative diseases investigated. There was an inverse association between expression of ATP6AP2, which encodes the (pro)renin receptor, and multiple sclerosis, Alzheimer's disease and Parkinson's disease. An association of AGTR, which encodes the AT1 angiotensin II receptor, and Parkinson's disease and Alzheimer's disease was also observed. To date, no single nucleotide polymorphisms in components of the RAS can be definitively linked to the neurodegenerative diseases evaluated in this study. However, altered gene expression of several components of the RAS is associated with several neurodegenerative diseases, which may indicate that the RAS contributes to the pathology of these diseases. © The Author(s) 2016.

  15. Dysregulation of Ubiquitin-Proteasome System in Neurodegenerative Diseases

    PubMed Central

    Zheng, Qiuyang; Huang, Timothy; Zhang, Lishan; Zhou, Ying; Luo, Hong; Xu, Huaxi; Wang, Xin

    2016-01-01

    The ubiquitin-proteasome system (UPS) is one of the major protein degradation pathways, where abnormal UPS function has been observed in cancer and neurological diseases. Many neurodegenerative diseases share a common pathological feature, namely intracellular ubiquitin-positive inclusions formed by aggregate-prone neurotoxic proteins. This suggests that dysfunction of the UPS in neurodegenerative diseases contributes to the accumulation of neurotoxic proteins and to instigate neurodegeneration. Here, we review recent findings describing various aspects of UPS dysregulation in neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. PMID:28018215

  16. Auditory Discrimination and Auditory Sensory Behaviours in Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Jones, Catherine R. G.; Happe, Francesca; Baird, Gillian; Simonoff, Emily; Marsden, Anita J. S.; Tregay, Jenifer; Phillips, Rebecca J.; Goswami, Usha; Thomson, Jennifer M.; Charman, Tony

    2009-01-01

    It has been hypothesised that auditory processing may be enhanced in autism spectrum disorders (ASD). We tested auditory discrimination ability in 72 adolescents with ASD (39 childhood autism; 33 other ASD) and 57 IQ and age-matched controls, assessing their capacity for successful discrimination of the frequency, intensity and duration…

  17. The Central Auditory Processing Kit[TM]. Book 1: Auditory Memory [and] Book 2: Auditory Discrimination, Auditory Closure, and Auditory Synthesis [and] Book 3: Auditory Figure-Ground, Auditory Cohesion, Auditory Binaural Integration, and Compensatory Strategies.

    ERIC Educational Resources Information Center

    Mokhemar, Mary Ann

    This kit for assessing central auditory processing disorders (CAPD), in children in grades 1 through 8 includes 3 books, 14 full-color cards with picture scenes, and a card depicting a phone key pad, all contained in a sturdy carrying case. The units in each of the three books correspond with auditory skill areas most commonly addressed in…

  18. The Central Auditory Processing Kit[TM]. Book 1: Auditory Memory [and] Book 2: Auditory Discrimination, Auditory Closure, and Auditory Synthesis [and] Book 3: Auditory Figure-Ground, Auditory Cohesion, Auditory Binaural Integration, and Compensatory Strategies.

    ERIC Educational Resources Information Center

    Mokhemar, Mary Ann

    This kit for assessing central auditory processing disorders (CAPD), in children in grades 1 through 8 includes 3 books, 14 full-color cards with picture scenes, and a card depicting a phone key pad, all contained in a sturdy carrying case. The units in each of the three books correspond with auditory skill areas most commonly addressed in…

  19. The need for harmonisation and innovation of neuropsychological assessment in neurodegenerative dementias in Europe: consensus document of the Joint Program for Neurodegenerative Diseases Working Group.

    PubMed

    Costa, Alberto; Bak, Thomas; Caffarra, Paolo; Caltagirone, Carlo; Ceccaldi, Mathieu; Collette, Fabienne; Crutch, Sebastian; Della Sala, Sergio; Démonet, Jean François; Dubois, Bruno; Duzel, Emrah; Nestor, Peter; Papageorgiou, Sokratis G; Salmon, Eric; Sikkes, Sietske; Tiraboschi, Pietro; van der Flier, Wiesje M; Visser, Pieter Jelle; Cappa, Stefano F

    2017-04-17

    Cognitive, behavioural, and functional assessment is crucial in longitudinal studies of neurodegenerative dementias (NDD). Central issues, such as the definition of the study population (asymptomatic, at risk, or individuals with dementia), the detection of change/decline, and the assessment of relevant outcomes depend on quantitative measures of cognitive, behavioural, and functional status.Currently, we are far from having available reliable protocols and tools for the assessment of dementias in Europe. The main problems are the heterogeneity of the tools used across different European countries, the lack of standardisation of administration and scoring methods across centres, and the limited information available about the psychometric properties of many tests currently in widespread use. This situation makes it hard to compare results across studies carried out in different centres, thus hampering research progress, in particular towards the contribution to a "big data" common data set.We present here the results of a project funded by the Joint Program for Neurodegenerative Diseases (JPND) and by the Italian Ministry of Health. The project aimed at providing a consensus framework for the harmonisation of assessment tools to be applied to research in neurodegenerative disorders affecting cognition across Europe. A panel of European experts reviewed the current methods of neuropsychological assessment, identified pending issues, and made recommendations for the harmonisation of neuropsychological assessment of neurodegenerative dementias in Europe.A consensus was achieved on the general recommendations to be followed in developing procedures and tools for neuropsychological assessment, with the aim of harmonising tools and procedures to achieve more reliable data on the cognitive-behavioural examination. The results of this study should be considered as a first step to enhancing a common view and practise on NDD assessment across European countries.

  20. Auditory Reserve and the Legacy of Auditory Experience

    PubMed Central

    Skoe, Erika; Kraus, Nina

    2014-01-01

    Musical training during childhood has been linked to more robust encoding of sound later in life. We take this as evidence for an auditory reserve: a mechanism by which individuals capitalize on earlier life experiences to promote auditory processing. We assert that early auditory experiences guide how the reserve develops and is maintained over the lifetime. Experiences that occur after childhood, or which are limited in nature, are theorized to affect the reserve, although their influence on sensory processing may be less long-lasting and may potentially fade over time if not repeated. This auditory reserve may help to explain individual differences in how individuals cope with auditory impoverishment or loss of sensorineural function. PMID:25405381

  1. Central auditory neurons have composite receptive fields

    PubMed Central

    Kozlov, Andrei S.; Gentner, Timothy Q.

    2016-01-01

    High-level neurons processing complex, behaviorally relevant signals are sensitive to conjunctions of features. Characterizing the receptive fields of such neurons is difficult with standard statistical tools, however, and the principles governing their organization remain poorly understood. Here, we demonstrate multiple distinct receptive-field features in individual high-level auditory neurons in a songbird, European starling, in response to natural vocal signals (songs). We then show that receptive fields with similar characteristics can be reproduced by an unsupervised neural network trained to represent starling songs with a single learning rule that enforces sparseness and divisive normalization. We conclude that central auditory neurons have composite receptive fields that can arise through a combination of sparseness and normalization in neural circuits. Our results, along with descriptions of random, discontinuous receptive fields in the central olfactory neurons in mammals and insects, suggest general principles of neural computation across sensory systems and animal classes. PMID:26787894

  2. Minimal effects of visual memory training on the auditory performance of adult cochlear implant users

    PubMed Central

    Oba, Sandra I.; Galvin, John J.; Fu, Qian-Jie

    2014-01-01

    Auditory training has been shown to significantly improve cochlear implant (CI) users’ speech and music perception. However, it is unclear whether post-training gains in performance were due to improved auditory perception or to generally improved attention, memory and/or cognitive processing. In this study, speech and music perception, as well as auditory and visual memory were assessed in ten CI users before, during, and after training with a non-auditory task. A visual digit span (VDS) task was used for training, in which subjects recalled sequences of digits presented visually. After the VDS training, VDS performance significantly improved. However, there were no significant improvements for most auditory outcome measures (auditory digit span, phoneme recognition, sentence recognition in noise, digit recognition in noise), except for small (but significant) improvements in vocal emotion recognition and melodic contour identification. Post-training gains were much smaller with the non-auditory VDS training than observed in previous auditory training studies with CI users. The results suggest that post-training gains observed in previous studies were not solely attributable to improved attention or memory, and were more likely due to improved auditory perception. The results also suggest that CI users may require targeted auditory training to improve speech and music perception. PMID:23516087

  3. Recent developments in tau-based therapeutics for neurodegenerative diseases.

    PubMed

    Medina, Miguel

    2011-01-01

    Neurodegenerative diseases constitute a major public health issue due to an increasingly aged population as a consequence of generally improved medical care and demographic changes. Current drug treatment of Alzheimer's disease (AD), the most prevalent dementia, with cholinesterase inhibitors or NMDA antagonists has demonstrated very modest, symptomatic efficacy, leaving an unmet medical need for new, more effective therapies. Drug development efforts for AD in the last two decades have primarily focused on targets defined by the amyloid cascade hypothesis, so far with disappointing results. In contrast, tau-based strategies have received little attention until recently despite that the presence of extensive tau pathology is central to the disease. The discovery of mutations within the tau gene that cause fronto-temporal dementia demonstrated that tau dysfunction, in the absence of amyloid pathology, was sufficient to cause neuronal loss and clinical dementia. This review focuses on emerging therapeutic strategies aimed at treating the underlying causes of the tau pathology in tauopathies and AD, including some targets with significant potential in the field and which might be on the verge of providing new treatment paradigms within the coming years. Among those strategies, immunotherapy approaches will be mostly discussed. An update on 2010 patents regarding different aspects of tau-based therapeutic strategies is also provided.

  4. Stress, Allostatic Load, Catecholamines, and Other Neurotransmitters in Neurodegenerative Diseases

    PubMed Central

    2016-01-01

    As populations age, the prevalence of geriatric neurodegenerative diseases will increase. These diseases generally are multifactorial, arising from complex interactions among genes, environment, concurrent morbidities, treatments, and time. This essay provides a concept for the pathogenesis of Lewy body diseases such as Parkinson disease, by considering them in the context of allostasis and allostatic load. Allostasis reflects active, adaptive processes that maintain apparent steady states, via multiple, interacting effectors regulated by homeostatic comparators—“homeostats.” Stress can be defined as a condition or state in which a sensed discrepancy between afferent information and a setpoint for response leads to activation of effectors, reducing the discrepancy. “Allostatic load” refers to the consequences of sustained or repeated activation of mediators of allostasis. From the analogy of an idling car, the revolutions per minute of the engine can be maintained at any of a variety of levels (allostatic states). Just as allostatic load (cumulative wear and tear) reflects design and manufacturing variations, byproducts of combustion, and time, eventually leading to engine breakdown, allostatic load in catecholaminergic neurons might eventually lead to Lewy body diseases. Central to the argument is that catecholaminergic neurons leak vesicular contents into the cytoplasm continuously during life and that catecholamines in the neuronal cytoplasm are autotoxic. These neurons therefore depend on vesicular sequestration to limit autotoxicity of cytosolic transmitter. Parkinson disease might be a disease of the elderly because of allostatic load, which depends on genetic predispositions, environmental exposures, repeated stress-related catecholamine release, and time. PMID:22297542

  5. Stress, Allostatic Load, Catecholamines, and Other Neurotransmitters in Neurodegenerative Diseases

    PubMed Central

    2017-01-01

    As populations age, the prevalence of geriatric neurodegenerative diseases will increase. These diseases generally are multifactorial, arising from complex interactions among genes, environment, concurrent morbidities, treatments, and time. This essay provides a concept for the pathogenesis of Lewy body diseases such as Parkinson disease, by considering them in the context of allostasis and allostatic load. Allostasis reflects active, adaptive processes that maintain apparent steady states, via multiple, interacting effectors regulated by homeostatic comparators—“homeostats.” Stress can be defined as a condition or state in which a sensed discrepancy between afferent information and a setpoint for response leads to activation of effectors, reducing the discrepancy. “Allostatic load” refers to the consequences of sustained or repeated activation of mediators of allostasis. From the analogy of an idling car, the revolutions per minute of the engine can be maintained at any of a variety of levels (allostatic states). Just as allostatic load (cumulative wear and tear) reflects design and manufacturing variations, byproducts of combustion, and time, eventually leading to engine breakdown, allostatic load in catecholaminergic neurons might eventually lead to Lewy body diseases. Central to the argument is that catecholaminergic neurons leak vesicular contents into the cytoplasm continuously during life and that catecholamines in the neuronal cytoplasm are autotoxic. These neurons therefore depend on vesicular sequestration to limit autotoxicity of cytosolic transmitter. Parkinson disease might be a disease of the elderly because of allostatic load, which depends on genetic predispositions, environmental exposures, repeated stress-related catecholamine release, and time. PMID:21615193

  6. Auditory neglect and related disorders.

    PubMed

    Gutschalk, Alexander; Dykstra, Andrew

    2015-01-01

    Neglect is a neurologic disorder, typically associated with lesions of the right hemisphere, in which patients are biased towards their ipsilesional - usually right - side of space while awareness for their contralesional - usually left - side is reduced or absent. Neglect is a multimodal disorder that often includes deficits in the auditory domain. Classically, auditory extinction, in which left-sided sounds that are correctly perceived in isolation are not detected in the presence of synchronous right-sided stimulation, has been considered the primary sign of auditory neglect. However, auditory extinction can also be observed after unilateral auditory cortex lesions and is thus not specific for neglect. Recent research has shown that patients with neglect are also impaired in maintaining sustained attention, on both sides, a fact that is reflected by an impairment of auditory target detection in continuous stimulation conditions. Perhaps the most impressive auditory symptom in full-blown neglect is alloacusis, in which patients mislocalize left-sided sound sources to their right, although even patients with less severe neglect still often show disturbance of auditory spatial perception, most commonly a lateralization bias towards the right. We discuss how these various disorders may be explained by a single model of neglect and review emerging interventions for patient rehabilitation.

  7. Auditory hallucinations in Parkinson's disease

    PubMed Central

    Inzelberg, R.; Kipervasser, S.; Korczyn, A.

    1998-01-01

    Whereas visual hallucinations are often found among patients with Parkinson's disease, the occurrence of auditory hallucinations has never been systematically documented. The occurrence, past and present, of auditory hallucinations has been studied in 121consecutive patients with Parkinson's disease attending a movement disorders clinic. The cognitive state was evaluated using the short mental test (SMT). Hallucinations were reported for 45patients (37%); 35 (29%) had only visual hallucinations and 10(8%) both visual and auditory hallucinations. No patient reported auditory hallucinations unaccompanied by visual hallucinations. The auditory hallucinations occurred repeatedly, consisting of human voices. They were non-imperative (n=9), non-paranoid (n=9), and often incomprehensible (n=5). They were not obviously influenced by the patients' age, duration of disease, or treatment with levodopa. Cognitive impairment was more common among hallucinating patients (64%, 50%, and 25% among patients with visual hallucinations, auditory hallucinations, and non-hallucinating parkinsonian patients respectively). Depression necessitating antidepressants was present in five of 10 and other psychotic features in six patients with auditory hallucinations. It is concluded that auditory hallucinations occur in Parkinson's disease, particularly in patients who also have visual hallucinations and are cognitively impaired.

 PMID:9576549

  8. Issues in Human Auditory Development

    ERIC Educational Resources Information Center

    Werner, Lynne A.

    2007-01-01

    The human auditory system is often portrayed as precocious in its development. In fact, many aspects of basic auditory processing appear to be adult-like by the middle of the first year of postnatal life. However, processes such as attention and sound source determination take much longer to develop. Immaturity of higher-level processes limits the…

  9. Word Recognition in Auditory Cortex

    ERIC Educational Resources Information Center

    DeWitt, Iain D. J.

    2013-01-01

    Although spoken word recognition is more fundamental to human communication than text recognition, knowledge of word-processing in auditory cortex is comparatively impoverished. This dissertation synthesizes current models of auditory cortex, models of cortical pattern recognition, models of single-word reading, results in phonetics and results in…

  10. Word Recognition in Auditory Cortex

    ERIC Educational Resources Information Center

    DeWitt, Iain D. J.

    2013-01-01

    Although spoken word recognition is more fundamental to human communication than text recognition, knowledge of word-processing in auditory cortex is comparatively impoverished. This dissertation synthesizes current models of auditory cortex, models of cortical pattern recognition, models of single-word reading, results in phonetics and results in…

  11. Attention to natural auditory signals.

    PubMed

    Caporello Bluvas, Emily; Gentner, Timothy Q

    2013-11-01

    The challenge of understanding how the brain processes natural signals is compounded by the fact that such signals are often tied closely to specific natural behaviors and natural environments. This added complexity is especially true for auditory communication signals that can carry information at multiple hierarchical levels, and often occur in the context of other competing communication signals. Selective attention provides a mechanism to focus processing resources on specific components of auditory signals, and simultaneously suppress responses to unwanted signals or noise. Although selective auditory attention has been well-studied behaviorally, very little is known about how selective auditory attention shapes the processing on natural auditory signals, and how the mechanisms of auditory attention are implemented in single neurons or neural circuits. Here we review the role of selective attention in modulating auditory responses to complex natural stimuli in humans. We then suggest how the current understanding can be applied to the study of selective auditory attention in the context natural signal processing at the level of single neurons and populations in animal models amenable to invasive neuroscience techniques. This article is part of a Special Issue entitled "Communication Sounds and the Brain: New Directions and Perspectives".

  12. Imaging plus X: multimodal models of neurodegenerative disease.

    PubMed

    Oxtoby, Neil P; Alexander, Daniel C

    2017-08-01

    This article argues that the time is approaching for data-driven disease modelling to take centre stage in the study and management of neurodegenerative disease. The snowstorm of data now available to the clinician defies qualitative evaluation; the heterogeneity of data types complicates integration through traditional statistical methods; and the large datasets becoming available remain far from the big-data sizes necessary for fully data-driven machine-learning approaches. The recent emergence of data-driven disease progression models provides a balance between imposed knowledge of disease features and patterns learned from data. The resulting models are both predictive of disease progression in individual patients and informative in terms of revealing underlying biological patterns. Largely inspired by observational models, data-driven disease progression models have emerged in the last few years as a feasible means for understanding the development of neurodegenerative diseases. These models have revealed insights into frontotemporal dementia, Huntington's disease, multiple sclerosis, Parkinson's disease and other conditions. For example, event-based models have revealed finer graded understanding of progression patterns; self-modelling regression and differential equation models have provided data-driven biomarker trajectories; spatiotemporal models have shown that brain shape changes, for example of the hippocampus, can occur before detectable neurodegeneration; and network models have provided some support for prion-like mechanistic hypotheses of disease propagation. The most mature results are in sporadic Alzheimer's disease, in large part because of the availability of the Alzheimer's disease neuroimaging initiative dataset. Results generally support the prevailing amyloid-led hypothetical model of Alzheimer's disease, while revealing finer detail and insight into disease progression. The emerging field of disease progression modelling provides a natural

  13. Imaging plus X: multimodal models of neurodegenerative disease

    PubMed Central

    Oxtoby, Neil P.; Alexander, Daniel C.

    2017-01-01

    Purpose of review This article argues that the time is approaching for data-driven disease modelling to take centre stage in the study and management of neurodegenerative disease. The snowstorm of data now available to the clinician defies qualitative evaluation; the heterogeneity of data types complicates integration through traditional statistical methods; and the large datasets becoming available remain far from the big-data sizes necessary for fully data-driven machine-learning approaches. The recent emergence of data-driven disease progression models provides a balance between imposed knowledge of disease features and patterns learned from data. The resulting models are both predictive of disease progression in individual patients and informative in terms of revealing underlying biological patterns. Recent findings Largely inspired by observational models, data-driven disease progression models have emerged in the last few years as a feasible means for understanding the development of neurodegenerative diseases. These models have revealed insights into frontotemporal dementia, Huntington's disease, multiple sclerosis, Parkinson's disease and other conditions. For example, event-based models have revealed finer graded understanding of progression patterns; self-modelling regression and differential equation models have provided data-driven biomarker trajectories; spatiotemporal models have shown that brain shape changes, for example of the hippocampus, can occur before detectable neurodegeneration; and network models have provided some support for prion-like mechanistic hypotheses of disease propagation. The most mature results are in sporadic Alzheimer's disease, in large part because of the availability of the Alzheimer's disease neuroimaging initiative dataset. Results generally support the prevailing amyloid-led hypothetical model of Alzheimer's disease, while revealing finer detail and insight into disease progression. Summary The emerging field of disease

  14. A future perspective on neurodegenerative diseases: nasopharyngeal and gut microbiota.

    PubMed

    Khan, F; Oloketuyi, S F

    2017-02-01

    Neurodegenerative diseases are considered a serious life-threatening issue regardless of age. Resulting nerve damage progressively affects important activities, such as movement, coordination, balance, breathing, speech and the functioning of vital organs. Reports on the subject have concluded that neurodegenerative disease can be caused by mutations of susceptible genes, alcohol consumption, toxins, chemicals and other unknown environmental factors. Although several diagnostic techniques can be used to determine aetiologies, the process is difficult and often fails. Research shows that nasopharyngeal and gut microbiota play important roles in brain to spinal cord coordination. However, no conclusive epidemiologic evidence is available on the roles played by respiratory and gut microbiota in the development of neurodegenerative diseases. Thus, understanding the connection between respiratory and gut microbiota and the nervous system could provide information on causal links. The present review describes future perspectives on the role played by nasopharyngeal and gut microbiota in the development of neurodegenerative diseases.

  15. Relationships between Stress Granules, Oxidative Stress, and Neurodegenerative Diseases

    PubMed Central

    2017-01-01

    Cytoplasmic stress granules (SGs) are critical for facilitating stress responses and for preventing the accumulation of misfolded proteins. SGs, however, have been linked to the pathogenesis of neurodegenerative diseases, in part because SGs share many components with neuronal granules. Oxidative stress is one of the conditions that induce SG formation. SGs regulate redox levels, and SG formation in turn is differently regulated by various types of oxidative stress. These associations and other evidences suggest that SG formation contributes to the development of neurodegenerative diseases. In this paper, we review the regulation of SG formation/assembly and discuss the interactions between oxidative stress and SG formation. We then discuss the links between SGs and neurodegenerative diseases and the current therapeutic approaches for neurodegenerative diseases that target SGs. PMID:28194255

  16. Neuro-Ophthalmic Manifestations of Pediatric Neurodegenerative Disease.

    PubMed

    Heidary, Gena

    2017-09-01

    The topic of pediatric neurodegenerative disease is broad and ever expanding. Children who suffer from neurodegenerative disease often have concomitant visual dysfunction. Neuro-ophthalmologists may become involved in clinical care to identify corroborating eye findings when a specific condition is suspected, to monitor for disease progression, and in some cases, to assess treatment efficacy. Ophthalmic findings also may be the harbinger of a neurodegenerative process so a keen awareness of the possible manifestations of these conditions is important. The purpose of this review is to highlight common examples of the neuro-ophthalmic manifestations of pediatric neurodegenerative disease using a case-based approach in an effort to provide a framework for approaching these complex patients.

  17. Neurodegenerative disorders: insights from the nematode Caenorhabditis elegans

    PubMed Central

    Dimitriadi, Maria; Hart, Anne C.

    2010-01-01

    Neurodegenerative diseases impose a burden on society, yet for the most part, the mechanisms underlying neuronal dysfunction and death in these disorders remain unclear despite the identification of relevant disease genes. Given the molecular conservation in neuronal signaling pathways across vertebrate and invertebrate species, many researchers have turned to the nematode Caenorhabditis elegans to identify the mechanisms underlying neurodegenerative disease pathology. C. elegans can be engineered to express human proteins associated with neurodegeneration; additionally, the function of C. elegans orthologs of human neurodegenerative disease genes can be dissected. Herein, we examine major C. elegans neurodegeneration models that recapitulate many aspects of human neurodegenerative disease and we survey the screens that have identified modifier genes. This review highlights how the C. elegans community has used this versatile organism to model several aspects of human neurodegeneration and how these studies have contributed to our understanding of human disease. PMID:20493260

  18. Neuron–astrocyte interactions in neurodegenerative diseases: Role of neuroinflammation

    PubMed Central

    Rama Rao, Kakulavarapu V.; Kielian, Tammy

    2015-01-01

    Selective neuron loss in discrete brain regions is a hallmark of various neurodegenerative disorders, although the mechanisms responsible for this regional vulnerability of neurons remain largely unknown. Earlier studies attributed neuron dysfunction and eventual loss during neurodegenerative diseases as exclusively cell autonomous. Although cell-intrinsic factors are one critical aspect in dictating neuron death, recent evidence also supports the involvement of other central nervous system cell types in propagating non-cell autonomous neuronal injury during neurodegenerative diseases. One such example is astrocytes, which support neuronal and synaptic function, but can also contribute to neuroinflammatory processes through robust chemokine secretion. Indeed, aberrations in astrocyte function have been shown to negatively impact neuronal integrity in several neurological diseases. The present review focuses on neuroinflammatory paradigms influenced by neuron–astrocyte cross-talk in the context of select neurodegenerative diseases. PMID:26543505

  19. The Perception of Auditory Motion

    PubMed Central

    Leung, Johahn

    2016-01-01

    The growing availability of efficient and relatively inexpensive virtual auditory display technology has provided new research platforms to explore the perception of auditory motion. At the same time, deployment of these technologies in command and control as well as in entertainment roles is generating an increasing need to better understand the complex processes underlying auditory motion perception. This is a particularly challenging processing feat because it involves the rapid deconvolution of the relative change in the locations of sound sources produced by rotational and translations of the head in space (self-motion) to enable the perception of actual source motion. The fact that we perceive our auditory world to be stable despite almost continual movement of the head demonstrates the efficiency and effectiveness of this process. This review examines the acoustical basis of auditory motion perception and a wide range of psychophysical, electrophysiological, and cortical imaging studies that have probed the limits and possible mechanisms underlying this perception. PMID:27094029

  20. Proceedings of the second international conference on auditory display, ICAD `94

    SciTech Connect

    Kramer, G.

    1995-12-31

    ICAD is a forum for presenting research on the use of sound to display data, monitor systems, and provide enhanced user interfaces for computers and virtual reality systems. It is unique in its singular focus on auditory displays and the array of perception, technology, and application areas that this encompasses. Research areas covered by ICAD include: auditory exploration of data via sonification (data controlled sound) and audification (audible playback of data samples); real time monitoring of multivariate data; sound in immersive interfaces (virtual reality) and teleoperation; perceptual issues in auditory display; sound in generalized computer interfaces; technologies supporting auditory display creation; data handling for auditory display systems; applications of auditory display. Included within each of these areas of inquiry are many issues concerning application, theory, hardware/software, and human factors. Integration with speech-audio implementations with graphical display techniques and their concomitant perception issues also pose significant challenges in each area.

  1. Pharmacogenetics in Neurodegenerative Diseases: Implications for Clinical Trials.

    PubMed

    Tortelli, Rosanna; Seripa, Davide; Panza, Francesco; Solfrizzi, Vincenzo; Logroscino, Giancarlo

    2016-01-01

    Pharmacogenetics has become extremely important over the last 20 years for identifying individuals more likely to be responsive to pharmacological interventions. The role of genetic background as a predictor of drug response is a young and mostly unexplored field in neurodegenerative diseases. Mendelian mutations in neurodegenerative diseases have been used as models for early diagnosis and intervention. On the other hand, genetic polymorphisms or risk factors for late-onset Alzheimer's disease (AD) or other neurodegenerative diseases, probably influencing drug response, are hardly taken into account in randomized clinical trial (RCT) design. The same is true for genetic variants in cytochrome P450 (CYP), the principal enzymes influencing drug metabolism. A better characterization of individual genetic background may optimize clinical trial design and personal drug response. This chapter describes the state of the art about the impact of genetic factors in RCTs on neurodegenerative disease, with AD, frontotemporal dementia, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease as examples. Furthermore, a brief description of the genetic bases of drug response focusing on neurodegenerative diseases will be conducted. The role of pharmacogenetics in RCTs for neurodegenerative diseases is still a young, unexplored, and promising field. Genetic tools allow increased sophistication in patient profiling and treatment optimization. Pharmaceutical companies are aware of the value of collecting genetic data during their RCTs. Pharmacogenetic research is bidirectional with RCTs: efficacy data are correlated with genetic polymorphisms, which in turn define subjects for treatment stratification. © 2016 S. Karger AG, Basel.

  2. Auditory color constancy

    NASA Astrophysics Data System (ADS)

    Kluender, Keith R.; Kiefte, Michael

    2003-10-01

    It is both true and efficient that sensorineural systems respond to change and little else. Perceptual systems do not record absolute level be it loudness, pitch, brightness, or color. This fact has been demonstrated in every sensory domain. For example, the visual system is remarkable at maintaining color constancy over widely varying illumination such as sunlight and varieties of artificial light (incandescent, fluorescent, etc.) for which spectra reflected from objects differ dramatically. Results will be reported for a series of experiments demonstrating how auditory systems similarly compensate for reliable characteristics of spectral shape in acoustic signals. Specifically, listeners' perception of vowel sounds, characterized by both local (e.g., formants) and broad (e.g., tilt) spectral composition, changes radically depending upon reliable spectral composition of precursor signals. These experiments have been conducted using a variety of precursor signals consisting of meaningful and time-reversed vocoded sentences, as well as novel nonspeech precursors consisting of multiple filter poles modulating sinusoidally across a source spectrum with specific local and broad spectral characteristics. Constancy across widely varying spectral compositions shares much in common with visual color constancy. However, auditory spectral constancy appears to be more effective than visual constancy in compensating for local spectral fluctuations. [Work supported by NIDCD DC-04072.

  3. Integrated processing of spatial cues in human auditory cortex.

    PubMed

    Salminen, Nelli H; Takanen, Marko; Santala, Olli; Lamminsalo, Jarkko; Altoè, Alessandro; Pulkki, Ville

    2015-09-01

    Human sound source localization relies on acoustical cues, most importantly, the interaural differences in time and level (ITD and ILD). For reaching a unified representation of auditory space the auditory nervous system needs to combine the information provided by these two cues. In search for such a unified representation, we conducted a magnetoencephalography (MEG) experiment that took advantage of the location-specific adaptation of the auditory cortical N1 response. In general, the attenuation caused by a preceding adaptor sound to the response elicited by a probe depends on their spatial arrangement: if the two sounds coincide, adaptation is stronger than when the locations differ. Here, we presented adaptor-probe pairs that contained different localization cues, for instance, adaptors with ITD and probes with ILD. We found that the adaptation of the N1 amplitude was location-specific across localization cues. This result can be explained by the existence of auditory cortical neurons that are sensitive to sound source location independent on which cue, ITD or ILD, provides the location information. Such neurons would form a cue-independent, unified representation of auditory space in human auditory cortex.

  4. Rapid estimation of high-parameter auditory-filter shapes

    PubMed Central

    Shen, Yi; Sivakumar, Rajeswari; Richards, Virginia M.

    2014-01-01

    A Bayesian adaptive procedure, the quick-auditory-filter (qAF) procedure, was used to estimate auditory-filter shapes that were asymmetric about their peaks. In three experiments, listeners who were naive to psychoacoustic experiments detected a fixed-level, pure-tone target presented with a spectrally notched noise masker. The qAF procedure adaptively manipulated the masker spectrum level and the position of the masker notch, which was optimized for the efficient estimation of the five parameters of an auditory-filter model. Experiment I demonstrated that the qAF procedure provided a convergent estimate of the auditory-filter shape at 2 kHz within 150 to 200 trials (approximately 15 min to complete) and, for a majority of listeners, excellent test-retest reliability. In experiment II, asymmetric auditory filters were estimated for target frequencies of 1 and 4 kHz and target levels of 30 and 50 dB sound pressure level. The estimated filter shapes were generally consistent with published norms, especially at the low target level. It is known that the auditory-filter estimates are narrower for forward masking than simultaneous masking due to peripheral suppression, a result replicated in experiment III using fewer than 200 qAF trials. PMID:25324086

  5. Rapid estimation of high-parameter auditory-filter shapes.

    PubMed

    Shen, Yi; Sivakumar, Rajeswari; Richards, Virginia M

    2014-10-01

    A Bayesian adaptive procedure, the quick-auditory-filter (qAF) procedure, was used to estimate auditory-filter shapes that were asymmetric about their peaks. In three experiments, listeners who were naive to psychoacoustic experiments detected a fixed-level, pure-tone target presented with a spectrally notched noise masker. The qAF procedure adaptively manipulated the masker spectrum level and the position of the masker notch, which was optimized for the efficient estimation of the five parameters of an auditory-filter model. Experiment I demonstrated that the qAF procedure provided a convergent estimate of the auditory-filter shape at 2 kHz within 150 to 200 trials (approximately 15 min to complete) and, for a majority of listeners, excellent test-retest reliability. In experiment II, asymmetric auditory filters were estimated for target frequencies of 1 and 4 kHz and target levels of 30 and 50 dB sound pressure level. The estimated filter shapes were generally consistent with published norms, especially at the low target level. It is known that the auditory-filter estimates are narrower for forward masking than simultaneous masking due to peripheral suppression, a result replicated in experiment III using fewer than 200 qAF trials.

  6. Evolutionary conservation and neuronal mechanisms of auditory perceptual restoration

    PubMed Central

    Petkov, Christopher I.; Sutter, Mitchell L.

    2013-01-01

    Auditory perceptual ‘restoration’ occurs when the auditory system restores an occluded or masked sound of interest. Behavioral work on auditory restoration in humans began over 50 years ago using it to model a noisy environmental scene with competing sounds. It has become clear that not only humans experience auditory restoration: restoration has been broadly conserved in many species. Behavioral studies in humans and animals provide a necessary foundation to link the insights being obtained from human EEG and fMRI to those from animal neurophysiology. The aggregate of data resulting from multiple approaches across species has begun to clarify the neuronal bases of auditory restoration. Different types of neural responses supporting restoration have been found, supportive of multiple mechanisms working within a species. Yet a general principle has emerged that responses correlated with restoration mimic the response that would have been given to the uninterrupted sound of interest. Using the same technology to study different species will help us to better harness animal models of ‘auditory scene analysis’ to clarify the conserved neural mechanisms shaping the perceptual organization of sound and to advance strategies to improve hearing in natural environmental settings. PMID:20541597

  7. PREFACE: Physics and biology of neurodegenerative diseases Physics and biology of neurodegenerative diseases

    NASA Astrophysics Data System (ADS)

    Pastore, Annalisa

    2012-06-01

    In 1939, William T Astbury, who was at the time a professor at the University of Leeds, wrote a letter to Dorothy Hodgkins, a crystallographer colleague who would eventually be awarded a Nobel Prize (1964) [1]. Astbury was working on determining the structure of silk and had found that these fibres had a so-called cross-beta arrangement, with the hydrogen bonds holding a beta-sheet structure perpendicular to the fibre axis. This structure was very robust and thus would account well for the properties of the silk fibre. Being very impressed by this structural solution at a time when protein structure was just being discovered, he wrote to Dorothy Hodgkins formulating the hypothesis that all proteins could adopt a cross-beta structure similar to that found for silk as a sort of ultimate solution. Approximately 70 years later, this prediction was reconsidered and is now generally accepted to be correct: most if not all proteins seem to be able to form fibrils, commonly named amyloids, that adopt the same structural features found in silk. The field of amyloid fibres bloomed in the mid-90s when several researchers—among them Chris Dobson, a professor first at Oxford and then at Cambridge—observed that proteins could aggregate by concomitant formation of fibrillar structures (reviewed in [2]). It was certainly not news that proteins could aggregate with an irreversible mechanism. However, what nearly came as a surprise was the realization that aggregation is often accompanied by a major structural rearrangement, which almost invariably associates with protein misfolding (i.e. loss of the native structure and adoption of a beta-rich structure) and amyloid fibre formation. Even more interesting was the growing evidence that amyloid fibres have very special mechanical properties, being extremely resilient and not easily degraded. At the same time it was noticed that different diseases, generically named amyloidoses, are associated with fibrillar aggregates. Today

  8. Auditory Cortex Characteristics in Schizophrenia: Associations With Auditory Hallucinations.

    PubMed

    Mørch-Johnsen, Lynn; Nesvåg, Ragnar; Jørgensen, Kjetil N; Lange, Elisabeth H; Hartberg, Cecilie B; Haukvik, Unn K; Kompus, Kristiina; Westerhausen, René; Osnes, Kåre; Andreassen, Ole A; Melle, Ingrid; Hugdahl, Kenneth; Agartz, Ingrid

    2017-01-01

    Neuroimaging studies have demonstrated associations between smaller auditory cortex volume and auditory hallucinations (AH) in schizophrenia. Reduced cortical volume can result from a reduction of either cortical thickness or cortical surface area, which may reflect different neuropathology. We investigate for the first time how thickness and surface area of the auditory cortex relate to AH in a large sample of schizophrenia spectrum patients. Schizophrenia spectrum (n = 194) patients underwent magnetic resonance imaging. Mean cortical thickness and surface area in auditory cortex regions (Heschl's gyrus [HG], planum temporale [PT], and superior temporal gyrus [STG]) were compared between patients with (AH+, n = 145) and without (AH-, n = 49) a lifetime history of AH and 279 healthy controls. AH+ patients showed significantly thinner cortex in the left HG compared to AH- patients (d = 0.43, P = .0096). There were no significant differences between AH+ and AH- patients in cortical thickness in the PT or STG, or in auditory cortex surface area in any of the regions investigated. Group differences in cortical thickness in the left HG was not affected by duration of illness or current antipsychotic medication. AH in schizophrenia patients were related to thinner cortex, but not smaller surface area of the left HG, a region which includes the primary auditory cortex. The results support that structural abnormalities of the auditory cortex underlie AH in schizophrenia. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  9. Early Blindness Results in Developmental Plasticity for Auditory Motion Processing within Auditory and Occipital Cortex

    PubMed Central

    Jiang, Fang; Stecker, G. Christopher; Boynton, Geoffrey M.; Fine, Ione

    2016-01-01

    Early blind subjects exhibit superior abilities for processing auditory motion, which are accompanied by enhanced BOLD responses to auditory motion within hMT+ and reduced responses within right planum temporale (rPT). Here, by comparing BOLD responses to auditory motion in hMT+ and rPT within sighted controls, early blind, late blind, and sight-recovery individuals, we were able to separately examine the effects of developmental and adult visual deprivation on cortical plasticity within these two areas. We find that both the enhanced auditory motion responses in hMT+ and the reduced functionality in rPT are driven by the absence of visual experience early in life; neither loss nor recovery of vision later in life had a discernable influence on plasticity within these areas. Cortical plasticity as a result of blindness has generally be presumed to be mediated by competition across modalities within a given cortical region. The reduced functionality within rPT as a result of early visual loss implicates an additional mechanism for cross modal plasticity as a result of early blindness—competition across different cortical areas for functional role. PMID:27458357

  10. Presentation of dynamically overlapping auditory messages in user interfaces

    SciTech Connect

    Papp, III, Albert Louis

    1997-09-01

    This dissertation describes a methodology and example implementation for the dynamic regulation of temporally overlapping auditory messages in computer-user interfaces. The regulation mechanism exists to schedule numerous overlapping auditory messages in such a way that each individual message remains perceptually distinct from all others. The method is based on the research conducted in the area of auditory scene analysis. While numerous applications have been engineered to present the user with temporally overlapped auditory output, they have generally been designed without any structured method of controlling the perceptual aspects of the sound. The method of scheduling temporally overlapping sounds has been extended to function in an environment where numerous applications can present sound independently of each other. The Centralized Audio Presentation System is a global regulation mechanism that controls all audio output requests made from all currently running applications. The notion of multimodal objects is explored in this system as well. Each audio request that represents a particular message can include numerous auditory representations, such as musical motives and voice. The Presentation System scheduling algorithm selects the best representation according to the current global auditory system state, and presents it to the user within the request constraints of priority and maximum acceptable latency. The perceptual conflicts between temporally overlapping audio messages are examined in depth through the Computational Auditory Scene Synthesizer. At the heart of this system is a heuristic-based auditory scene synthesis scheduling method. Different schedules of overlapped sounds are evaluated and assigned penalty scores. High scores represent presentations that include perceptual conflicts between over-lapping sounds. Low scores indicate fewer and less serious conflicts. A user study was conducted to validate that the perceptual difficulties predicted by

  11. Action-related auditory ERP attenuation: Paradigms and hypotheses.

    PubMed

    Horváth, János

    2015-11-11

    A number studies have shown that the auditory N1 event-related potential (ERP) is attenuated when elicited by self-induced or self-generated sounds. Because N1 is a correlate of auditory feature- and event-detection, it was generally assumed that N1-attenuation reflected the cancellation of auditory re-afference, enabled by the internal forward modeling of the predictable sensory consequences of the given action. Focusing on paradigms utilizing non-speech actions, the present review summarizes recent progress on action-related auditory attenuation. Following a critical analysis of the most widely used, contingent paradigm, two further hypotheses on the possible causes of action-related auditory ERP attenuation are presented. The attention hypotheses suggest that auditory ERP attenuation is brought about by a temporary division of attention between the action and the auditory stimulation. The pre-activation hypothesis suggests that the attenuation is caused by the activation of a sensory template during the initiation of the action, which interferes with the incoming stimulation. Although each hypothesis can account for a number of findings, none of them can accommodate the whole spectrum of results. It is suggested that a better understanding of auditory ERP attenuation phenomena could be achieved by systematic investigations of the types of actions, the degree of action-effect contingency, and the temporal characteristics of action-effect contingency representation-buildup and -deactivation. This article is part of a Special Issue entitled SI: Prediction and Attention. Copyright © 2015. Published by Elsevier B.V.

  12. The Process of Auditory Distraction: Disrupted Attention and Impaired Recall in a Simulated Lecture Environment

    ERIC Educational Resources Information Center

    Zeamer, Charlotte; Fox Tree, Jean E.

    2013-01-01

    Literature on auditory distraction has generally focused on the effects of particular kinds of sounds on attention to target stimuli. In support of extensive previous findings that have demonstrated the special role of language as an auditory distractor, we found that a concurrent speech stream impaired recall of a short lecture, especially for…

  13. The Process of Auditory Distraction: Disrupted Attention and Impaired Recall in a Simulated Lecture Environment

    ERIC Educational Resources Information Center

    Zeamer, Charlotte; Fox Tree, Jean E.

    2013-01-01

    Literature on auditory distraction has generally focused on the effects of particular kinds of sounds on attention to target stimuli. In support of extensive previous findings that have demonstrated the special role of language as an auditory distractor, we found that a concurrent speech stream impaired recall of a short lecture, especially for…

  14. Simple Test of Manual Dexterity Can Help to Identify Persons at High Risk for Neurodegenerative Diseases in the Community.

    PubMed

    Darweesh, Sirwan K L; Wolters, Frank J; Hofman, Albert; Stricker, Bruno H; Koudstaal, Peter J; Ikram, M Arfan

    2017-01-01

    Early identification of individuals at high risk of developing neurodegenerative diseases is essential for timely preventive intervention. However, simple methods that can be used for risk assessment in general practice are lacking. Within the population-based Rotterdam Study, we used the Purdue Pegboard Test (PPT) to assess manual dexterity in 4,856 persons (median age 70 years, 58% women) free of parkinsonism and dementia between 2000 and 2004. We followed these persons until January 1, 2012 for the onset of neurodegenerative diseases (defined as first diagnosis of parkinsonism or dementia). We determined the association of PPT scores with incident neurodegenerative disease, adjusting for age, sex, study cohort, level of education, smoking, preferred hand, parental history, memory complaints, and Mini-Mental State Examination. Furthermore, we determined the incremental predictive value of PPT, expressed as change in risk classification and discrimination. During follow-up (median 9.2 years), 277 participants were diagnosed with a neurodegenerative disease (227 with dementia and 50 with parkinsonism). Lower PPT scores were associated with higher risk of incident neurodegenerative diseases (hazard ratio [HR] = 1.28, 95% confidence interval [CI]: 1.18-1.41) and improved discrimination of incident neurodegenerative diseases. We also observed significant associations of PPT scores separately with incident dementia (HR = 1.25; 95% CI: 1.14-1.39]) and incident parkinsonism (HR = 1.41; 95% CI: 1.19-1.67). A rapid, nonlaboratory test of manual dexterity may help to identify persons at high risk for neurodegenerative diseases. This highlights the importance of motor function in the preclinical phase of both dementia and parkinsonism and may aid in selecting individuals for refined screening and neuroprotective trials. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e

  15. Schisandrin B as a Hormetic Agent for Preventing Age-Related Neurodegenerative Diseases

    PubMed Central

    Lam, Philip Y.; Ko, Kam Ming

    2012-01-01

    Oxidative stress and mitochondrial dysfunction have been implicated in the pathogenesis of neurodegenerative diseases, with the latter preceding the appearance of clinical symptoms. The energy failure resulting from mitochondrial dysfunction further impedes brain function, which demands large amounts of energy. Schisandrin B (Sch B), an active ingredient isolated from Fructus Schisandrae, has been shown to afford generalized tissue protection against oxidative damage in various organs, including the brain, of experimental animals. Recent experimental findings have further demonstrated that Sch B can protect neuronal cells against oxidative challenge, presumably by functioning as a hormetic agent to sustain cellular redox homeostasis and mitoenergetic capacity in neuronal cells. The combined actions of Sch B offer a promising prospect for preventing or possibly delaying the onset of neurodegenerative diseases, as well as enhancing brain health. PMID:22666518

  16. Increased BOLD Signals Elicited by High Gamma Auditory Stimulation of the Left Auditory Cortex in Acute State Schizophrenia.

    PubMed

    Kuga, Hironori; Onitsuka, Toshiaki; Hirano, Yoji; Nakamura, Itta; Oribe, Naoya; Mizuhara, Hiroaki; Kanai, Ryota; Kanba, Shigenobu; Ueno, Takefumi

    2016-10-01

    Recent MRI studies have shown that schizophrenia is characterized by reductions in brain gray matter, which progress in the acute state of the disease. Cortical circuitry abnormalities in gamma oscillations, such as deficits in the auditory steady state response (ASSR) to gamma frequency (>30-Hz) stimulation, have also been reported in schizophrenia patients. In the current study, we investigated neural responses during click stimulation by BOLD signals. We acquired BOLD responses elicited by click trains of 20, 30, 40 and 80-Hz frequencies from 15 patients with acute episode schizophrenia (AESZ), 14 symptom-severity-matched patients with non-acute episode schizophrenia (NASZ), and 24 healthy controls (HC), assessed via a standard general linear-model-based analysis. The AESZ group showed significantly increased ASSR-BOLD signals to 80-Hz stimuli in the left auditory cortex compared with the HC and NASZ groups. In addition, enhanced 80-Hz ASSR-BOLD signals were associated with more severe auditory hallucination experiences in AESZ participants. The present results indicate that neural over activation occurs during 80-Hz auditory stimulation of the left auditory cortex in individuals with acute state schizophrenia. Given the possible association between abnormal gamma activity and increased glutamate levels, our data may reflect glutamate toxicity in the auditory cortex in the acute state of schizophrenia, which might lead to progressive changes in the left transverse temporal gyrus.

  17. Perineuronal nets in the auditory system.

    PubMed

    Sonntag, Mandy; Blosa, Maren; Schmidt, Sophie; Rübsamen, Rudolf; Morawski, Markus

    2015-11-01

    Perineuronal nets (PNs) are a unique and complex meshwork of specific extracellular matrix molecules that ensheath a subset of neurons in many regions of the central nervous system (CNS). PNs appear late in development and are supposed to restrict synaptic plasticity and to stabilize functional neuronal connections. PNs were further hypothesized to create a charged milieu around the neurons and thus, might directly modulate synaptic activity. Although PNs were first described more than 120 years ago, their exact functions still remain elusive. The purpose of the present review is to propose the nuclei of the auditory system, which are highly enriched in PN-wearing neurons, as particularly suitable structures to study the functional significance of PNs. We provide a detailed description of the distribution of PNs from the cochlear nucleus to the auditory cortex considering distinct markers for detection of PNs. We further point to the suitability of specific auditory neurons to serve as promising model systems to study in detail the contribution of PNs to synaptic physiology and also more generally to the functionality of the brain.

  18. Auditory Discrimination Learning: Role of Working Memory

    PubMed Central

    Zhang, Yu-Xuan; Moore, David R.; Guiraud, Jeanne; Molloy, Katharine; Yan, Ting-Ting; Amitay, Sygal

    2016-01-01

    Perceptual training is generally assumed to improve perception by modifying the encoding or decoding of sensory information. However, this assumption is incompatible with recent demonstrations that transfer of learning can be enhanced by across-trial variation of training stimuli or task. Here we present three lines of evidence from healthy adults in support of the idea that the enhanced transfer of auditory discrimination learning is mediated by working memory (WM). First, the ability to discriminate small differences in tone frequency or duration was correlated with WM measured with a tone n-back task. Second, training frequency discrimination around a variable frequency transferred to and from WM learning, but training around a fixed frequency did not. The transfer of learning in both directions was correlated with a reduction of the influence of stimulus variation in the discrimination task, linking WM and its improvement to across-trial stimulus interaction in auditory discrimination. Third, while WM training transferred broadly to other WM and auditory discrimination tasks, variable-frequency training on duration discrimination did not improve WM, indicating that stimulus variation challenges and trains WM only if the task demands stimulus updating in the varied dimension. The results provide empirical evidence as well as a theoretic framework for interactions between cognitive and sensory plasticity during perceptual experience. PMID:26799068

  19. Central auditory onset responses, and temporal asymmetries in auditory perception.

    PubMed

    Phillips, D P; Hall, S E; Boehnke, S E

    2002-05-01

    Historically, central auditory responses have been studied for their sensitivity to various parameters of tone and noise burst stimulation, with response rate plotted as a function of the stimulus variable. The responses themselves are often quite brief, and locked in time to stimulus onset. In the stimulus amplitude domain, it has recently become clear that these responses are actually driven by properties of the stimulus' onset transient, and this has had important implications for how we interpret responses to manipulations of tone (or noise) burst plateau level. That finding was important in its own right, but a more general scrutiny of the available neurophysiological and psychophysical evidence reveals that there is a significant asymmetry in the neurophysiological and perceptual processing of stimulus onsets and offsets: sound onsets have a more elaborate neurophysiological representation, and receive a greater perceptual weighting. Hypotheses about origins of the asymmetries, derived independently from psychophysics and from neurophysiology, have in common a response threshold mechanism which adaptively tracks the ongoing level of stimulation.

  20. Auditory response to pulsed radiofrequency energy.

    PubMed

    Elder, J A; Chou, C K

    2003-01-01

    The human auditory response to pulses of radiofrequency (RF) energy, commonly called RF hearing, is a well established phenomenon. RF induced sounds can be characterized as low intensity sounds because, in general, a quiet environment is required for the auditory response. The sound is similar to other common sounds such as a click, buzz, hiss, knock, or chirp. Effective radiofrequencies range from 2.4 to 10000 MHz, but an individual's ability to hear RF induced sounds is dependent upon high frequency acoustic hearing in the kHz range above about 5 kHz. The site of conversion of RF energy to acoustic energy is within or peripheral to the cochlea, and once the cochlea is stimulated, the detection of RF induced sounds in humans and RF induced auditory responses in animals is similar to acoustic sound detection. The fundamental frequency of RF induced sounds is independent of the frequency of the radiowaves but dependent upon head dimensions. The auditory response has been shown to be dependent upon the energy in a single pulse and not on average power density. The weight of evidence of the results of human, animal, and modeling studies supports the thermoelastic expansion theory as the explanation for the RF hearing phenomenon. RF induced sounds involve the perception via bone conduction of thermally generated sound transients, that is, audible sounds are produced by rapid thermal expansion resulting from a calculated temperature rise of only 5 x 10(-6) degrees C in tissue at the threshold level due to absorption of the energy in the RF pulse. The hearing of RF induced sounds at exposure levels many orders of magnitude greater than the hearing threshold is considered to be a biological effect without an accompanying health effect. This conclusion is supported by a comparison of pressure induced in the body by RF pulses to pressure associated with hazardous acoustic energy and clinical ultrasound procedures.

  1. Idealized Computational Models for Auditory Receptive Fields

    PubMed Central

    Lindeberg, Tony; Friberg, Anders

    2015-01-01

    We present a theory by which idealized models of auditory receptive fields can be derived in a principled axiomatic manner, from a set of structural properties to (i) enable invariance of receptive field responses under natural sound transformations and (ii) ensure internal consistency between spectro-temporal receptive fields at different temporal and spectral scales. For defining a time-frequency transformation of a purely temporal sound signal, it is shown that the framework allows for a new way of deriving the Gabor and Gammatone filters as well as a novel family of generalized Gammatone filters, with additional degrees of freedom to obtain different trade-offs between the spectral selectivity and the temporal delay of time-causal temporal window functions. When applied to the definition of a second-layer of receptive fields from a spectrogram, it is shown that the framework leads to two canonical families of spectro-temporal receptive fields, in terms of spectro-temporal derivatives of either spectro-temporal Gaussian kernels for non-causal time or a cascade of time-causal first-order integrators over the temporal domain and a Gaussian filter over the logspectral domain. For each filter family, the spectro-temporal receptive fields can be either separable over the time-frequency domain or be adapted to local glissando transformations that represent variations in logarithmic frequencies over time. Within each domain of either non-causal or time-causal time, these receptive field families are derived by uniqueness from the assumptions. It is demonstrated how the presented framework allows for computation of basic auditory features for audio processing and that it leads to predictions about auditory receptive fields with good qualitative similarity to biological receptive fields measured in the inferior colliculus (ICC) and primary auditory cortex (A1) of mammals. PMID:25822973

  2. Idealized computational models for auditory receptive fields.

    PubMed

    Lindeberg, Tony; Friberg, Anders

    2015-01-01

    We present a theory by which idealized models of auditory receptive fields can be derived in a principled axiomatic manner, from a set of structural properties to (i) enable invariance of receptive field responses under natural sound transformations and (ii) ensure internal consistency between spectro-temporal receptive fields at different temporal and spectral scales. For defining a time-frequency transformation of a purely temporal sound signal, it is shown that the framework allows for a new way of deriving the Gabor and Gammatone filters as well as a novel family of generalized Gammatone filters, with additional degrees of freedom to obtain different trade-offs between the spectral selectivity and the temporal delay of time-causal temporal window functions. When applied to the definition of a second-layer of receptive fields from a spectrogram, it is shown that the framework leads to two canonical families of spectro-temporal receptive fields, in terms of spectro-temporal derivatives of either spectro-temporal Gaussian kernels for non-causal time or a cascade of time-causal first-order integrators over the temporal domain and a Gaussian filter over the logspectral domain. For each filter family, the spectro-temporal receptive fields can be either separable over the time-frequency domain or be adapted to local glissando transformations that represent variations in logarithmic frequencies over time. Within each domain of either non-causal or time-causal time, these receptive field families are derived by uniqueness from the assumptions. It is demonstrated how the presented framework allows for computation of basic auditory features for audio processing and that it leads to predictions about auditory receptive fields with good qualitative similarity to biological receptive fields measured in the inferior colliculus (ICC) and primary auditory cortex (A1) of mammals.

  3. Cortical auditory disorders: clinical and psychoacoustic features.

    PubMed Central

    Mendez, M F; Geehan, G R

    1988-01-01

    The symptoms of two patients with bilateral cortical auditory lesions evolved from cortical deafness to other auditory syndromes: generalised auditory agnosia, amusia and/or pure word deafness, and a residual impairment of temporal sequencing. On investigation, both had dysacusis, absent middle latency evoked responses, acoustic errors in sound recognition and matching, inconsistent auditory behaviours, and similarly disturbed psychoacoustic discrimination tasks. These findings indicate that the different clinical syndromes caused by cortical auditory lesions form a spectrum of related auditory processing disorders. Differences between syndromes may depend on the degree of involvement of a primary cortical processing system, the more diffuse accessory system, and possibly the efferent auditory system. Images PMID:2450968

  4. Coffee improves auditory neuropathy in diabetic mice.

    PubMed

    Hong, Bin Na; Yi, Tae Hoo; Park, Raekil; Kim, Sun Yeou; Kang, Tong Ho

    2008-08-29

    Coffee is a widely consumed beverage and has recently received considerable attention for its possible beneficial effects. Auditory neuropathy is a hearing disorder characterized by an abnormal auditory brainstem response. This study examined the auditory neuropathy induced by diabetes and investigated the action of coffee, trigonelline, and caffeine to determine whether they improved diabetic auditory neuropathy in mice. Auditory brainstem responses, auditory middle latency responses, and otoacoustic emissions were evaluated to assess auditory neuropathy. Coffee or trigonelline ameliorated the hearing threshold shift and delayed latency of the auditory evoked potential in diabetic neuropathy. These findings demonstrate that diabetes can produce a mouse model of auditory neuropathy and that coffee consumption potentially facilitates recovery from diabetes-induced auditory neuropathy. Furthermore, the active constituent in coffee may be trigonelline.

  5. Auditory-Induced Emotion Mediates Perceptual Categorization of Everyday Sounds

    PubMed Central

    Bergman, Penny; Västfjäll, Daniel; Tajadura-Jiménez, Ana; Asutay, Erkin

    2016-01-01

    Research has shown that emotion categorization plays an important role in perception and categorization in the visual domain. In the present paper, we investigated the role of auditory-induced emotions for auditory perception. We further investigated whether the emotional responses mediate other perceptual judgments of sounds. In an experiment, participants either rated general dissimilarities between sounds or dissimilarities of specific aspects of sounds. The results showed that the general perceptual salience map could be explained by both the emotional responses to, and perceptual aspects of, the sounds. Importantly, the perceptual aspects were mediated by emotional responses. Together these results show that emotions are an integral part of auditory perception that is used as the intuitive basis for categorizing everyday sounds. PMID:27790172

  6. Auditory brainstem responses and auditory thresholds in woodpeckers.

    PubMed

    Lohr, Bernard; Brittan-Powell, Elizabeth F; Dooling, Robert J

    2013-01-01

    Auditory sensitivity in three species of woodpeckers was estimated using the auditory brainstem response (ABR), a measure of the summed electrical activity of auditory neurons. For all species, the ABR waveform showed at least two, and sometimes three prominent peaks occurring within 10 ms of stimulus onset. Also ABR peak amplitude increased and latency decreased as a function of increasing sound pressure levels. Results showed no significant differences in overall auditory abilities between the three species of woodpeckers. The average ABR audiogram showed that woodpeckers have lowest thresholds between 1.5 and 5.7 kHz. The shape of the average woodpecker ABR audiogram was similar to the shape of the ABR-measured audiograms of other small birds at most frequencies, but at the highest frequency data suggest that woodpecker thresholds may be lower than those of domesticated birds, while similar to those of wild birds.

  7. Auditory perspective taking.

    PubMed

    Martinson, Eric; Brock, Derek

    2013-06-01

    Effective communication with a mobile robot using speech is a difficult problem even when you can control the auditory scene. Robot self-noise or ego noise, echoes and reverberation, and human interference are all common sources of decreased intelligibility. Moreover, in real-world settings, these problems are routinely aggravated by a variety of sources of background noise. Military scenarios can be punctuated by high decibel noise from materiel and weaponry that would easily overwhelm a robot's normal speaking volume. Moreover, in nonmilitary settings, fans, computers, alarms, and transportation noise can cause enough interference to make a traditional speech interface unusable. This work presents and evaluates a prototype robotic interface that uses perspective taking to estimate the effectiveness of its own speech presentation and takes steps to improve intelligibility for human listeners.

  8. Auditory-olfactory synesthesia coexisting with auditory-visual synesthesia.

    PubMed

    Jackson, Thomas E; Sandramouli, Soupramanien

    2012-09-01

    Synesthesia is an unusual condition in which stimulation of one sensory modality causes an experience in another sensory modality or when a sensation in one sensory modality causes another sensation within the same modality. We describe a previously unreported association of auditory-olfactory synesthesia coexisting with auditory-visual synesthesia. Given that many types of synesthesias involve vision, it is important that the clinician provide these patients with the necessary information and support that is available.

  9. Auditory short-term memory in the primate auditory cortex.

    PubMed

    Scott, Brian H; Mishkin, Mortimer

    2016-06-01

    Sounds are fleeting, and assembling the sequence of inputs at the ear into a coherent percept requires auditory memory across various time scales. Auditory short-term memory comprises at least two components: an active ׳working memory' bolstered by rehearsal, and a sensory trace that may be passively retained. Working memory relies on representations recalled from long-term memory, and their rehearsal may require phonological mechanisms unique to humans. The sensory component, passive short-term memory (pSTM), is tractable to study in nonhuman primates, whose brain architecture and behavioral repertoire are comparable to our own. This review discusses recent advances in the behavioral and neurophysiological study of auditory memory with a focus on single-unit recordings from macaque monkeys performing delayed-match-to-sample (DMS) tasks. Monkeys appear to employ pSTM to solve these tasks, as evidenced by the impact of interfering stimuli on memory performance. In several regards, pSTM in monkeys resembles pitch memory in humans, and may engage similar neural mechanisms. Neural correlates of DMS performance have been observed throughout the auditory and prefrontal cortex, defining a network of areas supporting auditory STM with parallels to that supporting visual STM. These correlates include persistent neural firing, or a suppression of firing, during the delay period of the memory task, as well as suppression or (less commonly) enhancement of sensory responses when a sound is repeated as a ׳match' stimulus. Auditory STM is supported by a distributed temporo-frontal network in which sensitivity to stimulus history is an intrinsic feature of auditory processing. This article is part of a Special Issue entitled SI: Auditory working memory.

  10. Neural Coding of Periodicity in Marmoset Auditory Cortex

    PubMed Central

    Wang, Xiaoqin

    2010-01-01

    Pitch, our perception of how high or low a sound is on a musical scale, crucially depends on a sound's periodicity. If an acoustic signal is temporally jittered so that it becomes aperiodic, the pitch will no longer be perceivable even though other acoustical features that normally covary with pitch are unchanged. Previous electrophysiological studies investigating pitch have typically used only periodic acoustic stimuli, and as such these studies cannot distinguish between a neural representation of pitch and an acoustical feature that only correlates with pitch. In this report, we examine in the auditory cortex of awake marmoset monkeys (Callithrix jacchus) the neural coding of a periodicity's repetition rate, an acoustic feature that covaries with pitch. We first examine if individual neurons show similar repetition rate tuning for different periodic acoustic signals. We next measure how sensitive these neural representations are to the temporal regularity of the acoustic signal. We find that neurons throughout auditory cortex covary their firing rate with the repetition rate of an acoustic signal. However, similar repetition rate tuning across acoustic stimuli and sensitivity to temporal regularity were generally only observed in a small group of neurons found near the anterolateral border of primary auditory cortex, the location of a previously identified putative pitch processing center. These results suggest that although the encoding of repetition rate is a general component of auditory cortical processing, the neural correlate of periodicity is confined to a special class of pitch-selective neurons within the putative pitch processing center of auditory cortex. PMID:20147419

  11. The Role of Environmental Exposures in Neurodegeneration and Neurodegenerative Diseases

    PubMed Central

    Cannon, Jason R.; Greenamyre, J. Timothy

    2011-01-01

    Neurodegeneration describes the loss of neuronal structure and function. Numerous neurodegenerative diseases are associated with neurodegeneration. Many are rare and stem from purely genetic causes. However, the prevalence of major neurodegenerative diseases is increasing with improvements in treating major diseases such as cancers and cardiovascular diseases, resulting in an aging population. The neurological consequences of neurodegeneration in patients can have devastating effects on mental and physical functioning. The causes of most cases of prevalent neurodegenerative diseases are unknown. The role of neurotoxicant exposures in neurodegenerative disease has long been suspected, with much effort devoted to identifying causative agents. However, causative factors for a significant number of cases have yet to be identified. In this review, the role of environmental neurotoxicant exposures on neurodegeneration in selected major neurodegenerative diseases is discussed. Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and amyotrophic lateral sclerosis were chosen because of available data on environmental influences. The special sensitivity the nervous system exhibits to toxicant exposure and unifying mechanisms of neurodegeneration are explored. PMID:21914720

  12. Advances in the treatment of neurodegenerative disorders employing nanoparticles.

    PubMed

    Spuch, Carlos; Saida, Ortolano; Navarro, Carmen

    2012-04-01

    Nanoparticles could potentially revolutionise treatment for neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD) and strokes. Nanotechnologies hold great promise in brain therapy as they protect the therapeutic agent and allow its sustained release; the nanoparticles can be used as gene delivery vehicles. The application of neurotrophic factors is able to modulate neuronal survival and synaptic connectivity and it is a promising therapeutic approach for many neurodegenerative diseases, however, due to limitations posed by the restrictive blood brain barrier (BBB), it is very difficult to ensure long-term administration in the brain. Drug delivery to the brain remains the major challenge for the treatment of all neurodegenerative diseases because of the numerous protective barriers surrounding the central nervous system (CNS). New therapeutics with the capacity to cross the BBB is critically needed for treatment of these diseases. In recent years, nanotechnology had patented new formulations and has evolved as a new treatment for brain diseases, especially for neurodegenerative diseases, where genetically engineered cells can be used to deliver specific growth factors to target cells. Overall, the aim of this review is to summarize the last patents, clinical trials and news related with nanoparticles technology for the treatment of neurodegenerative diseases.

  13. DNA Double Strand Breaks: A Common Theme in Neurodegenerative Diseases.

    PubMed

    Merlo, Daniela; Mollinari, Cristiana; Racaniello, Mauro; Garaci, Enrico; Cardinale, Alessio

    2016-01-01

    Accumulation of DNA damage and impairment of DNA repair systems are involved in the pathogenesis of different neurodegenerative diseases. Whenever DNA damage is too extensive, the DNA damage response pathway provides for triggering cellular senescence and/or apoptosis. However, whether the increased level of DNA damage in neurodegenerative disorders is a cause rather than the consequence of neurodegenerative events remains to be established. Among possible DNA lesions, DNA double strand breaks (DSBs) are rare events, nevertheless they are the most lethal form of DNA damage. In neurons, DSBs are particularly deleterious because of their reduced DNA repair capability as compared to proliferating cells. Here, we provide a description of DSB repair systems and describe human studies showing the presence of several types of DNA lesions in three major neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD). Then, we analyze the role of DSB accumulation and deficiency of DSB repair systems in neurodegeneration by examining studies on animal models of neurodegenerative diseases.

  14. Asparagine endopeptidase is an innovative therapeutic target for neurodegenerative diseases.

    PubMed

    Zhang, Zhentao; Xie, Manling; Ye, Keqiang

    2016-10-01

    Asparagine endopeptidase (AEP) is a pH-dependent endolysosomal cysteine protease that cleaves its substrates after asparagine residues. Our most recent study identifies that it possesses the delta-secretase activity, and that it is implicated in numerous neurological diseases such as Alzheimer's disease (AD) and stroke. Accumulating evidence supports that the inhibition of AEP exhibits beneficial effects for treating these devastating diseases. Based on recent evidence, it is clear that AEP cleaves its substrate, such as amyloid precursor protein (APP), tau and SET, and plays a critical role in neuronal cell death in various neurodegenerative diseases and stroke. In this article, the basic biology of AEP, its knockout phenotypes in mouse models, its substrates in neurodegenerative diseases, and its small peptidyl inhibitors and prodrugs are discussed. In addition, we discuss the potential of AEP as a novel therapeutic target for neurodegenerative diseases. AEP plays a unique role in numerous biological processes, depending on both pH and context. Most striking is our most recent finding; that AEP is activated in an age-dependent manner and simultaneously cleaves both APP and tau, thereby unifying both major pathological events in AD. Thus, AEP acts as an innovative trigger for neurodegenerative diseases. Inhibition of AEP will provide a disease-modifying treatment for neurodegenerative diseases including AD.

  15. Pharmacological intervention of early neuropathy in neurodegenerative diseases.

    PubMed

    Kwon, Min Jee; Kim, Jeong-Hoon; Kim, TaeSoo; Lee, Sung Bae

    2017-05-01

    Extensive studies have reported the significant roles of numerous cellular features and processes in properly maintaining neuronal morphology and function throughout the lifespan of an animal. Any alterations in their homeostasis appear to be strongly associated with neuronal aging and the pathogenesis of various neurodegenerative diseases, even before the occurrence of prominent neuronal death. However, until recently, the primary focus of studies regarding many neurodegenerative diseases has been on the massive cell death occurring at the late stages of disease progression. Thus, our understanding on early neuropathy in these diseases remains relatively limited. The complicated nature of various neuropathic features manifested early in neurodegenerative diseases suggests the involvement of a system-wide transcriptional regulation and epigenetic control. Epigenetic alterations and consequent changes in the neuronal transcriptome are now begun to be extensively studied in various neurodegenerative diseases. Upon the catastrophic incident of neuronal death in disease progression, it is utterly difficult to reverse the deleterious defects by pharmacological treatments, and therefore, therapeutics targeting the system-wide transcriptional dysregulation associated with specific early neuropathy is considered a better option. Here, we review our current understanding on the system-wide transcriptional dysregulation that is likely associated with early neuropathy shown in various neurodegenerative diseases and discuss the possible future developments of pharmaceutical therapeutics. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Motor Phenotype in Neurodegenerative Disorders: Gait and Balance Platform Study Design Protocol for the Ontario Neurodegenerative Research Initiative (ONDRI)

    PubMed Central

    Montero-Odasso, Manuel; Pieruccini-Faria, Frederico; Bartha, Robert; Black, Sandra E.; Finger, Elizabeth; Freedman, Morris; Greenberg, Barry; Grimes, David A.; Hegele, Robert A.; Hudson, Christopher; Kleinstiver, Peter W.; Lang, Anthony E.; Masellis, Mario; McLaughlin, Paula M.; Munoz, Douglas P.; Strother, Stephen; Swartz, Richard H.; Symons, Sean; Tartaglia, Maria Carmela; Zinman, Lorne; Strong, Michael J.; McIlroy, William

    2017-01-01

    Background: The association of cognitive and motor impairments in Alzheimer’s disease and other neurodegenerative diseases is thought to be related to damage in the common brain networks shared by cognitive and cortical motor control processes. These common brain networks play a pivotal role in selecting movements and postural synergies that meet an individual’s needs. Pathology in this “highest level” of motor control produces abnormalities of gait and posture referred to as highest-level gait disorders. Impairments in cognition and mobility, including falls, are present in almost all neurodegenerative diseases, suggesting common mechanisms that still need to be unraveled. Objective: To identify motor-cognitive profiles across neurodegenerative diseases in a large cohort of patients. Methods: Cohort study that includes up to 500 participants, followed every year for three years, across five neurodegenerative disease groups: Alzheimer’s disease/mild cognitive impairment, frontotemporal degeneration, vascular cognitive impairment, amyotrophic lateral sclerosis, and Parkinson’s disease. Gait and balance will be assessed using accelerometers and electronic walkways, evaluated at different levels of cognitive and sensory complexity, using the dual-task paradigm. Results: Comparison of cognitive and motor performances across neurodegenerative groups will allow the identification of motor-cognitive phenotypes through the standardized evaluation of gait and balance characteristics. Conclusions: As part of the Ontario Neurodegenerative Research Initiative (ONDRI), the gait and balance platform aims to identify motor-cognitive profiles across neurodegenerative diseases. Gait assessment, particularly while dual-tasking, will help dissect the cognitive and motor contribution in mobility and cognitive decline, progression to dementia syndromes, and future adverse outcomes including falls and mortality. PMID:28671116

  17. Motor Phenotype in Neurodegenerative Disorders: Gait and Balance Platform Study Design Protocol for the Ontario Neurodegenerative Research Initiative (ONDRI).

    PubMed

    Montero-Odasso, Manuel; Pieruccini-Faria, Frederico; Bartha, Robert; Black, Sandra E; Finger, Elizabeth; Freedman, Morris; Greenberg, Barry; Grimes, David A; Hegele, Robert A; Hudson, Christopher; Kleinstiver, Peter W; Lang, Anthony E; Masellis, Mario; McLaughlin, Paula M; Munoz, Douglas P; Strother, Stephen; Swartz, Richard H; Symons, Sean; Tartaglia, Maria Carmela; Zinman, Lorne; Strong, Michael J; McIlroy, William

    2017-01-01

    The association of cognitive and motor impairments in Alzheimer's disease and other neurodegenerative diseases is thought to be related to damage in the common brain networks shared by cognitive and cortical motor control processes. These common brain networks play a pivotal role in selecting movements and postural synergies that meet an individual's needs. Pathology in this "highest level" of motor control produces abnormalities of gait and posture referred to as highest-level gait disorders. Impairments in cognition and mobility, including falls, are present in almost all neurodegenerative diseases, suggesting common mechanisms that still need to be unraveled. To identify motor-cognitive profiles across neurodegenerative diseases in a large cohort of patients. Cohort study that includes up to 500 participants, followed every year for three years, across five neurodegenerative disease groups: Alzheimer's disease/mild cognitive impairment, frontotemporal degeneration, vascular cognitive impairment, amyotrophic lateral sclerosis, and Parkinson's disease. Gait and balance will be assessed using accelerometers and electronic walkways, evaluated at different levels of cognitive and sensory complexity, using the dual-task paradigm. Comparison of cognitive and motor performances across neurodegenerative groups will allow the identification of motor-cognitive phenotypes through the standardized evaluation of gait and balance characteristics. As part of the Ontario Neurodegenerative Research Initiative (ONDRI), the gait and balance platform aims to identify motor-cognitive profiles across neurodegenerative diseases. Gait assessment, particularly while dual-tasking, will help dissect the cognitive and motor contribution in mobility and cognitive decline, progression to dementia syndromes, and future adverse outcomes including falls and mortality.

  18. Impairments in musical abilities reflected in the auditory brainstem: evidence from congenital amusia.

    PubMed

    Lehmann, Alexandre; Skoe, Erika; Moreau, Patricia; Peretz, Isabelle; Kraus, Nina

    2015-07-01

    Congenital amusia is a neurogenetic condition, characterized by a deficit in music perception and production, not explained by hearing loss, brain damage or lack of exposure to music. Despite inferior musical performance, amusics exhibit normal auditory cortical responses, with abnormal neural correlates suggested to lie beyond auditory cortices. Here we show, using auditory brainstem responses to complex sounds in humans, that fine-grained automatic processing of sounds is impoverished in amusia. Compared with matched non-musician controls, spectral amplitude was decreased in amusics for higher harmonic components of the auditory brainstem response. We also found a delayed response to the early transient aspects of the auditory stimulus in amusics. Neural measures of spectral amplitude and response timing correlated with participants' behavioral assessments of music processing. We demonstrate, for the first time, that amusia affects how complex acoustic signals are processed in the auditory brainstem. This neural signature of amusia mirrors what is observed in musicians, such that the aspects of the auditory brainstem responses that are enhanced in musicians are degraded in amusics. By showing that gradients of music abilities are reflected in the auditory brainstem, our findings have implications not only for current models of amusia but also for auditory functioning in general.

  19. A hardware model of the auditory periphery to transduce acoustic signals into neural activity

    PubMed Central

    Tateno, Takashi; Nishikawa, Jun; Tsuchioka, Nobuyoshi; Shintaku, Hirofumi; Kawano, Satoyuki

    2013-01-01

    To improve the performance of cochlear implants, we have integrated a microdevice into a model of the auditory periphery with the goal of creating a microprocessor. We constructed an artificial peripheral auditory system using a hybrid model in which polyvinylidene difluoride was used as a piezoelectric sensor to convert mechanical stimuli into electric signals. To produce frequency selectivity, the slit on a stainless steel base plate was designed such that the local resonance frequency of the membrane over the slit reflected the transfer function. In the acoustic sensor, electric signals were generated based on the piezoelectric effect from local stress in the membrane. The electrodes on the resonating plate produced relatively large electric output signals. The signals were fed into a computer model that mimicked some functions of inner hair cells, inner hair cell–auditory nerve synapses, and auditory nerve fibers. In general, the responses of the model to pure-tone burst and complex stimuli accurately represented the discharge rates of high-spontaneous-rate auditory nerve fibers across a range of frequencies greater than 1 kHz and middle to high sound pressure levels. Thus, the model provides a tool to understand information processing in the peripheral auditory system and a basic design for connecting artificial acoustic sensors to the peripheral auditory nervous system. Finally, we discuss the need for stimulus control with an appropriate model of the auditory periphery based on auditory brainstem responses that were electrically evoked by different temporal pulse patterns with the same pulse number. PMID:24324432

  20. Auditory reafferences: the influence of real-time feedback on movement control

    PubMed Central

    Kennel, Christian; Streese, Lukas; Pizzera, Alexandra; Justen, Christoph; Hohmann, Tanja; Raab, Markus

    2015-01-01

    Auditory reafferences are real-time auditory products created by a person’s own movements. Whereas the interdependency of action and perception is generally well studied, the auditory feedback channel and the influence of perceptual processes during movement execution remain largely unconsidered. We argue that movements have a rhythmic character that is closely connected to sound, making it possible to manipulate auditory reafferences online to understand their role in motor control. We examined if step sounds, occurring as a by-product of running, have an influence on the performance of a complex movement task. Twenty participants completed a hurdling task in three auditory feedback conditions: a control condition with normal auditory feedback, a white noise condition in which sound was masked, and a delayed auditory feedback condition. Overall time and kinematic data were collected. Results show that delayed auditory feedback led to a significantly slower overall time and changed kinematic parameters. Our findings complement previous investigations in a natural movement situation with non-artificial auditory cues. Our results support the existing theoretical understanding of action–perception coupling and hold potential for applied work, where naturally occurring movement sounds can be implemented in the motor learning processes. PMID:25688230

  1. Leftward lateralization of auditory cortex underlies holistic sound perception in Williams syndrome.

    PubMed

    Wengenroth, Martina; Blatow, Maria; Bendszus, Martin; Schneider, Peter

    2010-08-23

    Individuals with the rare genetic disorder Williams-Beuren syndrome (WS) are known for their characteristic auditory phenotype including strong affinity to music and sounds. In this work we attempted to pinpoint a neural substrate for the characteristic musicality in WS individuals by studying the structure-function relationship of their auditory cortex. Since WS subjects had only minor musical training due to psychomotor constraints we hypothesized that any changes compared to the control group would reflect the contribution of genetic factors to auditory processing and musicality. Using psychoacoustics, magnetoencephalography and magnetic resonance imaging, we show that WS individuals exhibit extreme and almost exclusive holistic sound perception, which stands in marked contrast to the even distribution of this trait in the general population. Functionally, this was reflected by increased amplitudes of left auditory evoked fields. On the structural level, volume of the left auditory cortex was 2.2-fold increased in WS subjects as compared to control subjects. Equivalent volumes of the auditory cortex have been previously reported for professional musicians. There has been an ongoing debate in the neuroscience community as to whether increased gray matter of the auditory cortex in musicians is attributable to the amount of training or innate disposition. In this study musical education of WS subjects was negligible and control subjects were carefully matched for this parameter. Therefore our results not only unravel the neural substrate for this particular auditory phenotype, but in addition propose WS as a unique genetic model for training-independent auditory system properties.

  2. Modulation of Auditory Responses to Speech vs. Nonspeech Stimuli during Speech Movement Planning.

    PubMed

    Daliri, Ayoub; Max, Ludo

    2016-01-01

    Previously, we showed that the N100 amplitude in long latency auditory evoked potentials (LLAEPs) elicited by pure tone probe stimuli is modulated when the stimuli are delivered during speech movement planning as compared with no-speaking control conditions. Given that we probed the auditory system only with pure tones, it remained unknown whether the nature and magnitude of this pre-speech auditory modulation depends on the type of auditory stimulus. Thus, here, we asked whether the effect of speech movement planning on auditory processing varies depending on the type of auditory stimulus. In an experiment with nine adult subjects, we recorded LLAEPs that were elicited by either pure tones or speech syllables when these stimuli were presented prior to speech onset in a delayed-response speaking condition vs. a silent reading control condition. Results showed no statistically significant difference in pre-speech modulation of the N100 amplitude (early stages of auditory processing) for the speech stimuli as compared with the nonspeech stimuli. However, the amplitude of the P200 component (later stages of auditory processing) showed a statistically significant pre-speech modulation that was specific to the speech stimuli only. Hence, the overall results from this study indicate that, immediately prior to speech onset, modulation of the auditory system has a general effect on early processing stages but a speech-specific effect on later processing stages. This finding is consistent with the hypothesis that pre-speech auditory modulation may play a role in priming the auditory system for its role in monitoring auditory feedback during speech production.

  3. Mind the Gap: Two Dissociable Mechanisms of Temporal Processing in the Auditory System

    PubMed Central

    Anderson, Lucy A.

    2016-01-01

    High temporal acuity of auditory processing underlies perception of speech and other rapidly varying sounds. A common measure of auditory temporal acuity in humans is the threshold for detection of brief gaps in noise. Gap-detection deficits, observed in developmental disorders, are considered evidence for “sluggish” auditory processing. Here we show, in a mouse model of gap-detection deficits, that auditory brain sensitivity to brief gaps in noise can be impaired even without a general loss of central auditory temporal acuity. Extracellular recordings in three different subdivisions of the auditory thalamus in anesthetized mice revealed a stimulus-specific, subdivision-specific deficit in thalamic sensitivity to brief gaps in noise in experimental animals relative to controls. Neural responses to brief gaps in noise were reduced, but responses to other rapidly changing stimuli unaffected, in lemniscal and nonlemniscal (but not polysensory) subdivisions of the medial geniculate body. Through experiments and modeling, we demonstrate that the observed deficits in thalamic sensitivity to brief gaps in noise arise from reduced neural population activity following noise offsets, but not onsets. These results reveal dissociable sound-onset-sensitive and sound-offset-sensitive channels underlying auditory temporal processing, and suggest that gap-detection deficits can arise from specific impairment of the sound-offset-sensitive channel. SIGNIFICANCE STATEMENT The experimental and modeling results reported here suggest a new hypothesis regarding the mechanisms of temporal processing in the auditory system. Using a mouse model of auditory temporal processing deficits, we demonstrate the existence of specific abnormalities in auditory thalamic activity following sound offsets, but not sound onsets. These results reveal dissociable sound-onset-sensitive and sound-offset-sensitive mechanisms underlying auditory processing of temporally varying sounds. Furthermore, the

  4. Modulation of Auditory Responses to Speech vs. Nonspeech Stimuli during Speech Movement Planning

    PubMed Central

    Daliri, Ayoub; Max, Ludo

    2016-01-01

    Previously, we showed that the N100 amplitude in long latency auditory evoked potentials (LLAEPs) elicited by pure tone probe stimuli is modulated when the stimuli are delivered during speech movement planning as compared with no-speaking control conditions. Given that we probed the auditory system only with pure tones, it remained unknown whether the nature and magnitude of this pre-speech auditory modulation depends on the type of auditory stimulus. Thus, here, we asked whether the effect of speech movement planning on auditory processing varies depending on the type of auditory stimulus. In an experiment with nine adult subjects, we recorded LLAEPs that were elicited by either pure tones or speech syllables when these stimuli were presented prior to speech onset in a delayed-response speaking condition vs. a silent reading control condition. Results showed no statistically significant difference in pre-speech modulation of the N100 amplitude (early stages of auditory processing) for the speech stimuli as compared with the nonspeech stimuli. However, the amplitude of the P200 component (later stages of auditory processing) showed a statistically significant pre-speech modulation that was specific to the speech stimuli only. Hence, the overall results from this study indicate that, immediately prior to speech onset, modulation of the auditory system has a general effect on early processing stages but a speech-specific effect on later processing stages. This finding is consistent with the hypothesis that pre-speech auditory modulation may play a role in priming the auditory system for its role in monitoring auditory feedback during speech production. PMID:27242494

  5. Auditory Processing Disorder (For Parents)

    MedlinePlus

    ... or complicated? Does your child have reading, spelling, writing, or other speech-language difficulties? Are verbal (word) ... can affect following directions and reading, spelling, and writing skills, among others. Auditory attention problems: This is ...

  6. Classroom Demonstrations of Auditory Perception.

    ERIC Educational Resources Information Center

    Haws, LaDawn; Oppy, Brian J.

    2002-01-01

    Presents activities to help students gain understanding about auditory perception. Describes demonstrations that cover topics, such as sound localization, wave cancellation, frequency/pitch variation, and the influence of media on sound propagation. (CMK)

  7. Classroom Demonstrations of Auditory Perception.

    ERIC Educational Resources Information Center

    Haws, LaDawn; Oppy, Brian J.

    2002-01-01

    Presents activities to help students gain understanding about auditory perception. Describes demonstrations that cover topics, such as sound localization, wave cancellation, frequency/pitch variation, and the influence of media on sound propagation. (CMK)

  8. Auditory Processing Disorder in Children

    MedlinePlus

    ... free publications Find organizations Related Topics Auditory Neuropathy Autism Spectrum Disorder: Communication Problems in Children Dysphagia Quick Statistics About Voice, Speech, Language Speech and Language Developmental Milestones What Is ...

  9. Auditory Processing Disorder (For Parents)

    MedlinePlus

    ... or other speech-language difficulties? Are verbal (word) math problems difficult for your child? Is your child ... inferences from conversations, understanding riddles, or comprehending verbal math problems — require heightened auditory processing and language levels. ...

  10. Association between environmental exposure to pesticides and neurodegenerative diseases

    SciTech Connect

    Parron, Tesifon; Requena, Mar; Hernandez, Antonio F.; Alarcon, Raquel

    2011-11-15

    Preliminary studies have shown associations between chronic pesticide exposure in occupational settings and neurological disorders. However, data on the effects of long-term non-occupational exposures are too sparse to allow any conclusions. This study examines the influence of environmental pesticide exposure on a number of neuropsychiatric conditions and discusses their underlying pathologic mechanisms. An ecological study was conducted using averaged prevalence rates of Alzheimer's disease, Parkinson's disease, multiple sclerosis, cerebral degeneration, polyneuropathies, affective psychosis and suicide attempts in selected Andalusian health districts categorized into areas of high and low environmental pesticide exposure based on the number of hectares devoted to intensive agriculture and pesticide sales per capita. A total of 17,429 cases were collected from computerized hospital records (minimum dataset) between 1998 and 2005. Prevalence rates and the risk of having Alzheimer's disease, Parkinson's disease, multiple sclerosis and suicide were significantly higher in districts with greater pesticide use as compared to those with lower pesticide use. The multivariate analyses showed that the population living in areas with high pesticide use had an increased risk for Alzheimer's disease and suicide attempts and that males living in these areas had increased risks for polyneuropathies, affective disorders and suicide attempts. In conclusion, this study supports and extends previous findings and provides an indication that environmental exposure to pesticides may affect the human health by increasing the incidence of certain neurological disorders at the level of the general population. -- Highlights: Black-Right-Pointing-Pointer Environmental exposure to pesticides and neurodegenerative-psychiatric disorders. Black-Right-Pointing-Pointer Increased risk for Alzheimer's disease and suicide attempts in high exposure areas. Black-Right-Pointing-Pointer Males from

  11. Transcriptomics study of neurodegenerative disease: emphasis on synaptic dysfunction mechanism in Alzheimer's disease.

    PubMed

    Karim, Sajjad; Mirza, Zeenat; Ansari, Shakeel A; Rasool, Mahmood; Iqbal, Zafar; Sohrab, Sayed S; Kamal, Mohammad A; Abuzenadah, Adel M; Al-Qahtani, Mohammed H

    2014-01-01

    Alzheimer's disease (AD) is a common neurodegenerative disorder primarily affecting memory and thinking ability; caused by progressive degeneration and death of nerve cells. In this study, we integrated multiple dataset retrieved from the National Center for Biotechnology Information's Gene Expression Omnibus database, and took a systems-biology approach to compare and distinguish the molecular network based synaptic dysregulation associated with AD in particular and neurodegenerative diseases in general. We first identified 832 differentially expressed genes using cut off P value <0.5 and fold change > 2, followed by gene ontology study to identify genes associated with synapse (n=95) [membrane associated guanylate kinase, 2, amyloid beta precursor protein, neurotrophic tyrosine kinase, receptor, type 2], synapse part [γ-aminobutyric acid A receptor, γ1], synaptic vesicle [glutamate receptor, ionotropic, α-amino-3-hydroxy-5- methyl-4-isoxazole propionic acid receptor 2, synaptoporin], pre- and post-synaptic density [neuronal calcium sensor 1, glutamate receptor, metabotropic 3]. We integrated these data with known pathways using Ingenuity Pathway Analysis tool and found following synapse associated pathways to be most affected; γ-aminobutyric acid receptor signaling, synaptic long term potentiation/depression, nuclear factor-erythroid 2-related factor 2-mediated oxidative stress response, huntington's disease signaling and Reelin signaling in neurons. In conclusion, synaptic dysfunction is tightly associated with the development and progression of neurodegenerative diseases like AD.

  12. Effect of electromagnetic radiations on neurodegenerative diseases- technological revolution as a curse in disguise.

    PubMed

    Hasan, Gulam M; Sheikh, Ishfaq A; Karim, Sajjad; Haque, Absarul; Kamal, Mohammad A; Chaudhary, Adeel G; Azhar, Essam; Mirza, Zeenat

    2014-01-01

    In the present developed world, all of us are flooded with electromagnetic radiations (EMR) emanating from generation and transmission of electricity, domestic appliances and industrial equipments, to telecommunications and broadcasting. We have been exposed to EMR for last many decades; however their recent steady increase from artificial sources has been reported as millions of antennas and satellites irradiate the global population round the clock, year round. Needless to say, these are so integral to modern life that interaction with them on a daily basis is seemingly inevitable; hence, the EMR exposure load has increased to a point where their health effects are becoming a major concern. Delicate and sensitive electrical system of human body is affected by consistent penetration of electromagnetic frequencies causing DNA breakages and chromosomal aberrations. Technological innovations came with Pandora's Box of hazardous consequences including neurodegenerative disorders, hearing disabilities, diabetes, congenital abnormalities, infertility, cardiovascular diseases and cancer to name few, all on a sharp rise. Electromagnetic non-ionizing radiations pose considerable health threat with prolonged exposure. Mobile phones are usually held near to the brain and manifest progressive structural or functional alterations in neurons leading to neurodegenerative diseases and neuronal death. This has provoked awareness among both the general public and scientific community and international bodies acknowledge that further systematic research is needed. The aim of the present review was to have an insight in whether and how cumulative electro-magnetic field exposure is a risk factor for neurodegenerative disorders.

  13. Small-molecule modulation of HDAC6 activity: The propitious therapeutic strategy to vanquish neurodegenerative disorders.

    PubMed

    Ganai, Shabir Ahmad

    2017-02-08

    Histone deacetylases (HDACs) are epigenetic enzymes creating the transcriptionally inactive state of chromatin by erasing acetyl moiety from histone and non-histone substrates. HDAC6 modulates several biological pathways in dividing cells as well as in post-mitotic neurons, and has been implicated in the pathophysiology of neurodegeneration. The distinct cellular functions and survival in these cells are reliant on HDAC6-mediated processes including intracellular trafficking, chaperone-mediated stress responses, anti-oxidation and protein degradation. Consequently, the interest in HDAC6 as a promising therapeutic target to tackle neurodegenerative disorders has escalated markedly over the last decade. Taking these grim facts into consideration the current article focuses on structural organization of HDAC6. Importantly, we discuss the general role of HDACs in cognition and neuronal death. Further, we describe the unique involvement of HDAC6 in eliminating protein aggregates, oxidative stress and mitochondrial transport. Moreover, the article rigorously details how the impaired activity of HDAC6 culminates in neurodegenerative complications like Alzheimer disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). Lastly, we provide crystal clear view regarding the fascinating research areas which may lead to development of novel small-molecules for enhanced therapeutic benefit against these therapeutically arduous neurodegenerative maladies.

  14. Protein misfolding in neurodegenerative diseases: implications and strategies.

    PubMed

    Sweeney, Patrick; Park, Hyunsun; Baumann, Marc; Dunlop, John; Frydman, Judith; Kopito, Ron; McCampbell, Alexander; Leblanc, Gabrielle; Venkateswaran, Anjli; Nurmi, Antti; Hodgson, Robert

    2017-01-01

    A hallmark of neurodegenerative proteinopathies is the formation of misfolded protein aggregates that cause cellular toxicity and contribute to cellular proteostatic collapse. Therapeutic options are currently being explored that target different steps in the production and processing of proteins implicated in neurodegenerative disease, including synthesis, chaperone-assisted folding and trafficking, and degradation via the proteasome and autophagy pathways. Other therapies, like mTOR inhibitors and activators of the heat shock response, can rebalance the entire proteostatic network. However, there are major challenges that impact the development of novel therapies, including incomplete knowledge of druggable disease targets and their mechanism of action as well as a lack of biomarkers to monitor disease progression and therapeutic response. A notable development is the creation of collaborative ecosystems that include patients, clinicians, basic and translational researchers, foundations and regulatory agencies to promote scientific rigor and clinical data to accelerate the development of therapies that prevent, reverse or delay the progression of neurodegenerative proteinopathies.

  15. Neurodegenerative diseases in domestic animals: a comparative review.

    PubMed

    Sisó, S; Hanzlícek, D; Fluehmann, G; Kathmann, I; Tomek, A; Papa, V; Vandevelde, M

    2006-01-01

    Neurodegenerative diseases are characterised by selective damage to specific neurons in the nervous system. Interest in such diseases in humans has resulted in considerable progress in the molecular understanding of these disorders in recent decades. Numerous neurodegenerative diseases have also been described in domestic animals but relatively little molecular work has been reported. In the present review, we have classified neurodegenerative disease according to neuroanatomical criteria. We have established two large groups, based on whether the neuronal cell body or its axon was primarily affected. Conditions such as motor neuron diseases, cerebellar degenerations and neuroaxonal dystrophies are discussed in terms of their clinical and neuropathological features. In the most studied disorders, we also present what is known about underlying pathomechanisms, and compare them with their human counterparts. The purpose of this review is to re-kindle interest in this group of diseases and to encourage veterinary researchers to investigate molecular mechanisms by taking advantage of current diagnostic tools.

  16. Clinico-Pathological Correlations of the Most Common Neurodegenerative Dementias

    PubMed Central

    Taipa, Ricardo; Pinho, João; Melo-Pires, Manuel

    2012-01-01

    Neurodegenerative dementias are a group of neurological disorders characterized by deterioration in several cognitive domains in which there is selective and progressive loss of specific populations of neurons. The precise neurobiological basis for the different neurodegenerative dementias remains unknown. It is expected that different pathologies reflect different mechanisms, at least early in the neurodegeneration process. The next decades promise treatments directed to causes and mechanisms, bringing an outstanding challenge to clinicians due to heterogeneous clinical presentations with the same molecular pathology. The purpose of this brief review is to describe the key neuropathological features of the most common neurodegenerative dementias (Alzheimer disease, dementia with Lewy bodies and Parkinson’s disease dementia, and frontotemporal lobar degeneration) and the relationship with the clinical syndromes described in clinico-pathological studies. We expect this overview contributes for the understanding of this broad topic integrating the two ends of the spectrum: clinical and pathological. PMID:22557993

  17. Copper handling by astrocytes: insights into neurodegenerative diseases.

    PubMed

    Tiffany-Castiglioni, Evelyn; Hong, Sandra; Qian, Yongchang

    2011-12-01

    Copper (Cu) is an essential trace element in the brain that can be toxic at elevated levels. Cu accumulation is a suspected etiology in several neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and prion-induced disorders. Astrocytes are a proposed depot in the brain for Cu and other metals, including lead (Pb). This article describes the physiological roles of Cu in the central nervous system and in selected neurodegenerative diseases, and reviews evidence that astrocytes accumulate Cu and protect neurons from Cu toxicity. Findings from murine genetic models of Menkes disease and from cell culture models concerning the molecular mechanisms by which astrocytes take up, store, and buffer Cu intracellularly are discussed, as well as potential mechanistic linkages between astrocyte functions in Cu handling and neurodegenerative diseases.

  18. Eyelid Dysfunction in Neurodegenerative, Neurogenetic, and Neurometabolic Disease

    PubMed Central

    Hamedani, Ali G.; Gold, Daniel R.

    2017-01-01

    Eye movement abnormalities are among the earliest clinical manifestations of inherited and acquired neurodegenerative diseases and play an integral role in their diagnosis. Eyelid movement is neuroanatomically linked to eye movement, and thus eyelid dysfunction can also be a distinguishing feature of neurodegenerative disease and complements eye movement abnormalities in helping us to understand their pathophysiology. In this review, we summarize the various eyelid abnormalities that can occur in neurodegenerative, neurogenetic, and neurometabolic diseases. We discuss eyelid disorders, such as ptosis, eyelid retraction, abnormal spontaneous and reflexive blinking, blepharospasm, and eyelid apraxia in the context of the neuroanatomic pathways that are affected. We also review the literature regarding the prevalence of eyelid abnormalities in different neurologic diseases as well as treatment strategies (Table 1). PMID:28769865

  19. Biomarker Discovery in Neurodegenerative Diseases: A Proteomic Approach

    PubMed Central

    Shi, Min; Caudle, W. Michael; Zhang, Jing

    2010-01-01

    Biomarkers for neurodegenerative disorders are essential to facilitate disease diagnosis, ideally at early stages, monitor disease progression, and assess response to existing and future treatments. Application of proteomics to the human brain, cerebrospinal fluid and plasma has greatly hastened the unbiased and high-throughput searches for novel biomarkers. There are many steps critical to biomarker discovery, whether for neurodegenerative or other diseases, including sample preparation, protein/peptide separation and identification, as well as independent confirmation and validation. In this review we have summarized current proteomics technologies involved in discovery of biomarkers for neurodegenerative diseases, practical considerations and limitations of several major aspects, as well as the current status of candidate biomarkers revealed by proteomics for Alzheimer and Parkinson diseases. PMID:18938247

  20. On The Role of Natural Killer Cells in Neurodegenerative Diseases

    PubMed Central

    Maghazachi, Azzam A.

    2013-01-01

    Natural killer (NK) cells exert important immunoregulatory functions by releasing several inflammatory molecules, such as IFN-γ and members of chemokines, which include CCL3/MIP-1α and CCL4/MIP-1β. These cells also express heptahelical receptors, which are coupled to heterotrimeric G proteins that guide them into inflamed and injured tissues. NK cells have been shown to recognize and destroy transformed cells and virally-infected cells, but their roles in neurodegenerative diseases have not been examined in detail. In this review, I will summarize the effects of NK cells in two neurodegenerative diseases, namely multiple sclerosis and globoid cell leukodystrophy. It is hoped that the knowledge obtained from these diseases may facilitate building rational protocols for treating these and other neurodegenerative or autoimmune diseases using NK cells and drugs that activate them as therapeutic tools. PMID:23430541

  1. Redox Imbalance and Viral Infections in Neurodegenerative Diseases

    PubMed Central

    Limongi, Dolores

    2016-01-01

    Reactive oxygen species (ROS) are essential molecules for many physiological functions and act as second messengers in a large variety of tissues. An imbalance in the production and elimination of ROS is associated with human diseases including neurodegenerative disorders. In the last years the notion that neurodegenerative diseases are accompanied by chronic viral infections, which may result in an increase of neurodegenerative diseases progression, emerged. It is known in literature that enhanced viral infection risk, observed during neurodegeneration, is partly due to the increase of ROS accumulation in brain cells. However, the molecular mechanisms of viral infection, occurring during the progression of neurodegeneration, remain unclear. In this review, we discuss the recent knowledge regarding the role of influenza, herpes simplex virus type-1, and retroviruses infection in ROS/RNS-mediated Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS). PMID:27110325

  2. [Advances of researches on caspases in neurodegenerative diseases].

    PubMed

    Xue, Hongyu; Fang, Xuemei; Wang, Weiwei; Gao, Guizhen

    2013-04-01

    Acute and chronic neurodegenerative diseases are illnesses associated with high morbidity and mortality, and few or no effective options are available for their treatments. Many neurodegenerative diseases are included in them, for example, stroke, brain trauma, spinal cord injury, amyotrophic lateral sclerosis (ALS), Huntington's disease, Alzheimer's disease, and Parkinson's disease. Given that central nervous system tissue has very limited, if any, regenerative capacity, it is of utmost importance to limit the damage caused by neuronal death. During the past decade, considerable progress has been made in understanding the process of cell death. In this article, we review the causes and mechanisms of neuronal-cell death, especially as it pertains to the caspases family of proteases associated with cell death. The results may be helpful to the experimental research and clinical application of neurodegenerative diseases.

  3. Evaluation of Traditional Medicines for Neurodegenerative Diseases Using Drosophila Models

    PubMed Central

    Lee, Soojin; Bang, Se Min; Lee, Joon Woo; Cho, Kyoung Sang

    2014-01-01

    Drosophila is one of the oldest and most powerful genetic models and has led to novel insights into a variety of biological processes. Recently, Drosophila has emerged as a model system to study human diseases, including several important neurodegenerative diseases. Because of the genomic similarity between Drosophila and humans, Drosophila neurodegenerative disease models exhibit a variety of human-disease-like phenotypes, facilitating fast and cost-effective in vivo genetic modifier screening and drug evaluation. Using these models, many disease-associated genetic factors have been identified, leading to the identification of compelling drug candidates. Recently, the safety and efficacy of traditional medicines for human diseases have been evaluated in various animal disease models. Despite the advantages of the Drosophila model, its usage in the evaluation of traditional medicines is only nascent. Here, we introduce the Drosophila model for neurodegenerative diseases and some examples demonstrating the successful application of Drosophila models in the evaluation of traditional medicines. PMID:24790636

  4. Olfactory assays for mouse models of neurodegenerative disease.

    PubMed

    Lehmkuhl, Andrew M; Dirr, Emily R; Fleming, Sheila M

    2014-08-25

    In many neurodegenerative diseases and particularly in Parkinson's disease, deficits in olfaction are reported to occur early in the disease process and may be a useful behavioral marker for early detection. Earlier detection in neurodegenerative disease is a major goal in the field because this is when neuroprotective therapies have the best potential to be effective. Therefore, in preclinical studies testing novel neuroprotective strategies in rodent models of neurodegenerative disease, olfactory assessment could be highly useful in determining therapeutic potential of compounds and translation to the clinic. In the present study we describe a battery of olfactory assays that are useful in measuring olfactory function in mice. The tests presented in this study were chosen because they measure olfaction abilities in mice related to food odors, social odors, and non-social odors. These tests have proven useful in characterizing novel genetic mouse models of Parkinson's disease as well as in testing potential disease-modifying therapies.

  5. Mitochondrial dysfunctions in neurodegenerative diseases: relevance to Alzheimer's disease.

    PubMed

    Hroudová, Jana; Singh, Namrata; Fišar, Zdeněk

    2014-01-01

    Mitochondrial dysfunctions are supposed to be responsible for many neurodegenerative diseases dominating in Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). A growing body of evidence suggests that defects in mitochondrial metabolism and particularly of electron transport chain may play a role in pathogenesis of AD. Structurally and functionally damaged mitochondria do not produce sufficient ATP and are more prominent in producing proapoptotic factors and reactive oxygen species (ROS), and this can be an early stage of several mitochondrial disorders, including neurodegenerative diseases. Mitochondrial dysfunctions may be caused by both mutations in mitochondrial or nuclear DNA that code mitochondrial components and by environmental causes. In the following review, common aspects of mitochondrial impairment concerned about neurodegenerative diseases are summarized including ROS production, impaired mitochondrial dynamics, and apoptosis. Also, damaged function of electron transport chain complexes and interactions between pathological proteins and mitochondria are described for AD particularly and marginally for PD and HD.

  6. The Function of the Mitochondrial Calcium Uniporter in Neurodegenerative Disorders

    PubMed Central

    Liao, Yajin; Dong, Yuan; Cheng, Jinbo

    2017-01-01

    The mitochondrial calcium uniporter (MCU)—a calcium uniporter on the inner membrane of mitochondria—controls the mitochondrial calcium uptake in normal and abnormal situations. Mitochondrial calcium is essential for the production of adenosine triphosphate (ATP); however, excessive calcium will induce mitochondrial dysfunction. Calcium homeostasis disruption and mitochondrial dysfunction is observed in many neurodegenerative disorders. However, the role and regulatory mechanism of the MCU in the development of these diseases are obscure. In this review, we summarize the role of the MCU in controlling oxidative stress-elevated mitochondrial calcium and its function in neurodegenerative disorders. Inhibition of the MCU signaling pathway might be a new target for the treatment of neurodegenerative disorders. PMID:28208618

  7. The transition metals copper and iron in neurodegenerative diseases.

    PubMed

    Rivera-Mancía, Susana; Pérez-Neri, Iván; Ríos, Camilo; Tristán-López, Luis; Rivera-Espinosa, Liliana; Montes, Sergio

    2010-07-30

    Neurodegenerative diseases constitute a worldwide health problem. Metals like iron and copper are essential for life, but they are also involved in several neurodegenerative mechanisms such as protein aggregation, free radical generation and oxidative stress. The role of Fe and Cu, their pathogenic mechanisms and possible therapeutic relevance are discussed regarding four of the most common neurodegenerative diseases, Alzheimer's, Parkinson's and Huntington's diseases as well as amyotrophic lateral sclerosis. Metal-mediated oxidation by Fenton chemistry is a common feature for all those disorders and takes part of a self-amplifying damaging mechanism, leading to neurodegeneration. The interaction between metals and proteins in the nervous system seems to be a crucial factor for the development or absence of neurodegeneration. The present review also deals with the therapeutic strategies tested, mainly using metal chelating drugs. Metal accumulation within the nervous system observed in those diseases could be the result of compensatory mechanisms to improve metal availability for physiological processes.

  8. Failure of ubiquitin proteasome system: risk for neurodegenerative diseases.

    PubMed

    Zheng, Chen; Geetha, Thangiah; Babu, Jeganathan Ramesh

    2014-01-01

    The ubiquitin proteasome system (UPS) is the primary proteolytic quality control system in cells and has an essential function in the nervous system. UPS dysfunction has been linked to neurodegenerative conditions, including Alzheimer's, Parkinson's and Huntington's diseases. The pathology of neurodegenerative diseases is characterized by the abnormal accumulation of insoluble protein aggregates or inclusion bodies within neurons. The failure or dysregulation of the UPS prevents the degradation of misfolded/aberrant proteins, leading to deficient synaptic function that eventually affects the nervous system. In this review, we discuss the UPS and its physiological roles in the nervous system, its influence on neuronal function, and how UPS dysfunction contributes to the development of neurodegenerative diseases. © 2014 S. Karger AG, Basel.

  9. Bioinformatics Mining and Modeling Methods for the Identification of Disease Mechanisms in Neurodegenerative Disorders

    PubMed Central

    Hofmann-Apitius, Martin; Ball, Gordon; Gebel, Stephan; Bagewadi, Shweta; de Bono, Bernard; Schneider, Reinhard; Page, Matt; Kodamullil, Alpha Tom; Younesi, Erfan; Ebeling, Christian; Tegnér, Jesper; Canard, Luc

    2015-01-01

    Since the decoding of the Human Genome, techniques from bioinformatics, statistics, and machine learning have been instrumental in uncovering patterns in increasing amounts and types of different data produced by technical profiling technologies applied to clinical samples, animal models, and cellular systems. Yet, progress on unravelling biological mechanisms, causally driving diseases, has been limited, in part due to the inherent complexity of biological systems. Whereas we have witnessed progress in the areas of cancer, cardiovascular and metabolic diseases, the area of neurodegenerative diseases has proved to be very challenging. This is in part because the aetiology of neurodegenerative diseases such as Alzheimer´s disease or Parkinson´s disease is unknown, rendering it very difficult to discern early causal events. Here we describe a panel of bioinformatics and modeling approaches that have recently been developed to identify candidate mechanisms of neurodegenerative diseases based on publicly available data and knowledge. We identify two complementary strategies—data mining techniques using genetic data as a starting point to be further enriched using other data-types, or alternatively to encode prior knowledge about disease mechanisms in a model based framework supporting reasoning and enrichment analysis. Our review illustrates the challenges entailed in integrating heterogeneous, multiscale and multimodal information in the area of neurology in general and neurodegeneration in particular. We conclude, that progress would be accelerated by increasing efforts on performing systematic collection of multiple data-types over time from each individual suffering from neurodegenerative disease. The work presented here has been driven by project AETIONOMY; a project funded in the course of the Innovative Medicines Initiative (IMI); which is a public-private partnership of the European Federation of Pharmaceutical Industry Associations (EFPIA) and the European

  10. Bioinformatics Mining and Modeling Methods for the Identification of Disease Mechanisms in Neurodegenerative Disorders.

    PubMed

    Hofmann-Apitius, Martin; Ball, Gordon; Gebel, Stephan; Bagewadi, Shweta; de Bono, Bernard; Schneider, Reinhard; Page, Matt; Kodamullil, Alpha Tom; Younesi, Erfan; Ebeling, Christian; Tegnér, Jesper; Canard, Luc

    2015-12-07

    Since the decoding of the Human Genome, techniques from bioinformatics, statistics, and machine learning have been instrumental in uncovering patterns in increasing amounts and types of different data produced by technical profiling technologies applied to clinical samples, animal models, and cellular systems. Yet, progress on unravelling biological mechanisms, causally driving diseases, has been limited, in part due to the inherent complexity of biological systems. Whereas we have witnessed progress in the areas of cancer, cardiovascular and metabolic diseases, the area of neurodegenerative diseases has proved to be very challenging. This is in part because the aetiology of neurodegenerative diseases such as Alzheimer´s disease or Parkinson´s disease is unknown, rendering it very difficult to discern early causal events. Here we describe a panel of bioinformatics and modeling approaches that have recently been developed to identify candidate mechanisms of neurodegenerative diseases based on publicly available data and knowledge. We identify two complementary strategies-data mining techniques using genetic data as a starting point to be further enriched using other data-types, or alternatively to encode prior knowledge about disease mechanisms in a model based framework supporting reasoning and enrichment analysis. Our review illustrates the challenges entailed in integrating heterogeneous, multiscale and multimodal information in the area of neurology in general and neurodegeneration in particular. We conclude, that progress would be accelerated by increasing efforts on performing systematic collection of multiple data-types over time from each individual suffering from neurodegenerative disease. The work presented here has been driven by project AETIONOMY; a project funded in the course of the Innovative Medicines Initiative (IMI); which is a public-private partnership of the European Federation of Pharmaceutical Industry Associations (EFPIA) and the European

  11. Microtubule-Stabilizing Agents as Potential Therapeutics for Neurodegenerative Disease

    PubMed Central

    Brunden, Kurt R.; Trojanowski, John Q.; Smith, Amos B.; Lee, Virginia M.-Y.; Ballatore, Carlo

    2014-01-01

    Microtubules (MTs)1, cytoskeletal elements found in all mammalian cells, play a significant role in cell structure and in cell division. They are especially critical in the proper functioning of post-mitotic central nervous system neurons, where MTs serve as the structures on which key cellular constituents are trafficked in axonal projections. MTs are stabilized in axons by the MT-associated protein tau, and in several neurodegenerative diseases, including Alzheimer’s disease, frontotemporal lobar degeneration, and Parkinson’s disease, tau function appears to be compromised due to the protein dissociating from MTs and depositing into insoluble inclusions referred to as neurofibrillary tangles. This loss of tau function is believed to result in alterations of MT structure and function, resulting in aberrant axonal transport that likely contributes to the neurodegenerative process. There is also evidence of axonal transport deficiencies in other neurodegenerative diseases, including amyotrophic lateral sclerosis and Huntington’s disease, which may result, at least in part, from MT alterations. Accordingly, a possible therapeutic strategy for such neurodegenerative conditions is to treat with MT-stabilizing agents, such as those that have been used in the treatment of cancer. Here, we review evidence of axonal transport and MT deficiencies in a number of neurodegenerative diseases, and summarize the various classes of known MT-stabilizing agents. Finally, we highlight the growing evidence that small molecule MT-stabilizing agents provide benefit in animal models of neurodegenerative disease and discuss the desired features of such molecules for the treatment of these central nervous system disorders. PMID:24433963

  12. Microtubule-stabilizing agents as potential therapeutics for neurodegenerative disease.

    PubMed

    Brunden, Kurt R; Trojanowski, John Q; Smith, Amos B; Lee, Virginia M-Y; Ballatore, Carlo

    2014-09-15

    Microtubules (MTs), cytoskeletal elements found in all mammalian cells, play a significant role in cell structure and in cell division. They are especially critical in the proper functioning of post-mitotic central nervous system neurons, where MTs serve as the structures on which key cellular constituents are trafficked in axonal projections. MTs are stabilized in axons by the MT-associated protein tau, and in several neurodegenerative diseases, including Alzheimer's disease, frontotemporal lobar degeneration, and Parkinson's disease, tau function appears to be compromised due to the protein dissociating from MTs and depositing into insoluble inclusions referred to as neurofibrillary tangles. This loss of tau function is believed to result in alterations of MT structure and function, resulting in aberrant axonal transport that likely contributes to the neurodegenerative process. There is also evidence of axonal transport deficiencies in other neurodegenerative diseases, including amyotrophic lateral sclerosis and Huntington's disease, which may result, at least in part, from MT alterations. Accordingly, a possible therapeutic strategy for such neurodegenerative conditions is to treat with MT-stabilizing agents, such as those that have been used in the treatment of cancer. Here, we review evidence of axonal transport and MT deficiencies in a number of neurodegenerative diseases, and summarize the various classes of known MT-stabilizing agents. Finally, we highlight the growing evidence that small molecule MT-stabilizing agents provide benefit in animal models of neurodegenerative disease and discuss the desired features of such molecules for the treatment of these central nervous system disorders. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Global warming and neurodegenerative disorders: speculations on their linkage.

    PubMed

    Habibi, Laleh; Perry, George; Mahmoudi, Morteza

    2014-01-01

    Climate change is having considerable impact on biological systems. Eras of ice ages and warming shaped the contemporary earth and origin of creatures including humans. Warming forces stress conditions on cells. Therefore, cells evolved elaborate defense mechanisms, such as creation of heat shock proteins, to combat heat stress. Global warming is becoming a crisis and this process would yield an undefined increasing rate of neurodegenerative disorders in future decades. Since heat stress is known to have a degenerative effects on neurons and, conversely, cold conditions have protective effect on these cells, we hypothesize that persistent heat stress forced by global warming might play a crucial role in increasing neurodegenerative disorders.

  14. Apocynin, a Low Molecular Oral Treatment for Neurodegenerative Disease

    PubMed Central

    ‘t Hart, Bert A.; Copray, Sjef; Philippens, Ingrid

    2014-01-01

    Accumulating evidence suggests that inflammatory mediators secreted by activated resident or infiltrated innate immune cells have a significant impact on the pathogenesis of neurodegenerative diseases. This may imply that patients affected by a neurodegenerative disease may benefit from treatment with selective inhibitors of innate immune activity. Here we review the therapeutic potential of apocynin, an essentially nontoxic phenolic compound isolated from the medicinal plant Jatropha multifida. Apocynin is a selective inhibitor of the phagocyte NADPH oxidase Nox2 that can be applied orally and is remarkably effective at low dose. PMID:25140304

  15. Impaired autophagy: a link between neurodegenerative and neuropsychiatric diseases

    PubMed Central

    Polajnar, Mira; Žerovnik, Eva

    2014-01-01

    Protein misfolding, and subsequent aggregation have been proven as the leading cause of most known dementias. Many of these, in addition to neurodegeneration, show profound changes in behaviour and thinking, thus, psychiatric symptoms. On the basis of the observation that progressive myoclonic epilepsies and neurodegenerative diseases share some common features of neurodegeneration, we proposed autophagy as a possible common impairment in these diseases. Here, we argue along similar lines for some neuropsychiatric conditions, among them depression and schizophrenia. We propose that existing and new therapies for these seemingly different diseases could be augmented with drugs used for neurodegenerative or neuropsychiatric diseases, respectively, among them some which modulate or augment autophagy. PMID:25139375

  16. Sleep disturbance in mental health problems and neurodegenerative disease

    PubMed Central

    Anderson, Kirstie N; Bradley, Andrew J

    2013-01-01

    Sleep has been described as being of the brain, by the brain, and for the brain. This fundamental neurobiological behavior is controlled by homeostatic and circadian (24-hour) processes and is vital for normal brain function. This review will outline the normal sleep–wake cycle, the changes that occur during aging, and the specific patterns of sleep disturbance that occur in association with both mental health disorders and neurodegenerative disorders. The role of primary sleep disorders such as insomnia, obstructive sleep apnea, and REM sleep behavior disorder as potential causes or risk factors for particular mental health or neurodegenerative problems will also be discussed. PMID:23761983

  17. Nanomedicine and neurodegenerative disorders: so close yet so far.

    PubMed

    Tosi, Giovanni; Vandelli, Maria Angela; Forni, Flavio; Ruozi, Barbara

    2015-07-01

    This editorial provides an overview of the main advantages of the use of nanomedicine-based approach for innovation in the treatment of neurodegenerative diseases. Besides these aspects, a critical analysis on the main causes that slow the application of nanomedicine to brain disorders is given along with the identification of possible solutions and possible interventions. Better communication between the main players of research in this field and a detailed understanding of the most critical issues to be addressed should help in defining future directions towards the improvement and, finally, the clinical application of nanomedicine to neurodegenerative diseases.

  18. Prion-like transmission of protein aggregates in neurodegenerative diseases

    PubMed Central

    Brundin, Patrik; Melki, Ronald; Kopito, Ron

    2010-01-01

    Neurodegenerative diseases are commonly associated with the accumulation of intracellular or extracellular protein aggregates. Recent studies suggest that these aggregates are capable of crossing cellular membranes and can directly contribute to the propagation of neurodegenerative disease pathogenesis. We propose that, once initiated, neuropathological changes might spread in a ‘prion-like’ manner and that disease progression is associated with the intercellular transfer of pathogenic proteins. The transfer of naked infectious particles between cells could therefore be a target for new disease-modifying therapies. PMID:20308987

  19. Global warming and neurodegenerative disorders: speculations on their linkage

    PubMed Central

    Habibi, Laleh; Perry, George; Mahmoudi, Morteza

    2014-01-01

    Climate change is having considerable impact on biological systems. Eras of ice ages and warming shaped the contemporary earth and origin of creatures including humans. Warming forces stress conditions on cells. Therefore, cells evolved elaborate defense mechanisms, such as creation of heat shock proteins, to combat heat stress. Global warming is becoming a crisis and this process would yield an undefined increasing rate of neurodegenerative disorders in future decades. Since heat stress is known to have a degenerative effects on neurons and, conversely, cold conditions have protective effect on these cells, we hypothesize that persistent heat stress forced by global warming might play a crucial role in increasing neurodegenerative disorders. PMID:25671171

  20. Auditory short-term memory in the primate auditory cortex

    PubMed Central

    Scott, Brian H.; Mishkin, Mortimer

    2015-01-01

    Sounds are fleeting, and assembling the sequence of inputs at the ear into a coherent percept requires auditory memory across various time scales. Auditory short-term memory comprises at least two components: an active ‘working memory’ bolstered by rehearsal, and a sensory trace that may be passively retained. Working memory relies on representations recalled from long-term memory, and their rehearsal may require phonological mechanisms unique to humans. The sensory component, passive short-term memory (pSTM), is tractable to study in nonhuman primates, whose brain architecture and behavioral repertoire are comparable to our own. This review discusses recent advances in the behavioral and neurophysiological study of auditory memory with a focus on single-unit recordings from macaque monkeys performing delayed-match-to-sample (DMS) tasks. Monkeys appear to employ pSTM to solve these tasks, as evidenced by the impact of interfering stimuli on memory performance. In several regards, pSTM in monkeys resembles pitch memory in humans, and may engage similar neural mechanisms. Neural correlates of DMS performance have been observed throughout the auditory and prefrontal cortex, defining a network of areas supporting auditory STM with parallels to that supporting visual STM. These correlates include persistent neural firing, or a suppression of firing, during the delay period of the memory task, as well as suppression or (less commonly) enhancement of sensory responses when a sound is repeated as a ‘match’ stimulus. Auditory STM is supported by a distributed temporo-frontal network in which sensitivity to stimulus history is an intrinsic feature of auditory processing. PMID:26541581

  1. Auditory Brainstem Responses in Young Males with Fragile X Syndrome

    ERIC Educational Resources Information Center

    Roberts, Joanne; Hennon, Elizabeth A.; Anderson, Kathleen; Roush, Jackson; Gravel, Judith; Skinner, Martie; Misenheimer, Jan; Reitz, Patricia

    2005-01-01

    Fragile X syndrome (FXS) is the most common inherited cause of mental retardation resulting in developmental delays in males. Atypical outer ear morphology is characteristic of FXS and may serve as a marker for abnormal auditory function. Despite this abnormality, studies of the hearing of young males with FXS are generally lacking. A few studies…

  2. Are Auditory and Visual Processing Deficits Related to Developmental Dyslexia?

    ERIC Educational Resources Information Center

    Georgiou, George K.; Papadopoulos, Timothy C.; Zarouna, Elena; Parrila, Rauno

    2012-01-01

    The purpose of this study was to examine if children with dyslexia learning to read a consistent orthography (Greek) experience auditory and visual processing deficits and if these deficits are associated with phonological awareness, rapid naming speed and orthographic processing. We administered measures of general cognitive ability, phonological…

  3. Are Auditory and Visual Processing Deficits Related to Developmental Dyslexia?

    ERIC Educational Resources Information Center

    Georgiou, George K.; Papadopoulos, Timothy C.; Zarouna, Elena; Parrila, Rauno

    2012-01-01

    The purpose of this study was to examine if children with dyslexia learning to read a consistent orthography (Greek) experience auditory and visual processing deficits and if these deficits are associated with phonological awareness, rapid naming speed and orthographic processing. We administered measures of general cognitive ability, phonological…

  4. Auditory Brainstem Responses in Young Males with Fragile X Syndrome

    ERIC Educational Resources Information Center

    Roberts, Joanne; Hennon, Elizabeth A.; Anderson, Kathleen; Roush, Jackson; Gravel, Judith; Skinner, Martie; Misenheimer, Jan; Reitz, Patricia

    2005-01-01

    Fragile X syndrome (FXS) is the most common inherited cause of mental retardation resulting in developmental delays in males. Atypical outer ear morphology is characteristic of FXS and may serve as a marker for abnormal auditory function. Despite this abnormality, studies of the hearing of young males with FXS are generally lacking. A few studies…

  5. The role of augmentative visual training in auditory human-machine-interface performance.

    PubMed

    Hands, Gabrielle L; Larson, Eric; Stepp, Cara E

    2013-01-01

    The purpose of this study was to evaluate the effect of augmentative visual feedback training on performance using auditory feedback alone for human-machine interface (HMI) control. Sixteen healthy participants used bilateral facial surface electromyography to achieve two-dimensional control to reach vowel targets. Eight participants trained with combined visual and auditory feedback, while eight participants trained with real-time auditory feedback only. Each subject participated in four sessions over three days; three sessions with their designated feedback modality (auditory only or auditory with supplementary visual) and a fourth session on the third day using novel vowel targets to test generalization of auditory-motor learning. Analyses of variance performed on the percentage of total targets reached demonstrated a main effect of group and the interaction of group and session. Individuals provided with augmentative visual feedback during training outperformed individuals using auditory feedback alone in initial training sessions. However, training with augmentative visual feedback had no effect on individuals' training and generalization performance using auditory feedback alone after three days of training.

  6. Music training for the development of auditory skills.

    PubMed

    Kraus, Nina; Chandrasekaran, Bharath

    2010-08-01

    The effects of music training in relation to brain plasticity have caused excitement, evident from the popularity of books on this topic among scientists and the general public. Neuroscience research has shown that music training leads to changes throughout the auditory system that prime musicians for listening challenges beyond music processing. This effect of music training suggests that, akin to physical exercise and its impact on body fitness, music is a resource that tones the brain for auditory fitness. Therefore, the role of music in shaping individual development deserves consideration.

  7. Psychology of auditory perception.

    PubMed

    Lotto, Andrew; Holt, Lori

    2011-09-01

    Audition is often treated as a 'secondary' sensory system behind vision in the study of cognitive science. In this review, we focus on three seemingly simple perceptual tasks to demonstrate the complexity of perceptual-cognitive processing involved in everyday audition. After providing a short overview of the characteristics of sound and their neural encoding, we present a description of the perceptual task of segregating multiple sound events that are mixed together in the signal reaching the ears. Then, we discuss the ability to localize the sound source in the environment. Finally, we provide some data and theory on how listeners categorize complex sounds, such as speech. In particular, we present research on how listeners weigh multiple acoustic cues in making a categorization decision. One conclusion of this review is that it is time for auditory cognitive science to be developed to match what has been done in vision in order for us to better understand how humans communicate with speech and music. WIREs Cogni Sci 2011 2 479-489 DOI: 10.1002/wcs.123 For further resources related to this article, please visit the WIREs website. Copyright © 2010 John Wiley & Sons, Ltd.

  8. Methods for the analysis of auditory processing in the brain.

    PubMed

    Theunissen, Frédéric E; Woolley, Sarah M N; Hsu, Anne; Fremouw, Thane

    2004-06-01

    Understanding song perception and singing behavior in birds requires the study of auditory processing of complex sounds throughout the avian brain. We can divide the basics of auditory perception into two general processes: (1) encoding, the process whereby sound is transformed into neural activity and (2) decoding, the process whereby patterns of neural activity take on perceptual meaning and therefore guide behavioral responses to sounds. In birdsong research, most studies have focused on the decoding process: What are the responses of the specialized auditory neurons in the song control system? and What do they mean for the bird? Recently, new techniques addressing both encoding and decoding have been developed for use in songbirds. Here, we first describe some powerful methods for analyzing what acoustical aspects of complex sounds like songs are encoded by auditory processing neurons in songbird brain. These methods include the estimation and analysis of spectro-temporal receptive fields (STRFs) for auditory neurons. Then we discuss the decoding methods that have been used to understand how songbird neurons may discriminate among different songs and other sounds based on mean spike-count rates.

  9. Interactions across Multiple Stimulus Dimensions in Primary Auditory Cortex.

    PubMed

    Sloas, David C; Zhuo, Ran; Xue, Hongbo; Chambers, Anna R; Kolaczyk, Eric; Polley, Daniel B; Sen, Kamal

    2016-01-01

    Although sensory cortex is thought to be important for the perception of complex objects, its specific role in representing complex stimuli remains unknown. Complex objects are rich in information along multiple stimulus dimensions. The position of cortex in the sensory hierarchy suggests that cortical neurons may integrate across these dimensions to form a more gestalt representation of auditory objects. Yet, studies of cortical neurons typically explore single or few dimensions due to the difficulty of determining optimal stimuli in a high dimensional stimulus space. Evolutionary algorithms (EAs) provide a potentially powerful approach for exploring multidimensional stimulus spaces based on real-time spike feedback, but two important issues arise in their application. First, it is unclear whether it is necessary to characterize cortical responses to multidimensional stimuli or whether it suffices to characterize cortical responses to a single dimension at a time. Second, quantitative methods for analyzing complex multidimensional data from an EA are lacking. Here, we apply a statistical method for nonlinear regression, the generalized additive model (GAM), to address these issues. The GAM quantitatively describes the dependence between neural response and all stimulus dimensions. We find that auditory cortical neurons in mice are sensitive to interactions across dimensions. These interactions are diverse across the population, indicating significant integration across stimulus dimensions in auditory cortex. This result strongly motivates using multidimensional stimuli in auditory cortex. Together, the EA and the GAM provide a novel quantitative paradigm for investigating neural coding of complex multidimensional stimuli in auditory and other sensory cortices.

  10. Coding of melodic gestalt in human auditory cortex.

    PubMed

    Schindler, Andreas; Herdener, Marcus; Bartels, Andreas

    2013-12-01

    The perception of a melody is invariant to the absolute properties of its constituting notes, but depends on the relation between them-the melody's relative pitch profile. In fact, a melody's "Gestalt" is recognized regardless of the instrument or key used to play it. Pitch processing in general is assumed to occur at the level of the auditory cortex. However, it is unknown whether early auditory regions are able to encode pitch sequences integrated over time (i.e., melodies) and whether the resulting representations are invariant to specific keys. Here, we presented participants different melodies composed of the same 4 harmonic pitches during functional magnetic resonance imaging recordings. Additionally, we played the same melodies transposed in different keys and on different instruments. We found that melodies were invariantly represented by their blood oxygen level-dependent activation patterns in primary and secondary auditory cortices across instruments, and also across keys. Our findings extend common hierarchical models of auditory processing by showing that melodies are encoded independent of absolute pitch and based on their relative pitch profile as early as the primary auditory cortex.

  11. Heterogeneity of Auditory Verbal Working Memory in Schizophrenia

    PubMed Central

    Bruder, Gerard E.; Alschuler, Daniel M.; Kroppmann, Christopher J.; Fekri, Shiva; Gil, Roberto; Jarskog, Lars F.; Harkavy-Friedman, Jill M.; Goetz, Raymond; Kayser, Jürgen; Wexler, Bruce E.

    2011-01-01

    The heterogeneity of schizophrenia remains an obstacle for understanding its pathophysiology. Studies using a tone discrimination screening test to classify patients have found evidence for two subgroups having either a specific deficit in verbal working memory (WM) or deficits on both verbal and nonverbal memory tests. This study aimed to: (1) replicate in larger samples differences between these subgroups on the word serial position test (WSPT); (2) further evaluate their performance on additional tests of verbal WM, explicit memory, and sustained attention; (3) determine the relation of verbal WM deficits to auditory hallucinations and other symptoms; and (4) examine medication effects. WSPT of verbal WM and tone discrimination performance did not differ between medicated (n=45) and unmedicated (n=38) patients. Patients with schizophrenia who passed the auditory screening test (discriminators, n=60) were compared to those who did not (nondiscriminators, n=23), and healthy controls (n=47). The discriminator subgroup showed poorer verbal WM than controls and a deficit in verbal but not visual memory on Wechsler Memory Scale-Revised, whereas the nondiscriminator subgroup showed overall poorer performance on both verbal and nonverbal tests and a marked deficit in sustained attention. Verbal WM deficits in discriminators on WSPT were correlated with auditory hallucinations but not with negative symptoms. The results are consistent with a verbal memory deficit in a subgroup of schizophrenia having intact auditory perception, which may stem from dysfunction of language-related cortical regions, and a more generalized cognitive deficit in a subgroup having auditory perceptual and attentional dysfunction. PMID:21319926

  12. Interactions across Multiple Stimulus Dimensions in Primary Auditory Cortex

    PubMed Central

    Zhuo, Ran; Xue, Hongbo; Chambers, Anna R.; Kolaczyk, Eric; Polley, Daniel B.

    2016-01-01

    Although sensory cortex is thought to be important for the perception of complex objects, its specific role in representing complex stimuli remains unknown. Complex objects are rich in information along multiple stimulus dimensions. The position of cortex in the sensory hierarchy suggests that cortical neurons may integrate across these dimensions to form a more gestalt representation of auditory objects. Yet, studies of cortical neurons typically explore single or few dimensions due to the difficulty of determining optimal stimuli in a high dimensional stimulus space. Evolutionary algorithms (EAs) provide a potentially powerful approach for exploring multidimensional stimulus spaces based on real-time spike feedback, but two important issues arise in their application. First, it is unclear whether it is necessary to characterize cortical responses to multidimensional stimuli or whether it suffices to characterize cortical responses to a single dimension at a time. Second, quantitative methods for analyzing complex multidimensional data from an EA are lacking. Here, we apply a statistical method for nonlinear regression, the generalized additive model (GAM), to address these issues. The GAM quantitatively describes the dependence between neural response and all stimulus dimensions. We find that auditory cortical neurons in mice are sensitive to interactions across dimensions. These interactions are diverse across the population, indicating significant integration across stimulus dimensions in auditory cortex. This result strongly motivates using multidimensional stimuli in auditory cortex. Together, the EA and the GAM provide a novel quantitative paradigm for investigating neural coding of complex multidimensional stimuli in auditory and other sensory cortices. PMID:27622211

  13. The mismatch negativity in evaluating central auditory dysfunction in dyslexia.

    PubMed

    Kujala, T; Näätänen, R

    2001-08-01

    The mismatch negativity (MMN), a brain response elicited by a discriminable change in any repetitive aspect of auditory stimulation even in the absence of attention, has been widely used in both basic and clinical research during recent years. The fact that the MMN reflects the accuracy of auditory discrimination and that it can be obtained even from unattentive subjects makes it an especially attractive tool for studying various central auditory-system dysfunctions both in adults and children. In this review, we will discuss the applicability of the MMN to studies in dyslexia, which is currently thought, in the majority of the cases, to primarily result either from a dysfunction of the phonological system or a more general auditory deficit. Recent evidence indicates that the MMN enables one to determine which aspects of auditory information are deficiently processed in dyslexia. The MMN might also be helpful in the early definition of the dyslexia type, which would make it possible to start correctly-targeted training programmes before any major learning delays occur. Furthermore, the MMN holds promise of showing plastic changes in the brain of dyslexic individuals underlying the alleviation or remediation of dyslexia in the course of a successful training programme.

  14. Are auditory and visual processing deficits related to developmental dyslexia?

    PubMed

    Georgiou, George K; Papadopoulos, Timothy C; Zarouna, Elena; Parrila, Rauno

    2012-05-01

    The purpose of this study was to examine if children with dyslexia learning to read a consistent orthography (Greek) experience auditory and visual processing deficits and if these deficits are associated with phonological awareness, rapid naming speed and orthographic processing. We administered measures of general cognitive ability, phonological awareness, orthographic processing, short-term memory, rapid automatized naming, auditory and visual processing, and reading fluency to 21 Grade 6 children with dyslexia, 21 chronological age-matched controls and 20 Grade 3 reading age-matched controls. The results indicated that the children with dyslexia did not experience auditory processing deficits, but about half of them showed visual processing deficits. Both orthographic processing and rapid automatized naming deficits were associated with dyslexia in our sample, but it is less clear that they were associated with visual processing deficits. Copyright © 2012 John Wiley & Sons, Ltd.

  15. The role of vision in auditory distance perception.

    PubMed

    Calcagno, Esteban R; Abregú, Ezequiel L; Eguía, Manuel C; Vergara, Ramiro

    2012-01-01

    In humans, multisensory interaction is an important strategy for improving the detection of stimuli of different nature and reducing the variability of response. It is known that the presence of visual information affects the auditory perception in the horizontal plane (azimuth), but there are few researches that study the influence of vision in the auditory distance perception. In general, the data obtained from these studies are contradictory and do not completely define the way in which visual cues affect the apparent distance of a sound source. Here psychophysical experiments on auditory distance perception in humans are performed, including and excluding visual cues. The results show that the apparent distance from the source is affected by the presence of visual information and that subjects can store in their memory a representation of the environment that later improves the perception of distance.

  16. The impact of auditory distraction on retrieval of visual memories.

    PubMed

    Wais, Peter E; Gazzaley, Adam

    2011-12-01

    Recent research has revealed that the presence of irrelevant visual information during retrieval of long-term memories diminishes recollection of task-relevant visual details. Here, we explored the impact of irrelevant auditory information on remembering task-relevant visual details by probing recall of the same previously viewed images while participants were in complete silence, exposed to white noise, or exposed to ambient sounds recorded at a busy café. The presence of auditory distraction diminished objective recollection of goal-relevant details, relative to the silence and white noise conditions. Critically, a comparison with results from a previous study using visual distractors showed equivalent effects for auditory and visual distraction. These findings suggest that disruption of recollection by external stimuli is a domain-general phenomenon produced by interference between resource-limited, top-down mechanisms that guide the selection of mnemonic details and control processes that mediate our interactions with external distractors.

  17. A Computational Neurodegenerative Disease Progression Score: Method and Results with the Alzheimer’s Disease Neuroimaging Initiative Cohort

    PubMed Central

    Jedynak, Bruno M.; Lang, Andrew; Liu, Bo; Katz, Elyse; Zhang, Yanwei; Wyman, Bradley T.; Raunig, David; Jedynak, C. Pierre; Caffo, Brian; Prince, Jerry L.

    2012-01-01

    While neurodegenerative diseases are characterized by steady degeneration over relatively long timelines, it is widely believed that the early stages are the most promising for therapeutic intervention, before irreversible neuronal loss occurs. Developing a therapeutic response requires a precise measure of disease progression. However, since the early stages are for the most part asymptomatic, obtaining accurate measures of disease progression is difficult. Longitudinal databases of hundreds of subjects observed during several years with tens of validated biomarkers are becoming available, allowing the use of computational methods. We propose a widely applicable statistical methodology for creating a disease progression score (DPS), using multiple biomarkers, for subjects with a neurodegenerative disease. The proposed methodology was evaluated for Alzheimer’s disease (AD) using the publicly available AD Neuroimaging Initiative (ADNI) database, yielding an Alzheimer’s DPS or ADPS score for each subject and each time-point in the database. In addition, a common description of biomarker changes was produced allowing for an ordering of the biomarkers. The Rey Auditory Verbal Learning Test delayed recall was found to be the earliest biomarker to become abnormal. The group of biomarkers comprising the volume of the hippocampus and the protein concentration amyloid beta and Tau were next in the timeline, and these were followed by three cognitive biomarkers. The proposed methodology thus has potential to stage individuals according to their state of disease progression relative to a population and to deduce common behaviors of biomarkers in the disease itself. PMID:22885136

  18. Gene Therapy-Based Modeling of Neurodegenerative Disorders: Huntington's Disease.

    PubMed

    Young, Deborah

    2016-01-01

    Huntington's disease is a fatal neurodegenerative disease characterized by impairments in motor control, and cognitive and psychiatric disturbances. In this chapter, viral vector-mediated approaches used in modeling the key neuropathological features of the disease including the production of abnormal intracellular protein aggregates, neuronal dysfunction and degeneration and motor impairments in rodents are described.

  19. Les Liaisons Dangereuses: Cancer-Related Genes and Neurodegenerative Diseases

    NASA Astrophysics Data System (ADS)

    Ghetti, Bernardino; Buonaguro, Franco M.

    2014-07-01

    The following sections are included: * INTRODUCTION * MUTATIONS IN THE CSF1R GENE ASSOCIATED WITH DIFFUSE LEUKOENCEPHALOPATHY WITH SPHEROIDS AND HUMAN CANCERS. * A SPECIAL LINK HAS BEEN SHOWN BETWEEN PTEN AND AD. * ACETYLCHOLINE DEFICIENCY AND PATHOGENESIS OF AD. * MIRNAS AND COMMON PATHWAYS IN CANCER AND NEURODEGENERATIVE DISEASE. * SUMMARY * REFERENCES

  20. Neural stem cell-based treatment for neurodegenerative diseases.

    PubMed

    Kim, Seung U; Lee, Hong J; Kim, Yun B

    2013-10-01

    Human neurodegenerative diseases such as Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD) are caused by a loss of neurons and glia in the brain or spinal cord. Neurons and glial cells have successfully been generated from stem cells such as embryonic stem cells (ESCs), mesenchymal stem cells (MSCs) and neural stem cells (NSCs), and stem cell-based cell therapies for neurodegenerative diseases have been developed. A recent advance in generation of a new class of pluripotent stem cells, induced pluripotent stem cells (iPSCs), derived from patients' own skin fibroblasts, opens doors for a totally new field of personalized medicine. Transplantation of NSCs, neurons or glia generated from stem cells in animal models of neurodegenerative diseases, including PD, HD, ALS and AD, demonstrates clinical improvement and also life extension of these animals. Additional therapeutic benefits in these animals can be provided by stem cell-mediated gene transfer of therapeutic genes such as neurotrophic factors and enzymes. Although further research is still needed, cell and gene therapy based on stem cells, particularly using neurons and glia derived from iPSCs, ESCs or NSCs, will become a routine treatment for patients suffering from neurodegenerative diseases and also stroke and spinal cord injury.

  1. Molecular Chaperone Dysfunction in Neurodegenerative Diseases and Effects of Curcumin

    PubMed Central

    Frautschy, Sally

    2014-01-01

    The intra- and extracellular accumulation of misfolded and aggregated amyloid proteins is a common feature in several neurodegenerative diseases, which is thought to play a major role in disease severity and progression. The principal machineries maintaining proteostasis are the ubiquitin proteasomal and lysosomal autophagy systems, where heat shock proteins play a crucial role. Many protein aggregates are degraded by the lysosomes, depending on aggregate size, peptide sequence, and degree of misfolding, while others are selectively tagged for removal by heat shock proteins and degraded by either the proteasome or phagosomes. These systems are compromised in different neurodegenerative diseases. Therefore, developing novel targets and classes of therapeutic drugs, which can reduce aggregates and maintain proteostasis in the brains of neurodegenerative models, is vital. Natural products that can modulate heat shock proteins/proteosomal pathway are considered promising for treating neurodegenerative diseases. Here we discuss the current knowledge on the role of HSPs in protein misfolding diseases and knowledge gained from animal models of Alzheimer's disease, tauopathies, and Huntington's diseases. Further, we discuss the emerging treatment regimens for these diseases using natural products, like curcumin, which can augment expression or function of heat shock proteins in the cell. PMID:25386560

  2. Chronic hypothermia and water intoxication associated with a neurodegenerative disease.

    PubMed Central

    Corbett, E. L.; Sisodiya, S.; Sarkar, D.

    1993-01-01

    We describe a 71 year old man with a neurodegenerative condition who developed chronic inappropriate antidiuretic hormone secretion and hypothermia resulting in recurrent episodes of impaired consciousness. This combination of abnormalities is attributable to hypothalamic disease and has not to our knowledge been previously reported with clearly documented antidiuretic hormone excess. Images Figure 1 PMID:8121871

  3. Protection against neurodegenerative disease on Earth and in space.

    PubMed

    Takamatsu, Yoshiki; Koike, Wakako; Takenouchi, Takato; Sugama, Shuei; Wei, Jianshe; Waragai, Masaaki; Sekiyama, Kazunari; Hashimoto, Makoto

    2016-01-01

    All living organisms have evolutionarily adapted themselves to the Earth's gravity, and failure to adapt to gravity changes may lead to pathological conditions. This perspective may also apply to abnormal aging observed in bedridden elderly patients with aging-associated diseases such as osteoporosis and sarcopenia. Given that bedridden elderly patients are partially analogous to astronauts in that both cannot experience the beneficial effects of gravity on the skeletal system and may suffer from bone loss and muscle weakness, one may wonder whether there are gravity-related mechanisms underlying diseases among the elderly. In contrast to numerous studies of the relevance of microgravity in skeletal disorders, little attention has been paid to neurodegenerative diseases. Therefore, the objective of this paper is to discuss the possible relevance of microgravity in these diseases. We particularly noted a proteomics paper showing that levels of hippocampal proteins, including β-synuclein and carboxyl-terminal ubiquitin hydrolase L1, which have been linked to familial neurodegenerative diseases, were significantly decreased in the hippocampus of mice subjected to hindlimb suspension, a model of microgravity. We suggest that microgravity-induced neurodegeneration may be further exacerbated by diabetes and other factors. On the basis of this view, prevention of neurodegenerative diseases through 'anti-diabetes' and 'hypergravity' approaches may be important as a common therapeutic approach on Earth and in space. Collectively, neurodegenerative diseases and space medicine may be linked to each other more strongly than previously thought.

  4. The cellular basis of dendrite pathology in neurodegenerative diseases.

    PubMed

    Kweon, Jung Hyun; Kim, Sunhong; Lee, Sung Bae

    2017-01-01

    One of the characteristics of the neurons that distinguishes them from other cells is their complex and polarized structure consisting of dendrites, cell body, and axon. The complexity and diversity of dendrites are particularly well recognized, and accumulating evidences suggest that the alterations in the dendrite structure are associated with many neurodegenerative diseases. Given the importance of the proper dendritic structures for neuronal functions, the dendrite pathology appears to have crucial contribution to the pathogenesis of neurodegenerative diseases. Nonetheless, the cellular and molecular basis of dendritic changes in the neurodegenerative diseases remains largely elusive. Previous studies in normal condition have revealed that several cellular components, such as local cytoskeletal structures and organelles located locally in dendrites, play crucial roles in dendrite growth. By reviewing what has been unveiled to date regarding dendrite growth in terms of these local cellular components, we aim to provide an insight to categorize the potential cellular basis that can be applied to the dendrite pathology manifested in many neurodegenerative diseases. [BMB Reports 2017; 50(1): 5-11].

  5. Protection against neurodegenerative disease on Earth and in space

    PubMed Central

    Takamatsu, Yoshiki; Koike, Wakako; Takenouchi, Takato; Sugama, Shuei; Wei, Jianshe; Waragai, Masaaki; Sekiyama, Kazunari; Hashimoto, Makoto

    2016-01-01

    All living organisms have evolutionarily adapted themselves to the Earth’s gravity, and failure to adapt to gravity changes may lead to pathological conditions. This perspective may also apply to abnormal aging observed in bedridden elderly patients with aging-associated diseases such as osteoporosis and sarcopenia. Given that bedridden elderly patients are partially analogous to astronauts in that both cannot experience the beneficial effects of gravity on the skeletal system and may suffer from bone loss and muscle weakness, one may wonder whether there are gravity-related mechanisms underlying diseases among the elderly. In contrast to numerous studies of the relevance of microgravity in skeletal disorders, little attention has been paid to neurodegenerative diseases. Therefore, the objective of this paper is to discuss the possible relevance of microgravity in these diseases. We particularly noted a proteomics paper showing that levels of hippocampal proteins, including β-synuclein and carboxyl-terminal ubiquitin hydrolase L1, which have been linked to familial neurodegenerative diseases, were significantly decreased in the hippocampus of mice subjected to hindlimb suspension, a model of microgravity. We suggest that microgravity-induced neurodegeneration may be further exacerbated by diabetes and other factors. On the basis of this view, prevention of neurodegenerative diseases through ‘anti-diabetes’ and ‘hypergravity’ approaches may be important as a common therapeutic approach on Earth and in space. Collectively, neurodegenerative diseases and space medicine may be linked to each other more strongly than previously thought. PMID:28725728

  6. The cellular basis of dendrite pathology in neurodegenerative diseases

    PubMed Central

    Kweon, Jung Hyun; Kim, Sunhong; Lee, Sung Bae

    2017-01-01

    One of the characteristics of the neurons that distinguishes them from other cells is their complex and polarized structure consisting of dendrites, cell body, and axon. The complexity and diversity of dendrites are particularly well recognized, and accumulating evidences suggest that the alterations in the dendrite structure are associated with many neurodegenerative diseases. Given the importance of the proper dendritic structures for neuronal functions, the dendrite pathology appears to have crucial contribution to the pathogenesis of neurodegenerative diseases. Nonetheless, the cellular and molecular basis of dendritic changes in the neurodegenerative diseases remains largely elusive. Previous studies in normal condition have revealed that several cellular components, such as local cytoskeletal structures and organelles located locally in dendrites, play crucial roles in dendrite growth. By reviewing what has been unveiled to date regarding dendrite growth in terms of these local cellular components, we aim to provide an insight to categorize the potential cellular basis that can be applied to the dendrite pathology manifested in many neurodegenerative diseases. PMID:27502014

  7. Mechanisms of action of brain insulin against neurodegenerative diseases.

    PubMed

    Ramalingam, Mahesh; Kim, Sung-Jin

    2014-06-01

    Insulin, a pancreatic hormone, is best known for its peripheral effects on the metabolism of glucose, fats and proteins. There is a growing body of evidence linking insulin action in the brain to neurodegenerative diseases. Insulin present in central nervous system is a regulator of central glucose metabolism nevertheless this glucoregulation is not the main function of insulin in the brain. Brain is known to be specifically vulnerable to oxidative products relative to other organs and altered brain insulin signaling may cause or promote neurodegenerative diseases which invalidates and reduces the quality of life. Insulin located within the brain is mostly of pancreatic origin or is produced in the brain itself crosses the blood-brain barrier and enters the brain via a receptor-mediated active transport system. Brain Insulin, insulin receptor and insulin receptor substrate-mediated signaling pathways play important roles in the regulation of peripheral metabolism, feeding behavior, memory and maintenance of neural functions such as neuronal growth and differentiation, neuromodulation and neuroprotection. In the present review, we would like to summarize the novel biological and pathophysiological roles of neuronal insulin in neurodegenerative diseases and describe the main signaling pathways in use for therapeutic strategies in the use of insulin to the cerebral tissues and their biological applications to neurodegenerative diseases.

  8. Cytoplasmic dynein: a key player in neurodegenerative and neurodevelopmental diseases.

    PubMed

    Chen, Xiang-Jun; Xu, Huan; Cooper, Helen M; Liu, Yaobo

    2014-04-01

    Cytoplasmic dynein is the most important molecular motor driving the movement of a wide range of cargoes towards the minus ends of microtubules. As a molecular motor protein, dynein performs a variety of basic cellular functions including organelle transport and centrosome assembly. In the nervous system, dynein has been demonstrated to be responsible for axonal retrograde transport. Many studies have revealed direct or indirect evidence of dynein in neurodegenerative diseases such as amyotrophic lateral sclerosis, Charcot-Marie-Tooth disease, Alzheimer's disease, Parkinson's disease and Huntington's disease. Among them, a number of mutant proteins involved in various neurodegenerative diseases interact with dynein. Axonal transport disruption is presented as a common feature occurring in neurodegenerative diseases. Dynein heavy chain mutant mice also show features of neurodegenerative diseases. Moreover, defects of dynein-dependent processes such as autophagy or clearance of aggregation-prone proteins are found in most of these diseases. Lines of evidence have also shown that dynein is associated with neurodevelopmental diseases. In this review, we focus on dynein involvement in different neurological diseases and discuss potential underlying mechanisms.

  9. Tau mis-splicing in the pathogenesis of neurodegenerative disorders.

    PubMed

    Park, Sun Ah; Ahn, Sang Il; Gallo, Jean-Marc

    2016-08-01

    Tau proteins, which stabilize the structure and regulate the dynamics of microtubules, also play important roles in axonal transport and signal transduction. Tau proteins are missorted, aggregated, and found as tau inclusions under many pathological conditions associated with neurodegenerative disorders, which are collectively known as tauopathies. In the adult human brain, tau protein can be expressed in six isoforms due to alternative splicing. The aberrant splicing of tau pre-mRNA has been consistently identified in a variety of tauopathies but is not restricted to these types of disorders as it is also present in patients with non-tau proteinopathies and RNAopathies. Tau mis-splicing results in isoform-specific impairments in normal physiological function and enhanced recruitment of excessive tau isoforms into the pathological process. A variety of factors are involved in the complex set of mechanisms underlying tau mis-splicing, but variation in the cis-element, methylation of the MAPT gene, genetic polymorphisms, the quantity and activity of spliceosomal proteins, and the patency of other RNA-binding proteins, are related to aberrant splicing. Currently, there is a lack of appropriate therapeutic strategies aimed at correcting the tau mis-splicing process in patients with neurodegenerative disorders. Thus, a more comprehensive understanding of the relationship between tau mis-splicing and neurodegenerative disorders will aid in the development of efficient therapeutic strategies for patients with a tauopathy or other, related neurodegenerative disorders. [BMB Reports 2016; 49(8): 405-413].

  10. Molecular chaperone dysfunction in neurodegenerative diseases and effects of curcumin.

    PubMed

    Maiti, Panchanan; Manna, Jayeeta; Veleri, Shobi; Frautschy, Sally

    2014-01-01

    The intra- and extracellular accumulation of misfolded and aggregated amyloid proteins is a common feature in several neurodegenerative diseases, which is thought to play a major role in disease severity and progression. The principal machineries maintaining proteostasis are the ubiquitin proteasomal and lysosomal autophagy systems, where heat shock proteins play a crucial role. Many protein aggregates are degraded by the lysosomes, depending on aggregate size, peptide sequence, and degree of misfolding, while others are selectively tagged for removal by heat shock proteins and degraded by either the proteasome or phagosomes. These systems are compromised in different neurodegenerative diseases. Therefore, developing novel targets and classes of therapeutic drugs, which can reduce aggregates and maintain proteostasis in the brains of neurodegenerative models, is vital. Natural products that can modulate heat shock proteins/proteosomal pathway are considered promising for treating neurodegenerative diseases. Here we discuss the current knowledge on the role of HSPs in protein misfolding diseases and knowledge gained from animal models of Alzheimer's disease, tauopathies, and Huntington's diseases. Further, we discuss the emerging treatment regimens for these diseases using natural products, like curcumin, which can augment expression or function of heat shock proteins in the cell.

  11. Clinical Translation of Stem Cells in Neurodegenerative Disorders

    PubMed Central

    Lindvall, Olle; Barker, Roger A.; Brüstle, Oliver; Isacson, Ole; Svendsen, Clive N.

    2014-01-01

    Stem cells and their derivatives show tremendous potential for treating many disorders, including neurode-generative diseases. We discuss here the challenges and potential for the translation of stem-cell-based approaches into treatments for Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. PMID:22305565

  12. Neuroinflamm-aging and neurodegenerative diseases: an overview.

    PubMed

    Pizza, Vincenzo; Agresta, Anella; D'Acunto, Cosimo W; Festa, Michela; Capasso, Anna

    2011-08-01

    Neuroinflammation is considered a chronic activation of the immune response in the central nervous system (CNS) in response to different injuries. This brain immune activation results in various events: circulating immune cells infiltrate the CNS; resident cells are activated; and pro-inflammatory mediators produced and released induce neuroinflammatory brain disease. The effect of immune diffusible mediators on synaptic plasticity might result in CNS dysfunction during neuroinflammatory brain diseases. The CNS dysfunction may induce several human pathological conditions associated with both cognitive impairment and a variable degree of neuroinflammation. Furthermore, age has a powerful effect on enhanced susceptibility to neurodegenerative diseases and age-dependent enhanced neuroinflammatory processes may play an important role in toxin generation that causes death or dysfunction of neurons in neurodegenerative diseases This review will address current understanding of the relationship between ageing, neuroinflammation and neurodegenerative disease by focusing on the principal mechanisms by which the immune system influences the brain plastic phenomena. Also, the present review considers the principal human neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis and psychiatric disorders caused by aging and neuroinflammation.

  13. Chronic sleep disturbance and neural injury: links to neurodegenerative disease.

    PubMed

    Abbott, Sabra M; Videnovic, Aleksandar

    2016-01-01

    Sleep-wake disruption is frequently observed and often one of the earliest reported symptoms of many neurodegenerative disorders. This provides insight into the underlying pathophysiology of these disorders, as sleep-wake abnormalities are often accompanied by neurodegenerative or neurotransmitter changes. However, in addition to being a symptom of the underlying neurodegenerative condition, there is also emerging evidence that sleep disturbance itself may contribute to the development and facilitate the progression of several of these disorders. Due to its impact both as an early symptom and as a potential factor contributing to ongoing neurodegeneration, the sleep-wake cycle is an ideal target for further study for potential interventions not only to lessen the burden of these diseases but also to slow their progression. In this review, we will highlight the sleep phenotypes associated with some of the major neurodegenerative disorders, focusing on the circadian disruption associated with Alzheimer's disease, the rapid eye movement behavior disorder and sleep fragmentation associated with Parkinson's disease, and the insomnia and circadian dysregulation associated with Huntington's disease.

  14. Transcranial Magnetic Stimulation for the Assessment of Neurodegenerative Disease.

    PubMed

    Vucic, Steve; Kiernan, Matthew C

    2017-01-01

    Transcranial magnetic stimulation (TMS) is a noninvasive technique that has provided important information about cortical function across an array of neurodegenerative disorders, including Alzheimer's disease, frontotemporal dementia, Parkinson's disease, and related extrapyramidal disorders. Application of TMS techniques in neurodegenerative diseases has provided important pathophysiological insights, leading to the development of pathogenic and diagnostic biomarkers that could be used in the clinical setting and therapeutic trials. Abnormalities of TMS outcome measures heralding cortical hyperexcitability, as evidenced by a reduction of short-interval intracortical inhibition and increased in motor-evoked potential amplitude, have been consistently identified as early and intrinsic features of amyotrophic lateral sclerosis (ALS), preceding and correlating with the ensuing neurodegeneration. Cortical hyperexcitability appears to form the pathogenic basis of ALS, mediated by trans-synaptic glutamate-mediated excitotoxic mechanisms. As a consequence of these research findings, TMS has been developed as a potential diagnostic biomarker, capable of identifying upper motor neuronal pathology, at earlier stages of the disease process, and thereby aiding in ALS diagnosis. Of further relevance, marked TMS abnormalities have been reported in other neurodegenerative diseases, which have varied from findings in ALS. With time and greater utilization by clinicians, TMS outcome measures may prove to be of utility in future therapeutic trial settings across the neurodegenerative disease spectrum, including the monitoring of neuroprotective, stem-cell, and genetic-based strategies, thereby enabling assessment of biological effectiveness at early stages of drug development.

  15. Predictive gene testing for Huntington disease and other neurodegenerative disorders.

    PubMed

    Wedderburn, S; Panegyres, P K; Andrew, S; Goldblatt, J; Liebeck, T; McGrath, F; Wiltshire, M; Pestell, C; Lee, J; Beilby, J

    2013-12-01

    Controversies exist around predictive testing (PT) programmes in neurodegenerative disorders. This study sets out to answer the following questions relating to Huntington disease (HD) and other neurodegenerative disorders: differences between these patients in their PT journeys, why and when individuals withdraw from PT, and decision-making processes regarding reproductive genetic testing. A case series analysis of patients having PT from the multidisciplinary Western Australian centre for PT over the past 20 years was performed using internationally recognised guidelines for predictive gene testing in neurodegenerative disorders. Of 740 at-risk patients, 518 applied for PT: 466 at risk of HD, 52 at risk of other neurodegenerative disorders - spinocerebellar ataxias, hereditary prion disease and familial Alzheimer disease. Thirteen percent withdrew from PT - 80.32% of withdrawals occurred during counselling stages. Major withdrawal reasons related to timing in the patients' lives or unknown as the patient did not disclose the reason. Thirty-eight HD individuals had reproductive genetic testing: 34 initiated prenatal testing (of which eight withdrew from the process) and four initiated pre-implantation genetic diagnosis. There was no recorded or other evidence of major psychological reactions or suicides during PT. People withdrew from PT in relation to life stages and reasons that are unknown. Our findings emphasise the importance of: (i) adherence to internationally recommended guidelines for PT; (ii) the role of the multidisciplinary team in risk minimisation; and (iii) patient selection. © 2013 The Authors; Internal Medicine Journal © 2013 Royal Australasian College of Physicians.

  16. Glycoprotein NMB: an Emerging Role in Neurodegenerative Disease.

    PubMed

    Budge, Kevin M; Neal, Matthew L; Richardson, Jason R; Safadi, Fayez F

    2017-08-30

    Neurodegeneration is characterized by severe neuronal loss leading to the cognitive and physical impairments that define various neurodegenerative diseases. Neuroinflammation is one hallmark of neurodegenerative diseases and can ultimately contribute to disease progression. Increased inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-1β (IL-1 β), and tumor necrosis factor-α (TNF-α) are associated with Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). Unfortunately, current therapeutic options lack ability to stop or effectively slow progression of these diseases and are primarily aimed at alleviating symptoms. Thus, it is crucial to discover novel treatment candidates for neurodegenerative diseases. Glycoprotein nonmetastatic melanoma protein B (GPNMB) is a type-I transmembrane glycoprotein first identified in a melanoma cell line. GPNMB augments bone mineral deposition by stimulating osteoblast differentiation. Aside from its anabolic function in the bone, emerging evidence suggests that GPNMB has anti-inflammatory and reparative functions. GPNMB has also been demonstrated to be neuroprotective in an animal model of ALS, cerebral ischemia, and other disease models. Given these discoveries, GPNMB should be investigated as a potential therapeutic option for multiple neurodegenerative diseases.

  17. Tau mis-splicing in the pathogenesis of neurodegenerative disorders

    PubMed Central

    Park, Sun Ah; Ahn, Sang Il; Gallo, Jean-Marc

    2016-01-01

    Tau proteins, which stabilize the structure and regulate the dynamics of microtubules, also play important roles in axonal transport and signal transduction. Tau proteins are missorted, aggregated, and found as tau inclusions under many pathological conditions associated with neurodegenerative disorders, which are collectively known as tauopathies. In the adult human brain, tau protein can be expressed in six isoforms due to alternative splicing. The aberrant splicing of tau pre-mRNA has been consistently identified in a variety of tauopathies but is not restricted to these types of disorders as it is also present in patients with non-tau proteinopathies and RNAopathies. Tau mis-splicing results in isoform-specific impairments in normal physiological function and enhanced recruitment of excessive tau isoforms into the pathological process. A variety of factors are involved in the complex set of mechanisms underlying tau mis-splicing, but variation in the cis-element, methylation of the MAPT gene, genetic polymorphisms, the quantity and activity of spliceosomal proteins, and the patency of other RNA-binding proteins, are related to aberrant splicing. Currently, there is a lack of appropriate therapeutic strategies aimed at correcting the tau mis-splicing process in patients with neurodegenerative disorders. Thus, a more comprehensive understanding of the relationship between tau mis-splicing and neurodegenerative disorders will aid in the development of efficient therapeutic strategies for patients with a tauopathy or other, related neurodegenerative disorders. [BMB Reports 2016; 49(8): 405-413] PMID:27222125

  18. Epigenetic programming of neurodegenerative diseases by an adverse environment.

    PubMed

    Babenko, Olena; Kovalchuk, Igor; Metz, Gerlinde A

    2012-03-20

    Experience and environment can critically influence the risk and progression of neurodegenerative disorders. Epigenetic mechanisms, such as miRNA expression, DNA methylation, and histone modifications, readily respond to experience and environmental factors. Here we propose that epigenetic regulation of gene expression and environmental modulation thereof may play a key role in the onset and course of common neurological conditions, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and multiple sclerosis. For example, epigenetic mechanisms may mediate long-term responses to adverse experience, such as stress, to affect disease susceptibility and the course of neurodegenerative events. This review introduces the epigenetic components and their possible role in mediating neuropathological processes in response to stress. We argue that epigenetic modifications will affect neurodegenerative events through altered gene function. The study of epigenetic states in neurodegenerative diseases presents an opportunity to gain new insights into risk factors and pathogenic mechanisms. Moreover, research into epigenetic regulation of disease may revolutionize health care by opening new avenues of personalized, preventive and curative medicine.

  19. Auditory Training Effects on the Listening Skills of Children With Auditory Processing Disorder.

    PubMed

    Loo, Jenny Hooi Yin; Rosen, Stuart; Bamiou, Doris-Eva

    2016-01-01

    various configurations of masking speech, and in which the target speakers and test materials were unrelated to the training materials; (2) the Children's Auditory Performance Scale that assesses listening skills, completed by the children's teachers; and (3) the Clinical Evaluation of Language Fundamental-4 pragmatic profile that assesses pragmatic language use, completed by parents. All outcome measures significantly improved at immediate postintervention in the intervention group only, with effect sizes ranging from 0.76 to 1.7. Improvements in speech-in-noise performance correlated with improved scores in the Children's Auditory Performance Scale questionnaire in the trained group only. Baseline language and cognitive assessments did not predict better training outcome. Improvements in speech-in-noise performance were sustained 3 months postintervention. Broad speech-based auditory training led to improved auditory processing skills as reflected in speech-in-noise test performance and in better functional listening in real life. The observed correlation between improved functional listening with improved speech-in-noise perception in the trained group suggests that improved listening was a direct generalization of the auditory training.

  20. Auditory and non-auditory effects of noise on health.

    PubMed

    Basner, Mathias; Babisch, Wolfgang; Davis, Adrian; Brink, Mark; Clark, Charlotte; Janssen, Sabine; Stansfeld, Stephen

    2014-04-12

    Noise is pervasive in everyday life and can cause both auditory and non-auditory health effects. Noise-induced hearing loss remains highly prevalent in occupational settings, and is increasingly caused by social noise exposure (eg, through personal music players). Our understanding of molecular mechanisms involved in noise-induced hair-cell and nerve damage has substantially increased, and preventive and therapeutic drugs will probably become available within 10 years. Evidence of the non-auditory effects of environmental noise exposure on public health is growing. Observational and experimental studies have shown that noise exposure leads to annoyance, disturbs sleep and causes daytime sleepiness, affects patient outcomes and staff performance in hospitals, increases the occurrence of hypertension and cardiovascular disease, and impairs cognitive performance in schoolchildren. In this Review, we stress the importance of adequate noise prevention and mitigation strategies for public health.

  1. Auditory and non-auditory effects of noise on health

    PubMed Central

    Basner, Mathias; Babisch, Wolfgang; Davis, Adrian; Brink, Mark; Clark, Charlotte; Janssen, Sabine; Stansfeld, Stephen

    2014-01-01

    Noise is pervasive in everyday life and can cause both auditory and non-auditory health effects. Noise-induced hearing loss remains highly prevalent in occupational settings, and is increasingly caused by social noise exposure (eg, through personal music players). Our understanding of molecular mechanisms involved in noise-induced hair-cell and nerve damage has substantially increased, and preventive and therapeutic drugs will probably become available within 10 years. Evidence of the non-auditory effects of environmental noise exposure on public health is growing. Observational and experimental studies have shown that noise exposure leads to annoyance, disturbs sleep and causes daytime sleepiness, affects patient outcomes and staff performance in hospitals, increases the occurrence of hypertension and cardiovascular disease, and impairs cognitive performance in schoolchildren. In this Review, we stress the importance of adequate noise prevention and mitigation strategies for public health. PMID:24183105

  2. Modulation of Auditory Spatial Attention by Angry Prosody: An fMRI Auditory Dot-Probe Study

    PubMed Central

    Ceravolo, Leonardo; Frühholz, Sascha; Grandjean, Didier

    2016-01-01

    Emotional stimuli have been shown to modulate attentional orienting through signals sent by subcortical brain regions that modulate visual perception at early stages of processing. Fewer studies, however, have investigated a similar effect of emotional stimuli on attentional orienting in the auditory domain together with an investigation of brain regions underlying such attentional modulation, which is the general aim of the present study. Therefore, we used an original auditory dot-probe paradigm involving simultaneously presented neutral and angry non-speech vocal utterances lateralized to either the left or the right auditory space, immediately followed by a short and lateralized single sine wave tone presented in the same (valid trial) or in the opposite space as the preceding angry voice (invalid trial). Behavioral results showed an expected facilitation effect for target detection during valid trials while functional data showed greater activation in the middle and posterior superior temporal sulci (STS) and in the medial frontal cortex for valid vs. invalid trials. The use of reaction time facilitation [absolute value of the Z-score of valid-(invalid+neutral)] as a group covariate extended enhanced activity in the amygdalae, auditory thalamus, and visual cortex. Taken together, our results suggest the involvement of a large and distributed network of regions among which the STS, thalamus, and amygdala are crucial for the decoding of angry prosody, as well as for orienting and maintaining attention within an auditory space that was previously primed by a vocal emotional event. PMID:27242420

  3. Modulation of Auditory Spatial Attention by Angry Prosody: An fMRI Auditory Dot-Probe Study.

    PubMed

    Ceravolo, Leonardo; Frühholz, Sascha; Grandjean, Didier

    2016-01-01

    Emotional stimuli have been shown to modulate attentional orienting through signals sent by subcortical brain regions that modulate visual perception at early stages of processing. Fewer studies, however, have investigated a similar effect of emotional stimuli on attentional orienting in the auditory domain together with an investigation of brain regions underlying such attentional modulation, which is the general aim of the present study. Therefore, we used an original auditory dot-probe paradigm involving simultaneously presented neutral and angry non-speech vocal utterances lateralized to either the left or the right auditory space, immediately followed by a short and lateralized single sine wave tone presented in the same (valid trial) or in the opposite space as the preceding angry voice (invalid trial). Behavioral results showed an expected facilitation effect for target detection during valid trials while functional data showed greater activation in the middle and posterior superior temporal sulci (STS) and in the medial frontal cortex for valid vs. invalid trials. The use of reaction time facilitation [absolute value of the Z-score of valid-(invalid+neutral)] as a group covariate extended enhanced activity in the amygdalae, auditory thalamus, and visual cortex. Taken together, our results suggest the involvement of a large and distributed network of regions among which the STS, thalamus, and amygdala are crucial for the decoding of angry prosody, as well as for orienting and maintaining attention within an auditory space that was previously primed by a vocal emotional event.

  4. Auditory discrimination of force of impact.

    PubMed

    Lutfi, Robert A; Liu, Ching-Ju; Stoelinga, Christophe N J

    2011-04-01

    The auditory discrimination of force of impact was measured for three groups of listeners using sounds synthesized according to first-order equations of motion for the homogenous, isotropic bar [Morse and Ingard (1968). Theoretical Acoustics pp. 175-191]. The three groups were professional percussionists, nonmusicians, and individuals recruited from the general population without regard to musical background. In the two-interval, forced-choice procedure, listeners chose the sound corresponding to the greater force of impact as the length of the bar varied from one presentation to the next. From the equations of motion, a maximum-likelihood test for the task was determined to be of the form Δlog A + αΔ log f > 0, where A and f are the amplitude and frequency of any one partial and α = 0.5. Relative decision weights on Δ log f were obtained from the trial-by-trial responses of listeners and compared to α. Percussionists generally outperformed the other groups; however, the obtained decision weights of all listeners deviated significantly from α and showed variability within groups far in excess of the variability associated with replication. Providing correct feedback after each trial had little effect on the decision weights. The variability in these measures was comparable to that seen in studies involving the auditory discrimination of other source attributes.

  5. Auditory discrimination of force of impact

    PubMed Central

    Lutfi, Robert A.; Liu, Ching-Ju; Stoelinga, Christophe N. J.

    2011-01-01

    The auditory discrimination of force of impact was measured for three groups of listeners using sounds synthesized according to first-order equations of motion for the homogenous, isotropic bar [Morse and Ingard (1968). Theoretical Acoustics pp. 175–191]. The three groups were professional percussionists, nonmusicians, and individuals recruited from the general population without regard to musical background. In the two-interval, forced-choice procedure, listeners chose the sound corresponding to the greater force of impact as the length of the bar varied from one presentation to the next. From the equations of motion, a maximum-likelihood test for the task was determined to be of the form Δlog A + αΔ log f > 0, where A and f are the amplitude and frequency of any one partial and α = 0.5. Relative decision weights on Δ log f were obtained from the trial-by-trial responses of listeners and compared to α. Percussionists generally outperformed the other groups; however, the obtained decision weights of all listeners deviated significantly from α and showed variability within groups far in excess of the variability associated with replication. Providing correct feedback after each trial had little effect on the decision weights. The variability in these measures was comparable to that seen in studies involving the auditory discrimination of other source attributes. PMID:21476666

  6. Neuropsychological correlates of dominance, warmth, and extraversion in neurodegenerative disease.

    PubMed

    Sollberger, Marc; Stanley, Christine M; Ketelle, Robin; Beckman, Victoria; Growdon, Matthew; Jang, Jung; Neuhaus, John; Kramer, Joel H; Miller, Bruce L; Rankin, Katherine P

    2012-06-01

    Changes in personality differ qualitatively and quantitatively among patients with different neurodegenerative diseases, likely due to divergent patterns of regional neurodegeneration. Regional damage to circuits underlying various cognitive and emotional functions have been associated with interpersonal traits like dominance, extraversion, and warmth in patients with neurodegenerative diseases, suggesting that personality may in part be mediated by these more basic neuropsychological functions. In this study, we hypothesized that different combinations of cognitive, neuropsychiatric, and emotional measures would predict different interpersonal traits in patients with neurodegenerative diseases. A battery of cognitive, neuropsychiatric, and emotional measures was administered to 286 patients with various neurodegenerative diseases such as Alzheimer's disease, behavioral variant frontotemporal dementia, semantic dementia, and progressive supranuclear palsy, and informants described patients' dominance, extraversion, and warmth using the Interpersonal Adjective Scales (IAS) personality questionnaire. Regression modeling was performed to identify which neuropsychological factors uniquely predicted current personality, controlling for age, gender, and premorbid personality. Social dominance covaried with patients' capacity for cognitive control and verbal fluency. Conversely, warmth did not rely on these executive or verbal skills, but covaried primarily with patients' capacity for emotional responsiveness. Extraversion, representing a blend of dominance and warmth, demonstrated an intermediate degree of relationship to both executive/verbal and emotional functions. These findings suggest that different personality traits are partly subserved by specific cognitive and emotional functions in neurodegenerative disease patients. While this study was performed in the context of brain damage, the results raise the question of whether individual differences in these

  7. Therapeutic potential of systemic brain rejuvenation strategies for neurodegenerative disease

    PubMed Central

    Horowitz, Alana M.; Villeda, Saul A.

    2017-01-01

    Neurodegenerative diseases are a devastating group of conditions that cause progressive loss of neuronal integrity, affecting cognitive and motor functioning in an ever-increasing number of older individuals. Attempts to slow neurodegenerative disease advancement have met with little success in the clinic; however, a new therapeutic approach may stem from classic interventions, such as caloric restriction, exercise, and parabiosis. For decades, researchers have reported that these systemic-level manipulations can promote major functional changes that extend organismal lifespan and healthspan. Only recently, however, have the functional effects of these interventions on the brain begun to be appreciated at a molecular and cellular level. The potential to counteract the effects of aging in the brain, in effect rejuvenating the aged brain, could offer broad therapeutic potential to combat dementia-related neurodegenerative disease in the elderly. In particular, results from heterochronic parabiosis and young plasma administration studies indicate that pro-aging and rejuvenating factors exist in the circulation that can independently promote or reverse age-related phenotypes. The recent demonstration that human umbilical cord blood similarly functions to rejuvenate the aged brain further advances this work to clinical translation. In this review, we focus on these blood-based rejuvenation strategies and their capacity to delay age-related molecular and functional decline in the aging brain. We discuss new findings that extend the beneficial effects of young blood to neurodegenerative disease models. Lastly, we explore the translational potential of blood-based interventions, highlighting current clinical trials aimed at addressing therapeutic applications for the treatment of dementia-related neurodegenerative disease in humans. PMID:28815019

  8. Therapeutic potential of systemic brain rejuvenation strategies for neurodegenerative disease.

    PubMed

    Horowitz, Alana M; Villeda, Saul A

    2017-01-01

    Neurodegenerative diseases are a devastating group of conditions that cause progressive loss of neuronal integrity, affecting cognitive and motor functioning in an ever-increasing number of older individuals. Attempts to slow neurodegenerative disease advancement have met with little success in the clinic; however, a new therapeutic approach may stem from classic interventions, such as caloric restriction, exercise, and parabiosis. For decades, researchers have reported that these systemic-level manipulations can promote major functional changes that extend organismal lifespan and healthspan. Only recently, however, have the functional effects of these interventions on the brain begun to be appreciated at a molecular and cellular level. The potential to counteract the effects of aging in the brain, in effect rejuvenating the aged brain, could offer broad therapeutic potential to combat dementia-related neurodegenerative disease in the elderly. In particular, results from heterochronic parabiosis and young plasma administration studies indicate that pro-aging and rejuvenating factors exist in the circulation that can independently promote or reverse age-related phenotypes. The recent demonstration that human umbilical cord blood similarly functions to rejuvenate the aged brain further advances this work to clinical translation. In this review, we focus on these blood-based rejuvenation strategies and their capacity to delay age-related molecular and functional decline in the aging brain. We discuss new findings that extend the beneficial effects of young blood to neurodegenerative disease models. Lastly, we explore the translational potential of blood-based interventions, highlighting current clinical trials aimed at addressing therapeutic applications for the treatment of dementia-related neurodegenerative disease in humans.

  9. Neuropsychological correlates of dominance, warmth, and extraversion in neurodegenerative disease

    PubMed Central

    Sollberger, Marc; Stanley, Christine M.; Ketelle, Robin; Beckman, Victoria; Growdon, Matthew; Jang, Jung; Neuhaus, John; Kramer, Joel H.; Miller, Bruce L.; Rankin, Katherine P.

    2011-01-01

    Introduction Changes in personality differ qualitatively and quantitatively between patients with different neurodegenerative diseases, likely due to divergent patterns of regional neurodegeneration. Regional damage to circuits underlying various cognitive and emotional functions have been associated with interpersonal traits like dominance, extraversion, and warmth in patients with neurodegenerative diseases, suggesting that personality may in part be mediated by these more basic neuropsychological functions. In this study, we hypothesized that different combinations of cognitive, neuropsychiatric, and emotional measures would predict different interpersonal traits in patients with neurodegenerative diseases. Methods A battery of cognitive, neuropsychiatric, and emotional measures was administered to 286 patients with various neurodegenerative diseases such as Alzheimer’s disease, behavioral variant frontotemporal dementia, semantic dementia, and progressive supranuclear palsy, and informants described patients’ dominance, extraversion, and warmth using the Interpersonal Adjective Scales (IAS) personality questionnaire. Regression modeling was performed to identify which neuropsychological factors uniquely predicted current personality, controlling for age, gender, and premorbid personality. Results Social dominance covaried with patients’ capacity for cognitive control and verbal fluency. Conversely, warmth did not rely on these executive or verbal skills, but covaried primarily with patients’ capacity for emotional responsiveness. Extraversion, representing a blend of dominance and warmth, demonstrated an intermediate degree of relationship to both executive/verbal and emotional functions. Conclusions These findings suggest that different personality traits are partly subserved by specific cognitive and emotional functions in neurodegenerative disease patients. While this study was performed in the context of brain damage, the results raise the question

  10. Functional specializations of primary auditory afferents on the Mauthner cells: Interactions between membrane and synaptic properties

    PubMed Central

    Curti, Sebastian; Pereda, Alberto E.

    2009-01-01

    Primary auditory afferents are usually perceived as passive, timing-preserving, lines of communication. Contrasting this view, a special class of auditory afferents to teleost Mauthner cells, a command neuron that organizes tail-flip escape responses, undergoes potentiation of their mixed (electrical and chemical) synapses in response to high frequency cellular activity. This property is likely to represent a mechanism of input sensitization as these neurons provide the Mauthner cell with essential information for the initiation of an escape response. We review here the anatomical and physiological specializations of these identifiable auditory afferents. In particular, we discuss how their membrane and synaptic properties act in concert to more efficaciously activate the Mauthner cells. The striking functional specializations of these neurons suggest that primary auditory afferents might be capable of more sophisticated contributions to auditory processing than has been generally recognized. PMID:19941953

  11. Current understanding of auditory neuropathy.

    PubMed

    Boo, Nem-Yun

    2008-12-01

    Auditory neuropathy is defined by the presence of normal evoked otoacoustic emissions (OAE) and absent or abnormal auditory brainstem responses (ABR). The sites of lesion could be at the cochlear inner hair cells, spiral ganglion cells of the cochlea, synapse between the inner hair cells and auditory nerve, or the auditory nerve itself. Genetic, infectious or neonatal/perinatal insults are the 3 most commonly identified underlying causes. Children usually present with delay in speech and language development while adult patients present with hearing loss and disproportionately poor speech discrimination for the degree of hearing loss. Although cochlear implant is the treatment of choice, current evidence show that it benefits only those patients with endocochlear lesions, but not those with cochlear nerve deficiency or central nervous system disorders. As auditory neuropathy is a disorder with potential long-term impact on a child's development, early hearing screen using both OAE and ABR should be carried out on all newborns and infants to allow early detection and intervention.

  12. Auditory processing in dysphonic children.

    PubMed

    Arnaut, Mirian Aratangy; Agostinho, Caroline Vieira; Pereira, Liliane Desgualdo; Weckx, Luc Louis Maurice; Avila, Clara Regina Brandão de

    2011-06-01

    Contemporary cross-sectional cohort study. There is evidence of the auditory perception influence on the development of oral and written language, as well as on the self-perception of vocal conditions. The auditory system maturation can impact on this process. To characterize the auditory skills of temporal ordering and localization in dysphonic children. We assessed 42 children (4 to 8 years). 31 dysphonic children; Comparison group: 11 children without vocal change complaints. They all had normal auditory thresholds and also normal cochleo-eyelid reflexes. They were submitted to a Simplified assessment of the auditory process (Pereira, 1993). In order to compare the groups, we used the Mann-Whitney and Kruskal-Wallis statistical tests. Level of significance: 0.05 (5%). Upon simplified assessment, 100% of the Control Group and 61.29% of the Study Group had normal results. The groups were similar in the localization and verbal sequential memory tests. The nonverbal sequential memory showed worse results on dysphonic children. In this group, the performance was worse among the four to six years. The dysphonic children showed changes on the localization or temporal ordering skills, the skill of non-verbal temporal ordering differentiated the dysphonic group. In this group, the Sound Location improved with age.

  13. Mouse Auditory Brainstem Response Testing

    PubMed Central

    Akil, Omar; Oursler, A. E.; Fan, Kevin; Lustig, Lawrence R.

    2016-01-01

    The auditory brainstem response (ABR) test provides information about the inner ear (cochlea) and the central pathways for hearing. The ABR reflects the electrical responses of both the cochlear ganglion neurons and the nuclei of the central auditory pathway to sound stimulation (Zhou et al., 2006; Burkard et al., 2007). The ABR contains 5 identifiable wave forms, labeled as I-V. Wave I represents the summated response from the spiral ganglion and auditory nerve while waves II-V represent responses from the ascending auditory pathway. The ABR is recorded via electrodes placed on the scalp of an anesthetized animal. ABR thresholds refer to the lowest sound pressure level (SPL) that can generate identifiable electrical response waves. This protocol describes the process of measuring the ABR of small rodents (mouse, rat, guinea pig, etc.), including anesthetizing the mouse, placing the electrodes on the scalp, recording click and tone burst stimuli and reading the obtained waveforms for ABR threshold values. As technology continues to evolve, ABR will likely provide more qualitative and quantitative information regarding the function of the auditory nerve and brainstem pathways involved in hearing.

  14. The Perception of Auditory Motion.

    PubMed

    Carlile, Simon; Leung, Johahn

    2016-04-19

    The growing availability of efficient and relatively inexpensive virtual auditory display technology has provided new research platforms to explore the perception of auditory motion. At the same time, deployment of these technologies in command and control as well as in entertainment roles is generating an increasing need to better understand the complex processes underlying auditory motion perception. This is a particularly challenging processing feat because it involves the rapid deconvolution of the relative change in the locations of sound sources produced by rotational and translations of the head in space (self-motion) to enable the perception of actual source motion. The fact that we perceive our auditory world to be stable despite almost continual movement of the head demonstrates the efficiency and effectiveness of this process. This review examines the acoustical basis of auditory motion perception and a wide range of psychophysical, electrophysiological, and cortical imaging studies that have probed the limits and possible mechanisms underlying this perception. © The Author(s) 2016.

  15. Auditory brainstem responses in the Eastern Screech Owl: An estimate of auditory thresholds

    NASA Astrophysics Data System (ADS)

    Brittan-Powell, Elizabeth F.; Lohr, Bernard; Hahn, D. Caldwell; Dooling, Robert J.

    2005-07-01

    The auditory brainstem response (ABR), a measure of neural synchrony, was used to estimate auditory sensitivity in the eastern screech owl (Megascops asio). The typical screech owl ABR waveform showed two to three prominent peaks occurring within 5 ms of stimulus onset. As sound pressure levels increased, the ABR peak amplitude increased and latency decreased. With an increasing stimulus presentation rate, ABR peak amplitude decreased and latency increased. Generally, changes in the ABR waveform to stimulus intensity and repetition rate are consistent with the pattern found in several avian families. The ABR audiogram shows that screech owls hear best between 1.5 and 6.4 kHz with the most acute sensitivity between 4-5.7 kHz. The shape of the average screech owl ABR audiogram is similar to the shape of the behaviorally measured audiogram of the barn owl, except at the highest frequencies. Our data also show differences in overall auditory sensitivity between the color morphs of screech owls.

  16. Auditory brainstem responses in the Eastern Screech Owl: an estimate of auditory thresholds.

    PubMed

    Brittan-Powell, Elizabeth F; Lohr, Bernard; Hahn, D Caldwell; Dooling, Robert J

    2005-07-01

    The auditory brainstem response (ABR), a measure of neural synchrony, was used to estimate auditory sensitivity in the eastern screech owl (Megascops asio). The typical screech owl ABR waveform showed two to three prominent peaks occurring within 5 ms of stimulus onset. As sound pressure levels increased, the ABR peak amplitude increased and latency decreased. With an increasing stimulus presentation rate, ABR peak amplitude decreased and latency increased. Generally, changes in the ABR waveform to stimulus intensity and repetition rate are consistent with the pattern found in several avian families. The ABR audiogram shows that screech owls hear best between 1.5 and 6.4 kHz with the most acute sensitivity between 4-5.7 kHz. The shape of the average screech owl ABR audiogram is similar to the shape of the behaviorally measured audiogram of the barn owl, except at the highest frequencies. Our data also show differences in overall auditory sensitivity between the color morphs of screech owls.

  17. Auditory brainstem responses in the Eastern Screech Owl: An estimate of auditory thresholds

    USGS Publications Warehouse

    Brittan-Powell, E.F.; Lohr, B.; Hahn, D.C.; Dooling, R.J.

    2005-01-01

    The auditory brainstem response (ABR), a measure of neural synchrony, was used to estimate auditory sensitivity in the eastern screech owl (Megascops asio). The typical screech owl ABR waveform showed two to three prominent peaks occurring within 5 ms of stimulus onset. As sound pressure levels increased, the ABR peak amplitude increased and latency decreased. With an increasing stimulus presentation rate, ABR peak amplitude decreased and latency increased. Generally, changes in the ABR waveform to stimulus intensity and repetition rate are consistent with the pattern found in several avian families. The ABR audiogram shows that screech owls hear best between 1.5 and 6.4 kHz with the most acute sensitivity between 4?5.7 kHz. The shape of the average screech owl ABR audiogram is similar to the shape of the behaviorally measured audiogram of the barn owl, except at the highest frequencies. Our data also show differences in overall auditory sensitivity between the color morphs of screech owls.

  18. Auditory middle-latency components to fusion of speech elements forming an auditory object.

    PubMed

    Pratt, Hillel; Mittelman, Nomi; Bleich, Naomi; Laufer, Ilan

    2004-05-01

    The purpose of this study was to define early brain activity associated with fusion of speech elements to form an auditory object in the middle-latency range preceding the F-Complex. Stimuli were binaural formant transition and base, that were presented separately or fused to form the vowel-consonant-vowel sequence /ada/. Eleven right-handed, adult, native Hebrew speakers listened to 2/s presentations, and the brain potentials from C(z) during the 250 msec following transition onset (in the responses to transition and to the fused word) or following the time it would have been presented (in the response to base alone) were recorded. The net-fusion response was extracted by subtracting the sum of potentials to the base and the formant transition from the potentials to the fused sound. Auditory middle-latency components, comprising of 9 peaks and troughs were recorded in response to the base, to the formant transition and to the fused /ada/. In general, the responses to the fused object were significantly smaller in peak amplitude and in total activity (area under the curve) resulting in the difference waveform of the net-fusion response that also included 9 peaks, but with opposite polarities. The early middle-latency components to fusion indicate that the fusion of speech elements to a word involves inhibition, occlusion or both. The results are in line with the uniqueness of speech perception and the early role of the auditory cortex in speech analysis.

  19. Auditory agnosia and auditory spatial deficits following left hemispheric lesions: evidence for distinct processing pathways.

    PubMed

    Clarke, S; Bellmann, A; Meuli, R A; Assal, G; Steck, A J

    2000-01-01

    Auditory recognition and auditory spatial functions were studied in four patients with circumscribed left hemispheric lesions. Patient FD was severely deficient in recognition of environmental sounds but normal in auditory localisation and auditory motion perception. The lesion included the left superior, middle and inferior temporal gyri and lateral auditory areas (as identified in previous anatomical studies), but spared Heschl's gyrus, the acoustic radiation and the thalamus. Patient SD had the same profile as FD, with deficient recognition of environmental sounds but normal auditory localisation and motion perception. The lesion comprised the postero-inferior part of the frontal convexity and the anterior third of the temporal lobe; data from non-human primates indicate that the latter are interconnected with lateral auditory areas. Patient MA was deficient in recognition of environmental sounds, auditory localisation and auditory motion perception, confirming that auditory spatial functions can be disturbed by left unilateral damage; the lesion involved the supratemporal region as well as the temporal, postero-inferior frontal and antero-inferior parietal convexities. Patient CZ was severely deficient in auditory motion perception and partially deficient in auditory localisation, but normal in recognition of environmental sounds; the lesion involved large parts of the parieto-frontal convexity and the supratemporal region. We propose that auditory information is processed in the human auditory cortex along two distinct pathways, one lateral devoted to auditory recognition and one medial and posterior devoted to auditory spatial functions.

  20. Devices and Procedures for Auditory Learning.

    ERIC Educational Resources Information Center

    Ling, Daniel

    1986-01-01

    The article summarizes information on assistive devices (hearing aids, cochlear implants, tactile aids, visual aids) and rehabilitation procedures (auditory training, speechreading, cued speech, and speech production) to aid the auditory learning of the hearing impaired.(DB)

  1. Behind the scenes of auditory perception.

    PubMed

    Shamma, Shihab A; Micheyl, Christophe

    2010-06-01

    'Auditory scenes' often contain contributions from multiple acoustic sources. These are usually heard as separate auditory 'streams', which can be selectively followed over time. How and where these auditory streams are formed in the auditory system is one of the most fascinating questions facing auditory scientists today. Findings published within the past two years indicate that both cortical and subcortical processes contribute to the formation of auditory streams, and they raise important questions concerning the roles of primary and secondary areas of auditory cortex in this phenomenon. In addition, these findings underline the importance of taking into account the relative timing of neural responses, and the influence of selective attention, in the search for neural correlates of the perception of auditory streams.

  2. Seeing sounds and hearing colors: an event-related potential study of auditory-visual synesthesia.

    PubMed

    Goller, Aviva I; Otten, Leun J; Ward, Jamie

    2009-10-01

    In auditory-visual synesthesia, sounds automatically elicit conscious and reliable visual experiences. It is presently unknown whether this reflects early or late processes in the brain. It is also unknown whether adult audiovisual synesthesia resembles auditory-induced visual illusions that can sometimes occur in the general population or whether it resembles the electrophysiological deflection over occipital sites that has been noted in infancy and has been likened to synesthesia. Electrical brain activity was recorded from adult synesthetes and control participants who were played brief tones and required to monitor for an infrequent auditory target. The synesthetes were instructed to attend either to the auditory or to the visual (i.e., synesthetic) dimension of the tone, whereas the controls attended to the auditory dimension alone. There were clear differences between synesthetes and controls that emerged early (100 msec after tone onset). These differences tended to lie in deflections of the auditory-evoked potential (e.g., the auditory N1, P2, and N2) rather than the presence of an additional posterior deflection. The differences occurred irrespective of what the synesthetes attended to (although attention had a late effect). The results suggest that differences between synesthetes and others occur early in time, and that synesthesia is qualitatively different from similar effects found in infants and certain auditory-induced visual illusions in adults. In addition, we report two novel cases of synesthesia in which colors elicit sounds, and vice versa.

  3. Auditory presentation and synchronization in Adobe Flash and HTML5/JavaScript Web experiments.

    PubMed

    Reimers, Stian; Stewart, Neil

    2016-09-01

    Substantial recent research has examined the accuracy of presentation durations and response time measurements for visually presented stimuli in Web-based experiments, with a general conclusion that accuracy is acceptable for most kinds of experiments. However, many areas of behavioral research use auditory stimuli instead of, or in addition to, visual stimuli. Much less is known about auditory accuracy using standard Web-based testing procedures. We used a millisecond-accurate Black Box Toolkit to measure the actual durations of auditory stimuli and the synchronization of auditory and visual presentation onsets. We examined the distribution of timings for 100 presentations of auditory and visual stimuli across two computers with difference specs, three commonly used browsers, and code written in either Adobe Flash or JavaScript. We also examined different coding options for attempting to synchronize the auditory and visual onsets. Overall, we found that auditory durations were very consistent, but that the lags between visual and auditory onsets varied substantially across browsers and computer systems.

  4. Capuchin monkeys (Cebus apella) use positive, but not negative, auditory cues to infer food location.

    PubMed

    Heimbauer, Lisa A; Antworth, Rebecca L; Owren, Michael J

    2012-01-01

    Nonhuman primates appear to capitalize more effectively on visual cues than corresponding auditory versions. For example, studies of inferential reasoning have shown that monkeys and apes readily respond to seeing that food is present ("positive" cuing) or absent ("negative" cuing). Performance is markedly less effective with auditory cues, with many subjects failing to use this input. Extending recent work, we tested eight captive tufted capuchins (Cebus apella) in locating food using positive and negative cues in visual and auditory domains. The monkeys chose between two opaque cups to receive food contained in one of them. Cup contents were either shown or shaken, providing location cues from both cups, positive cues only from the baited cup, or negative cues from the empty cup. As in previous work, subjects readily used both positive and negative visual cues to secure reward. However, auditory outcomes were both similar to and different from those of earlier studies. Specifically, all subjects came to exploit positive auditory cues, but none responded to negative versions. The animals were also clearly different in visual versus auditory performance. Results indicate that a significant proportion of capuchins may be able to use positive auditory cues, with experience and learning likely playing a critical role. These findings raise the possibility that experience may be significant in visually based performance in this task as well, and highlight that coming to grips with evident differences between visual versus auditory processing may be important for understanding primate cognition more generally.

  5. Minimal effects of visual memory training on auditory performance of adult cochlear implant users.

    PubMed

    Oba, Sandra I; Galvin, John J; Fu, Qian-Jie

    2013-01-01

    Auditory training has been shown to significantly improve cochlear implant (CI) users' speech and music perception. However, it is unclear whether posttraining gains in performance were due to improved auditory perception or to generally improved attention, memory, and/or cognitive processing. In this study, speech and music perception, as well as auditory and visual memory, were assessed in 10 CI users before, during, and after training with a nonauditory task. A visual digit span (VDS) task was used for training, in which subjects recalled sequences of digits presented visually. After the VDS training, VDS performance significantly improved. However, there were no significant improvements for most auditory outcome measures (auditory digit span, phoneme recognition, sentence recognition in noise, digit recognition in noise), except for small (but significant) improvements in vocal emotion recognition and melodic contour identification. Posttraining gains were much smaller with the nonauditory VDS training than observed in previous auditory training studies with CI users. The results suggest that posttraining gains observed in previous studies were not solely attributable to improved attention or memory and were more likely due to improved auditory perception. The results also suggest that CI users may require targeted auditory training to improve speech and music perception.

  6. Context effects on auditory distraction

    PubMed Central

    Chen, Sufen; Sussman, Elyse S.

    2014-01-01

    The purpose of the study was to test the hypothesis that sound context modulates the magnitude of auditory distraction, indexed by behavioral and electrophysiological measures. Participants were asked to identify tone duration, while irrelevant changes occurred in tone frequency, tone intensity, and harmonic structure. Frequency deviants were randomly intermixed with standards (Uni-Condition), with intensity deviants (Bi-Condition), and with both intensity and complex deviants (Tri-Condition). Only in the Tri-Condition did the auditory distraction effect reflect the magnitude difference among the frequency and intensity deviants. The mixture of the different types of deviants in the Tri-Condition modulated the perceived level of distraction, demonstrating that the sound context can modulate the effect of deviance level on processing irrelevant acoustic changes in the environment. These findings thus indicate that perceptual contrast plays a role in change detection processes that leads to auditory distraction. PMID:23886958

  7. Octave effect in auditory attention

    PubMed Central

    Borra, Tobias; Versnel, Huib; Kemner, Chantal; van Opstal, A. John; van Ee, Raymond

    2013-01-01

    After hearing a tone, the human auditory system becomes more sensitive to similar tones than to other tones. Current auditory models explain this phenomenon by a simple bandpass attention filter. Here, we demonstrate that auditory attention involves multiple pass-bands around octave-related frequencies above and below the cued tone. Intriguingly, this “octave effect” not only occurs for physically presented tones, but even persists for the missing fundamental in complex tones, and for imagined tones. Our results suggest neural interactions combining octave-related frequencies, likely located in nonprimary cortical regions. We speculate that this connectivity scheme evolved from exposure to natural vibrations containing octave-related spectral peaks, e.g., as produced by vocal cords. PMID:24003112

  8. Encoding frequency contrast in primate auditory cortex

    PubMed Central

    Scott, Brian H.; Semple, Malcolm N.

    2014-01-01

    Changes in amplitude and frequency jointly determine much of the communicative significance of complex acoustic signals, including human speech. We have previously described responses of neurons in the core auditory cortex of awake rhesus macaques to sinusoidal amplitude modulation (SAM) signals. Here we report a complementary study of sinusoidal frequency modulation (SFM) in the same neurons. Responses to SFM were analogous to SAM responses in that changes in multiple parameters defining SFM stimuli (e.g., modulation frequency, modulation depth, carrier frequency) were robustly encoded in the temporal dynamics of the spike trains. For example, changes in the carrier frequency produced highly reproducible changes in shapes of the modulation period histogram, consistent with the notion that the instantaneous probability of discharge mirrors the moment-by-moment spectrum at low modulation rates. The upper limit for phase locking was similar across SAM and SFM within neurons, suggesting shared biophysical constraints on temporal processing. Using spike train classification methods, we found that neural thresholds for modulation depth discrimination are typically far lower than would be predicted from frequency tuning to static tones. This “dynamic hyperacuity” suggests a substantial central enhancement of the neural representation of frequency changes relative to the auditory periphery. Spike timing information was superior to average rate information when discriminating among SFM signals, and even when discriminating among static tones varying in frequency. This finding held even when differences in total spike count across stimuli were normalized, indicating both the primacy and generality of temporal response dynamics in cortical auditory processing. PMID:24598525

  9. Protein misfolding in the late-onset neurodegenerative diseases: common themes and the unique case of amyotrophic lateral sclerosis.

    PubMed

    Mulligan, Vikram Khipple; Chakrabartty, Avijit

    2013-08-01

    Enormous strides have been made in the last 100 years to extend human life expectancy and to combat the major infectious diseases. Today, the major challenges for medical science are age-related diseases, including cancer, heart disease, lung disease, renal disease, and late-onset neurodegenerative disease. Of these, only the neurodegenerative diseases represent a class of disease so poorly understood that no general strategies for prevention or treatment exist. These diseases, which include Alzheimer's disease, Parkinson's disease, Huntington's disease, the transmissible spongiform encephalopathies, and amyotrophic lateral sclerosis (ALS), are generally fatal and incurable. The first section of this review summarizes the diversity and common features of the late-onset neurodegenerative diseases, with a particular focus on protein misfolding and aggregation-a recurring theme in the molecular pathology. The second section focuses on the particular case of ALS, a late-onset neurodegenerative disease characterized by the death of central nervous system motor neurons, leading to paralysis and patient death. Of the 10% of ALS cases that show familial inheritance (familial ALS), the largest subset is caused by mutations in the SOD1 gene, encoding the Cu, Zn superoxide dismutase (SOD1). The unusual kinetic stability of SOD1 has provided a unique opportunity for detailed structural characterization of conformational states potentially involved in SOD1-associated ALS. This review discusses past studies exploring the stability, folding, and misfolding behavior of SOD1, as well as the therapeutic possibilities of using detailed knowledge of misfolding pathways to target the molecular mechanisms underlying ALS and other neurodegenerative diseases. Copyright © 2013 Wiley Periodicals, Inc.

  10. Ageing and the auditory system

    PubMed Central

    Howarth, A; Shone, G R

    2006-01-01

    There are a number of pathophysiological processes underlying age related changes in the auditory system. The effects of hearing loss can have consequences beyond the immediate loss of hearing, and may have profound effects on the functioning of the person. While a deficit in hearing can be corrected to some degree by a hearing aid, auditory rehabilitation requires much more than simply amplifying external sound. It is important that those dealing with elderly people are aware of all the issues involved in age related hearing loss. PMID:16517797

  11. Loudspeaker equalization for auditory research.

    PubMed

    MacDonald, Justin A; Tran, Phuong K

    2007-02-01

    The equalization of loudspeaker frequency response is necessary to conduct many types of well-controlled auditory experiments. This article introduces a program that includes functions to measure a loudspeaker's frequency response, design equalization filters, and apply the filters to a set of stimuli to be used in an auditory experiment. The filters can compensate for both magnitude and phase distortions introduced by the loudspeaker. A MATLAB script is included in the Appendix to illustrate the details of the equalization algorithm used in the program.

  12. Auditory training in students with learning disabilities.

    PubMed

    Pinheiro, Fábio Henrique; Capellini, Simone Aparecida

    2010-01-01

    auditory training program in students with learning disabilities. to verify the efficacy of an auditory training program in students with learning disabilities; to compare the results of students with and without learning disabilities, who were and were not submitted to the auditory training program, in pre and post-testing. participants were 40 students who were divided according to the following: GI, subdivided in: GIe (10 students with learning disabilities who were submitted to the program), GIc (10 students with learning difficulties who were not submitted to auditory training) and GII, subdivided in: GIIe (10 students without learning difficulties submitted to the auditory training program) and GIIc (10 students without learning difficulties who were not submitted to auditory training). The auditory training program Audio Training was used. the results indicate that GI presented a lower performance when compared to GII in activities related to auditory skills and phonological awareness. When comparing the pre and post-testing results, GIe and GIIe presented better performances in activities involving auditory skills and phonological awareness after the auditory training program. the performance of the students with learning disabilities in auditory and phonological tasks is lower when compared to the students without learning disabilities. The use of the auditory training program was effective and allowed students to develop these skills.

  13. Feature Assignment in Perception of Auditory Figure

    ERIC Educational Resources Information Center

    Gregg, Melissa K.; Samuel, Arthur G.

    2012-01-01

    Because the environment often includes multiple sounds that overlap in time, listeners must segregate a sound of interest (the auditory figure) from other co-occurring sounds (the unattended auditory ground). We conducted a series of experiments to clarify the principles governing the extraction of auditory figures. We distinguish between auditory…

  14. Feature Assignment in Perception of Auditory Figure

    ERIC Educational Resources Information Center

    Gregg, Melissa K.; Samuel, Arthur G.

    2012-01-01

    Because the environment often includes multiple sounds that overlap in time, listeners must segregate a sound of interest (the auditory figure) from other co-occurring sounds (the unattended auditory ground). We conducted a series of experiments to clarify the principles governing the extraction of auditory figures. We distinguish between auditory…

  15. An Auditory-Masking-Threshold-Based Noise Suppression Algorithm GMMSE-AMT[ERB] for Listeners with Sensorineural Hearing Loss

    NASA Astrophysics Data System (ADS)

    Natarajan, Ajay; Hansen, John H. L.; Arehart, Kathryn Hoberg; Rossi-Katz, Jessica

    2005-12-01

    This study describes a new noise suppression scheme for hearing aid applications based on the auditory masking threshold (AMT) in conjunction with a modified generalized minimum mean square error estimator (GMMSE) for individual subjects with hearing loss. The representation of cochlear frequency resolution is achieved in terms of auditory filter equivalent rectangular bandwidths (ERBs). Estimation of AMT and spreading functions for masking are implemented in two ways: with normal auditory thresholds and normal auditory filter bandwidths (GMMSE-AMT[ERB]-NH) and with elevated thresholds and broader auditory filters characteristic of cochlear hearing loss (GMMSE-AMT[ERB]-HI). Evaluation is performed using speech corpora with objective quality measures (segmental SNR, Itakura-Saito), along with formal listener evaluations of speech quality rating and intelligibility. While no measurable changes in intelligibility occurred, evaluations showed quality improvement with both algorithm implementations. However, the customized formulation based on individual hearing losses was similar in performance to the formulation based on the normal auditory system.

  16. Auditory hedonic phenotypes in dementia: A behavioural and neuroanatomical analysis

    PubMed Central

    Fletcher, Phillip D.; Downey, Laura E.; Golden, Hannah L.; Clark, Camilla N.; Slattery, Catherine F.; Paterson, Ross W.; Schott, Jonathan M.; Rohrer, Jonathan D.; Rossor, Martin N.; Warren, Jason D.

    2015-01-01

    Patients with dementia may exhibit abnormally altered liking for environmental sounds and music but such altered auditory hedonic responses have not been studied systematically. Here we addressed this issue in a cohort of 73 patients representing major canonical dementia syndromes (behavioural variant frontotemporal dementia (bvFTD), semantic dementia (SD), progressive nonfluent aphasia (PNFA) amnestic Alzheimer's disease (AD)) using a semi-structured caregiver behavioural questionnaire and voxel-based morphometry (VBM) of patients' brain MR images. Behavioural responses signalling abnormal aversion to environmental sounds, aversion to music or heightened pleasure in music (‘musicophilia’) occurred in around half of the cohort but showed clear syndromic and genetic segregation, occurring in most patients with bvFTD but infrequently in PNFA and more commonly in association with MAPT than C9orf72 mutations. Aversion to sounds was the exclusive auditory phenotype in AD whereas more complex phenotypes including musicophilia were common in bvFTD and SD. Auditory hedonic alterations correlated with grey matter loss in a common, distributed, right-lateralised network including antero-mesial temporal lobe, insula, anterior cingulate and nucleus accumbens. Our findings suggest that abnormalities of auditory hedonic processing are a significant issue in common dementias. Sounds may constitute a novel probe of brain mechanisms for emotional salience coding that are targeted by neurodegenerative disease. PMID:25929717

  17. Auditory Detection of the Human Brainstem Auditory Evoked Response.

    ERIC Educational Resources Information Center

    Kidd, Gerald, Jr.; And Others

    1993-01-01

    This study evaluated whether listeners can distinguish human brainstem auditory evoked responses elicited by acoustic clicks from control waveforms obtained with no acoustic stimulus when the waveforms are presented auditorily. Detection performance for stimuli presented visually was slightly, but consistently, superior to that which occurred for…

  18. Glia proinflammatory cytokine upregulation as a therapeutic target for neurodegenerative diseases: function-based and target-based discovery approaches.

    PubMed

    Van Eldik, Linda J; Thompson, Wendy L; Ralay Ranaivo, Hantamalala; Behanna, Heather A; Martin Watterson, D

    2007-01-01

    Inflammation is the body's defense mechanism against threats such as bacterial infection, undesirable substances, injury, or illness. The process is complex and involves a variety of specialized cells that mobilize to neutralize and dispose of the injurious material so that the body can heal. In the brain, a similar inflammation process occurs when glia, especially astrocytes and microglia, undergo activation in response to stimuli such as injury, illness, or infection. Like peripheral immune cells, glia in the central nervous system also increase production of inflammatory cytokines and neutralize the threat to the brain. This brain inflammation, or neuroinflammation, is generally beneficial and allows the brain to respond to changes in its environment and dispose of damaged tissue or undesirable substances. Unfortunately, this beneficial process sometimes gets out of balance and the neuroinflammatory process persists, even when the inflammation-provoking stimulus is eliminated. Uncontrolled chronic neuroinflammation is now known to play a key role in the progression of damage in a number of neurodegenerative diseases. Thus, overproduction of proinflammatory cytokines offers a pathophysiology progression mechanism that can be targeted in new therapeutic development for multiple neurodegenerative diseases. We summarize in this chapter the evidence supporting proinflammatory cytokine upregulation as a therapeutic target for neurodegenerative disorders, with a focus on Alzheimer's disease. In addition, we discuss the drug discovery process and two approaches, function-driven and target-based, that show promise for development of neuroinflammation-targeted, disease-modifying therapeutics for multiple neurodegenerative disorders.

  19. Pharmacological effects of active compounds on neurodegenerative disease with gastrodia and uncaria decoction, a commonly used poststroke decoction.

    PubMed

    Chik, Stanley C C; Or, Terry C T; Luo, D; Yang, Cindy L H; Lau, Allan S Y

    2013-11-14

    Neurodegenerative diseases refer to the selective loss of neuronal systems in patients. The diseases cause high morbidity and mortality to approximately 22 million people worldwide and the number is expected to be tripled by 2050. Up to now, there is no effective prevention and treatment for the neurodegenerative diseases. Although some of the clinical therapies target at slowing down the progression of symptoms of the diseases, the general effectiveness of the drugs has been far from satisfactory. Traditional Chinese medicine becomes popular alternative remedies as it has been practiced clinically for more than thousands of years in China. As neurodegenerative diseases are mediated through different pathways, herbal decoction with multiple herbs is used as an effective therapeutic approach to work on multiple targets. Gastrodia and Uncaria Decoction, a popular TCM decoction, has been used to treat stroke in China. The decoction contains compounds including alkaloids, flavonoids, iridoids, carotenoids, and natural phenols, which have been found to possess anti-inflammatory, antioxidative, and antiapoptotic effects. In this review, we will summarize the recent publications of the pharmacological effects of these five groups of compounds. Understanding the mechanisms of action of these compounds may provide new treatment opportunities for the patients with neurodegenerative diseases.

  20. Thalamic and parietal brain morphology predicts auditory category learning.

    PubMed

    Scharinger, Mathias; Henry, Molly J; Erb, Julia; Meyer, Lars; Obleser, Jonas

    2014-01-01

    Auditory categorization is a vital skill involving the attribution of meaning to acoustic events, engaging domain-specific (i.e., auditory) as well as domain-general (e.g., executive) brain networks. A listener's ability to categorize novel acoustic stimuli should therefore depend on both, with the domain-general network being particularly relevant for adaptively changing listening strategies and directing attention to relevant acoustic cues. Here we assessed adaptive listening behavior, using complex acoustic stimuli with an initially salient (but later degraded) spectral cue and a secondary, duration cue that remained nondegraded. We employed voxel-based morphometry (VBM) to identify cortical and subcortical brain structures whose individual neuroanatomy predicted task performance and the ability to optimally switch to making use of temporal cues after spectral degradation. Behavioral listening strategies were assessed by logistic regression and revealed mainly strategy switches in the expected direction, with considerable individual differences. Gray-matter probability in the left inferior parietal lobule (BA 40) and left precentral gyrus was predictive of "optimal" strategy switch, while gray-matter probability in thalamic areas, comprising the medial geniculate body, co-varied with overall performance. Taken together, our findings suggest that successful auditory categorization relies on domain-specific neural circuits in the ascending auditory pathway, while adaptive listening behavior depends more on brain structure in parietal cortex, enabling the (re)direction of attention to salient stimulus properties. © 2013 Published by Elsevier Ltd.

  1. English Language Teaching: phonetics, phonology and auditory processing contributions.

    PubMed

    Araújo, Letícia Maria Martins; Feniman, Mariza Ribeiro; Carvalho, Fernanda Ribeiro Pinto de; Lopes-Herrera, Simone Aparecida

    2010-01-01

    interrelation of phonetics, phonology and auditory processing in English Language Teaching. to determine whether prior contact with English phonetics favors general learning of this language (L2), i.e. second language, in Portuguese speakers; to verify performance of these individuals in an auditory processing test prior to and after being taught L2. participants of the study were eight college students who had only studied English in high school. These participants were divided into two groups: control group - were only enrolled in English classes; experimental group - were enrolled in English phonetic classes prior to their enrollment in English classes. Participants were submitted to an auditory processing test and to an oral test in English (Oral Test) prior to and after the classes. Data were analyzed in the same way, i.e. prior to and after the classes. these were expressed statistically by T-Student's test. Analyses indicated no difference in performance between groups. Scores indicated better performance of the control group for answering questions in English in the Oral Test. The experimental group had better performance in the auditory processing test after being enrolled to English phonetic classes and English course. prior basic knowledge of English did not enhance general learning (improvement in pronunciation) of the second language, however, it improved the ability of temporal processing in the used test.

  2. Multisensory Training Improves Auditory Spatial Processing following Bilateral Cochlear Implantation

    PubMed Central

    Isaiah, Amal; Vongpaisal, Tara; King, Andrew J.

    2014-01-01

    Cochlear implants (CIs) partially restore hearing to the deaf by directly stimulating the inner ear. In individuals fitted with CIs, lack of auditory experience due to loss of hearing before language acquisition can adversely impact outcomes. For example, adults with early-onset hearing loss generally do not integrate inputs from both ears effectively when fitted with bilateral CIs (BiCIs). Here, we used an animal model to investigate the effects of long-term deafness on auditory localization with BiCIs and approaches for promoting the use of binaural spatial cues. Ferrets were deafened either at the age of hearing onset or as adults. All animals were implanted in adulthood, either unilaterally or bilaterally, and were subsequently assessed for their ability to localize sound in the horizontal plane. The unilaterally implanted animals were unable to perform this task, regardless of the duration of deafness. Among animals with BiCIs, early-onset hearing loss was associated with poor auditory localization performance, compared with late-onset hearing loss. However, performance in the early-deafened group with BiCIs improved significantly after multisensory training with interleaved auditory and visual stimuli. We demonstrate a possible neural substrate for this by showing a training-induced improvement in the responsiveness of auditory cortical neurons and in their sensitivity to interaural level differences, the principal localization cue available to BiCI users. Importantly, our behavioral and physiological evidence demonstrates a facilitative role for vision in restoring auditory spatial processing following potential cross-modal reorganization. These findings support investigation of a similar training paradigm in human CI users. PMID:25122908

  3. Auditory Distraction and Acclimatization to Hearing Aids.

    PubMed

    Dawes, Piers; Munro, Kevin J

    It is widely recognized by hearing aid users and audiologists that a period of auditory acclimatization and adjustment is needed for new users to become accustomed to their devices. The aim of the present study was to test the idea that auditory acclimatization and adjustment to hearing aids involves a process of learning to "tune out" newly audible but undesirable sounds, which are described by new hearing aid users as annoying and distracting. It was hypothesized that (1) speech recognition thresholds in noise would improve over time for new hearing aid users, (2) distractibility to noise would reduce over time for new hearing aid users, (3) there would be a correlation between improved speech recognition in noise and reduced distractibility to background sounds, (4) improvements in speech recognition and distraction would be accompanied by self-report of reduced annoyance, and (5) improvements in speech recognition and distraction would be associated with higher general cognitive ability and more hearing aid use. New adult hearing aid users (n = 35) completed a test of aided speech recognition in noise (SIN) and a test of auditory distraction by background sound amplified by hearing aids on the day of fitting and 1, 7, 14, and 30 days post fitting. At day 30, participants completed self-ratings of the annoyance of amplified sounds. Daily hearing aid use was measured via hearing aid data logging, and cognitive ability was measured with the Wechsler Abbreviated Scale of Intelligence block design test. A control group of experienced hearing aid users (n = 20) completed the tests over a similar time frame. At day 30, there was no statistically significant improvement in SIN among new users versus experienced users. However, levels of hearing loss and hearing aid use varied widely among new users. A subset of new users with moderate hearing loss who wore their hearing aids at least 6 hr/day (n = 10) had significantly improved SIN (by ~3-dB signal to noise ratio

  4. Early auditory enrichment with music enhances auditory discrimination learning and alters NR2B protein expression in rat auditory cortex.

    PubMed

    Xu, Jinghong; Yu, Liping; Cai, Rui; Zhang, Jiping; Sun, Xinde

    2009-01-03

    Previous studies have shown that the functional development of auditory system is substantially influenced by the structure of environmental acoustic inputs in early life. In our present study, we investigated the effects of early auditory enrichment with music on rat auditory discrimination learning. We found that early auditory enrichment with music from postnatal day (PND) 14 enhanced learning ability in auditory signal-detection task and in sound duration-discrimination task. In parallel, a significant increase was noted in NMDA receptor subunit NR2B protein expression in the auditory cortex. Furthermore, we found that auditory enrichment with music starting from PND 28 or 56 did not influence NR2B expression in the auditory cortex. No difference was found in the NR2B expression in the inferior colliculus (IC) between music-exposed and normal rats, regardless of when the auditory enrichment with music was initiated. Our findings suggest that early auditory enrichment with music influences NMDA-mediated neural plasticity, which results in enhanced auditory discrimination learning.

  5. Therapeutic targeting of autophagy in neurodegenerative and infectious diseases

    PubMed Central

    Bento, Carla F.

    2015-01-01

    Autophagy is a conserved process that uses double-membrane vesicles to deliver cytoplasmic contents to lysosomes for degradation. Although autophagy may impact many facets of human biology and disease, in this review we focus on the ability of autophagy to protect against certain neurodegenerative and infectious diseases. Autophagy enhances the clearance of toxic, cytoplasmic, aggregate-prone proteins and infectious agents. The beneficial roles of autophagy can now be extended to supporting cell survival and regulating inflammation. Autophagic control of inflammation is one area where autophagy may have similar benefits for both infectious and neurodegenerative diseases beyond direct removal of the pathogenic agents. Preclinical data supporting the potential therapeutic utility of autophagy modulation in such conditions is accumulating. PMID:26101267

  6. Neuronal network disintegration: common pathways linking neurodegenerative diseases

    PubMed Central

    Ahmed, Rebekah M; Devenney, Emma M; Irish, Muireann; Ittner, Arne; Naismith, Sharon; Ittner, Lars M; Rohrer, Jonathan D; Halliday, Glenda M; Eisen, Andrew; Hodges, John R; Kiernan, Matthew C

    2016-01-01

    Neurodegeneration refers to a heterogeneous group of brain disorders that progressively evolve. It has been increasingly appreciated that many neurodegenerative conditions overlap at multiple levels and therefore traditional clinicopathological correlation approaches to better classify a disease have met with limited success. Neuronal network disintegration is fundamental to neurodegeneration, and concepts based around such a concept may better explain the overlap between their clinical and pathological phenotypes. In this Review, promoters of overlap in neurodegeneration incorporating behavioural, cognitive, metabolic, motor, and extrapyramidal presentations will be critically appraised. In addition, evidence that may support the existence of large-scale networks that might be contributing to phenotypic differentiation will be considered across a neurodegenerative spectrum. Disintegration of neuronal networks through different pathological processes, such as prion-like spread, may provide a better paradigm of disease and thereby facilitate the identification of novel therapies for neurodegeneration. PMID:27172939

  7. Aberrant Protein S-Nitrosylation in Neurodegenerative Diseases

    PubMed Central

    Nakamura, Tomohiro; Tu, Shichun; Akhtar, Mohd Waseem; Sunico, Carmen R.; Okamoto, Shu-ichi; Lipton, Stuart A.

    2013-01-01

    S-Nitrosylation is a redox-mediated posttranslational modification that regulates protein function via covalent reaction of nitric oxide (NO)-related species with a cysteine thiol group on the target protein. Under physiological conditions, S-nitrosylation can be an important modulator of signal transduction pathways, akin to phosphorylation. However, with aging or environmental toxins that generate excessive NO, aberrant S-nitrosylation reactions can occur and affect protein misfolding, mitochondrial fragmentation, synaptic function, apoptosis or autophagy. Here, we discuss how aberrantly S-nitrosylated proteins (SNO-proteins) play a crucial role in the pathogenesis of neurodegenerative diseases, including Alzheimer’s and Parkinson’s diseases. Insight into the pathophysiological role of aberrant S-nitrosylation pathways will enhance our understanding of molecular mechanisms leading to neurodegenerative diseases and point to potential therapeutic interventions. PMID:23719160

  8. Genetics Underlying Atypical Parkinsonism and Related Neurodegenerative Disorders.

    PubMed

    Scholz, Sonja W; Bras, Jose

    2015-10-16

    Atypical parkinsonism syndromes, such as dementia with Lewy bodies, multiple system atrophy, progressive supranuclear palsy and corticobasal degeneration, are neurodegenerative diseases with complex clinical and pathological features. Heterogeneity in clinical presentations, possible secondary determinants as well as mimic syndromes pose a major challenge to accurately diagnose patients suffering from these devastating conditions. Over the last two decades, significant advancements in genomic technologies have provided us with increasing insights into the molecular pathogenesis of atypical parkinsonism and their intriguing relationships to related neurodegenerative diseases, fueling new hopes to incorporate molecular knowledge into our diagnostic, prognostic and therapeutic approaches towards managing these conditions. In this review article, we summarize the current understanding of genetic mechanisms implicated in atypical parkinsonism syndromes. We further highlight mimic syndromes relevant to differential considerations and possible future directions.

  9. Yeast buddies helping to unravel the complexity of neurodegenerative disorders.

    PubMed

    Fruhmann, Gernot; Seynnaeve, David; Zheng, Ju; Ven, Karen; Molenberghs, Sofie; Wilms, Tobias; Liu, Beidong; Winderickx, Joris; Franssens, Vanessa

    2017-01-01

    Neurodegenerative disorders have a profound effect on the quality of life of patients and their environment. However, the development of adequate therapies requires accurate understanding of the underlying disease pathogenesis. On that account, yeast models can play an important role, as they enable the elucidation of the mechanisms leading to neurodegenerative disorders. Furthermore, by using so-called humanized yeast systems, the findings in yeast can be interpolated to humans. In this review, we will give an overview of the current body of knowledge on the use of yeast models with regard to Huntington's, Parkinson's and Alzheimer's disease. In addition to the results, obtained with the baker's yeast Saccharomyces cerevisiae, we also consider the existing literature on the less common but promising fission yeast Schizosaccharomyces pombe. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Unbiased approaches to biomarker discovery in neurodegenerative diseases

    PubMed Central

    Chen-Plotkin, Alice S.

    2014-01-01

    Neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and frontotemporal dementia have several important features in common. They are progressive, they affect a relatively inaccessible organ, and we have no disease-modifying therapies for them. For these brain-based diseases, current diagnosis and evaluation of disease severity rely almost entirely on clinical examination, which may only be a rough approximation of disease state. Thus, the development of biomarkers – objective, relatively easily measured and precise indicators of pathogenic processes – could improve patient care and accelerate therapeutic discovery. Yet existing, rigorously tested neurodegenerative disease biomarkers are few, and even fewer biomarkers have translated into clinical use. To find new biomarkers for these diseases, an unbiased, high-throughput screening approach may be needed. In this review, I will describe the potential utility of such an approach to biomarker discovery, using Parkinson’s disease as a case example. PMID:25442938

  11. Protein aggregation, misfolding and consequential human neurodegenerative diseases.

    PubMed

    Sami, Neha; Rahman, Safikur; Kumar, Vijay; Zaidi, Sobia; Islam, Asimul; Ali, Sher; Ahmad, Faizan; Hassan, Md Imtaiyaz

    2017-11-01

    Proteins are major components of the biological functions in a cell. Biology demands that a protein must fold into its stable three-dimensional structure to become functional. In an unfavorable cellular environment, protein may get misfolded resulting in its aggregation. These conformational disorders are directly related to the tissue damage resulting in cellular dysfunction giving rise to different diseases. This way, several neurodegenerative diseases such as Alzheimer, Parkinson Huntington diseases and amyotrophic lateral sclerosis are caused. Misfolding of the protein is prevented by innate molecular chaperones of different classes. It is envisaged that work on this line is likely to translate the knowledge into the development of possible strategies for early diagnosis and efficient management of such related human diseases. The present review deals with the human neurodegenerative diseases caused due to the protein misfolding highlighting pathomechanisms and therapeutic intervention.

  12. Advances in epigenetics and epigenomics for neurodegenerative diseases.

    PubMed

    Qureshi, Irfan A; Mehler, Mark F

    2011-10-01

    In the post-genomic era, epigenetic factors-literally those that are "over" or "above" genetic ones and responsible for controlling the expression and function of genes-have emerged as important mediators of development and aging; gene-gene and gene-environmental interactions; and the pathophysiology of complex disease states. Here, we provide a brief overview of the major epigenetic mechanisms (ie, DNA methylation, histone modifications and chromatin remodeling, and non-coding RNA regulation). We highlight the nearly ubiquitous profiles of epigenetic dysregulation that have been found in Alzheimer's and other neurodegenerative diseases. We also review innovative methods and technologies that enable the characterization of individual epigenetic modifications and more widespread epigenomic states at high resolution. We conclude that, together with complementary genetic, genomic, and related approaches, interrogating epigenetic and epigenomic profiles in neurodegenerative diseases represent important and increasingly practical strategies for advancing our understanding of and the diagnosis and treatment of these disorders.

  13. [Neurodegenerative disorders: review of current classification and diagnostic neuropathological criteria].

    PubMed

    Matej, R; Rusina, R

    2012-04-01

    Neurodegenerative disorders are progressive diseases characterized by loss of specific neuronal populations followed by a clinical picture of a different neurodegenerative entity. Current classification of these diseases respects the names of the main pathophysiological processes involved in the groups of disorders. This is the reason why key proteins which represent neuropathological and biochemical hallmarks of diseases are found in their names. Neuropathological diagnosis is a synthesis of neurohistological changes in the brain and spinal cord and identification of pathological proteinaceous aggregates in neurons and/or glial cells. These inclusions are predominant diagnostic micromorphological and biochemical markers of disease. In the text, there is a brief summary of current knowledge about pathophysiology of neurodegenerations and diagnostic criteria for the most frequent entities.

  14. Prions and Prion-Like Pathogens in Neurodegenerative Disorders

    PubMed Central

    Peggion, Caterina; Sorgato, Maria Catia; Bertoli, Alessandro

    2014-01-01

    Prions are unique elements in biology, being able to transmit biological information from one organism to another in the absence of nucleic acids. They have been identified as self-replicating proteinaceous agents responsible for the onset of rare and fatal neurodegenerative disorders—known as transmissible spongiform encephalopathies, or prion diseases—which affect humans and other animal species. More recently, it has been proposed that other proteins associated with common neurodegenerative disorders, such as Alzheimer’s and Parkinson’s disease, can self-replicate like prions, thus sustaining the spread of neurotoxic entities throughout the nervous system. Here, we review findings that have contributed to expand the prion concept, and discuss if the involved toxic species can be considered bona fide prions, including the capacity to infect other organisms, or whether these pathogenic aggregates share with prions only the capability to self-replicate. PMID:25437612

  15. Searching for MIND: microRNAs in neurodegenerative diseases.

    PubMed

    Barbato, Christian; Ruberti, Francesca; Cogoni, Carlo

    2009-01-01

    In few years our understanding of microRNA (miRNA) biogenesis, molecular mechanisms by which miRNAs regulate gene expression, and the functional roles of miRNAs has been expanded. Interestingly, numerous miRNAs are expressed in a spatially and temporally controlled manner in the nervous system, suggesting that their posttrascriptional regulation may be particularly relevant in neural development and function. MiRNA studies in neurobiology showed their involvement in synaptic plasticity and brain diseases. In this review ,correlations between miRNA-mediated gene silencing and Alzheimer's, Parkinson's, and other neurodegenerative diseases will be discussed. Molecular and cellular neurobiological studies of the miRNAs in neurodegeneration represent the exploration of a new Frontier of miRNAs biology and the potential development of new diagnostic tests and genetic therapies for neurodegenerative diseases.

  16. Searching for MIND: MicroRNAs in Neurodegenerative Diseases

    PubMed Central

    Barbato, Christian; Ruberti, Francesca; Cogoni, Carlo

    2009-01-01

    In few years our understanding of microRNA (miRNA) biogenesis, molecular mechanisms by which miRNAs regulate gene expression, and the functional roles of miRNAs has been expanded. Interestingly, numerous miRNAs are expressed in a spatially and temporally controlled manner in the nervous system, suggesting that their posttrascriptional regulation may be particularly relevant in neural development and function. MiRNA studies in neurobiology showed their involvement in synaptic plasticity and brain diseases. In this review ,correlations between miRNA-mediated gene silencing and Alzheimer's, Parkinson's, and other neurodegenerative diseases will be discussed. Molecular and cellular neurobiological studies of the miRNAs in neurodegeneration represent the exploration of a new Frontier of miRNAs biology and the potential development of new diagnostic tests and genetic therapies for neurodegenerative diseases. PMID:19707536

  17. Translating protein phosphatase research into treatments for neurodegenerative diseases.

    PubMed

    Sundaram, Jeyapriya R; Lee, Irene C J; Shenolikar, Shirish

    2017-02-08

    Many of the major neurodegenerative disorders are characterized by the accumulation of intracellular protein aggregates in neurons and other cells in brain, suggesting that errors in protein quality control mechanisms associated with the aging process play a critical role in the onset and progression of disease. The increased understanding of the unfolded protein response (UPR) signaling network and, more specifically, the structure and function of eIF2α phosphatases has enabled the development or discovery of small molecule inhibitors that show great promise in restoring protein homeostasis and ameliorating neuronal damage and death. While this review focuses attention on one or more eIF2α phosphatases, the wide range of UPR proteins that are currently being explored as potential drug targets bodes well for the successful future development of therapies to preserve neuronal function and treat neurodegenerative disease. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  18. Prions and prion-like pathogens in neurodegenerative disorders.

    PubMed

    Peggion, Caterina; Sorgato, Maria Catia; Bertoli, Ales