Science.gov

Sample records for neurodegenerative generalized auditory

  1. 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

  2. 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…

  3. 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…

  4. 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.

  5. 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 measures of…

  6. Operant generalization of auditory tempo in quail neonates.

    PubMed

    Schneider, Susan M; Lickliter, Robert

    2009-02-01

    Operant generalization, a building block of cognition, has never been studied in neonates. We developed a preparation for newly hatched quail in order to investigate the form of the generalization gradient very early in development. For their first 4-5 days after hatching, northern bobwhite chicks pecked for brief heat presentations while hearing a high-pitched sound repeated at a constant rate (nondifferential training). Tempo generalization was then assessed in extinction. A significantly excitatory average gradient resulted despite minimal postnatal experience.

  7. Driving and neurodegenerative diseases.

    PubMed

    Uc, Ergun Y; Rizzo, Matthew

    2008-09-01

    The proportion of elderly people in the general population is rising, resulting in greater numbers of drivers with neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. These neurodegenerative disorders impair cognition, visual perception, and motor function, leading to reduced driver fitness and greater crash risk. Yet neither medical diagnosis nor age alone is reliable enough to predict driver safety or crashes or to revoke the driving privileges of these individuals. Driving research utilizes tools such as questionnaires about driving habits and history, driving simulators, standardized road tests utilizing instrumented vehicles, and state driving records. Research challenges include outlining the evolution of driving safety, understanding the mechanisms of driving impairment, and developing a reliable and efficient standardized test battery for prediction of driver safety in neurodegenerative disorders. This information will enable healthcare providers to advise their patients with neurodegenerative disorders with more certainty, affect policy, and help develop rehabilitative measures for driving. PMID:18713573

  8. Generalization of fear-potentiated startle in the presence of auditory cues: a parametric analysis

    PubMed Central

    Norrholm, Seth Davin; Jovanovic, Tanja; Briscione, Maria A.; Anderson, Kemp M.; Kwon, Cliffe K.; Warren, Victor T.; Bosshardt, Lauren; Bradley, Bekh

    2014-01-01

    Intense fear responses observed in trauma-, stressor-, and anxiety-related disorders can be elicited by a wide range of stimuli similar to those that were present during the traumatic event. The present study investigated the experimental utility of fear-potentiated startle paradigms to study this phenomenon, known as stimulus generalization, in healthy volunteers. Fear-potentiated startle refers to a relative increase in the acoustic startle response to a previously neutral stimulus that has been paired with an aversive stimulus. Specifically, in Experiment 1 an auditory pure tone (500 Hz) was used as the conditioned stimulus (CS+) and was reinforced with an unconditioned stimulus (US), an airblast to the larynx. A distinct tone (4000 Hz) was used as the nonreinforced stimulus (CS−) and was never paired with an airblast. Twenty-four hours later subjects underwent Re-training followed by a Generalization test, during which subjects were exposed to a range of generalization stimuli (GS) (250, 1000, 2000, 4000, 8000 Hz). In order to further examine the point at which fear no longer generalizes, a follow-up experiment (Experiment 2) was performed where a 4000 Hz pure tone was used as the CS+, and during the Generalization test, 2000 and 8000 Hz were used as GS. In both Experiment 1 and 2 there was significant discrimination in US expectancy responses on all stimuli during the Generalization Test, indicating the stimuli were perceptually distinct. In Experiment 1, participants showed similar levels of fear-potentiated startle to the GS that were adjacent to the CS+, and discriminated between stimuli that were 2 or more degrees from the CS+. Experiment 2 demonstrated no fear-potentiated startle generalization. The current study is the first to use auditory cues to test generalization of conditioned fear responses; such cues may be especially relevant to combat posttraumatic stress disorder (PTSD) where much of the traumatic exposure may involve sounds. PMID:25368559

  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 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.

  12. 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. PMID:25728173

  13. Cerebral responses to local and global auditory novelty under general anesthesia.

    PubMed

    Uhrig, Lynn; Janssen, David; Dehaene, Stanislas; Jarraya, Béchir

    2016-11-01

    Primate brains can detect a variety of unexpected deviations in auditory sequences. The local-global paradigm dissociates two hierarchical levels of auditory predictive coding by examining the brain responses to first-order (local) and second-order (global) sequence violations. Using the macaque model, we previously demonstrated that, in the awake state, local violations cause focal auditory responses while global violations activate a brain circuit comprising prefrontal, parietal and cingulate cortices. Here we used the same local-global auditory paradigm to clarify the encoding of the hierarchical auditory regularities in anesthetized monkeys and compared their brain responses to those obtained in the awake state as measured with fMRI. Both, propofol, a GABAA-agonist, and ketamine, an NMDA-antagonist, left intact or even enhanced the cortical response to auditory inputs. The local effect vanished during propofol anesthesia and shifted spatially during ketamine anesthesia compared with wakefulness. Under increasing levels of propofol, we observed a progressive disorganization of the global effect in prefrontal, parietal and cingulate cortices and its complete suppression under ketamine anesthesia. Anesthesia also suppressed thalamic activations to the global effect. These results suggest that anesthesia preserves initial auditory processing, but disturbs both short-term and long-term auditory predictive coding mechanisms. The disorganization of auditory novelty processing under anesthesia relates to a loss of thalamic responses to novelty and to a disruption of higher-order functional cortical networks in parietal, prefrontal and cingular cortices.

  14. Cerebral responses to local and global auditory novelty under general anesthesia.

    PubMed

    Uhrig, Lynn; Janssen, David; Dehaene, Stanislas; Jarraya, Béchir

    2016-11-01

    Primate brains can detect a variety of unexpected deviations in auditory sequences. The local-global paradigm dissociates two hierarchical levels of auditory predictive coding by examining the brain responses to first-order (local) and second-order (global) sequence violations. Using the macaque model, we previously demonstrated that, in the awake state, local violations cause focal auditory responses while global violations activate a brain circuit comprising prefrontal, parietal and cingulate cortices. Here we used the same local-global auditory paradigm to clarify the encoding of the hierarchical auditory regularities in anesthetized monkeys and compared their brain responses to those obtained in the awake state as measured with fMRI. Both, propofol, a GABAA-agonist, and ketamine, an NMDA-antagonist, left intact or even enhanced the cortical response to auditory inputs. The local effect vanished during propofol anesthesia and shifted spatially during ketamine anesthesia compared with wakefulness. Under increasing levels of propofol, we observed a progressive disorganization of the global effect in prefrontal, parietal and cingulate cortices and its complete suppression under ketamine anesthesia. Anesthesia also suppressed thalamic activations to the global effect. These results suggest that anesthesia preserves initial auditory processing, but disturbs both short-term and long-term auditory predictive coding mechanisms. The disorganization of auditory novelty processing under anesthesia relates to a loss of thalamic responses to novelty and to a disruption of higher-order functional cortical networks in parietal, prefrontal and cingular cortices. PMID:27502046

  15. Prevalence of auditory verbal hallucinations in a general population: A group comparison study.

    PubMed

    Kråkvik, Bodil; Larøi, Frank; Kalhovde, Anne Martha; Hugdahl, Kenneth; Kompus, Kristiina; Salvesen, Øyvind; Stiles, Tore C; Vedul-Kjelsås, Einar

    2015-10-01

    The present study was specifically designed to investigate the prevalence of auditory verbal hallucinations (AVH) in the general population, and sought to compare similarities and differences regarding socio-demographics, mental health and severe life events between individuals who have never experienced AVH with those who had. The study also aimed to compare those who sought professional help for their experience of AVH with those who had not sought help. Through a postal questionnaire, 2,533 participants ages 18 and over from a national survey completed the Launay-Slade Hallucinations Scale and other measures examining AVH characteristics and other areas related to AVH. In total, 7.3% of the sample reported a life-time prevalence of AVH. Those with AVH were more likely to be single and unemployed, reported higher levels of depression and anxiety, and experienced a higher number of severe life events compared with those without AVH. Only 16% of those who experienced AVH in the general population sought professional help for these experiences. Compared to those who did not seek professional help, participants that had were more likely to experience AVH with a negative content, experience them on a daily basis, undergo negative reactions when experiencing AVH, and resist AVH. In conclusion, the prevalence of AVH was found to be relatively high. The results also revealed higher levels of reduced mental health for individuals who sought professional help, followed by those who did not, compared with those who had never experienced AVH. PMID:26079977

  16. Utility of an airframe referenced spatial auditory display for general aviation operations

    NASA Astrophysics Data System (ADS)

    Naqvi, M. Hassan; Wigdahl, Alan J.; Ranaudo, Richard J.

    2009-05-01

    The University of Tennessee Space Institute (UTSI) completed flight testing with an airframe-referenced localized audio cueing display. The purpose was to assess its affect on pilot performance, workload, and situational awareness in two scenarios simulating single-pilot general aviation operations under instrument meteorological conditions. Each scenario consisted of 12 test procedures conducted under simulated instrument meteorological conditions, half with the cue off, and half with the cue on. Simulated aircraft malfunctions were strategically inserted at critical times during each test procedure. Ten pilots participated in the study; half flew a moderate workload scenario consisting of point to point navigation and holding pattern operations and half flew a high workload scenario consisting of non precision approaches and missed approach procedures. Flight data consisted of aircraft and navigation state parameters, NASA Task Load Index (TLX) assessments, and post-flight questionnaires. With localized cues there was slightly better pilot technical performance, a reduction in workload, and a perceived improvement in situational awareness. Results indicate that an airframe-referenced auditory display has utility and pilot acceptance in general aviation operations.

  17. 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

  18. 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

  19. Auditory hallucinations.

    PubMed

    Blom, Jan Dirk

    2015-01-01

    Auditory hallucinations constitute a phenomenologically rich group of endogenously mediated percepts which are associated with psychiatric, neurologic, otologic, and other medical conditions, but which are also experienced by 10-15% of all healthy individuals in the general population. The group of phenomena is probably best known for its verbal auditory subtype, but it also includes musical hallucinations, echo of reading, exploding-head syndrome, and many other types. The subgroup of verbal auditory hallucinations has been studied extensively with the aid of neuroimaging techniques, and from those studies emerges an outline of a functional as well as a structural network of widely distributed brain areas involved in their mediation. The present chapter provides an overview of the various types of auditory hallucination described in the literature, summarizes our current knowledge of the auditory networks involved in their mediation, and draws on ideas from the philosophy of science and network science to reconceptualize the auditory hallucinatory experience, and point out directions for future research into its neurobiologic substrates. In addition, it provides an overview of known associations with various clinical conditions and of the existing evidence for pharmacologic and non-pharmacologic treatments.

  20. Categorization of Extremely Brief Auditory Stimuli: Domain-Specific or Domain-General Processes?

    PubMed Central

    Bigand, Emmanuel; Delbé, Charles; Gérard, Yannick; Tillmann, Barbara

    2011-01-01

    The present study investigated the minimum amount of auditory stimulation that allows differentiation of spoken voices, instrumental music, and environmental sounds. Three new findings were reported. 1) All stimuli were categorized above chance level with 50 ms-segments. 2) When a peak-level normalization was applied, music and voices started to be accurately categorized with 20 ms-segments. When the root-mean-square (RMS) energy of the stimuli was equalized, voice stimuli were better recognized than music and environmental sounds. 3) Further psychoacoustical analyses suggest that the categorization of extremely brief auditory stimuli depends on the variability of their spectral envelope in the used set. These last two findings challenge the interpretation of the voice superiority effect reported in previously published studies and propose a more parsimonious interpretation in terms of an emerging property of auditory categorization processes. PMID:22046436

  1. 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.

  2. Prions mediated neurodegenerative disorders.

    PubMed

    Huang, W-J; Chen, W-W; Zhang, X

    2015-11-01

    Prions are unprecedented infectious pathogens that are devoid of nucleic acid and cause a group of rare and invariably fatal neurodegenerative disorders, affecting approximately 1 person per 1 million inhabitants annually worldwide. These disorders include Creutzfeld-Jacob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome (GSS), kuru, fatal insomnia (FI), and variable protease-sensitive prionopathy (VPSPr), all of which involve a conformational change of the normal cellular prion protein (PrPC) into the abnormal scrapie prion protein (PrPSc) through a posttranslational process during which PrPc acquires high β-sheet content. This structural change is accompanied by profound changes in the physicochemical properties of PrPC, rendering the molecule resistant to proteolysis. The conformational change of PrPC can occur due to either spontaneous conversion, dominant mutations in the prion protein (PRNP) gene encoding PrPC, or infection with pathogenic isoform PrPsc from exogenous sources. There is general agreement that PrPC serves as a substrate for conversion to abnormal PrPSc. This latter multiplies exponentially and aggregates in the brain, forming deposits that are associated with the neurodegenerative changes. Although the understanding of the primary causes of prion-induced neurodegeneration is still limited, propagation of PrPSc and neurotoxic signaling seem to interplay in pathogenic process of prions. Here, we review recent findings that have provided fresh insights into this process, and present an overview of incidence, causes and spectrum of related disorders.

  3. 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

  4. Auditory same/different concept learning and generalization in black-capped chickadees (Poecile atricapillus).

    PubMed

    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.

  5. 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

  6. 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

  7. Optical Brain Imaging Reveals General Auditory and Language-Specific Processing in Early Infant Development

    PubMed Central

    Minagawa-Kawai, Yasuyo; van der Lely, Heather; Ramus, Franck; Sato, Yutaka; Mazuka, Reiko; Dupoux, Emmanuel

    2011-01-01

    This study uses near-infrared spectroscopy in young infants in order to elucidate the nature of functional cerebral processing for speech. Previous imaging studies of infants’ speech perception revealed left-lateralized responses to native language. However, it is unclear if these activations were due to language per se rather than to some low-level acoustic correlate of spoken language. Here we compare native (L1) and non-native (L2) languages with 3 different nonspeech conditions including emotional voices, monkey calls, and phase scrambled sounds that provide more stringent controls. Hemodynamic responses to these stimuli were measured in the temporal areas of Japanese 4 month-olds. The results show clear left-lateralized responses to speech, prominently to L1, as opposed to various activation patterns in the nonspeech conditions. Furthermore, implementing a new analysis method designed for infants, we discovered a slower hemodynamic time course in awake infants. Our results are largely explained by signal-driven auditory processing. However, stronger activations to L1 than to L2 indicate a language-specific neural factor that modulates these responses. This study is the first to discover a significantly higher sensitivity to L1 in 4 month-olds and reveals a neural precursor of the functional specialization for the higher cognitive network. PMID:20497946

  8. 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.

  9. 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.

  10. Sleep in Neurodegenerative Diseases.

    PubMed

    Iranzo, Alex

    2016-03-01

    Disorders of sleep are an integral part of neurodegenerative diseases and include insomnia, sleep-wake cycle disruption, excessive daytime sleepiness that may be manifested as persistent somnolence or sudden onset of sleep episodes, obstructive and central sleep apnea, rapid eye movement sleep behavior disorder, and restless legs syndrome. The origin of these sleep disorders is multifactorial including degeneration of the brain areas that modulate sleep, the symptoms of the disease, and the effect of medications. Treatment of sleep disorders in patients with neurodegenerative diseases should be individualized and includes behavioral therapy, sleep hygiene, bright light therapy, melatonin, hypnotics, waking-promoting agents, and continuous positive airway pressure. PMID:26972029

  11. Ceruloplasmin in neurodegenerative diseases.

    PubMed

    Vassiliev, Vadim; Harris, Zena Leah; Zatta, Paolo

    2005-11-01

    For decades, abnormalities in ceruloplasmin (Cp) synthesis have been associated with neurodegenerative disease. From the early observation that low circulating serum ceruloplasmin levels served as a marker for Wilson's disease to the recent characterization of a neurodegenerative disorder associated with a complete lack of serum ceruloplasmin, the link between Cp and neuropathology has strengthened. The mechanisms associated with these different central nervous system abnormalities are very distinct. In Wilson's disease, a defect in the P-type ATPase results in abnormal hepatic copper accumulation that eventually leaks into the circulation and is abnormally deposited in the brain. In this case, copper deposition results in the neurodegenerative phenotype observed. Patients with autosomal recessive condition, aceruloplasminemia, lack the ferroxidase activity inherent to the multi-copper oxidase ceruloplasmin and develop abnormal iron accumulation within the central nervous system. In the following review ceruloplasmin gene expression, structure and function will be presented and the role of ceruloplasmin in iron metabolism will be discussed. The molecular events underlying the different forms of neurodegeneration observed will be presented. Understanding the role of ceruloplasmin within the central nervous system is fundamental to further our understanding of the pathology observed. Is the ferroxidase function more essential than the antioxidant role? Does Cp help maintain nitrosothiol stores or does it oxidize critical brain substrates? The answers to these questions hold the promise for the treatment of devastating neurodegenerative conditions such as Alzheimer's and Parkinson's diseases. It is essential to further elucidate the mechanism of the neuronal injury associated with these disorders.

  12. Perceptual learning and generalization resulting from training on an auditory amplitude-modulation detection task.

    PubMed

    Fitzgerald, Matthew B; Wright, Beverly A

    2011-02-01

    Fluctuations in sound amplitude provide important cues to the identity of many sounds including speech. Of interest here was whether the ability to detect these fluctuations can be improved with practice, and if so whether this learning generalizes to untrained cases. To address these issues, normal-hearing adults (n = 9) were trained to detect sinusoidal amplitude modulation (SAM; 80-Hz rate, 3-4 kHz bandpass carrier) 720 trials/day for 6-7 days and were tested before and after training on related SAM-detection and SAM-rate-discrimination conditions. Controls (n = 9) only participated in the pre- and post-tests. The trained listeners improved more than the controls on the trained condition between the pre- and post-tests, but different subgroups of trained listeners required different amounts of practice to reach asymptotic performance, ranging from 1 (n = 6) to 4-6 (n = 3) sessions. This training-induced learning did not generalize to detection with two untrained carrier spectra (5 kHz low-pass and 0.5-1.5 kHz bandpass) or to rate discrimination with the trained rate and carrier spectrum, but there was some indication that it generalized to detection with two untrained rates (30 and 150 Hz). Thus, practice improved the ability to detect amplitude modulation, but the generalization of this learning to untrained cases was somewhat limited.

  13. Aquaporins and Neurodegenerative Diseases

    PubMed Central

    Foglio, Eleonora; Rodella, Luigi Fabrizio

    2010-01-01

    Aquaporins (AQPs) are a family of widely distributed membrane-inserted water channel proteins providing a pathway for osmotically-driven water, glycerol, urea or ions transport through cell membranes and mechanisms to control particular aspects of homeostasis. Beside their physiological expression patterns in Central Nervous System (CNS), it is conceivable that AQPs are also abnormally expressed in some pathological conditions interesting CNS (e.g. neurodegenerative diseases) in which preservation of brain homeostasis is at risk. The purpose of this review was to take in consideration those neurodegenerative diseases in whose pathogenetic processes it was possible to hypothesize some alterations in CNS AQPs expression or modulation leading to damages of brain water homeostasis. PMID:21119882

  14. 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.

  15. Aquatherapy for neurodegenerative disorders.

    PubMed

    Plecash, Alyson R; Leavitt, Blair R

    2014-01-01

    Aquatherapy is used for rehabilitation and exercise; water provides a challenging, yet safe exercise environment for many special populations. We have reviewed the use of aquatherapy programs in four neurodegenerative disorders: Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington's disease. Results support the use of aquatherapy in Parkinson's disease and multiple sclerosis, however further evidence is required to make specific recommendations in all of the aforementioned disorders.

  16. 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

  17. 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

  18. Visual hallucinations in the psychosis spectrum and comparative information from neurodegenerative disorders and eye disease.

    PubMed

    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

    2014-07-01

    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.

  19. Serotonergic innervation of the inner ear: is it involved in the general physiological control of the auditory receptor?

    PubMed

    Bartolomé, M Visitación; Gil-Loyzaga, Pablo

    2005-01-01

    The auditory pathway of mammals is composed of two complementary ascending afferent and descending efferent independent systems. The brainstem nuclei and cochlear projections for these systems are now well-known. In addition, a highly conspicuous distribution for serotonergic fibers was recently reported. This study focused on these serotonergic fibers and their neurons of origin. We identified several different types of serotonergic brainstem neurons surrounding the superior olivary complex and around the periolivary nuclei. Even though the 5-hydroxytryptamine (5-HT) efferent cochlear innervation originates in the periolivary area of the superior olivary complex system projecting to the cochlea, it is not involved in the transduction of pure tones during auditory processing. However, recent findings, after cochlear blockade of serotonin transporters, strongly suggested that this neuroactive substance has an important turnover within the auditory receptor. The presence of a conspicuous peripheral nerve distribution together with a particular brainstem origin could define a complex role for this innervation. Therefore, 5-HT fibers projecting to the cochlea might be involved, as in other parts of the auditory pathway, in alertness, attention, control of sleep or wakefulness cycles, and state of urgency prior to the transduction processing at the auditory receptor. A lack, or reduction, of the function of these fibers could result in pathological alterations. PMID:16639911

  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. Stem cells and neurodegenerative diseases.

    PubMed

    Hou, LingLing; Hong, Tao

    2008-04-01

    Neurodegenerative diseases are characterized by the neurodegenerative changes or apoptosis of neurons involved in networks, which are important to specific physiological functions. With the development of old-aging society, the incidence of neurodegenerative diseases is on the increase. However, it is difficult to diagnose for most of neurodegenerative diseases. At present, there are too few effective therapies. Advances in stem cell biology have raised the hope and possibility for the therapy of neurodegenerative diseases. Recently, stem cells have been widely attempted to treat neurodegenerative diseases of animal model. Here we review the progress and prospects of various stem cells, including embryonic stem cells, mesenchymal stem cell and neural stem cells and so on, for the treatments of neurodegenerative diseases, such as Parkinson's disease, Alzheimer's disease, Huntington' disease and Amyotrophic lateral sclerosis/Lou Gehrig's disease.

  2. Auditory object cognition in dementia

    PubMed Central

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

    2011-01-01

    The cognition of nonverbal sounds in dementia has been relatively little explored. Here we undertook a systematic study of nonverbal sound processing in patient groups with canonical dementia syndromes comprising clinically diagnosed typical amnestic Alzheimer's disease (AD; n = 21), progressive nonfluent aphasia (PNFA; n = 5), logopenic progressive aphasia (LPA; n = 7) and aphasia in association with a progranulin gene mutation (GAA; n = 1), and in healthy age-matched controls (n = 20). Based on a cognitive framework treating complex sounds as ‘auditory objects’, we designed a novel neuropsychological battery to probe auditory object cognition at early perceptual (sub-object), object representational (apperceptive) and semantic levels. All patients had assessments of peripheral hearing and general neuropsychological functions in addition to the experimental auditory battery. While a number of aspects of auditory object analysis were impaired across patient groups and were influenced by general executive (working memory) capacity, certain auditory deficits had some specificity for particular dementia syndromes. Patients with AD had a disproportionate deficit of auditory apperception but preserved timbre processing. Patients with PNFA had salient deficits of timbre and auditory semantic processing, but intact auditory size and apperceptive processing. Patients with LPA had a generalised auditory deficit that was influenced by working memory function. In contrast, the patient with GAA showed substantial preservation of auditory function, but a mild deficit of pitch direction processing and a more severe deficit of auditory apperception. The findings provide evidence for separable stages of auditory object analysis and separable profiles of impaired auditory object cognition in different dementia syndromes. PMID:21689671

  3. Hoofbeats and zebras: neurodegenerative disorder presenting as a "first episode" of psychosis.

    PubMed

    Ozkan, Banu; Phutane, Vivek; Jonas, Elizabeth; Tek, Cenk; Srihari, Vinod

    2011-01-01

    Neurodegenerative disorders can include diverse neuropsychiatric symptoms. Here we present a case referred to a "first-episode" psychosis clinic with socio-occupational decline, auditory hallucinations and paranoid ideation who subsequently exhibited a rapid, severe cognitive and behavioral decline. The brain magnetic resonance imaging findings of the patient have shown a progressive cortical atrophy prominent in the frontal lobes due to a neurodegenerative disorder.

  4. Role of neuroinflammation in neurodegenerative diseases (Review)

    PubMed Central

    CHEN, WEI-WEI; ZHANG, XIA; HUANG, WEN-JUAN

    2016-01-01

    Neurodegeneration is a phenomenon that occurs in the central nervous system through the hallmarks associating the loss of neuronal structure and function. Neurodegeneration is observed after viral insult and mostly in various so-called 'neurodegenerative diseases', generally observed in the elderly, such as Alzheimer's disease, multiple sclerosis, Parkinson's disease and amyotrophic lateral sclerosis that negatively affect mental and physical functioning. Causative agents of neurodegeneration have yet to be identified. However, recent data have identified the inflammatory process as being closely linked with multiple neurodegenerative pathways, which are associated with depression, a consequence of neurodegenerative disease. Accordingly, pro-inflammatory cytokines are important in the pathophysiology of depression and dementia. These data suggest that the role of neuroinflammation in neurodegeneration must be fully elucidated, since pro-inflammatory agents, which are the causative effects of neuroinflammation, occur widely, particularly in the elderly in whom inflammatory mechanisms are linked to the pathogenesis of functional and mental impairments. In this review, we investigated the role played by the inflammatory process in neurodegenerative diseases. PMID:26935478

  5. DNA damage in neurodegenerative diseases.

    PubMed

    Coppedè, Fabio; Migliore, Lucia

    2015-06-01

    Following the observation of increased oxidative DNA damage in nuclear and mitochondrial DNA extracted from post-mortem brain regions of patients affected by neurodegenerative diseases, the last years of the previous century and the first decade of the present one have been largely dedicated to the search of markers of DNA damage in neuronal samples and peripheral tissues of patients in early, intermediate or late stages of neurodegeneration. Those studies allowed to demonstrate that oxidative DNA damage is one of the earliest detectable events in neurodegeneration, but also revealed cytogenetic damage in neurodegenerative conditions, such as for example a tendency towards chromosome 21 malsegregation in Alzheimer's disease. As it happens for many neurodegenerative risk factors the question of whether DNA damage is cause or consequence of the neurodegenerative process is still open, and probably both is true. The research interest in markers of oxidative stress was shifted, in recent years, towards the search of epigenetic biomarkers of neurodegenerative disorders, following the accumulating evidence of a substantial contribution of epigenetic mechanisms to learning, memory processes, behavioural disorders and neurodegeneration. Increasing evidence is however linking DNA damage and repair with epigenetic phenomena, thereby opening the way to a very attractive and timely research topic in neurodegenerative diseases. We will address those issues in the context of Alzheimer's disease, Parkinson's disease, and Amyotrophic Lateral Sclerosis, which represent three of the most common neurodegenerative pathologies in humans. PMID:26255941

  6. Auditory Channel Problems.

    ERIC Educational Resources Information Center

    Mann, Philip H.; Suiter, Patricia A.

    This teacher's guide contains a list of general auditory problem areas where students have the following problems: (a) inability to find or identify source of sound; (b) difficulty in discriminating sounds of words and letters; (c) difficulty with reproducing pitch, rhythm, and melody; (d) difficulty in selecting important from unimportant sounds;…

  7. 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

  8. Auditory synesthesias.

    PubMed

    Afra, Pegah

    2015-01-01

    Synesthesia is experienced when sensory stimulation of one sensory modality (the inducer) elicits an involuntary or automatic sensation in another sensory modality or different aspect of the same sensory modality (the concurrent). Auditory synesthesias (AS) occur when auditory stimuli trigger a variety of concurrents, or when non-auditory sensory stimulations trigger auditory synesthetic perception. The AS are divided into three types: developmental, acquired, and induced. Developmental AS are not a neurologic disorder but a different way of experiencing one's environment. They are involuntary and highly consistent experiences throughout one's life. Acquired AS have been reported in association with neurologic diseases that cause deafferentation of anterior optic pathways, with pathologic lesions affecting the central nervous system (CNS) outside of the optic pathways, as well as non-lesional cases associated with migraine, and epilepsy. It also has been reported with mood disorders as well as a single idiopathic case. Induced AS has been reported in experimental and postsurgical blindfolding, as well as intake of hallucinogenics or psychedelics. In this chapter the three different types of synesthesia, their characteristics, and phenomologic differences, as well as their possible neural mechanisms are discussed. PMID:25726281

  9. 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.

  10. Mitochondrial Dysfunction in Neurodegenerative Diseases

    PubMed Central

    Johri, Ashu

    2012-01-01

    Neurodegenerative diseases are a large group of disabling disorders of the nervous system, characterized by the relative selective death of neuronal subtypes. In most cases, there is overwhelming evidence of impaired mitochondrial function as a causative factor in these diseases. More recently, evidence has emerged for impaired mitochondrial dynamics (shape, size, fission-fusion, distribution, movement etc.) in neurodegenerative diseases such as Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and Alzheimer's disease. Here, we provide a concise overview of the major findings in recent years highlighting the importance of healthy mitochondria for a healthy neuron. PMID:22700435

  11. 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. PMID:27651261

  12. 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

  13. [Stem cell therapy for neurodegenerative disorders].

    PubMed

    Meyer, Morten; Jensen, Pia; Rasmussen, Jens Zimmer

    2010-09-20

    Intrastriatal, foetal neural transplants can ameliorate symptoms in patients with Parkinson's and Huntington's disease, although not stop the primary cell-loss. Several issues must, however, be addressed before general or extended clinical use of cell therapy in neurodegenerative diseases can become a reality. Improvements include standardized and safe master cell-lines derived from human embryonic stem cells, induced pluripotent stem cells and neural stem cells. Cells from these sources are expected to become available for cell replacement therapies or therapeutic production of trophic, anti-inflammatory and restorative factors within a few years.

  14. 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

  15. Molecular diagnostics of neurodegenerative disorders

    PubMed Central

    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. PMID:26442283

  16. Drosophila Models of Neurodegenerative Diseases

    PubMed Central

    Lu, Bingwei; Vogel, Hannes

    2011-01-01

    Neurodegenerative diseases are progressive disorders of the nervous system that affect specific cellular populations in the central and peripheral nervous systems. Although most cases are sporadic, genes associated with familial cases have been identified, thus enabling the development of animal models. Invertebrates such as Drosophila have recently emerged as model systems for studying mechanisms of neurodegeneration in several major neurodegenerative diseases. These models are also excellent in vivo systems for the testing of therapeutic compounds. Genetic studies using these animal models have provided novel insights into the disease process. We anticipate that further exploration of the animal models will further our understanding of mechanisms of neurodegeneration as well as facilitate the development of rational treatments for debilitating degenerative diseases. PMID:18842101

  17. Seeing the Song: Left Auditory Structures May Track Auditory-Visual Dynamic Alignment

    PubMed Central

    Mossbridge, Julia A.; Grabowecky, Marcia; Suzuki, Satoru

    2013-01-01

    Auditory and visual signals generated by a single source tend to be temporally correlated, such as the synchronous sounds of footsteps and the limb movements of a walker. Continuous tracking and comparison of the dynamics of auditory-visual streams is thus useful for the perceptual binding of information arising from a common source. Although language-related mechanisms have been implicated in the tracking of speech-related auditory-visual signals (e.g., speech sounds and lip movements), it is not well known what sensory mechanisms generally track ongoing auditory-visual synchrony for non-speech signals in a complex auditory-visual environment. To begin to address this question, we used music and visual displays that varied in the dynamics of multiple features (e.g., auditory loudness and pitch; visual luminance, color, size, motion, and organization) across multiple time scales. Auditory activity (monitored using auditory steady-state responses, ASSR) was selectively reduced in the left hemisphere when the music and dynamic visual displays were temporally misaligned. Importantly, ASSR was not affected when attentional engagement with the music was reduced, or when visual displays presented dynamics clearly dissimilar to the music. These results appear to suggest that left-lateralized auditory mechanisms are sensitive to auditory-visual temporal alignment, but perhaps only when the dynamics of auditory and visual streams are similar. These mechanisms may contribute to correct auditory-visual binding in a busy sensory environment. PMID:24194873

  18. 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

  19. 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

  20. Preventing distraction: Assessing stimulus-specific and general effects of the predictive cueing of deviant auditory events

    PubMed Central

    Horváth, János; Sussman, Elyse; Winkler, István; Schröger, Erich

    2011-01-01

    Rare irregular sounds (deviants) embedded into a regular sound sequence have large potential to draw attention to themselves (distraction). It has been previously shown that distraction, as manifested by behavioral response delay, and the P3a and reorienting negativity (RON) event-related potentials, could be reduced when the forthcoming deviant was signaled by visual cues preceding the sounds. In the present study, we investigated the type of information used in the prevention of distraction by manipulating the information content of the visual cues preceding the sounds. Cues could signal the specific variant of the forthcoming deviant, or they could just signal that the next tone was a deviant. We found that stimulus-specific cue information was used in reducing distraction. The results also suggest that early P3a and RON index processes related to the specific deviating stimulus feature, whereas late P3a reflects a general distraction-related process. PMID:21310210

  1. 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. PMID:25773618

  2. Auditory sequence analysis and phonological skill.

    PubMed

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

    2012-11-01

    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

  3. Oxidative stress in neurodegenerative diseases.

    PubMed

    Chen, Xueping; Guo, Chunyan; Kong, Jiming

    2012-02-15

    Reactive oxygen species are constantly produced in aerobic organisms as by-products of normal oxygen metabolism and include free radicals such as superoxide anion (O2 (-)) and hydroxyl radical (OH(-)), and non-radical hydrogen peroxide (H2O2). The mitochondrial respiratory chain and enzymatic reactions by various enzymes are endogenous sources of reactive oxygen species. Exogenous reactive oxygen species -inducing stressors include ionizing radiation, ultraviolet light, and divergent oxidizing chemicals. At low concentrations, reactive oxygen species serve as an important second messenger in cell signaling; however, at higher concentrations and long-term exposure, reactive oxygen species can damage cellular macromolecules such as DNA, proteins, and lipids, which leads to necrotic and apoptotic cell death. Oxidative stress is a condition of imbalance between reactive oxygen species formation and cellular antioxidant capacity due to enhanced ROS generation and/or dysfunction of the antioxidant system. Biochemical alterations in these macromolecular components can lead to various pathological conditions and human diseases, especially neurodegenerative diseases. Neurodegenerative diseases are morphologically featured by progressive cell loss in specific vulnerable neuronal cells, often associated with cytoskeletal protein aggregates forming inclusions in neurons and/or glial cells. Deposition of abnormal aggregated proteins and disruption of metal ions homeostasis are highly associated with oxidative stress. The main aim of this review is to present as much detailed information as possible that is available on various neurodegenerative disorders and their connection with oxidative stress. A variety of therapeutic strategies designed to address these pathological processes are also described. For the future therapeutic direction, one specific pathway that involves the transcription factor nuclear factor erythroid 2-related factor 2 is receiving considerable attention.

  4. 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

  5. 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)

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

    PubMed

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

    2016-01-01

    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. PMID:26919851

  7. 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

  8. 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

  9. 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.

  10. Oxidative stress treatment for clinical trials in neurodegenerative diseases.

    PubMed

    Ienco, Elena Caldarazzo; LoGerfo, Annalisa; Carlesi, Cecilia; Orsucci, Daniele; Ricci, Giulia; Mancuso, Michelangelo; Siciliano, Gabriele

    2011-01-01

    Oxidative stress is a metabolic condition arising from imbalance between the production of potentially reactive oxygen species and the scavenging activities. Mitochondria are the main providers but also the main scavengers of cell oxidative stress. The role of mitochondrial dysfunction and oxidative stress in the pathogenesis of neurodegenerative diseases is well documented. Therefore, therapeutic approaches targeting mitochondrial dysfunction and oxidative damage hold great promise in neurodegenerative diseases. Despite this evidence, human experience with antioxidant neuroprotectants has generally been negative with regards to the clinical progress of disease, with unclear results in biochemical assays. Here we review the antioxidant approaches performed so far in neurodegenerative diseases and the future challenges in modern medicine. PMID:21422516

  11. 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.

  12. 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.

  13. 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.

  14. Amyloidosis in Retinal Neurodegenerative Diseases.

    PubMed

    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

  15. Systems biology of neurodegenerative diseases.

    PubMed

    Wood, Levi B; Winslow, Ashley R; Strasser, Samantha Dale

    2015-07-01

    Neurodegenerative diseases (NDs) collectively afflict more than 40 million people worldwide. The majority of these diseases lack therapies to slow or stop progression due in large part to the challenge of disentangling the simultaneous presentation of broad, multifaceted pathophysiologic changes. Present technologies and computational capabilities suggest an optimistic future for deconvolving these changes to identify novel mechanisms driving ND onset and progression. In particular, integration of highly multi-dimensional omic analytical techniques (e.g., microarray, mass spectrometry) with computational systems biology approaches provides a systematic methodology to elucidate new mechanisms driving NDs. In this review, we begin by summarizing the complex pathophysiology of NDs associated with protein aggregation, emphasizing the shared complex dysregulation found in all of these diseases, and discuss available experimental ND models. Next, we provide an overview of technological and computational techniques used in systems biology that are applicable to studying NDs. We conclude by reviewing prior studies that have applied these approaches to NDs and comment on the necessity of combining analysis from both human tissues and model systems to identify driving mechanisms. We envision that the integration of computational approaches with multiple omic analyses of human tissues, and mouse and in vitro models, will enable the discovery of new therapeutic strategies for these devastating diseases.

  16. Peptide aggregation in neurodegenerative disease.

    PubMed

    Murphy, Regina M

    2002-01-01

    In the not-so-distant past, insoluble aggregated protein was considered as uninteresting and bothersome as yesterday's trash. More recently, protein aggregates have enjoyed considerable scientific interest, as it has become clear that these aggregates play key roles in many diseases. In this review, we focus attention on three polypeptides: beta-amyloid, prion, and huntingtin, which are linked to three feared neurodegenerative diseases: Alzheimer's, "mad cow," and Huntington's disease, respectively. These proteins lack any significant primary sequence homology, yet their aggregates possess very similar features, specifically, high beta-sheet content, fibrillar morphology, relative insolubility, and protease resistance. Because the aggregates are noncrystalline, secrets of their structure at nanometer resolution are only slowly yielding to X-ray diffraction, solid-state NMR, and other techniques. Besides structure, the aggregates may possess similar pathways of assembly. Two alternative assembly pathways have been proposed: the nucleation-elongation and the template-assisted mode. These two modes may be complementary, not mutually exclusive. Strategies for interfering with aggregation, which may provide novel therapeutic approaches, are under development. The structural similarities between protein aggregates of dissimilar origin suggest that therapeutic strategies successful against one disease may have broad utility in others. PMID:12117755

  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. 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)…

  19. Auditory Training for Central Auditory Processing Disorder.

    PubMed

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

    2015-11-01

    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

  20. 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

  1. 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

  2. Sound Naming in Neurodegenerative Disease

    PubMed Central

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

    2010-01-01

    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 of objects that required manipulation when producing the sound, and 28 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 premotor region, extending from area 6 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 premotor cortex. Our results support the hypothesis that retrieval of action-related semantic knowledge involves motor regions in the brain. PMID:20089342

  3. [Microglial Phagocytosis in the Neurodegenerative Diseases].

    PubMed

    Cao, Sheng-nan; Bao, Xiu-qi; Sun, Hua; Zhang, Dan

    2016-04-01

    Microglia are the resident innate immune cells in the brain. Under endogenous or exogenous stimulates, they become activated and play an important role in the neurodegenerative diseases. Microglial phagocytosis is a process of receptor-mediated engulfment and degradation of apoptotic cells. In addition, microglia can phagocyte brain-specific cargo, such as myelin debris and abnormal protein aggregation. However, recent studies have shown that microglia can also phagocyte stressed-but-viable neurons, causing loss of neurons in the brain. Thus, whether microglial phagocytosis is beneficial or not in neurodegenerative disease remains controversial. This article reviews microglial phagocytosis related mechanisms and its potential roles in neurodegenerative diseases, with an attempt to provide new insights in the treatment of neurodegenerative diseases. PMID:27181903

  4. [Microglial Phagocytosis in the Neurodegenerative Diseases].

    PubMed

    Cao, Sheng-nan; Bao, Xiu-qi; Sun, Hua; Zhang, Dan

    2016-04-01

    Microglia are the resident innate immune cells in the brain. Under endogenous or exogenous stimulates, they become activated and play an important role in the neurodegenerative diseases. Microglial phagocytosis is a process of receptor-mediated engulfment and degradation of apoptotic cells. In addition, microglia can phagocyte brain-specific cargo, such as myelin debris and abnormal protein aggregation. However, recent studies have shown that microglia can also phagocyte stressed-but-viable neurons, causing loss of neurons in the brain. Thus, whether microglial phagocytosis is beneficial or not in neurodegenerative disease remains controversial. This article reviews microglial phagocytosis related mechanisms and its potential roles in neurodegenerative diseases, with an attempt to provide new insights in the treatment of neurodegenerative diseases.

  5. 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). PMID:20192565

  6. 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).

  7. 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.

  8. 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

  9. 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

  10. 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

  11. Extracting regional brain patterns for classification of neurodegenerative diseases

    NASA Astrophysics Data System (ADS)

    Pulido, Andrea; Rueda, Andrea; Romero, Eduardo

    2013-11-01

    In structural Magnetic Resonance Imaging (MRI), neurodegenerative diseases generally present complex brain patterns that can be correlated with di erent clinical onsets of this pathologies. An objective method that aims to determine both global and local changes is not usually available in clinical practice, thus the interpretation of these images is strongly dependent on the radiologist's skills. In this paper, we propose a strategy which interprets the brain structure using a framework that highlights discriminant brain patterns for neurodegenerative diseases. This is accomplished by combining a probabilistic learning technique, which identi es and groups regions with similar visual features, with a visual saliency method that exposes relevant information within each region. The association of such patterns with a speci c disease is herein evaluated in a classi cation task, using a dataset including 80 Alzheimer's disease (AD) patients and 76 healthy subjects (NC). Preliminary results show that the proposed method reaches a maximum classi cation accuracy of 81.39%.

  12. Theory of Mind in normal ageing and neurodegenerative pathologies.

    PubMed

    Kemp, Jennifer; Després, Olivier; Sellal, François; Dufour, André

    2012-04-01

    This paper reviews findings in three subcomponents of social cognition (i.e., Theory of Mind, facial emotion recognition, empathy) during ageing. Changes over time in social cognition were evaluated in normal ageing and in patients with various neurodegenerative pathologies, such as Alzheimer's disease, mild cognitive impairment, frontal and temporal variants of frontotemporal lobar degeneration and Parkinson's disease. Findings suggest a decline in social cognition with normal ageing, a decline that is at least partially independent of a more general cognitive or executive decline. The investigation of neurodegenerative pathologies showing specific deficits in Theory of Mind in relation to damage to specific cerebral regions led us to suggest a neural network involved in Theory of Mind processes, namely a fronto-subcortical loop linking the basal ganglia to the regions of the frontal lobes.

  13. Early Diagnosis and Monitoring of Neurodegenerative Langerhans Cell Histiocytosis

    PubMed Central

    Mortilla, Marzia; Savelli, Sara; Grisotto, Laura; Di Giacomo, Gianpiero; Romano, Katiuscia; Fonda, Claudio; Biggeri, Annibale; Guerrini, Renzo; Aricò, Maurizio

    2015-01-01

    Background Neurodegenerative Langerhans Cell Histiocytosis (ND-LCH) is a rare, unpredictable consequence that may devastate the quality of life of patients cured from LCH. We prospectively applied a multidisciplinary diagnostic work-up to early identify and follow-up patients with ND-LCH, with the ultimate goal of better determining the appropriate time for starting therapy. Methods We studied 27 children and young adults with either ND-LCH verified by structural magnetic resonance imaging (MRI) (group 1) or specific risk factors for (diabetes insipidus, craniofacial bone lesions), but no evidence of, neurodegenerative MRI changes (group 2). All patients underwent clinical, neurophysiological and MRI studies. Results Seventeen patients had MRI alterations typical for ND-LCH. Nine showed neurological impairment but only three were symptomatic; 11 had abnormal somatosensory evoked potentials (SEPs), and five had abnormal brainstem auditory evoked potentials (BAEPs). MR spectroscopy (MRS) showed reduced cerebellar NAA/Cr ratio in nine patients. SEPs showed sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for predicting ND-LCH of 70.6% (95%CI, 44.0%-89.7%), 100% (69.2%-100%), 100% (73.5%-100%), and 66.7% (38.4%-88.2%), respectively. Repeated investigations in group 1 revealed increasingly abnormal EP parameters, or neurological examination, or both, in nine of fifteen patients while MRI remained unchanged in all but one patient. Conclusion A targeted MRI study should be performed in all patients with risk factors for ND-LCH for early identification of demyelination. The combined use of SEPs and careful neurological evaluation may represent a valuable, low-cost, well-tolerated and easily available methodology to monitor patients from pre-symptomatic to symptomatic stages. We suggest a multidisciplinary protocol including clinical, MRS, and neurophysiological investigations to identify a population target for future

  14. 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. PMID:26446984

  15. 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

  16. 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

  17. 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.

  18. 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

  19. Summary of cerebrospinal fluid routine parameters in neurodegenerative diseases.

    PubMed

    Jesse, Sarah; Brettschneider, Johannes; Süssmuth, Sigurd D; Landwehrmeyer, Bernhard G; von Arnim, Christine A F; Ludolph, Albert C; Tumani, Hayrettin; Otto, Markus

    2011-06-01

    In neurodegenerative diseases, cerebrospinal fluid analysis (CSF) is predominantly performed to exclude inflammatory diseases and to perform a risk assessment in dementive disorders by measurement of tau proteins and amyloid beta peptides. However, large scale data on basic findings of CSF routine parameters are generally lacking. The objective of the study was to define a normal reference spectrum of routine CSF parameters in neurodegenerative diseases. Routine CSF parameters (white cell count, lactate and albumin concentrations, CSF/serum quotients of albumin (Q (alb)), IgG, IgA, IgM, and oligoclonal IgG bands (OCB)) were retrospectively analyzed in an academic research setting. A total of 765 patients (Alzheimer's disease (AD), Parkinson's disease (PD), Parkinson's disease dementia (PDD), vascular dementia (VD), frontotemporal lobar degeneration (FTLD), progressive supranuclear palsy (PSP), multisystem atrophy (MSA), motor neuron diseases (MND), spinocerebellar ataxia (SCA), Huntington's disease (HD)) and non-demented control groups including a group of patients with muscular disorders (MD). The main outcome measures included statistical analyses of routine CSF parameters. Mildly elevated Q (alb) were found in a small percentage of nearly all subgroups and in a higher proportion of patients with PSP, MSA, VD, PDD, and MND. With the exception of 1 MND patient, no intrathecal Ig synthesis was observed. Isolated OCBs in CSF were sometimes found in patients with neurodegenerative diseases without elevated cell counts; lactate levels were always normal. A slightly elevated Q (alb) was observed in a subgroup of patients with neurodegenerative diseases and does not exclude the diagnosis. Extensive elevation of routine parameters is not characteristic and should encourage a re-evaluation of the clinical diagnosis.

  20. 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

  1. 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.

  2. 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.

  3. Mitochondrial drug targets in neurodegenerative diseases.

    PubMed

    Lee, Jiyoun

    2016-02-01

    Growing evidence suggests that mitochondrial dysfunction is the main culprit in neurodegenerative diseases. Given the fact that mitochondria participate in diverse cellular processes, including energetics, metabolism, and death, the consequences of mitochondrial dysfunction in neuronal cells are inevitable. In fact, new strategies targeting mitochondrial dysfunction are emerging as potential alternatives to current treatment options for neurodegenerative diseases. In this review, we focus on mitochondrial proteins that are directly associated with mitochondrial dysfunction. We also examine recently identified small molecule modulators of these mitochondrial targets and assess their potential in research and therapeutic applications.

  4. Managing anxiety associated with neurodegenerative disorders

    PubMed Central

    Kumar, Anand

    2015-01-01

    Anxiety is a common symptom among patients with cognitive impairment. The presence of anxiety is correlated with poorer outcomes; despite this, there is limited research on anxiety related to neurodegenerative disorder. In this article, we discuss the prevalence of anxiety and factors involved in the etiology of anxiety in patients with diagnosed neurodegenerative disorders and related states of cognitive impairment as well as the evidence for currently available methods of evaluating and treating these symptoms. Specific treatments are highlighted in light of current evidence, followed by a discussion of the difficulties inherent in the study and treatment of anxiety in this population. PMID:25705388

  5. 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. PMID:22271265

  6. 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.

  7. 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.

  8. 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.

  9. Circulating microRNAs in Neurodegenerative Diseases.

    PubMed

    Grasso, Margherita; Piscopo, Paola; Crestini, Alessio; Confaloni, Annamaria; Denti, Michela A

    2015-01-01

    Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), are caused by a combination of events that impair normal neuronal function. Although they are considered different disorders, there are overlapping features among them from the clinical, pathological, and genetic points of view. Synaptic dysfunction and loss, neurite retraction, and the appearance of other abnormalities such as axonal transport defects normally precede the neuronal loss that is a relatively late event. The diagnosis of many neurodegenerative diseases is mainly based on patient's cognitive function analysis, and the development of diagnostic methods is complicated by the brain's capacity to compensate for neuronal loss over a long period of time. This results in the late clinical manifestation of symptoms, a time when successful treatment is no longer feasible. Thus, a noninvasive diagnostic method based on early events detection is particularly important. In the last years, some biomarkers expressed in human body fluids have been proposed. microRNAs (miRNAs), with their high stability, tissue- or cell type-specific expression, lower cost, and shorter time in the assay development, could constitute a good tool to obtain an early disease diagnosis for a wide number of human pathologies, including neurodegenerative diseases. The possibilities and challenges of using these small RNA molecules as a signature for neurodegenerative disorders is a highly promising approach for developing minimally invasive screening tests and to identify new therapeutic targets.

  10. Neuronal Network Oscillations in Neurodegenerative Diseases.

    PubMed

    Nimmrich, Volker; Draguhn, Andreas; Axmacher, Nikolai

    2015-09-01

    Cognitive and behavioral acts go along with highly coordinated spatiotemporal activity patterns in neuronal networks. Most of these patterns are synchronized by coherent membrane potential oscillations within and between local networks. By entraining multiple neurons into a common time regime, such network oscillations form a critical interface between cellular activity and large-scale systemic functions. Synaptic integrity is altered in neurodegenerative diseases, and it is likely that this goes along with characteristic changes of coordinated network activity. This notion is supported by EEG recordings from human patients and from different animal models of such disorders. However, our knowledge about the pathophysiology of network oscillations in neurodegenerative diseases is surprisingly incomplete, and increased research efforts are urgently needed. One complicating factor is the pronounced diversity of network oscillations between different brain regions and functional states. Pathological changes must, therefore, be analyzed separately in each condition and affected area. However, cumulative evidence from different diseases may result, in the future, in more unifying "oscillopathy" concepts of neurodegenerative diseases. In this review, we report present evidence for pathological changes of network oscillations in Alzheimer's disease (AD), one of the most prominent and challenging neurodegenerative disorders. The heterogeneous findings from AD are contrasted to Parkinson's disease, where motor-related changes in specific frequency bands do already fulfill criteria of a valid biomarker. PMID:25920466

  11. Prism Management in Patients with Neurodegenerative Disease.

    PubMed

    Gilligan, Rikki

    2015-01-01

    Patients with motility problems due to neurodegenerative disease such as Parkinson's and its variations often present challenging cases for the orthoptist. A few "tricks of the trade" will be presented on how to make a Parkinson's patient's daily life a little easier.

  12. 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.

  13. Dysregulation of Glutathione Homeostasis in Neurodegenerative Diseases

    PubMed Central

    Johnson, William M.; Wilson-Delfosse, Amy L.; Mieyal, John. J.

    2012-01-01

    Dysregulation of glutathione homeostasis and alterations in glutathione-dependent enzyme activities are increasingly implicated in the induction and progression of neurodegenerative diseases, including Alzheimer’s, Parkinson’s and Huntington’s diseases, amyotrophic lateral sclerosis, and Friedreich’s ataxia. In this review background is provided on the steady-state synthesis, regulation, and transport of glutathione, with primary focus on the brain. A brief overview is presented on the distinct but vital roles of glutathione in cellular maintenance and survival, and on the functions of key glutathione-dependent enzymes. Major contributors to initiation and progression of neurodegenerative diseases are considered, including oxidative stress, protein misfolding, and protein aggregation. In each case examples of key regulatory mechanisms are identified that are sensitive to changes in glutathione redox status and/or in the activities of glutathione-dependent enzymes. Mechanisms of dysregulation of glutathione and/or glutathione-dependent enzymes are discussed that are implicated in pathogenesis of each neurodegenerative disease. Limitations in information or interpretation are identified, and possible avenues for further research are described with an aim to elucidating novel targets for therapeutic interventions. The pros and cons of administration of N-acetylcysteine or glutathione as therapeutic agents for neurodegenerative diseases, as well as the potential utility of serum glutathione as a biomarker, are critically evaluated. PMID:23201762

  14. Catalpol: a potential therapeutic for neurodegenerative diseases.

    PubMed

    Jiang, B; Shen, R F; Bi, J; Tian, X S; Hinchliffe, T; Xia, Y

    2015-01-01

    Neurodegenerative disorders, e.g., Alzheimer's disease (AD) and Parkinson's disease (PD) are characterized by the progressive loss of neurons and subsequent cognitive decline. They are mainly found in older populations. Due to increasing life expectancies, the toll inflicted upon society by these disorders continues to become heavier and more prominent. Despite extensive research, however, the exact etiology of these disorders is still unknown, though the pathophysiological mechanisms have been attributed to oxidative, inflammatory and apoptotic injury in the brain. Moreover, there is currently no promising therapeutic agent against these neurodegenerative changes. Catalpol, an iridoid glucoside contained richly in the roots of the small flowering plant species Rehmannia glutinosa Libosch, has been shown to have antioxidation, anti-inflammation, anti-apoptosis and other neuroprotective properties and plays a role in neuroprotection against hypoxic/ischemic injury, AD and PD in both in vivo and in vitro models. It may therefore represent a potential therapeutical agent for the treatment of hypoxic/ischemic injury and neurodegenerative diseases. Based on our studies and those of others in the literature, here we comprehensively review the role of Catalpol in neuroprotection against pathological conditions, especially in neurodegenerative states and the potential mechanisms involved.

  15. 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

  16. The Distributed Auditory Cortex

    PubMed Central

    Winer, Jeffery A.; Lee, Charles C.

    2009-01-01

    A synthesis of cat auditory cortex (AC) organization is presented in which the extrinsic and intrinsic connections interact to derive a unified profile of the auditory stream and use it to direct and modify cortical and subcortical information flow. Thus, the thalamocortical input provides essential sensory information about peripheral stimulus events, which AC redirects locally for feature extraction, and then conveys to parallel auditory, multisensory, premotor, limbic, and cognitive centers for further analysis. The corticofugal output influences areas as remote as the pons and the cochlear nucleus, structures whose effects upon AC are entirely indirect, and has diverse roles in the transmission of information through the medial geniculate body and inferior colliculus. The distributed AC is thus construed as a functional network in which the auditory percept is assembled for subsequent redistribution in sensory, premotor, and cognitive streams contingent on the derived interpretation of the acoustic events. The confluence of auditory and multisensory streams likely precedes cognitive processing of sound. The distributed AC constitutes the largest and arguably the most complete representation of the auditory world. Many facets of this scheme may apply in rodent and primate AC as well. We propose that the distributed auditory cortex contributes to local processing regimes in regions as disparate as the frontal pole and the cochlear nucleus to construct the acoustic percept. PMID:17329049

  17. Auditory based neuropsychology in neurosurgery.

    PubMed

    Wester, Knut

    2008-04-01

    In this article, an account is given on the author's experience with auditory based neuropsychology in a clinical, neurosurgical setting. The patients that were included in the studies are patients with traumatic or vascular brain lesions, patients undergoing brain surgery to alleviate symptoms of Parkinson's disease, or patients harbouring an intracranial arachnoid cyst affecting the temporal or the frontal lobe. The aims of these investigations were to collect information about the location of cognitive processes in the human brain, or to disclose dyscognition in patients with an arachnoid cyst. All the patients were tested with the DL technique. In addition, the cyst patients were subjected to a number of non-auditory, standard neuropsychological tests, such as Benton Visual Retention Test, Street Gestalt Test, Stroop Test and Trails Test A and B. The neuropsychological tests revealed that arachnoid cysts in general cause dyscognition that also includes auditory processes, and more importantly, that these cognition deficits normalise after surgical removal of the cyst. These observations constitute strong evidence in favour of surgical decompression. PMID:18024027

  18. 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.

  19. 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

  20. [Central auditory prosthesis].

    PubMed

    Lenarz, T; Lim, H; Joseph, G; Reuter, G; Lenarz, M

    2009-06-01

    Deaf patients with severe sensory hearing loss can benefit from a cochlear implant (CI), which stimulates the auditory nerve fibers. However, patients who do not have an intact auditory nerve cannot benefit from a CI. The majority of these patients are neurofibromatosis type 2 (NF2) patients who developed neural deafness due to growth or surgical removal of a bilateral acoustic neuroma. The only current solution is the auditory brainstem implant (ABI), which stimulates the surface of the cochlear nucleus in the brainstem. Although the ABI provides improvement in environmental awareness and lip-reading capabilities, only a few NF2 patients have achieved some limited open set speech perception. In the search for alternative procedures our research group in collaboration with Cochlear Ltd. (Australia) developed a human prototype auditory midbrain implant (AMI), which is designed to electrically stimulate the inferior colliculus (IC). The IC has the potential as a new target for an auditory prosthesis as it provides access to neural projections necessary for speech perception as well as a systematic map of spectral information. In this paper the present status of research and development in the field of central auditory prostheses is presented with respect to technology, surgical technique and hearing results as well as the background concepts of ABI and AMI. PMID:19517084

  1. 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.

  2. 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

  3. Dysregulated microRNAs in neurodegenerative disorders.

    PubMed

    Lau, Pierre; de Strooper, Bart

    2010-09-01

    The complexity of the nervous system arises in part, from the large diversity of neural cell types that support the architecture of neuronal circuits. Recent studies have highlighted microRNAs as important players in regulating gene expression at the post-transcriptional level and therefore the phenotype of neural cells. A link between microRNAs and neurodegenerative diseases such as Alzheimer's disease, Huntington's disease and Parkinson's disease is becoming increasingly evident. Here, we discuss microRNAs in neurodegeneration, from the fruit fly and mouse utilized as experimental models to dysregulated microRNAs in human neurodegenerative disorders. We propose that studying microRNAs and their mRNA targets in the context of neurodegeneration will significantly contribute to the identification of proteins important for neuronal function and might reveal underlying molecular networks that drive these diseases.

  4. 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. PMID:23016644

  5. Endocytic membrane trafficking and neurodegenerative disease.

    PubMed

    Schreij, Andrea M A; Fon, Edward A; McPherson, Peter S

    2016-04-01

    Neurodegenerative diseases are amongst the most devastating of human disorders. New technologies have led to a rapid increase in the identification of disease-related genes with an enhanced appreciation of the key roles played by genetics in the etiology of these disorders. Importantly, pinpointing the normal function of disease gene proteins leads to new understanding of the cellular machineries and pathways that are altered in the disease process. One such emerging pathway is membrane trafficking in the endosomal system. This key cellular process controls the localization and levels of a myriad of proteins and is thus critical for normal cell function. In this review we will focus on three neurodegenerative diseases; Parkinson disease, amyotrophic lateral sclerosis, and hereditary spastic paraplegias, for which a large number of newly discovered disease genes encode proteins that function in endosomal membrane trafficking. We will describe how alterations in these proteins affect endosomal function and speculate on the contributions of these disruptions to disease pathophysiology. PMID:26721251

  6. 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

  7. 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.

  8. 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

  9. 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

    2015-09-01

    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.

  10. Efficacy of Natural Compounds in Neurodegenerative Disorders.

    PubMed

    Srivastava, Pranay; Yadav, Rajesh Singh

    2016-01-01

    Neurodegenerative disorders represent clusters of serious diseases that results in progressive deterioration of normal structure and physiology of central nervous system. Pathophysiology of Alzheimer's, Parkinson's or other neurodegenerative disorders involves multifaceted permutation of genetic and environmental factors. Combinations of lifestyle modification linked with environmental factor jointly or alone represent the largest share of cases of these disorders. Etiology of such neuronal degeneration involves manifestation of toxic reaction in the form of functional anomalies leading to dysfunction of the ubiquitin-proteasome system, activated inflammatory cascade, compromised neuronal survival pathway, mitochondrial dysfunction and finally neuronal apoptosis/necrosis and cell death. Furthermore, evidences from various studies exhibited role of oxidative stress and compromised anti-oxidant defense system as one of the prime factors associated with activation of various signal transduction pathways that would ultimately lead to the formation of amyloid beta or alpha synuclein in the brain. Keeping in view of complex etiology and pathophysiology along with a miniscule of available treatment options associated with these neurodegenerative disorders, the role of natural agents and herbal extracts as therapeutic alternatives alone or in combination with synthetic drugs could not be ruled out. In the same context the present chapter has been aimed to investigate the role of selected natural plants like Withania somnifera, Bacopa monnieri, Curcuma longa, Centella asiatica, Ocimum sanctum, Nardostachys jatamansi and Emblica officinalis in various neurodegenerative disorders and explore their targets to ameliorate neurotoxicity in various experimental models. The rationale for selection of these plants was based on their strong anti-inflammatory and anti-oxidant potential and large body of evidence that suggest their efficacy in preclinical as well as in clinical studies

  11. Nitric Oxide Homeostasis in Neurodegenerative Diseases.

    PubMed

    Hannibal, Luciana

    2016-01-01

    The role of nitric oxide in the pathogenesis and progression of neurodegenerative illnesses such as Parkinson's and Alzheimer's diseases has become prominent over the years. Increased activity of the enzymes that produce reactive oxygen species, decreased activity of antioxidant enzymes and imbalances in glutathione pools mediate and mark the neurodegenerative process. Much of the oxidative damage of proteins is brought about by the overproduction of nitric oxide by nitric oxide synthases (NOS) and its subsequent reactivity with reactive oxygen species. Proteomic methods have advanced the field tremendously, by facilitating the quantitative assessment of differential expression patterns and oxidative modifications of proteins and alongside, mapping their non-canonical functions. As a signaling molecule involved in multiple biochemical pathways, the level of nitric oxide is subject to tight regulation. All three NOS isoforms display aberrant patterns of expression in Alzheimer's disease, altering intracellular signaling and routing oxidative stress in directions that are uncompounded. This review discusses the prime factors that control nitric oxide biosynthesis, reactivity footprints and ensuing effects in the development of neurodegenerative diseases.

  12. MicroRNAs in neurodegenerative disorders.

    PubMed

    Junn, Eunsung; Mouradian, M Maral

    2010-05-01

    MicroRNAs (miRNAs) are endogenous, small, noncoding RNAs regulating eukaryotic gene expression at the post-transcriptional level. During the last decade, considerable advances have been made in our understanding the biogenesis of miRNAs, the molecular mechanisms by which they regulate gene expression and their functional role in various physiological situations. miRNAs are abundant in the brain where they have crucial roles in development and synaptic plasticity. Accumulating evidence from postmortem brain analyses and animal model studies has begun to suggest that miRNA dysfunction contributes to neurodegenerative disorders. Here, we discuss several examples of investigations demonstrating the role of miRNAs in neurodegenerative disorders. As the expression of disease-causing genes is regulated by certain miRNA(s), changes in these miRNAs could lead to the accumulation of disease-causing proteins, and subsequently to neuronal dysfunction and death. Detailed understanding of these mechanisms can provide potential new therapeutic approaches to slow down or halt the progression of neurodegenerative diseases.

  13. Congenital cholesteatoma of external auditory canal.

    PubMed

    Quantin, Laura; Carrera Fernández, Sandra; Moretti, Jorge

    2002-02-01

    A 7-month-old male child is reported with congenital cholesteatoma of the external auditory canal. We describe the clinical features, computed tomography finding and surgical treatment. Congenital cholesteatomas can occur within the temporal bone. There are six places of location: (1) petrous apex, (2) mastoid, (3) middle ear, (4) both middle ear and mastoid, (5) external ear canal and (6) within the squamous portion of the temporal bone. Congenital cholesteatoma of the external auditory canal is rare. Generally, it appears in the canal floor without lesions in the tympanic membrane. Computed tomography completes the study. Treatment consists of excision of the mass.

  14. 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.

  15. 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. PMID:24142731

  16. Auditory processing--speech, space and auditory objects.

    PubMed

    Scott, Sophie K

    2005-04-01

    There have been recent developments in our understanding of the auditory neuroscience of non-human primates that, to a certain extent, can be integrated with findings from human functional neuroimaging studies. This framework can be used to consider the cortical basis of complex sound processing in humans, including implications for speech perception, spatial auditory processing and auditory scene segregation. PMID:15831402

  17. 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

  18. Neurodegenerative disease high-field imaging

    PubMed Central

    van der Grond, J.; van Buchem, M.A.; van Zijl, P.; Webb, A.G.

    2012-01-01

    High field magnetic resonance imaging is showing potential for imaging of neurodegenerative diseases. 7 T MRI is beginning to be used in a clinical research setting and the theoretical benefits, i.e. higher signal-to-noise, sensitivity to iron, improved MRA and increased spectral resolution in spectroscopy are being confirmed. Despite the limited number of studies to date, initial results in patients with multiple sclerosis, Alzheimer’s disease and Huntington’s disease show promising additional features in contrast that may assist in better diagnosis of these disorders. PMID:22548926

  19. Overcoming obstacles to repurposing for neurodegenerative disease

    PubMed Central

    Shineman, Diana W; Alam, John; Anderson, Margaret; Black, Sandra E; Carman, Aaron J; Cummings, Jeffrey L; Dacks, Penny A; Dudley, Joel T; Frail, Donald E; Green, Allan; Lane, Rachel F; Lappin, Debra; Simuni, Tanya; Stefanacci, Richard G; Sherer, Todd; Fillit, Howard M

    2014-01-01

    Repurposing Food and Drug Administration (FDA)-approved drugs for a new indication may offer an accelerated pathway for new treatments to patients but is also fraught with significant commercial, regulatory, and reimbursement challenges. The Alzheimer’s Drug Discovery Foundation (ADDF) and the Michael J. Fox Foundation for Parkinson’s Research (MJFF) convened an advisory panel in October 2013 to understand stakeholder perspectives related to repurposing FDA-approved drugs for neurodegenerative diseases. Here, we present opportunities on how philanthropy, industry, and government can begin to address these challenges, promote policy changes, and develop targeted funding strategies to accelerate the potential of FDA-approved repurposed drugs. PMID:25356422

  20. Prion-like Mechanisms in Neurodegenerative Diseases

    PubMed Central

    Frost, Bess; Diamond, Marc I.

    2013-01-01

    Many non-infectious neurodegenerative diseases are associated with the accumulation of fibrillar protein. These diseases all exhibit phenotypic diversity and propagation of pathology that is reminiscent of prionopathies. Furthermore, emerging studies of amyloid-β, α–synuclein, and tau proteins suggest that they share key biophysical and biochemical characteristics with prions. Propagation of protein misfolding in these diseases may therefore occur via mechanisms similar to those underlying prion pathogenesis. If verified in vivo, this will suggest new therapeutic strategies to block propagation of protein misfolding throughout the brain. PMID:20029438

  1. The promises of neurodegenerative disease modeling.

    PubMed

    Lepesant, Jean-Antoine

    2015-01-01

    The rise in the prevalence of neurodegenerative diseases parallels the rapid increase in human lifespan. Despite intensive research, the molecular and cellular mechanisms underlying the onset and progression of these devastating diseases with age are still poorly understood. Many aspects of these diseases have been modelled successfully in experimental animals such as the mouse, the zebrafish Brachydanio rero, the nematode worm Caenorhaditis elegans and the fruit fly Drosophila melanogaster. This review will focus on the advantages offered by the genetic tools available in Drosophila for combining powerful strategies in order to tackle the causative factors of these complex pathologies and help to elaborate efficient drugs to treat them.

  2. 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.

  3. 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…

  4. 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…

  5. 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

  6. Auditory motion affects visual biological motion processing.

    PubMed

    Brooks, A; van der Zwan, R; Billard, A; Petreska, B; Clarke, S; Blanke, O

    2007-02-01

    The processing of biological motion is a critical, everyday task performed with remarkable efficiency by human sensory systems. Interest in this ability has focused to a large extent on biological motion processing in the visual modality (see, for example, Cutting, J. E., Moore, C., & Morrison, R. (1988). Masking the motions of human gait. Perception and Psychophysics, 44(4), 339-347). In naturalistic settings, however, it is often the case that biological motion is defined by input to more than one sensory modality. For this reason, here in a series of experiments we investigate behavioural correlates of multisensory, in particular audiovisual, integration in the processing of biological motion cues. More specifically, using a new psychophysical paradigm we investigate the effect of suprathreshold auditory motion on perceptions of visually defined biological motion. Unlike data from previous studies investigating audiovisual integration in linear motion processing [Meyer, G. F. & Wuerger, S. M. (2001). Cross-modal integration of auditory and visual motion signals. Neuroreport, 12(11), 2557-2560; Wuerger, S. M., Hofbauer, M., & Meyer, G. F. (2003). The integration of auditory and motion signals at threshold. Perception and Psychophysics, 65(8), 1188-1196; Alais, D. & Burr, D. (2004). No direction-specific bimodal facilitation for audiovisual motion detection. Cognitive Brain Research, 19, 185-194], we report the existence of direction-selective effects: relative to control (stationary) auditory conditions, auditory motion in the same direction as the visually defined biological motion target increased its detectability, whereas auditory motion in the opposite direction had the inverse effect. Our data suggest these effects do not arise through general shifts in visuo-spatial attention, but instead are a consequence of motion-sensitive, direction-tuned integration mechanisms that are, if not unique to biological visual motion, at least not common to all types of

  7. A verbal behavior analysis of auditory hallucinations.

    PubMed

    Burns, C E; Heiby, E M; Tharp, R G

    1983-01-01

    A review of recent research on the non-medical control of auditory hallucinations is presented. It is suggested that the decreases in hallucinatory behavior obtained in studies using aversive contingencies may be attributable to the disruption of the chains of behavior involved. The results of several additional studies are interpreted as indicating that methods of stimulus control and the use of incompatible behaviors may be effective in reducing the rate of auditory hallucinations. Research relating auditory hallucinations to subvocalizations is presented in support of the view that hallucinatory phenomena are sometimes related to the subject's own vocal productions. Skinner's views (1934, 1936, 1953, 1957, 1980) are then presented as possible explanations of some hallucinatory behavior. It is suggested that some auditory hallucinations consit of the mishearing of environmental and physiological stimuli as voices in a fashion similar to that which Skinner observed in his work with the verbal summator. The maintenance of long chains of such responses may be largely attributable to self-intraverbal influences (such as are present during automatic writing). With some auditory hallucinations, this progression involves first mishearing ambiguous stimuli as voices and then attributing the voices to some cause (e.g., insanity, the television, radio, or God). Later, the frequent and ongoing chains of such behavior may contaminate other verbal responses. Such verbal behavior may be parasitic on "normal verbal behavior" (and hence, not directly dependent on consquences for maintenance), may be cued by various stimuli (including respiration), and may interfere with other covert and overt behavior. Several studies to investigate this view are presented. It is hoped that such research will lead to a better understanding of the major issues involved in the etiology and treatment of auditory hallucinations in particular and perhaps of psychosis in general.

  8. 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. PMID:24329535

  9. 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

  10. 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

  11. Biomarker-based dissection of neurodegenerative diseases.

    PubMed

    Olsson, Bob; Zetterberg, Henrik; Hampel, Harald; Blennow, Kaj

    2011-12-01

    The diagnosis of neurodegenerative diseases within neurology and psychiatry are hampered by the difficulty in getting biopsies and thereby validating the diagnosis by pathological findings. Biomarkers for other types of disease have been readily adopted into the clinical practice where for instance troponins are standard tests when myocardial infarction is suspected. However, the use of biomarkers for neurodegeneration has not been fully incorporated into the clinical routine. With the development of cerebrospinal fluid (CSF) biomarkers that reflect pathological events within the central nervous system (CNS), important clinical diagnostic tools are becoming available. This review summarizes the most promising biomarker candidates that may be used to monitor different types of neurodegeneration and protein inclusions, as well as different types of metabolic changes, in living patients in relation to the clinical phenotype and disease progression over time. Our aim is to provide the reader with an updated lexicon on currently available biomarker candidates, how far they have come in development and how well they reflect pathogenic processes in different neurodegenerative diseases. Biomarkers for specific pathogenetic processes would also be valuable tools both to study disease pathogenesis directly in patients and to identify and monitor the effect of novel treatment strategies.

  12. 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. PMID:25917917

  13. [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.

  14. 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.

  15. 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

  16. 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

  17. 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

  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. The neglected neglect: auditory neglect.

    PubMed

    Gokhale, Sankalp; Lahoti, Sourabh; Caplan, Louis R

    2013-08-01

    Whereas visual and somatosensory forms of neglect are commonly recognized by clinicians, auditory neglect is often not assessed and therefore neglected. The auditory cortical processing system can be functionally classified into 2 distinct pathways. These 2 distinct functional pathways deal with recognition of sound ("what" pathway) and the directional attributes of the sound ("where" pathway). Lesions of higher auditory pathways produce distinct clinical features. Clinical bedside evaluation of auditory neglect is often difficult because of coexisting neurological deficits and the binaural nature of auditory inputs. In addition, auditory neglect and auditory extinction may show varying degrees of overlap, which makes the assessment even harder. Shielding one ear from the other as well as separating the ear from space is therefore critical for accurate assessment of auditory neglect. This can be achieved by use of specialized auditory tests (dichotic tasks and sound localization tests) for accurate interpretation of deficits. Herein, we have reviewed auditory neglect with an emphasis on the functional anatomy, clinical evaluation, and basic principles of specialized auditory tests.

  20. Unpleasant auditory illusions and related avoidance behaviour in a child.

    PubMed

    Barba, Carmen; Guerrini, Renzo

    2008-03-01

    Auditory aura is a rare symptom in focal epilepsy. It has been described in autosomal dominant partial epilepsy with auditory features, but is, in general, poorly documented. We report on a 7-year-old, right-handed boy, who suffered seizures characterized by positive auditory illusions with verbal and gestural automatisms and noticeable attempts at covering his ears. Clinical evaluation and video-recording of the seizures, confirmed that most of the ictal behavior was deliberately directed at trying to prevent the unpleasant sensations reaching his ears. [Published with video sequences]. PMID:18367430

  1. 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

  2. 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

  3. CSF biomarkers in neurodegenerative and vascular dementias.

    PubMed

    Llorens, Franc; Schmitz, Matthias; Ferrer, Isidro; Zerr, Inga

    2016-01-01

    Neurodegenerative diseases with abnormal protein aggregates such as Alzheimer's disease, tauopathies, synucleinopathies, and prionopathies, together with vascular encephalopathies, are cause of cognitive impairment and dementia. Identification of reliable biomarkers in biological fluids, particularly in the cerebrospinal fluid (CSF), is of extreme importance in optimizing the precise early clinical diagnosis of distinct entities and predicting the outcome in particular settings. In addition, the study of CSF biomarkers is useful to identify and monitor the underlying pathological processes developing in the central nervous system of affected individuals. Evidence suggests that levels of key CSF molecules correlate, in some circumstances, with prediction, disease progression, and severity of cognitive decline. Correlation of CSF markers and underlying pathological molecular substrates in brain is an exciting field for further study. However, while some dementias such as Creutzfeldt-Jakob disease have accurate CSF biomarkers, other disease types such as dementia with Lewy bodies, vascular dementia, and frontotemporal dementia lack reliable biomarkers for their specific clinical diagnosis. PMID:27016008

  4. 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

  5. Antisense Gene Silencing: Therapy for Neurodegenerative Disorders?

    PubMed Central

    Nielsen, Troels T.; Nielsen, Jørgen E.

    2013-01-01

    Since the first reports that double-stranded RNAs can efficiently silence gene expression in C. elegans, the technology of RNA interference (RNAi) has been intensively exploited as an experimental tool to study gene function. With the subsequent discovery that RNAi could also be applied to mammalian cells, the technology of RNAi expanded from being a valuable experimental tool to being an applicable method for gene-specific therapeutic regulation, and much effort has been put into further refinement of the technique. This review will focus on how RNAi has developed over the years and how the technique is exploited in a pre-clinical and clinical perspective in relation to neurodegenerative disorders. PMID:24705213

  6. Quantitative interaction proteomics of neurodegenerative disease proteins.

    PubMed

    Hosp, Fabian; Vossfeldt, Hannes; Heinig, Matthias; Vasiljevic, Djordje; Arumughan, Anup; Wyler, Emanuel; Landthaler, Markus; Hubner, Norbert; Wanker, Erich E; Lannfelt, Lars; Ingelsson, Martin; Lalowski, Maciej; Voigt, Aaron; Selbach, Matthias

    2015-05-19

    Several proteins have been linked to neurodegenerative disorders (NDDs), but their molecular function is not completely understood. Here, we used quantitative interaction proteomics to identify binding partners of Amyloid beta precursor protein (APP) and Presenilin-1 (PSEN1) for Alzheimer's disease (AD), Huntingtin (HTT) for Huntington's disease, Parkin (PARK2) for Parkinson's disease, and Ataxin-1 (ATXN1) for spinocerebellar ataxia type 1. Our network reveals common signatures of protein degradation and misfolding and recapitulates known biology. Toxicity modifier screens and comparison to genome-wide association studies show that interaction partners are significantly linked to disease phenotypes in vivo. Direct comparison of wild-type proteins and disease-associated variants identified binders involved in pathogenesis, highlighting the value of differential interactome mapping. Finally, we show that the mitochondrial protein LRPPRC interacts preferentially with an early-onset AD variant of APP. This interaction appears to induce mitochondrial dysfunction, which is an early phenotype of AD.

  7. How many biomarkers to discriminate neurodegenerative dementia?

    PubMed

    Sancesario, Giulia M; Bernardini, Sergio

    2015-01-01

    A number of cerebrospinal fluid (CSF) biomarkers are currently used for the diagnosis of dementia. Opposite changes in the level of amyloid-β(1-42) versus total tau and phosphorylated-tau181 in the CSF reflect the specific pathology of Alzheimer's disease (AD) in the brain. This panel of biomarkers has proven to be effective to differentiate AD from controls and from the major types of neurodegenerative dementia, and to evaluate the progression from mild cognitive impairment to AD. In the absence of specific biomarkers reflecting the pathologies of the other most common forms of dementia, such as Lewy Body disease, Frontotemporal lobar degeneration, Creutzfeldt-Jakob disease, etc., the evaluation of biomarkers of AD pathology is used, attempting to exclude rather than to confirm AD. Other biomarkers included in the common clinical practice do not clearly relate to the underlying pathology: progranulin (PGRN) is a selective marker of frontotemporal dementia with mutations in the PGRN gene; the 14-3-3 protein is a highly sensitive and specific marker for Creutzfeldt-Jakob disease, but has to be used carefully in differentiating rapid progressive dementia; and α-synuclein is an emerging candidate biomarker of the different forms of synucleinopathy. This review summarizes several biomarkers of neurodegenerative dementia validated based on the neuropathological processes occurring in brain tissue. Notwithstanding the paucity of pathologically validated biomarkers and their high analytical variability, the combinations of these biomarkers may well represent a key and more precise analytical and diagnostic tool in the complex plethora of degenerative dementia. PMID:26292074

  8. 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

  9. 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

  10. 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. PMID:26245316

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. 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

  18. 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. PMID:26601261

  19. 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

  20. 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.

  1. Clinical assessment of auditory dysfunction.

    PubMed Central

    Thomas, W G

    1982-01-01

    Many drugs, chemical substances and agents are potentially toxic to the human auditory system. The extent of toxicity depends on numerous factors. With few exceptions, toxicity in the auditory system affects various organs or cells within the cochlea or vestibular system, with brain stem and other central nervous system involvement reported with some chemicals and agents. This ototoxicity usually presents as a decrease in auditory sensitivity, tinnitus and/or vertigo or loss of balance. Classical and newer audiological techniques used in clinical assessment are beneficial in specifying the site of lesion in the cochlea, although auditory test results, themselves, give little information regarding possible pathology or etiology within the cochlea. Typically,, ototoxicity results in high frequency hearing loss, progressive as a function of frequency, usually accompanied by tinnitus and occasionally by vertigo or loss of balance. Auditory testing protocols are necessary to document this loss in auditory function. PMID:7044778

  2. 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.

  3. 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

  4. The Essential Complexity of Auditory Receptive Fields

    PubMed Central

    Thorson, Ivar L.; Liénard, Jean; David, Stephen V.

    2015-01-01

    Encoding properties of sensory neurons are commonly modeled using linear finite impulse response (FIR) filters. For the auditory system, the FIR filter is instantiated in the spectro-temporal receptive field (STRF), often in the framework of the generalized linear model. Despite widespread use of the FIR STRF, numerous formulations for linear filters are possible that require many fewer parameters, potentially permitting more efficient and accurate model estimates. To explore these alternative STRF architectures, we recorded single-unit neural activity from auditory cortex of awake ferrets during presentation of natural sound stimuli. We compared performance of > 1000 linear STRF architectures, evaluating their ability to predict neural responses to a novel natural stimulus. Many were able to outperform the FIR filter. Two basic constraints on the architecture lead to the improved performance: (1) factorization of the STRF matrix into a small number of spectral and temporal filters and (2) low-dimensional parameterization of the factorized filters. The best parameterized model was able to outperform the full FIR filter in both primary and secondary auditory cortex, despite requiring fewer than 30 parameters, about 10% of the number required by the FIR filter. After accounting for noise from finite data sampling, these STRFs were able to explain an average of 40% of A1 response variance. The simpler models permitted more straightforward interpretation of sensory tuning properties. They also showed greater benefit from incorporating nonlinear terms, such as short term plasticity, that provide theoretical advances over the linear model. Architectures that minimize parameter count while maintaining maximum predictive power provide insight into the essential degrees of freedom governing auditory cortical function. They also maximize statistical power available for characterizing additional nonlinear properties that limit current auditory models. PMID:26683490

  5. The Essential Complexity of Auditory Receptive Fields.

    PubMed

    Thorson, Ivar L; Liénard, Jean; David, Stephen V

    2015-12-01

    Encoding properties of sensory neurons are commonly modeled using linear finite impulse response (FIR) filters. For the auditory system, the FIR filter is instantiated in the spectro-temporal receptive field (STRF), often in the framework of the generalized linear model. Despite widespread use of the FIR STRF, numerous formulations for linear filters are possible that require many fewer parameters, potentially permitting more efficient and accurate model estimates. To explore these alternative STRF architectures, we recorded single-unit neural activity from auditory cortex of awake ferrets during presentation of natural sound stimuli. We compared performance of > 1000 linear STRF architectures, evaluating their ability to predict neural responses to a novel natural stimulus. Many were able to outperform the FIR filter. Two basic constraints on the architecture lead to the improved performance: (1) factorization of the STRF matrix into a small number of spectral and temporal filters and (2) low-dimensional parameterization of the factorized filters. The best parameterized model was able to outperform the full FIR filter in both primary and secondary auditory cortex, despite requiring fewer than 30 parameters, about 10% of the number required by the FIR filter. After accounting for noise from finite data sampling, these STRFs were able to explain an average of 40% of A1 response variance. The simpler models permitted more straightforward interpretation of sensory tuning properties. They also showed greater benefit from incorporating nonlinear terms, such as short term plasticity, that provide theoretical advances over the linear model. Architectures that minimize parameter count while maintaining maximum predictive power provide insight into the essential degrees of freedom governing auditory cortical function. They also maximize statistical power available for characterizing additional nonlinear properties that limit current auditory models. PMID:26683490

  6. 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.

  7. 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. PMID:26163900

  8. 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

  9. The Role of Oxidative Stress in Neurodegenerative Diseases

    PubMed Central

    Kim, Geon Ha; Kim, Jieun E.; Rhie, Sandy Jeong

    2015-01-01

    Oxidative stress is induced by an imbalanced redox states, involving either excessive generation of reactive oxygen species (ROS) or dysfunction of the antioxidant system. The brain is one of organs especially vulnerable to the effects of ROS because of its high oxygen demand and its abundance of peroxidation-susceptible lipid cells. Previous studies have demonstrated that oxidative stress plays a central role in a common pathophysiology of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Antioxidant therapy has been suggested for the prevention and treatment of neurodegenerative diseases, although the results with regard to their efficacy of treating neurodegenerative disease have been inconsistent. In this review, we will discuss the role of oxidative stress in the pathophysiology of neurodegenerative diseases and in vivo measurement of an index of damage by oxidative stress. Moreover, the present knowledge on antioxidant in the treatment of neurodegenerative diseases and future directions will be outlined. PMID:26713080

  10. 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. PMID:24478375

  11. 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

  12. microRNAs and Neurodegenerative Diseases.

    PubMed

    Qiu, Lifeng; Tan, Eng King; Zeng, Li

    2015-01-01

    microRNAs (miRNAs) are small, noncoding RNA molecules that through imperfect base-pairing with complementary sequences of target mRNA molecules, typically cleave target mRNA, causing subsequent degradation or translation inhibition. Although an increasing number of studies have identified misregulated miRNAs in the neurodegenerative diseases (NDDs) Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, which suggests that alterations in the miRNA regulatory pathway could contribute to disease pathogenesis, the molecular mechanisms underlying the pathological implications of misregulated miRNA expression and the regulation of the key genes involved in NDDs remain largely unknown. In this chapter, we provide evidence of the function and regulation of miRNAs and their association with the neurological events in NDDs. This will help improve our understanding of how miRNAs govern the biological functions of key pathogenic genes in these diseases, which potentially regulate several pathways involved in the progression of neurodegeneration. Additionally, given the growing interest in the therapeutic potential of miRNAs, we discuss current clinical challenges to developing miRNA-based therapeutics for NDDs.

  13. Adrenoleukodystrophy: new approaches to a neurodegenerative disease.

    PubMed

    Moser, Hugo W; Raymond, Gerald V; Dubey, Prachi

    2005-12-28

    X-linked adrenoleukodystrophy (X-ALD), which was first described in 1923, was viewed until 1976 as a rare and inexorably fatal neurodegenerative disorder that affected boys. The genetic defect and biochemical abnormalities have now been defined. Ongoing research has resulted in new findings: (1) there is a wide range of phenotypic expression. At least half of patients with X-ALD are adults with somewhat milder manifestations, and women who are carriers may become symptomatic. X-ALD is often misdiagnosed as attention-deficit/hyperactivity disorder in boys and as multiple sclerosis in men and women, and is not an uncommon cause of Addison disease; (2) the incidence of X-ALD, estimated to be 1:17,000 in all ethnic groups, approximates that of phenylketonuria; (3) noninvasive and presymptomatic diagnosis and prenatal diagnosis are available; family screening and genetic counseling are key to disease prevention; and (4) new therapies, applied early, show promise. Neonatal screening is likely to become available, and a wider awareness of X-ALD and its various modes of presentation permit new proactive approaches to this distressing disorder.

  14. Adaptive Immunity in Neurodegenerative and Neuropsychological Disorders.

    PubMed

    Mosley, R Lee

    2015-12-01

    Neurodegenerative and neuropsychological disorders are becoming a greater proportion of the global disease burden; however the pathogenic mechanisms by which these disorders originate and contribute to disease progression are not well-described. Increasing evidence supports neuroinflammation as a common underlying component associated with the neuropathological processes that effect disease progression. This collection of articles explores the role of adaptive immunity in autoimmunity, neurodegeneration, neurotrauma, and psychological disorders. The section emphasizes the interactions of T cells with innate cellular responses within the CNS and the effects on neurological functions. One recurrent theme is that modified and aggregated self-proteins upregulate innate-mediated inflammation and provide a permissive environment for polarization of T cells to proinflammatory effector cells. Moreover, infiltration and reactivation of those T effector cells exacerbate neuroinflammation and oxidative stress to greater neurotoxic levels. Another recurrent theme in these disorders promotes diminished regulatory functions that reduce control over activated T effector cells and microglia, and ultimately augment proinflammatory conditions. Augmentation of regulatory control is discussed as therapeutic strategies to attenuate neuroinflammation, mitigate neurodegeneration or neuronal dysfunction, and lessen disease progression.

  15. History of innate immunity in neurodegenerative disorders.

    PubMed

    McGeer, Patrick L; McGeer, Edith G

    2011-01-01

    The foundations of innate immunity in neurodegenerative disorders were first laid by Del Rio Hortega (1919). He identified and named microglia, recognizing them as cells of mesodermal origin. Van Furth in 1969 elaborated the monocyte phagocytic system with microglia as the brain representatives. Validation of these concepts did not occur until 1987 when HLA-DR was identified on activated microglia in a spectrum of neurological disorders. HLA-DR had already been established as a definitive marker of immunocompetent cells of mesodermal origin. It was soon determined that the observed inflammatory reaction was an innate immune response. A rapid expansion of the field took place as other markers of an innate immune response were found that were made by neurons, astrocytes, oligodendroglia, and endothelial cells. The molecules included complement proteins and their regulators, inflammatory cytokines, chemokines, acute phase reactants, prostaglandins, proteases, protease inhibitors, coagulation factors, fibrinolytic factors, anaphylatoxins, integrins, free radical generators, and other unidentified neurotoxins. The Nimmerjahn movies demonstrated that resting microglia were constantly active, sampling the surround, and responding rapidly to brain damage. Ways of reducing the neurotoxic innate immune response and stimulating a healing response continue to be sought as a means for ameliorating the pathology in a spectrum of chronic degenerative disorders. PMID:22144960

  16. 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

  17. Biomolecular Modulation of Neurodegenerative Events during Ageing.

    PubMed

    Nebbioso, Marcella; Scarsella, Gianfranco; Librando, Aloisa; Pescosolido, Nicola

    2015-01-01

    The objective is to assess the modulation of retinal and optic nerve degenerative events induced by the combination of α-lipoic acid (ALA) and superoxide dismutase (SOD) in an animal model of ageing. For this study, 24 male Wistar-Harlan strain rats were left to age for up to 24 months. One group of rats was subjected to a diet supplemented with ALA and SOD for 8 weeks, while another group was used as a positive control and not subjected to any dietary treatment. To assess the cytoprotective effects of the antioxidants, a morphological analysis was carried out on sections of retina and optic nerve head, stained with haematoxylin-eosin, followed by an analysis of the modifications to nuclear DNA detected by the TUNEL technique. The lipid peroxidation assay was used to assess the damage induced by oxidative stress at cell membrane level. The molecules involved in apoptosis mediated by oxidative stress, such as caspase-3 and inducible nitric oxide synthase, were also assayed by immunolocalization and western blot. ALA and SOD are able to counteract senile neurodegenerative deterioration to the retina and optic nerve. Indeed, the combination of these antioxidant molecules can reduce oxidative stress levels and thus prevent both nuclear degradation and subsequent cell death.

  18. Structural anatomy of empathy in neurodegenerative disease.

    PubMed

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

    2006-11-01

    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.

  19. Biomolecular Modulation of Neurodegenerative Events during Ageing

    PubMed Central

    Nebbioso, Marcella; Scarsella, Gianfranco; Librando, Aloisa; Pescosolido, Nicola

    2015-01-01

    The objective is to assess the modulation of retinal and optic nerve degenerative events induced by the combination of α-lipoic acid (ALA) and superoxide dismutase (SOD) in an animal model of ageing. For this study, 24 male Wistar-Harlan strain rats were left to age for up to 24 months. One group of rats was subjected to a diet supplemented with ALA and SOD for 8 weeks, while another group was used as a positive control and not subjected to any dietary treatment. To assess the cytoprotective effects of the antioxidants, a morphological analysis was carried out on sections of retina and optic nerve head, stained with haematoxylin-eosin, followed by an analysis of the modifications to nuclear DNA detected by the TUNEL technique. The lipid peroxidation assay was used to assess the damage induced by oxidative stress at cell membrane level. The molecules involved in apoptosis mediated by oxidative stress, such as caspase-3 and inducible nitric oxide synthase, were also assayed by immunolocalization and western blot. ALA and SOD are able to counteract senile neurodegenerative deterioration to the retina and optic nerve. Indeed, the combination of these antioxidant molecules can reduce oxidative stress levels and thus prevent both nuclear degradation and subsequent cell death. PMID:26583065

  20. Apolipoprotein E genotype in diverse neurodegenerative disorders.

    PubMed

    Schneider, J A; Gearing, M; Robbins, R S; de l'Aune, W; Mirra, S S

    1995-07-01

    While the apolipoprotein E (ApoE) epsilon 4 allele is a recognized risk factor for Alzheimer's disease (AD), an association of epsilon 4 with other neurodegenerative diseases (NDs) has not been extensively explored. We examined 51 cases of neuropathologically confirmed ND. After eliminating 18 cases exhibiting pathology sufficient to warrant an additional diagnosis of AD, three disorders characterized by tau-related cytoskeletal pathology, i.e., Pick's disease, corticobasal degeneration, and progressive supra-nuclear palsy, showed increased epsilon 4 frequencies. Since the number of cases within each category was small, these increased epsilon 4 frequencies were not statistically significant. beta-Amyloid (beta A4) immunoreactive diffuse plaques were observed in many of these cases. While we cannot eliminate the possibility that these patients were destined to develop AD, these changes may merely reflect an independent association of epsilon 4 with amyloid deposition. These preliminary data affirm the need for further study of well-characterized cases to explore the relationship of ApoE to cytoskeletal pathology and ND. PMID:7611717

  1. Neuromechanistic Model of Auditory Bistability

    PubMed Central

    Rankin, James; Sussman, Elyse; Rinzel, John

    2015-01-01

    Sequences of higher frequency A and lower frequency B tones repeating in an ABA- triplet pattern are widely used to study auditory streaming. One may experience either an integrated percept, a single ABA-ABA- stream, or a segregated percept, separate but simultaneous streams A-A-A-A- and -B---B--. During minutes-long presentations, subjects may report irregular alternations between these interpretations. We combine neuromechanistic modeling and psychoacoustic experiments to study these persistent alternations and to characterize the effects of manipulating stimulus parameters. Unlike many phenomenological models with abstract, percept-specific competition and fixed inputs, our network model comprises neuronal units with sensory feature dependent inputs that mimic the pulsatile-like A1 responses to tones in the ABA- triplets. It embodies a neuronal computation for percept competition thought to occur beyond primary auditory cortex (A1). Mutual inhibition, adaptation and noise are implemented. We include slow NDMA recurrent excitation for local temporal memory that enables linkage across sound gaps from one triplet to the next. Percepts in our model are identified in the firing patterns of the neuronal units. We predict with the model that manipulations of the frequency difference between tones A and B should affect the dominance durations of the stronger percept, the one dominant a larger fraction of time, more than those of the weaker percept—a property that has been previously established and generalized across several visual bistable paradigms. We confirm the qualitative prediction with our psychoacoustic experiments and use the behavioral data to further constrain and improve the model, achieving quantitative agreement between experimental and modeling results. Our work and model provide a platform that can be extended to consider other stimulus conditions, including the effects of context and volition. PMID:26562507

  2. 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…

  3. 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…

  4. Duration tuning in the mouse auditory midbrain.

    PubMed

    Brand, A; Urban, R; Grothe, B

    2000-10-01

    Temporal cues, including sound duration, are important for sound identification. Neurons tuned to the duration of pure tones were first discovered in the auditory system of frogs and bats and were discussed as specific adaptations in these animals. More recently duration sensitivity has also been described in the chinchilla midbrain and the cat auditory cortex, indicating that it might be a more general phenomenon than previously thought. However, it is unclear whether duration tuning in mammals is robust in face of changes of stimulus parameters other than duration. Using extracellular single-cell recordings in the mouse inferior colliculus, we found 55% of cells to be sensitive to stimulus duration showing long-pass, short-pass, or band-pass filter characteristics. For most neurons, a change in some other stimulus parameter, (e.g., intensity, frequency, binaural conditions, or using noise instead of pure tones) altered and sometimes abolished duration-tuning characteristics. Thus in many neurons duration tuning is interdependent with other stimulus parameters and, hence, might be context dependent. A small number of inferior colliculus neurons, in particular band-pass neurons, exhibited stable filter characteristics and could therefore be referred to as "duration selective." These findings support the idea that duration tuning is a general phenomenon in the mammalian auditory system.

  5. Motor induced suppression of auditory cortex

    PubMed Central

    Aliu, Sheye O.; Houde, John F.; Nagarajan, Srikantan S.

    2010-01-01

    Sensory responses to stimuli that are triggered by a self-initiated motor act are suppressed when compared with the response to the same stimuli triggered externally, a phenomenon referred to as motor-induced suppression (MIS) of sensory cortical feedback. Studies in the somatosensory system suggest that such suppression might be sensitive to delays between the motor act and the stimulus-onset, and a recent study in the auditory system suggests that such MIS develops rapidly. In three MEG experiments, we characterize the properties of MIS, by examining the M100 response from the auditory cortex to a simple tone triggered by a button press. In Experiment 1, we found that MIS develops for zero-delays but does not generalize to non-zero delays. In Experiment 2, we found that MIS developed for 100 ms delays within 300 trials and occurs in excess of auditory habituation. In Experiment 3, we found that unlike MIS for zero-delays, MIS for non-zero delays does not exhibit sensitivity to sensory, delay or motor-command changes. These results are discussed in relation to suppression to self-produced speech and a general model of sensory motor control. PMID:18593265

  6. 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

  7. Delayed auditory feedback in polyglot simultaneous interpreters.

    PubMed

    Fabbro, F; Darò, V

    1995-03-01

    Twelve polyglot students of simultaneous interpretation and 12 controls (students of the faculty of Medicine) were submitted to a task of verbal fluency under amplified normal auditory feedback (NAF) and under three delayed auditory feedback (DAF) conditions with three different delay intervals (150, 200, and 250 msec). The control group showed a significant reduction in verbal fluency and a significant increase in the number of mistakes in all three DAF conditions. The interpreters' group, however, did not show any significant speech disruption neither in the subjects' mother tongue (L1) nor in their second language (L2) across all DAF conditions. Interpreters' general high verbal fluency along with their ability to pay less attention to their own verbal output make them more resistant to the interfering effects of DAF on speech. PMID:7757448

  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. 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.

  11. Mitochondria as a Therapeutic Target for Aging and Neurodegenerative Diseases

    PubMed Central

    Reddy, P. Hemachandra; Reddy, Tejaswini P.

    2012-01-01

    Mitochondria are cytoplasmic organelles responsible for life and death. Extensive evidence from animal models, postmortem brain studies of and clinical studies of aging and neurodegenerative diseases suggests that mitochondrial function is defective in aging and neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. Several lines of research suggest that mitochondrial abnormalities, including defects in oxidative phosphorylation, increased accumulation of mitochondrial DNA defects, impaired calcium influx, accumulation of mutant proteins in mitochondria, and mitochondrial membrane potential dissipation are important cellular changes in both early and late-onset neurodegenerative diseases. Further, emerging evidence suggests that structural changes in mitochondria, including increased mitochondrial fragmentation and decreased mitochondrial fusion, are critical factors associated with mitochondrial dysfunction and cell death in aging and neurodegenerative diseases. This paper discusses research that elucidates features of mitochondria that are associated with cellular dysfunction in aging and neurodegenerative diseases and discusses mitochondrial structural and functional changes, and abnormal mitochondrial dynamics in neurodegenerative diseases. It also outlines mitochondria-targeted therapeutics in neurodegenerative diseases. PMID:21470101

  12. Midbrain auditory selectivity to natural sounds

    PubMed Central

    Moss, Cynthia F.

    2016-01-01

    This study investigated auditory stimulus selectivity in the midbrain superior colliculus (SC) of the echolocating bat, an animal that relies on hearing to guide its orienting behaviors. Multichannel, single-unit recordings were taken across laminae of the midbrain SC of the awake, passively listening big brown bat, Eptesicus fuscus. Species-specific frequency-modulated (FM) echolocation sound sequences with dynamic spectrotemporal features served as acoustic stimuli along with artificial sound sequences matched in bandwidth, amplitude, and duration but differing in spectrotemporal structure. Neurons in dorsal sensory regions of the bat SC responded selectively to elements within the FM sound sequences, whereas neurons in ventral sensorimotor regions showed broad response profiles to natural and artificial stimuli. Moreover, a generalized linear model (GLM) constructed on responses in the dorsal SC to artificial linear FM stimuli failed to predict responses to natural sounds and vice versa, but the GLM produced accurate response predictions in ventral SC neurons. This result suggests that auditory selectivity in the dorsal extent of the bat SC arises through nonlinear mechanisms, which extract species-specific sensory information. Importantly, auditory selectivity appeared only in responses to stimuli containing the natural statistics of acoustic signals used by the bat for spatial orientation—sonar vocalizations—offering support for the hypothesis that sensory selectivity enables rapid species-specific orienting behaviors. The results of this study are the first, to our knowledge, to show auditory spectrotemporal selectivity to natural stimuli in SC neurons and serve to inform a more general understanding of mechanisms guiding sensory selectivity for natural, goal-directed orienting behaviors. PMID:26884152

  13. Midbrain auditory selectivity to natural sounds.

    PubMed

    Wohlgemuth, Melville J; Moss, Cynthia F

    2016-03-01

    This study investigated auditory stimulus selectivity in the midbrain superior colliculus (SC) of the echolocating bat, an animal that relies on hearing to guide its orienting behaviors. Multichannel, single-unit recordings were taken across laminae of the midbrain SC of the awake, passively listening big brown bat, Eptesicus fuscus. Species-specific frequency-modulated (FM) echolocation sound sequences with dynamic spectrotemporal features served as acoustic stimuli along with artificial sound sequences matched in bandwidth, amplitude, and duration but differing in spectrotemporal structure. Neurons in dorsal sensory regions of the bat SC responded selectively to elements within the FM sound sequences, whereas neurons in ventral sensorimotor regions showed broad response profiles to natural and artificial stimuli. Moreover, a generalized linear model (GLM) constructed on responses in the dorsal SC to artificial linear FM stimuli failed to predict responses to natural sounds and vice versa, but the GLM produced accurate response predictions in ventral SC neurons. This result suggests that auditory selectivity in the dorsal extent of the bat SC arises through nonlinear mechanisms, which extract species-specific sensory information. Importantly, auditory selectivity appeared only in responses to stimuli containing the natural statistics of acoustic signals used by the bat for spatial orientation-sonar vocalizations-offering support for the hypothesis that sensory selectivity enables rapid species-specific orienting behaviors. The results of this study are the first, to our knowledge, to show auditory spectrotemporal selectivity to natural stimuli in SC neurons and serve to inform a more general understanding of mechanisms guiding sensory selectivity for natural, goal-directed orienting behaviors. PMID:26884152

  14. Midbrain auditory selectivity to natural sounds.

    PubMed

    Wohlgemuth, Melville J; Moss, Cynthia F

    2016-03-01

    This study investigated auditory stimulus selectivity in the midbrain superior colliculus (SC) of the echolocating bat, an animal that relies on hearing to guide its orienting behaviors. Multichannel, single-unit recordings were taken across laminae of the midbrain SC of the awake, passively listening big brown bat, Eptesicus fuscus. Species-specific frequency-modulated (FM) echolocation sound sequences with dynamic spectrotemporal features served as acoustic stimuli along with artificial sound sequences matched in bandwidth, amplitude, and duration but differing in spectrotemporal structure. Neurons in dorsal sensory regions of the bat SC responded selectively to elements within the FM sound sequences, whereas neurons in ventral sensorimotor regions showed broad response profiles to natural and artificial stimuli. Moreover, a generalized linear model (GLM) constructed on responses in the dorsal SC to artificial linear FM stimuli failed to predict responses to natural sounds and vice versa, but the GLM produced accurate response predictions in ventral SC neurons. This result suggests that auditory selectivity in the dorsal extent of the bat SC arises through nonlinear mechanisms, which extract species-specific sensory information. Importantly, auditory selectivity appeared only in responses to stimuli containing the natural statistics of acoustic signals used by the bat for spatial orientation-sonar vocalizations-offering support for the hypothesis that sensory selectivity enables rapid species-specific orienting behaviors. The results of this study are the first, to our knowledge, to show auditory spectrotemporal selectivity to natural stimuli in SC neurons and serve to inform a more general understanding of mechanisms guiding sensory selectivity for natural, goal-directed orienting behaviors.

  15. 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

  16. Drosophila as a model for human neurodegenerative disease.

    PubMed

    Bilen, Julide; Bonini, Nancy M

    2005-01-01

    Among many achievements in the neurodegeneration field in the past decade, two require special attention due to the huge impact on our understanding of molecular and cellular pathogenesis of human neurodegenerative diseases. First is defining specific mutations in familial neurodegenerative diseases and second is modeling these diseases in easily manipulable model organisms including the fruit fly, nematode, and yeast. The power of these genetic systems has revealed many genetic factors involved in the various pathways affected, as well as provided potential drug targets for therapeutics. This review focuses on fruit fly models of human neurodegenerative diseases, with emphasis on how fly models have provided new insights into various aspects of human diseases.

  17. Molecular imaging of stem cell transplantation for neurodegenerative diseases.

    PubMed

    Wang, Ping; Moore, Anna

    2012-01-01

    Cell replacement therapy with stem cells holds tremendous therapeutic potential for treating neurodegenerative diseases. Over the last decade, molecular imaging techniques have proven to be of great value in tracking transplanted cells and assessing the therapeutic efficacy. This current review summarizes the role and capabilities of different molecular imaging modalities including optical imaging, nuclear imaging and magnetic resonance imaging in the field of stem cell therapy for neurodegenerative disorders. We discuss current challenges and perspectives of these techniques and encompass updated information such as theranostic imaging and optogenetics in stem cell-based treatment of neurodegenerative diseases.

  18. Auditory induction of discrete tones in signal detection tasks

    NASA Astrophysics Data System (ADS)

    Bennett, K. B.; Parasuraman, R.; Howard, J. H., Jr.; Otoole, A. J.

    1983-10-01

    Auditory induction is the apparent continuation of a fainter sound when alternated rapidly with a more intense interrupting sound. In the present study induction of discrete (non-alternating) tones by contextual tones was examined in three experiments using signal detection methods. Listeners were asked to detect pure tone signals of constant, rising, or falling frequency embedded in noise bursts. The noise bursts were preceded and followed by contextual tones that were designed to produce a constant or changing frequency context. Results indicated that auditory induction is a general factor influencing auditory perception and can be demonstrated either for discrete as well as continuous presentation of sounds. While induction of missing sounds can be beneficial, especially in speech perception, auditory induction can also impair perceptual performance, particularly in monitoring nonspeech sounds for faint signals. Finally, auditory-induction effects can be distinguished from peripheral-masking effects, and although a relation between auditory induction and central masking cannot be ruled out, induction and masking appear to be separate, independent factors, one largely central, and other largely peripheral in nature.

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

    PubMed

    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

  20. 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

  1. Presentation of dynamically overlapping auditory messages in user interfaces

    SciTech Connect

    Papp, A.L.

    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

  2. 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…

  3. Why neurodegenerative diseases are progressive: uncontrolled inflammation drives disease progression

    PubMed Central

    Gao, Hui-Ming; Hong, Jau-Shyong

    2016-01-01

    Neurodegenerative diseases are a group of chronic, progressive disorders characterized by the gradual loss of neurons in discrete areas of the central nervous system (CNS). The mechanism(s) underlying their progressive nature remains unknown but a timely and well-controlled inflammatory reaction is essential for the integrity and proper function of the CNS. Substantial evidence has documented a common inflammatory mechanism in various neurodegenerative diseases. We hypothesize that in the diseased CNS, interactions between damaged neurons and dysregulated, overactivated microglia create a vicious self-propagating cycle causing uncontrolled, prolonged inflammation that drives the chronic progression of neurodegenerative diseases. We further propose that dynamic modulation of this inflammatory reaction by interrupting the vicious cycle might become a disease-modifying therapeutic strategy for neurodegenerative diseases. PMID:18599350

  4. 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

  5. A network approach to clinical intervention in neurodegenerative diseases.

    PubMed

    Santiago, Jose A; Potashkin, Judith A

    2014-12-01

    Network biology has become a powerful tool to dissect the molecular mechanisms triggering neurodegeneration. Recent developments in network biology have led to the discovery of disease-causing genes, diagnostic biomarkers, and therapeutic targets for several neurodegenerative diseases including Alzheimer's, Parkinson's, and Huntington's diseases. Network-based approaches have provided the molecular rationale for the relationship among cancer, diabetes, and neurodegenerative diseases, and have uncovered unexpected links between apparently unrelated diseases. Here, we summarize the recent advances in network biology to untangle the molecular underpinnings giving rise to the most prevalent neurodegenerative diseases. We propose that network analysis provides a feasible and practical tool for identifying biologically meaningful biomarkers and potential therapeutic targets for clinical intervention in neurodegenerative diseases. PMID:25455073

  6. Neurodegenerative disease-specific induced pluripotent stem cell research.

    PubMed

    Inoue, Haruhisa

    2010-10-01

    Neurodegenerative disease-specific induced pluripotent stem cell (iPSC) research contributes to the following 3 areas; "Disease modeling", "Disease material" and "Disease therapy". "Disease modeling", by recapitulating the disease phenotype in vitro, will reveal the pathomechanisms. Neurodegenerative disease-specific iPSC-derived non-neuronal cells harboring disease-causative protein(s), which play critical roles in neurodegeneration including motor neuron degeneration in amyotrophic lateral sclerosis, could be "Disease material", the target cell(s) for drug screening. These differentiated cells also could be used for "Disease therapy", an autologous cellular replacement/neuroprotection strategy, for patients with neurodegenerative disease. Further progress in these areas of research can be made for currently incurable neurodegenerative diseases.

  7. Stem cell therapy in neurodegenerative diseases: From principles to practice.

    PubMed

    Sakthiswary, Rajalingham; Raymond, Azman Ali

    2012-08-15

    The lack of curative therapies for neurodegenerative diseases has high economic impact and places huge burden on the society. The contribution of stem cells to cure neurodegenerative diseases has been unraveled and explored extensively over the past few years. Beyond substitution of the lost neurons, stem cells act as immunomodulators and neuroprotectors. A large number of preclinical and a small number of clinical studies have shown beneficial outcomes in this context. In this review, we have summarized the current concepts of stem cell therapy in neurodegenerative diseases and the recent advances in this field, particularly between 2010 and 2012. Further studies should be encouraged to resolve the clinical issues and vague translational findings for maximum optimization of the efficacy of stem cell therapy in neurodegenerative diseases.

  8. Auditory hallucinations treated by radio headphones.

    PubMed

    Feder, R

    1982-09-01

    A young man with chronic auditory hallucinations was treated according to the principle that increasing external auditory stimulation decreases the likelihood of auditory hallucinations. Listening to a radio through stereo headphones in conditions of low auditory stimulation eliminated the patient's hallucinations.

  9. Language Development Activities through the Auditory Channel.

    ERIC Educational Resources Information Center

    Fitzmaurice, Peggy, Comp.; And Others

    Presented primarily for use with educable mentally retarded and learning disabled children are approximately 100 activities for language development through the auditory channel. Activities are grouped under the following three areas: receptive skills (auditory decoding, auditory memory, and auditory discrimination); expressive skills (auditory…

  10. 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

  11. Matrix Metalloproteinases, New Insights into the Understanding of Neurodegenerative Disorders

    PubMed Central

    Kim, Yoon-Seong; Joh, Tong H.

    2012-01-01

    Matrix metalloproteinases (MMPs) are a subfamily of zinc-dependent proteases that are responsible for degradation and remodeling of extracellular matrix proteins. The activity of MMPs is tightly regulated at several levels including cleavage of prodomain, allosteric activation, compartmentalization and complex formation with tissue inhibitor of metalloproteinases (TIMPs). In the central nervous system (CNS), MMPs play a wide variety of roles ranging from brain development, synaptic plasticity and repair after injury to the pathogenesis of various brain disorders. Following general discussion on the domain structure and the regulation of activity of MMPs, we emphasize their implication in various brain disorder conditions such as Alzheimer’s disease, multiple sclerosis, ischemia/reperfusion and Parkinson’s disease. We further highlight accumulating evidence that MMPs might be the culprit in Parkinson’s disease (PD). Among them, MMP-3 appears to be involved in a range of pathogenesis processes in PD including neuroinflammation, apoptosis and degradation of α-synuclein and DJ-1. MMP inhibitors could represent potential novel therapeutic strategies for treatments of neurodegenerative diseases. PMID:24116286

  12. Auditory Discrimination Learning: Role of Working Memory.

    PubMed

    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

  13. Reprogramming therapeutics: iPS cell prospects for neurodegenerative disease.

    PubMed

    Abeliovich, Asa; Doege, Claudia A

    2009-02-12

    The recent description of somatic cell reprogramming to an embryonic stem (ES) cell-like phenotype, termed induced pluripotent stem (iPS) cell technology, presents an exciting potential venue toward cell-based therapeutics and disease models for neurodegenerative disorders. Two recent studies (Dimos et al. and Ebert et al.) describe the initial characterization of neurodegenerative disease patient-derived iPS cell cultures as proof of concept for the utility of this technology.

  14. 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

  15. 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. PMID:25822973

  16. 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

  17. Immunotherapy for neurodegenerative diseases: focus on α-synucleinopathies

    PubMed Central

    Valera, Elvira; Masliah, Eliezer

    2013-01-01

    Immunotherapy is currently being intensively explored as much-needed disease-modifying treatment for neurodegenerative diseases. While Alzheimer’s disease (AD) has been the focus of numerous immunotherapeutic studies, less attention has been paid to Parkinson’s disease (PD) and other neurodegenerative disorders. The reason for this difference is that the amyloid beta (Aβ) protein in AD is a secreted molecule that circulates in blood and is readably recognized by antibodies. In contrast, α-synuclein (α-syn), tau, huntingtin and other proteins involved in neurodegenerative diseases have been considered to be exclusively of intracellular nature. However, the recent discovery that toxic oligomeric versions of α-syn and tau accumulate in the membrane and can be excreted to the extracellular environment has provided a rationale for the development of immunotherapeutic approaches for PD, dementia with Lewy bodies, frontotemporal dementia, and other neurodegenerative disorders characterized by the abnormal accumulation of these proteins. Active immunization, passive immunization, and T cell-mediated cellular immunotherapeutic approaches have been developed targeting Aβ, α-syn and tau. Most advanced studies, including results from phase III clinical trials for passive immunization in AD, have been recently reported. Results suggest that immunotherapy might be a promising therapeutic approach for neurodegenerative diseases that progress with the accumulation and propagation of toxic protein aggregates. In this manuscript we provide an overview on immunotherapeutic advances for neurodegenerative disorders, with special emphasis on α-synucleinopathies. PMID:23384597

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. 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

  3. Auditory Processing Disorder in Children

    MedlinePlus

    ... free publications Find organizations Related Topics Auditory Neuropathy Autism Spectrum Disorder: Communication Problems in Children Dysphagia Quick ... NIH… Turning Discovery Into Health ® National Institute on Deafness and Other Communication Disorders 31 Center Drive, MSC ...

  4. Leiomyoma of External Auditory Canal.

    PubMed

    George, M V; Puthiyapurayil, Jamsheeda

    2016-09-01

    This article reports a case of piloleiomyoma of external auditory canal, which is the 7th case of leiomyoma of the external auditory canal being reported and the 2nd case of leiomyoma arising from arrectores pilorum muscles, all the other five cases were angioleiomyomas, arising from blood vessels. A 52 years old male presented with a mass in the right external auditory canal and decreased hearing of 6 months duration. Tumor excision done by end aural approach. Histopathological examination report was leiomyoma. It is extremely rare for leiomyoma to occur in the external auditory canal because of the non-availability of smooth muscles in the external canal. So it should be considered as a very rare differential diagnosis for any tumor or polyp in the ear canal. PMID:27508144

  5. 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)

  6. Maps of the Auditory Cortex.

    PubMed

    Brewer, Alyssa A; Barton, Brian

    2016-07-01

    One of the fundamental properties of the mammalian brain is that sensory regions of cortex are formed of multiple, functionally specialized cortical field maps (CFMs). Each CFM comprises two orthogonal topographical representations, reflecting two essential aspects of sensory space. In auditory cortex, auditory field maps (AFMs) are defined by the combination of tonotopic gradients, representing the spectral aspects of sound (i.e., tones), with orthogonal periodotopic gradients, representing the temporal aspects of sound (i.e., period or temporal envelope). Converging evidence from cytoarchitectural and neuroimaging measurements underlies the definition of 11 AFMs across core and belt regions of human auditory cortex, with likely homology to those of macaque. On a macrostructural level, AFMs are grouped into cloverleaf clusters, an organizational structure also seen in visual cortex. Future research can now use these AFMs to investigate specific stages of auditory processing, key for understanding behaviors such as speech perception and multimodal sensory integration. PMID:27145914

  7. 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

  8. 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

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

    PubMed

    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

  10. 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

  11. 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

  12. Is there evidence for neurodegenerative change following traumatic brain injury in children and youth? A scoping review

    PubMed Central

    Keightley, Michelle L.; Sinopoli, Katia J.; Davis, Karen D.; Mikulis, David J.; Wennberg, Richard; Tartaglia, Maria C.; Chen, Jen-Kai; Tator, Charles H.

    2014-01-01

    While generalized cerebral atrophy and neurodegenerative change following traumatic brain injury (TBI) is well recognized in adults, it remains comparatively understudied in the pediatric population, suggesting that research should address the potential for neurodegenerative change in children and youth following TBI. This focused review examines original research findings documenting evidence for neurodegenerative change following TBI of all severities in children and youth. Our relevant inclusion and exclusion criteria identified a total of 16 articles for review. Taken together, the studies reviewed suggest there is evidence for long-term neurodegenerative change following TBI in children and youth. In particular both cross-sectional and longitudinal studies revealed volume loss in selected brain regions including the hippocampus, amygdala, globus pallidus, thalamus, periventricular white matter, cerebellum, and brain stem as well as overall decreased whole brain volume and increased CSF and ventricular space. Diffusion Tensor Imaging (DTI) studies also report evidence for decreased cellular integrity, particularly in the corpus callosum. Sensitivity of the hippocampus and deep limbic structures in pediatric populations are similar to findings in the adult literature and we consider the data supporting these changes as well as the need to investigate the possibility of neurodegenerative onset in childhood associated with mild traumatic brain injury (mTBI). PMID:24678292

  13. Effectiveness of direct and non-direct auditory stimulation on coma arousal after traumatic brain injury.

    PubMed

    Park, Soohyun; Davis, Alice E

    2016-08-01

    The aim of this study was to evaluate the effect of direct and non-direct auditory stimulation on arousal in coma patients with severe traumatic brain injury and to compare the effects of direct vs. non-direct auditory stimulation. A crossover intervention study design was used. Nine participants who were comatose after a severe traumatic brain injury underwent direct and non-direct auditory stimulation. Direct auditory stimulation requires a higher level of interpersonal interaction between the patient and stimuli such as voices of family members, orientation by a nurse or family member and familiar music. In contrast, non-direct auditory stimuli were characterized as more general, less familiar, less interactive, indirect and not lively such as general music and TV sounds. Participants received both direct and non-direct auditory stimulation in randomized order for 15 minutes. Recovery of consciousness was measured with the Glasgow Coma Scale (GCS) and Sensory Stimulation Assessment Measure (SSAM). The Friedman test with post hoc analysis by Wilcoxon's signed-rank test comparisons was used for data analysis. Patients who received both direct and non-direct auditory stimulation exhibited significantly increased GCS (p = 0.008) and SSAM scores (p = 0.008) over baseline. The improvement in SSAM scores after direct auditory stimulation was significantly greater than that after non-direct auditory stimulation (p = 0.021), but there was no statistically significant difference in GCS scores (p = 0.139). Auditory stimulation, in particular direct auditory stimulation, might be useful for improving the recovery of consciousness and increasing the arousal of comatose patients. The SSAM is more useful for detecting subtle changes from stimulation intervention than the GCS. PMID:27241789

  14. Stem cell-based models and therapies for neurodegenerative diseases.

    PubMed

    Iyer, Shilpa; Alsayegh, Khaled; Abraham, Sheena; Rao, Raj R

    2009-01-01

    Multiple neurodegenerative disorders typically result from irrevocable damage and improper functioning of specialized neuronal cells or populations of neuronal cells. These disorders have the potential to contribute to an already overburdened health care system unless the progression of neurodegeneration can be altered. Progress in understanding neurodegenerative cell biology has been hampered by a lack of predictive and, some would claim, relevant cellular models. Additionally, the research needed to develop new drugs and determine methods for repair or replacement of damaged neurons is severely hampered by the lack of an adequate in vitro human neuron cell-based model. In this context, pluripotent stem cells and neural progenitors and their properties including unlimited proliferation, plasticity to generate other cell types, and a readily available source of cells--pose an excellent alternative to ex vivo primary cultures or established immortalized cell lines in contributing to our understanding of neurodegenerative cell biology and our ability to analyze the therapeutic or cytotoxic effects of chemicals, drugs, and xenobiotics. Many questions that define the underlying "genesis" of the neuronal death in these disorders also remain unanswered, with evidence suggesting a key role for mitochondrial dysfunction. The assessment of stem cells, neural progenitors, and engineered adult cells can provide useful insights into neuronal development and neurodegenerative processes. Finally, the potential for a combination of cell- and gene-based therapeutics for neurodegenerative disorders is also discussed.

  15. 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…

  16. Teaching Vocational Skills with a Faded Auditory Prompting System.

    ERIC Educational Resources Information Center

    Mitchell, Rebecca J.; Schuster, John W.; Collins, Belva C.; Gassaway, Linda J.

    2000-01-01

    Three students (ages 14-16) with mild mental retardation were taught to use an auditory prompting system to complete the vocational tasks of cleaning a bathroom in a classroom setting. Students acquired the skills and generalized them to a novel setting. There were mixed results concerning maintenance of the skills. (Contains 10 references.)…

  17. 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…

  18. External auditory osteoma.

    PubMed

    Carbone, Peter N; Nelson, Brenda L

    2012-06-01

    External auditory canal (EAC) osteomas are rare, benign bony neoplasms that occur in wide range of patients. While chronic irritation and inflammation have been suggested as causal factors in several cases, significant data is lacking to support these suspicions. Symptoms are rare and can include hearing loss, vertigo, pain and tinnitus. Diagnosis is made based on a combination of clinical history and examination, radiographic imaging, and histopathology. Osteomas of the EAC are usually found incidentally and are unilateral and solitary. Computed tomography reveals a hyperdense, pedunculated mass arising from the tympanosquamous suture and lateral of the isthmus. Histopathologically, EAC osteomas are covered with periosteum and squamous epithelium, and consist of lamalleted bone surrounding fibrovascular channels with minimal osteocysts. Osteomas have historically been compared and contrasted with exostoses of the EAC. While they share similarities, more often than not it is possible to distinguish the two bony neoplasms based on clinical history and radiographic studies. Debate remains in the medical literature as to whether basic histopathology can distinguish osteomas of the EAC from exostoses. Surgical excision is the standard treatment for EAC osteomas, however close observation is considered acceptable in asymptomatic patients.

  19. 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.

  20. 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. PMID:25230228

  1. 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

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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

  7. Auditory hallucinations: A review of the ERC "VOICE" project.

    PubMed

    Hugdahl, Kenneth

    2015-06-22

    In this invited review I provide a selective overview of recent research on brain mechanisms and cognitive processes involved in auditory hallucinations. The review is focused on research carried out in the "VOICE" ERC Advanced Grant Project, funded by the European Research Council, but I also review and discuss the literature in general. Auditory hallucinations are suggested to be perceptual phenomena, with a neuronal origin in the speech perception areas in the temporal lobe. The phenomenology of auditory hallucinations is conceptualized along three domains, or dimensions; a perceptual dimension, experienced as someone speaking to the patient; a cognitive dimension, experienced as an inability to inhibit, or ignore the voices, and an emotional dimension, experienced as the "voices" having primarily a negative, or sinister, emotional tone. I will review cognitive, imaging, and neurochemistry data related to these dimensions, primarily the first two. The reviewed data are summarized in a model that sees auditory hallucinations as initiated from temporal lobe neuronal hyper-activation that draws attentional focus inward, and which is not inhibited due to frontal lobe hypo-activation. It is further suggested that this is maintained through abnormal glutamate and possibly gamma-amino-butyric-acid transmitter mediation, which could point towards new pathways for pharmacological treatment. A final section discusses new methods of acquiring quantitative data on the phenomenology and subjective experience of auditory hallucination that goes beyond standard interview questionnaires, by suggesting an iPhone/iPod app.

  8. 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. PMID:27622211

  9. RNA processing-associated molecular mechanisms of neurodegenerative diseases.

    PubMed

    Tang, Anna Y

    2016-08-01

    Dysfunctions of RNA processing and mutations of RNA binding proteins (RBPs) play a fundamental role in the pathogenesis of many neurodegenerative diseases. To elucidate the function of RNA processing and RBPs mutations in neuronal cells and to increase our understanding on the pathogenic mechanisms of neurodegeneration, I have reviewed recent advances on RNA processing-associated molecular mechanisms of neurodegenerative diseases, including RBPs-mediated dysfunction of RNA processing, dysfunctional microRNA (miRNA)-based regulation of gene expression, and oxidative RNA modification. I have focused on neurodegeneration induced by RBPs mutations, by dysfunction of miRNA regulation, and by the oxidized RNAs within neurons, and discuss how these dysfunctions have pathologically contributed to neurodegenerative diseases. The advances overviewed above will be valuable to basic investigation and clinical application of target diagnostic tests and therapies.

  10. 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.

  11. 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

  12. Contributions of isolated Pacific populations to understanding neurodegenerative diseases.

    PubMed

    Garruto, Ralph M; Yanagihara, Richard

    2009-01-01

    Isolated human populations have provided a natural experimental laboratory for the ongoing study of human disease. In the mid-20th century a number of high-incidence foci of neurodegenerative diseases were brought to medical attention including kuru, amyotrophic lateral sclerosis, and parkinsonism-dementia. These foci were discovered in Papua New Guinea, West New Guinea, the Kii Peninsula of Japan, and in the Mariana Islands. The study of these diseases in isolated human groups has significantly contributed to our understanding of the cause and mechanisms of pathogenesis of these and related neurodegenerative disorders globally. This paper is dedicated to D. Carleton Gajdusek, a pioneer in the study of neurodegenerative diseases, whose decades of fieldwork and laboratory studies have led to numerous scientific discoveries that have reshaped our thinking and understanding about neurodegeneration.

  13. What can pluripotent stem cells teach us about neurodegenerative diseases?

    PubMed

    Wichterle, Hynek; Przedborski, Serge

    2010-07-01

    Neurodegenerative diseases represent a growing public health challenge. Current medications treat symptoms, but none halt or retard neurodegeneration. The recent advent of pluripotent cell biology has opened new avenues for neurodegenerative disease research. The greatest potential for induced pluripotent cells derived from affected individuals is likely to be their utility for modeling and understanding the mechanisms underlying neurodegenerative processes, and for searching for new treatments, including cell replacement therapies. However, much work remains to be done before pluripotent cells can be used for preclinical and clinical applications. Here we discuss the challenges of generating specific neural cell subtypes from pluripotent stem cells, the use of pluripotent stem cells to model both cell-autonomous and non-cell-autonomous mechanisms of neurodegeneration, whether adult-onset neurodegeneration can be emulated in short-term cultures and the hurdles of cell replacement therapy. Progress in these four areas will substantially accelerate effective application of pluripotent stem cells.

  14. 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

  15. 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

  16. 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

    2015-01-01

    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

  17. Circulating miRNAs as biomarkers for neurodegenerative disorders.

    PubMed

    Grasso, Margherita; Piscopo, Paola; Confaloni, Annamaria; Denti, Michela A

    2014-05-23

    Neurodegenerative disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD) and frontotemporal dementias (FTD), are considered distinct entities, however, there is increasing evidence of an overlap from the clinical, pathological and genetic points of view. All neurodegenerative diseases are characterized by neuronal loss and death in specific areas of the brain, for example, hippocampus and cortex for AD, midbrain for PD, frontal and temporal lobes for FTD. Loss of neurons is a relatively late event in the progression of neurodegenerative diseases that is typically preceded by other events such as metabolic changes, synaptic dysfunction and loss, neurite retraction, and the appearance of other abnormalities, such as axonal transport defects. The brain's ability to compensate for these dysfunctions occurs over a long period of time and results in late clinical manifestation of symptoms, when successful pharmacological intervention is no longer feasible. Currently, diagnosis of AD, PD and different forms of dementia is based primarily on analysis of the patient's cognitive function. It is therefore important to find non-invasive diagnostic methods useful to detect neurodegenerative diseases during early, preferably asymptomatic stages, when a pharmacological intervention is still possible. Altered expression of microRNAs (miRNAs) in many disease states, including neurodegeneration, and increasing relevance of miRNAs in biofluids in different pathologies has prompted the study of their possible application as neurodegenerative diseases biomarkers in order to identify new therapeutic targets. Here, we review what is known about the role of miRNAs in the pathogenesis of neurodegeneration and the possibilities and challenges of using these small RNA molecules as a signature for neurodegenerative conditions.

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. 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

  3. From target identification to drug screening assays for neurodegenerative diseases.

    PubMed

    Zuccato, Chiara; Tartari, Marzia; Goffredo, Donato; Cattaneo, Elena; Rigamonti, Dorotea

    2005-09-01

    Treatment of neurodegenerative diseases represents a major challenge for the pharmaceutical industry. Key to developing novel and efficacious therapeutics is the discovery of new druggable targets. Toward this aim, the current drug discovery process is strongly relying on the improved understanding of disease mechanisms and on a synergistic approach with chemistry, molecular biology and robotics. In this scenario, we present the case of a newly discovered molecular mechanism that may be of interest for drug discovery programmes in Huntington's disease and other neurodegenerative diseases. PMID:15916902

  4. Neuroprotective effects of berry fruits on neurodegenerative diseases

    PubMed Central

    Subash, Selvaraju; Essa, Musthafa Mohamed; Al-Adawi, Samir; Memon, Mushtaq A.; Manivasagam, Thamilarasan; Akbar, Mohammed

    2014-01-01

    Recent clinical research has demonstrated that berry fruits can prevent age-related neurodegenerative diseases and improve motor and cognitive functions. The berry fruits are also capable of modulating signaling pathways involved in inflammation, cell survival, neurotransmission and enhancing neuroplasticity. The neuroprotective effects of berry fruits on neurodegenerative diseases are related to phytochemicals such as anthocyanin, caffeic acid, catechin, quercetin, kaempferol and tannin. In this review, we made an attempt to clearly describe the beneficial effects of various types of berries as promising neuroprotective agents. PMID:25317174

  5. 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.

  6. 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. PMID:27242420

  7. 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

  8. Functional specializations of primary auditory afferents on the Mauthner cells: interactions between membrane and synaptic properties.

    PubMed

    Curti, Sebastian; Pereda, Alberto E

    2010-01-01

    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

  9. Subcortical neural coding mechanisms for auditory temporal processing.

    PubMed

    Frisina, R D

    2001-08-01

    Biologically relevant sounds such as speech, animal vocalizations and music have distinguishing temporal features that are utilized for effective auditory perception. Common temporal features include sound envelope fluctuations, often modeled in the laboratory by amplitude modulation (AM), and starts and stops in ongoing sounds, which are frequently approximated by hearing researchers as gaps between two sounds or are investigated in forward masking experiments. The auditory system has evolved many neural processing mechanisms for encoding important temporal features of sound. Due to rapid progress made in the field of auditory neuroscience in the past three decades, it is not possible to review all progress in this field in a single article. The goal of the present report is to focus on single-unit mechanisms in the mammalian brainstem auditory system for encoding AM and gaps as illustrative examples of how the system encodes key temporal features of sound. This report, following a systems analysis approach, starts with findings in the auditory nerve and proceeds centrally through the cochlear nucleus, superior olivary complex and inferior colliculus. Some general principles can be seen when reviewing this entire field. For example, as one ascends the central auditory system, a neural encoding shift occurs. An emphasis on synchronous responses for temporal coding exists in the auditory periphery, and more reliance on rate coding occurs as one moves centrally. In addition, for AM, modulation transfer functions become more bandpass as the sound level of the signal is raised, but become more lowpass in shape as background noise is added. In many cases, AM coding can actually increase in the presence of background noise. For gap processing or forward masking, coding for gaps changes from a decrease in spike firing rate for neurons of the peripheral auditory system that have sustained response patterns, to an increase in firing rate for more central neurons with

  10. 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.

  11. 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.

  12. Auditory learning: a developmental method.

    PubMed

    Zhang, Yilu; Weng, Juyang; Hwang, Wey-Shiuan

    2005-05-01

    Motivated by the human autonomous development process from infancy to adulthood, we have built a robot that develops its cognitive and behavioral skills through real-time interactions with the environment. We call such a robot a developmental robot. In this paper, we present the theory and the architecture to implement a developmental robot and discuss the related techniques that address an array of challenging technical issues. As an application, experimental results on a real robot, self-organizing, autonomous, incremental learner (SAIL), are presented with emphasis on its audition perception and audition-related action generation. In particular, the SAIL robot conducts the auditory learning from unsegmented and unlabeled speech streams without any prior knowledge about the auditory signals, such as the designated language or the phoneme models. Neither available before learning starts are the actions that the robot is expected to perform. SAIL learns the auditory commands and the desired actions from physical contacts with the environment including the trainers.

  13. 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

  14. 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.

  15. Integration of auditory and vibrotactile stimuli: Effects of phase and stimulus-onset asynchrony

    PubMed Central

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

    2009-01-01

    The perceptual integration of 250 Hz, 500 ms vibrotactile and auditory tones was studied in detection experiments as a function of (1) relative phase and (2) temporal asynchrony of the tone pulses. Vibrotactile stimuli were delivered through a single-channel vibrator to the left middle fingertip and auditory stimuli were presented diotically through headphones in a background of 50 dB sound pressure level broadband noise. The vibrotactile and auditory stimulus levels used each yielded 63%–77%-correct unimodal detection performance in a 2-I, 2-AFC task. Results for combined vibrotactile and auditory detection indicated that (1) performance improved for synchronous presentation, (2) performance was not affected by the relative phase of the auditory and tactile sinusoidal stimuli, and (3) performance for non-overlapping stimuli improved only if the tactile stimulus preceded the auditory. The results are generally more consistent with a “Pythagorean Sum” model than with either an “Algebraic Sum” or an “Optimal Single-Channel” Model of perceptual integration. Thus, certain combinations of auditory and tactile signals result in significant integrative effects. The lack of phase effect suggests an envelope rather than fine-structure operation for integration. The effects of asynchronous presentation of the auditory and tactile stimuli are consistent with time constants deduced from single-modality masking experiments. PMID:19813808

  16. 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. PMID:27421976

  17. 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.

  18. Quantitative analysis on electrooculography (EOG) for neurodegenerative disease

    NASA Astrophysics Data System (ADS)

    Liu, Chang-Chia; Chaovalitwongse, W. Art; Pardalos, Panos M.; Seref, Onur; Xanthopoulos, Petros; Sackellares, J. C.; Skidmore, Frank M.

    2007-11-01

    Many studies have documented abnormal horizontal and vertical eye movements in human neurodegenerative disease as well as during altered states of consciousness (including drowsiness and intoxication) in healthy adults. Eye movement measurement may play an important role measuring the progress of neurodegenerative diseases and state of alertness in healthy individuals. There are several techniques for measuring eye movement, Infrared detection technique (IR). Video-oculography (VOG), Scleral eye coil and EOG. Among those available recording techniques, EOG is a major source for monitoring the abnormal eye movement. In this real-time quantitative analysis study, the methods which can capture the characteristic of the eye movement were proposed to accurately categorize the state of neurodegenerative subjects. The EOG recordings were taken while 5 tested subjects were watching a short (>120 s) animation clip. In response to the animated clip the participants executed a number of eye movements, including vertical smooth pursued (SVP), horizontal smooth pursued (HVP) and random saccades (RS). Detection of abnormalities in ocular movement may improve our diagnosis and understanding a neurodegenerative disease and altered states of consciousness. A standard real-time quantitative analysis will improve detection and provide a better understanding of pathology in these disorders.

  19. 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

  20. 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

  1. 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]. PMID:27222125

  2. 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

  3. 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.

  4. 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.

  5. [Caregivers of people with neurodegenerative diseases: from help to delegation].

    PubMed

    Delzescaux, Sabine; Blondel, Frédéric

    2015-01-01

    Being a caregiver is difficult, even more so when it comes to helping people with a neurodegenerative disease. These caregivers, either family members or close friends, are confronted with an unexpected delegation which can prove to be highly complex as the pitfalls can indeed be significant. Moreover, the support the caregivers can provide depends on the support they can get for themselves. PMID:26364815

  6. Adult neurogenesis in the olfactory system and neurodegenerative disease.

    PubMed

    Gallarda, B W; Lledo, P-M

    2012-12-01

    The olfactory system is unique in many respects-two of which include the process of adult neurogenesis which continually supplies it with newborn neurons, and the fact that neurodegenerative diseases are often accompanied by a loss of smell. A link between these two phenomena has been hypothesized, but recent evidence for the lack of robust adult neurogenesis in the human olfactory system calls into question this hypothesis. Nevertheless, model organisms continue to play a critical role in the exploration of neurodegenerative disease. In part one of this review we discuss the most promising recent technological advancements for studying adult neurogenesis in the murine olfactory system. Part two continues by looking at emerging evidence related to adult neurogenesis in neurodegenerative disease studied in model organisms and the differences between animal and human olfactory system adult neurogenesis. Hopefully, the careful application of advanced research methods to the study of neurodegenerative disease in model organisms, while taking into account the recently reported differences between the human and model organism olfactory system, will lead to a better understanding of the reasons for the susceptibility of olfaction to disease.

  7. Clinical translation of stem cells in neurodegenerative disorders.

    PubMed

    Lindvall, Olle; Barker, Roger A; Brüstle, Oliver; Isacson, Ole; Svendsen, Clive N

    2012-02-01

    Stem cells and their derivatives show tremendous potential for treating many disorders, including neurodegenerative 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.

  8. 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.

  9. The role of mitochondria in inherited neurodegenerative diseases.

    PubMed

    Kwong, Jennifer Q; Beal, M Flint; Manfredi, Giovanni

    2006-06-01

    In the past decade, the genetic causes underlying familial forms of many neurodegenerative disorders, such as Huntington's disease, Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, Friedreich ataxia, hereditary spastic paraplegia, dominant optic atrophy, Charcot-Marie-Tooth type 2A, neuropathy ataxia and retinitis pigmentosa, and Leber's hereditary optic atrophy have been elucidated. However, the common pathogenic mechanisms of neuronal death are still largely unknown. Recently, mitochondrial dysfunction has emerged as a potential 'lowest common denominator' linking these disorders. In this review, we discuss the body of evidence supporting the role of mitochondria in the pathogenesis of hereditary neurodegenerative diseases. We summarize the principal features of genetic diseases caused by abnormalities of mitochondrial proteins encoded by the mitochondrial or the nuclear genomes. We then address genetic diseases where mutant proteins are localized in multiple cell compartments, including mitochondria and where mitochondrial defects are likely to be directly caused by the mutant proteins. Finally, we describe examples of neurodegenerative disorders where mitochondrial dysfunction may be 'secondary' and probably concomitant with degenerative events in other cell organelles, but may still play an important role in the neuronal decay. Understanding the contribution of mitochondrial dysfunction to neurodegeneration and its pathophysiological basis will significantly impact our ability to develop more effective therapies for neurodegenerative diseases. PMID:16805775

  10. 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.

  11. Sensitivity to Auditory Velocity Contrast.

    PubMed

    Locke, Shannon M; Leung, Johahn; Carlile, Simon

    2016-06-13

    A natural auditory scene often contains sound moving at varying velocities. Using a velocity contrast paradigm, we compared sensitivity to velocity changes between continuous and discontinuous trajectories. Subjects compared the velocities of two stimulus intervals that moved along a single trajectory, with and without a 1 second inter stimulus interval (ISI). We found thresholds were threefold larger for velocity increases in the instantaneous velocity change condition, as compared to instantaneous velocity decreases or thresholds for the delayed velocity transition condition. This result cannot be explained by the current static "snapshot" model of auditory motion perception and suggest a continuous process where the percept of velocity is influenced by previous history of stimulation.

  12. Effects of Auditory Input in Individuation Tasks

    ERIC Educational Resources Information Center

    Robinson, Christopher W.; Sloutsky, Vladimir M.

    2008-01-01

    Under many conditions auditory input interferes with visual processing, especially early in development. These interference effects are often more pronounced when the auditory input is unfamiliar than when the auditory input is familiar (e.g. human speech, pre-familiarized sounds, etc.). The current study extends this research by examining how…

  13. Pre-Attentive Auditory Processing of Lexicality

    ERIC Educational Resources Information Center

    Jacobsen, Thomas; Horvath, Janos; Schroger, Erich; Lattner, Sonja; Widmann, Andreas; Winkler, Istvan

    2004-01-01

    The effects of lexicality on auditory change detection based on auditory sensory memory representations were investigated by presenting oddball sequences of repeatedly presented stimuli, while participants ignored the auditory stimuli. In a cross-linguistic study of Hungarian and German participants, stimulus sequences were composed of words that…

  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. 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…

  16. The molecular mechanisms of scrapie encephalopathy and relevance to human neurodegenerative disease.

    PubMed Central

    Lukiw, W J; Cho, H J; Kaufmann, J C; Crapper McLachlan, D R

    1990-01-01

    We have investigated alterations in the structure and function of nuclei isolated from normal and pathological brains in a number of neurodegenerative diseases including scrapie and Alzheimer's disease. Here we summarize both general and specific changes in chromatin structure, gene expression, and neuropathological features for each encephalopathy and compare them in terms of their molecular biological similarities and differences. While both scrapie and Alzheimer's disease share a number of common alterations in genomic organization and gene activity during the pathogenic process, each neurological disease appears to operate on fundamentally different mechanisms. Images Fig. 2. Fig. 3. Fig. 4A. Fig. 5A. PMID:2407330

  17. 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

  18. 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

  19. Happiness increases distraction by auditory deviant stimuli.

    PubMed

    Pacheco-Unguetti, Antonia Pilar; Parmentier, Fabrice B R

    2016-08-01

    Rare and unexpected changes (deviants) in an otherwise repeated stream of task-irrelevant auditory distractors (standards) capture attention and impair behavioural performance in an ongoing visual task. Recent evidence indicates that this effect is increased by sadness in a task involving neutral stimuli. We tested the hypothesis that such effect may not be limited to negative emotions but reflect a general depletion of attentional resources by examining whether a positive emotion (happiness) would increase deviance distraction too. Prior to performing an auditory-visual oddball task, happiness or a neutral mood was induced in participants by means of the exposure to music and the recollection of an autobiographical event. Results from the oddball task showed significantly larger deviance distraction following the induction of happiness. Interestingly, the small amount of distraction typically observed on the standard trial following a deviant trial (post-deviance distraction) was not increased by happiness. We speculate that happiness might interfere with the disengagement of attention from the deviant sound back towards the target stimulus (through the depletion of cognitive resources and/or mind wandering) but help subsequent cognitive control to recover from distraction. PMID:26302716

  20. Cooperative Nonlinearities in Auditory Cortical Neurons

    PubMed Central

    Atencio, Craig A.; Sharpee, Tatyana O.; Schreiner, Christoph E.

    2008-01-01

    SUMMARY Cortical receptive fields represent the signal preferences of sensory neurons. Receptive fields are thought to provide a representation of sensory experience from which the cerebral cortex may make interpretations. While it is essential to determine a neuron’s receptive field, it remains unclear which features of the acoustic environment are specifically represented by neurons in the primary auditory cortex (AI). We characterized cat AI spectrotemporal receptive fields (STRFs) by finding both the spike-triggered average (STA) and stimulus dimensions that maximized the mutual information between response and stimulus. We derived a nonlinearity relating spiking to stimulus projection onto two maximally informative dimensions (MIDs). The STA was highly correlated with the first MID. Generally, the nonlinearity for the first MID was asymmetric and often monotonic in shape, while the second MID nonlinearity was symmetric and non-monotonic. The joint nonlinearity for both MIDs revealed that most first and second MIDs were synergistic, and thus should be considered conjointly. The difference between the nonlinearities suggests different possible roles for the MIDs in auditory processing. PMID:18579084

  1. Happiness increases distraction by auditory deviant stimuli.

    PubMed

    Pacheco-Unguetti, Antonia Pilar; Parmentier, Fabrice B R

    2016-08-01

    Rare and unexpected changes (deviants) in an otherwise repeated stream of task-irrelevant auditory distractors (standards) capture attention and impair behavioural performance in an ongoing visual task. Recent evidence indicates that this effect is increased by sadness in a task involving neutral stimuli. We tested the hypothesis that such effect may not be limited to negative emotions but reflect a general depletion of attentional resources by examining whether a positive emotion (happiness) would increase deviance distraction too. Prior to performing an auditory-visual oddball task, happiness or a neutral mood was induced in participants by means of the exposure to music and the recollection of an autobiographical event. Results from the oddball task showed significantly larger deviance distraction following the induction of happiness. Interestingly, the small amount of distraction typically observed on the standard trial following a deviant trial (post-deviance distraction) was not increased by happiness. We speculate that happiness might interfere with the disengagement of attention from the deviant sound back towards the target stimulus (through the depletion of cognitive resources and/or mind wandering) but help subsequent cognitive control to recover from distraction.

  2. Auditory Temporal Conditioning in Neonates.

    ERIC Educational Resources Information Center

    Franz, W. K.; And Others

    Twenty normal newborns, approximately 36 hours old, were tested using an auditory temporal conditioning paradigm which consisted of a slow rise, 75 db tone played for five seconds every 25 seconds, ten times. Responses to the tones were measured by instantaneous, beat-to-beat heartrate; and the test trial was designated as the 2 1/2-second period…

  3. Central Auditory Function in Stutterers

    ERIC Educational Resources Information Center

    Hall, James W.; Jerger, James

    1978-01-01

    Central auditory function was assessed in 10 stutterers and 10 nonstutterers between the ages of 10 and 35 years, and the performance of the two groups compared for seven audiometric procedures, including acoustic reflex threshold and acoustic reflex amplitude function. (Author)

  4. Developing Linguistic Auditory Memory Patterns.

    ERIC Educational Resources Information Center

    Valett, Robert E.

    1983-01-01

    For learning handicapped children with impaired language associations, patterns, and expressions, this paper summarizes relevant linguistic research and instructional strategies. Linguistic auditory memory pattern exercises and examples are then presented as an integrated multisensory approach which has been found useful by special educators.…

  5. Delayed Auditory Feedback and Movement

    ERIC Educational Resources Information Center

    Pfordresher, Peter Q.; Dalla Bella, Simone

    2011-01-01

    It is well known that timing of rhythm production is disrupted by delayed auditory feedback (DAF), and that disruption varies with delay length. We tested the hypothesis that disruption depends on the state of the movement trajectory at the onset of DAF. Participants tapped isochronous rhythms at a rate specified by a metronome while hearing DAF…

  6. Dynamics of auditory working memory

    PubMed Central

    Kaiser, Jochen

    2015-01-01

    Working memory denotes the ability to retain stimuli in mind that are no longer physically present and to perform mental operations on them. Electro- and magnetoencephalography allow investigating the short-term maintenance of acoustic stimuli at a high temporal resolution. Studies investigating working memory for non-spatial and spatial auditory information have suggested differential roles of regions along the putative auditory ventral and dorsal streams, respectively, in the processing of the different sound properties. Analyses of event-related potentials have shown sustained, memory load-dependent deflections over the retention periods. The topography of these waves suggested an involvement of modality-specific sensory storage regions. Spectral analysis has yielded information about the temporal dynamics of auditory working memory processing of individual stimuli, showing activation peaks during the delay phase whose timing was related to task performance. Coherence at different frequencies was enhanced between frontal and sensory cortex. In summary, auditory working memory seems to rely on the dynamic interplay between frontal executive systems and sensory representation regions. PMID:26029146

  7. Reverse engineering human neurodegenerative disease using pluripotent stem cell technology.

    PubMed

    Liu, Ying; Deng, Wenbin

    2016-05-01

    With the technology of reprogramming somatic cells by introducing defined transcription factors that enables the generation of "induced pluripotent stem cells (iPSCs)" with pluripotency comparable to that of embryonic stem cells (ESCs), it has become possible to use this technology to produce various cells and tissues that have been difficult to obtain from living bodies. This advancement is bringing forth rapid progress in iPSC-based disease modeling, drug screening, and regenerative medicine. More and more studies have demonstrated that phenotypes of adult-onset neurodegenerative disorders could be rather faithfully recapitulated in iPSC-derived neural cell cultures. Moreover, despite the adult-onset nature of the diseases, pathogenic phenotypes and cellular abnormalities often exist in early developmental stages, providing new "windows of opportunity" for understanding mechanisms underlying neurodegenerative disorders and for discovering new medicines. The cell reprogramming technology enables a reverse engineering approach for modeling the cellular degenerative phenotypes of a wide range of human disorders. An excellent example is the study of the human neurodegenerative disease amyotrophic lateral sclerosis (ALS) using iPSCs. ALS is a progressive neurodegenerative disease characterized by the loss of upper and lower motor neurons (MNs), culminating in muscle wasting and death from respiratory failure. The iPSC approach provides innovative cell culture platforms to serve as ALS patient-derived model systems. Researchers have converted iPSCs derived from ALS patients into MNs and various types of glial cells, all of which are involved in ALS, to study the disease. The iPSC technology could be used to determine the role of specific genetic factors to track down what's wrong in the neurodegenerative disease process in the "disease-in-a-dish" model. Meanwhile, parallel experiments of targeting the same specific genes in human ESCs could also be performed to control

  8. The Encoding of Auditory Objects in Auditory Cortex: Insights from Magnetoencephalography

    PubMed Central

    Simon, Jonathan Z.

    2014-01-01

    Auditory objects, like their visual counterparts, are perceptually defined constructs, but nevertheless must arise from underlying neural circuitry. Using magnetoencephalography (MEG) recordings of the neural responses of human subjects listening to complex auditory scenes, we review studies that demonstrate that auditory objects are indeed neurally represented in auditory cortex. The studies use neural responses obtained from different experiments in which subjects selectively listen to one of two competing auditory streams embedded in a variety of auditory scenes. The auditory streams overlap spatially and often spectrally. In particular, the studies demonstrate that selective attentional gain does not act globally on the entire auditory scene, but rather acts differentially on the separate auditory streams. This stream-based attentional gain is then used as a tool to individually analyze the different neural representations of the competing auditory streams. The neural representation of the attended stream, located in posterior auditory cortex, dominates the neural responses. Critically, when the intensities of the attended and background streams are separately varied over a wide intensity range, the neural representation of the attended speech adapts only to the intensity of that speaker, irrespective of the intensity of the background speaker. This demonstrates object-level intensity gain control in addition to the above object-level selective attentional gain. Overall, these results indicate that concurrently streaming auditory objects, even if spectrally overlapping and not resolvable at the auditory periphery, are individually neurally encoded in auditory cortex, as separate objects. PMID:24841996

  9. Nutraceuticals and amyloid neurodegenerative diseases: a focus on natural phenols.

    PubMed

    Rigacci, Stefania; Stefani, Massimo

    2015-01-01

    A common molecular feature of amyloid neurodegenerative diseases is the unfolding/misfolding of specific proteins/peptides which consequently become prone to aggregate into toxic assemblies and deposits that are the key histopathological trait of these pathologies. Apart from the rare early-onset familiar forms, these neurodegenerative diseases are age-associated disorders whose symptoms appear in aged people after long incubation periods. This makes the therapeutic approach particularly compelling and boosts the search for both early diagnostic tools and preventive approaches. In this last respect, natural compounds commonly present in foods and beverages are considered promising molecules, at least on the bench side. The so-called 'nutraceutical approach' suggests life-long healthy diets, particularly focusing on food molecules that are candidates to enter clinical trials as such or following a targeted molecular engineering. Natural phenols abundant in 'healthy' foods such as extra virgin olive oil, red wine, green tea, red berries and spices, appear particularly promising. PMID:25418871

  10. [Are we underestimating occupational risks for neurodegenerative diseases?].

    PubMed

    Oddone, Enrico; Imbriani, Marcello

    2015-01-01

    In recent years a great number of studies suggests that occupational exposures could play a role in the onset of some neurodegenerative diseases. The literature data are more numerous for Parkinson's disease, Multiple Sclerosis and Amyotrophic Lateral Sclerosis, although to date no specific occupational exposure was proved to be a definite causal factor. This lack of information is attributable both to the complex patogenesis of these diseases and to a delay regarding this field of research with respect to others pathologies. Nevertheless, available evidence oblige researchers to deepen the studies of occupational exposures as risk factors of neurodegenerative diseases, in order to provide a solid basis possible preventive measures for a class of pathologies with high social impact, both in terms of therapies and in terms of disability.

  11. 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.

  12. 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.

  13. Genetics Underlying Atypical Parkinsonism and Related Neurodegenerative Disorders

    PubMed Central

    Scholz, Sonja W.; Bras, Jose

    2015-01-01

    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. PMID:26501269

  14. Neuropeptide Y (NPY) as a therapeutic target for neurodegenerative diseases.

    PubMed

    Duarte-Neves, Joana; Pereira de Almeida, Luís; Cavadas, Cláudia

    2016-11-01

    Neuropeptide Y (NPY) and NPY receptors are widely expressed in the mammalian central nervous system. Studies in both humans and rodent models revealed that brain NPY levels are altered in some neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, Huntington's disease and Machado-Joseph disease. In this review, we will focus on the roles of NPY in the pathological mechanisms of these disorders, highlighting NPY as a neuroprotective agent, as a neural stem cell proliferative agent, as an agent that increases trophic support, as a stimulator of autophagy and as an inhibitor of excitotoxicity and neuroinflammation. Moreover, the effect of NPY in some clinical manifestations commonly observed in Alzheimer's disease, Parkinson's disease, Huntington's disease and Machado-Joseph disease, such as depressive symptoms and body weight loss, are also discussed. In conclusion, this review highlights NPY system as a potential therapeutic target in neurodegenerative diseases.

  15. Transposable Elements in TDP-43-Mediated Neurodegenerative Disorders

    PubMed Central

    Hammell, Molly; Dubnau, Josh

    2012-01-01

    Elevated expression of specific transposable elements (TEs) has been observed in several neurodegenerative disorders. TEs also can be active during normal neurogenesis. By mining a series of deep sequencing datasets of protein-RNA interactions and of gene expression profiles, we uncovered extensive binding of TE transcripts to TDP-43, an RNA-binding protein central to amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Second, we find that association between TDP-43 and many of its TE targets is reduced in FTLD patients. Third, we discovered that a large fraction of the TEs to which TDP-43 binds become de-repressed in mouse TDP-43 disease models. We propose the hypothesis that TE mis-regulation contributes to TDP-43 related neurodegenerative diseases. PMID:22957047

  16. Prions and prion-like pathogens in neurodegenerative disorders.

    PubMed

    Peggion, Caterina; Sorgato, Maria Catia; Bertoli, Alessandro

    2014-02-18

    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.

  17. 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

  18. POTENTIAL FUTURE NEUROPROTECTIVE THERAPIES FOR NEURODEGENERATIVE DISORDERS AND STROKE

    PubMed Central

    Tarawneh, Rawan; Galvin, James E.

    2009-01-01

    The cellular mechanisms underlying neuronal loss and neurodegeneration have been an area of interest in the last decade. Although neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and Huntington’s disease (HD) each have distinct clinical symptoms and pathologies, they all share common mechanisms such as protein aggregation, oxidative injury, inflammation, apoptosis and mitochondrial injury that contribute to neuronal loss. Although cerebrovascular disease is due to etiologies quite different from the neurodegenerative disorders, many of the same common disease mechanisms come into play following a stroke. Novel therapies that target each of these mechanisms may be effective in decreasing the risk of disease, abating symptoms or slowing down their progression. While most of these therapies are experimental, and require further investigation, a few seem to offer promise in the near future. PMID:20176298

  19. Representation of speech in human auditory cortex: Is it special?

    PubMed Central

    Steinschneider, Mitchell; Nourski, Kirill V.; Fishman, Yonatan I.

    2013-01-01

    Successful categorization of phonemes in speech requires that the brain analyze the acoustic signal along both spectral and temporal dimensions. Neural encoding of the stimulus amplitude envelope is critical for parsing the speech stream into syllabic units. Encoding of voice onset time (VOT) and place of articulation (POA), cues necessary for determining phonemic identity, occurs within shorter time frames. An unresolved question is whether the neural representation of speech is based on processing mechanisms that are unique to humans and shaped by learning and experience, or is based on rules governing general auditory processing that are also present in non-human animals. This question was examined by comparing the neural activity elicited by speech and other complex vocalizations in primary auditory cortex of macaques, who are limited vocal learners, with that in Heschl’s gyrus, the putative location of primary auditory cortex in humans. Entrainment to the amplitude envelope is neither specific to humans nor to human speech. VOT is represented by responses time-locked to consonant release and voicing onset in both humans and monkeys. Temporal representation of VOT is observed both for isolated syllables and for syllables embedded in the more naturalistic context of running speech. The fundamental frequency of male speakers is represented by more rapid neural activity phase-locked to the glottal pulsation rate in both humans and monkeys. In both species, the differential representation of stop consonants varying in their POA can be predicted by the relationship between the frequency selectivity of neurons and the onset spectra of the speech sounds. These findings indicate that the neurophysiology of primary auditory cortex is similar in monkeys and humans despite their vastly different experience with human speech, and that Heschl’s gyrus is engaged in general auditory, and not language-specific, processing. PMID:23792076

  20. Pharmacotherapy for Neurodegenerative Diseases: Are We Approaching the Tipping Point?

    PubMed

    Honig, P K

    2015-11-01

    Neurodegenerative diseases continue to represent major unmet medical and public health needs and will increasingly strain the healthcare system as people live longer due to medical advances in other diseases. Hopefully the emergence of increased understanding of the biology of these conditions coupled with novel clinical pharmacology tools, clinical trial designs, and regulatory innovation will allow the emergence of highly effective symptomatic and disease modifying pharmacotherapies. PMID:26478996

  1. Stem cell challenges in the treatment of neurodegenerative disease.

    PubMed

    Feng, Zhongling; Gao, Feng

    2012-02-01

    Neurodegenerative diseases result from the gradual and progressive loss of neural cells and lead to nervous system dysfunction. The rapidly advancing stem cell field is providing attractive alternative options for fighting these diseases. Results have provided proof of principle that cell replacement can work in humans with Parkinson's disease (PD). However, three clinical studies of cell transplantation were published that found no net benefit, while patients in two of the studies developed dyskinesias that persisted despite reductions in treatment. Induced pluripotent stem cells (iPSC) have major potential advantages because patient-specific neuroblasts are suitable for transplantation, avoid immune reactions, and can be produced without the use of human ES cells (hESC). Although iPSCs have not been successfully used in clinical trials for PD, patients with amyotrophic lateral sclerosis (ALS) were treated with autologous stem cells and, though they had some degree of decline one year after treatment, they were still improved compared with the preoperative period or without any drug therapy. In addition, neural stem cells (NSCs), via brain-derived neurotrophic factor (BDNF), have been shown to ameliorate complex behavioral deficits associated with widespread Alzheimer's disease (AD) pathology in a transgenic mouse model of AD. So far, the FDA lists 18 clinical trials treating multiple sclerosis (MS), but most are in preliminary stages. This article serves as an overview of recent studies in stem cell and regenerative approaches to the above chronic neurodegenerative disorders. There are still many obstacles to the use of stem cells as a cure for neurodegenerative disease, especially because we still don't fully understand the true mechanisms of these diseases. However, there is hope in the potential of stem cells to help us learn and understand a great deal more about the mechanisms underlying these devastating neurodegenerative diseases.

  2. Hyperactive Somatostatin Interneurons Contribute to Excitotoxicity in Neurodegenerative Disorders

    PubMed Central

    Liang, Bo; Schroeder, David; Zhang, Zhong-wei; Cox, Gregory A.; Li, Yun; Lin, Da-Ting

    2016-01-01

    Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are overlapping neurodegenerative disorders whose pathogenesis remains largely unknown. Here using TDP-43A315T mice, an ALS and FTD model with profound cortical pathology, we demonstrated that hyperactive somatostatin interneurons disinhibited layer 5 pyramidal neurons (L5-PN) and contributed to their excitotoxicity. Focal ablation of somatostatin interneurons efficiently restored normal excitability of L5-PN and alleviated neurodegeneration, suggesting a novel therapeutic target for ALS and FTD. PMID:26900927

  3. Potential application of lithium in Parkinson's and other neurodegenerative diseases.

    PubMed

    Lazzara, Carol A; Kim, Yong-Hwan

    2015-01-01

    Lithium, the long-standing hallmark treatment for bipolar disorder, has recently been identified as a potential neuroprotective agent in neurodegeneration. Here we focus on introducing numerous in vitro and in vivo studies that have shown lithium treatment to be efficacious in reducing oxidative stress and inflammation, increasing autophagy, inhibiting apoptosis, and decreasing the accumulation of α-synulcein, with an emphasis on Parkinson's disease. A number of biological pathways have been shown to be involved in causing these neuroprotective effects. The inhibition of GSK-3β has been the mechanism most studied; however, other modes of action include the regulation of apoptotic proteins and glutamate excitotoxicity as well as down-regulation of calpain. This review provides a framework of the neuroprotective effects of lithium in neurodegenerative diseases and the putative mechanisms by which lithium provides the protection. Lithium-only treatment may not be a suitable therapeutic option for neurodegenerative diseases due to inconsistent efficacy and potential side-effects, however, the use of low dose lithium in combination with other potential or existing therapeutic compounds may be a promising approach to reduce symptoms and disease progression in neurodegenerative diseases.

  4. Epidemiology of mild traumatic brain injury and neurodegenerative disease

    PubMed Central

    Gardner, Raquel C.; Yaffe, Kristine

    2015-01-01

    Every year an estimated 42 million people worldwide suffer a mild traumatic brain injury (MTBI) or concussion. More severe traumatic brain injury (TBI) is a well-established risk factor for a variety of neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS). Recently, large epidemiological studies have additionally identified MTBI as a risk factor for dementia. The role of MTBI in risk of PD or ALS is less well established. Repetitive MTBI and repetitive sub-concussive head trauma has been linked to increased risk for a variety of neurodegenerative diseases including chronic traumatic encephalopathy (CTE). CTE is a unique neurodegenerative tauopathy first described in boxers but more recently described in a variety of contact sport athletes, military veterans, and civilians exposed to repetitive MTBI. Studies of repetitive MTBI and CTE have been limited by referral bias, lack of consensus clinical criteria for CTE, challenges of quantifying MTBI exposure, and potential for confounding. The prevalence of CTE is unknown and the amount of MTBI or sub-concussive trauma exposure necessary to produce CTE is unclear. This review will summarize the current literature regarding the epidemiology of MTBI, post-TBI dementia and Parkinson's disease, and CTE while highlighting methodological challenges and critical future directions of research in this field. PMID:25748121

  5. Heavy metals and neurodegenerative diseases: an observational study.

    PubMed

    Giacoppo, Sabrina; Galuppo, Maria; Calabrò, Rocco Salvatore; D'Aleo, Giangaetano; Marra, Angela; Sessa, Edoardo; Bua, Daniel Giuseppe; Potortì, Angela Giorgia; Dugo, Giacomo; Bramanti, Placido; Mazzon, Emanuela

    2014-11-01

    In this study, we evaluated the levels of some of the most investigated metals (Cu, Se, Zn, Pb, and Hg) in the blood of patients affected by the most common chronic neurodegenerative diseases like Alzheimer's disease (AD) and multiple sclerosis (MS), in order to better clarify their involvement. For the first time, we investigated a Sicilian population living in an area exposed to a potentially contaminated environment from dust and fumes of volcano Etna and consumer of a considerable quantity of fish in their diet, so that this represents a good cohort to demonstrate a possible link between metals levels and development of neurodegenerative disorders. More specifically, 15 patients affected by AD, 41 patients affected by MS, 23 healthy controls, and 10 healthy elderly controls were recruited and subjected to a venous blood sampling. Quantification of heavy metals was performed by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). This technique has allowed us to establish that there is a concomitance of heavy metal unbalance associated with AD more than in other neurodegenerative pathologies, such as MS. Also, we can assess that the concentration of these elements is independent from the diet, especially from occasional or habitual consumption of fruits and vegetables, prevalence in the diet of meat or fish, possible exposure to contaminated environment due both to the occupation and place of residence.

  6. Drosophila as an In Vivo Model for Human Neurodegenerative Disease

    PubMed Central

    McGurk, Leeanne; Berson, Amit; Bonini, Nancy M.

    2015-01-01

    With the increase in the ageing population, neurodegenerative disease is devastating to families and poses a huge burden on society. The brain and spinal cord are extraordinarily complex: they consist of a highly organized network of neuronal and support cells that communicate in a highly specialized manner. One approach to tackling problems of such complexity is to address the scientific questions in simpler, yet analogous, systems. The fruit fly, Drosophila melanogaster, has been proven tremendously valuable as a model organism, enabling many major discoveries in neuroscientific disease research. The plethora of genetic tools available in Drosophila allows for exquisite targeted manipulation of the genome. Due to its relatively short lifespan, complex questions of brain function can be addressed more rapidly than in other model organisms, such as the mouse. Here we discuss features of the fly as a model for human neurodegenerative disease. There are many distinct fly models for a range of neurodegenerative diseases; we focus on select studies from models of polyglutamine disease and amyotrophic lateral sclerosis that illustrate the type and range of insights that can be gleaned. In discussion of these models, we underscore strengths of the fly in providing understanding into mechanisms and pathways, as a foundation for translational and therapeutic research. PMID:26447127

  7. Implications of glial nitric oxide in neurodegenerative diseases

    PubMed Central

    Yuste, Jose Enrique; Tarragon, Ernesto; Campuzano, Carmen María; Ros-Bernal, Francisco

    2015-01-01

    Nitric oxide (NO) is a pleiotropic janus-faced molecule synthesized by nitric oxide synthases (NOS) which plays a critical role in a number of physiological and pathological processes in humans. The physiological roles of NO depend on its local concentrations, as well as its availability and the nature of downstream target molecules. Its double-edged sword action has been linked to neurodegenerative disorders. Excessive NO production, as the evoked by inflammatory signals, has been identified as one of the major causative reasons for the pathogenesis of several neurodegenerative diseases. Moreover, excessive NO synthesis under neuroinflammation leads to the formation of reactive nitrogen species and neuronal cell death. There is an intimate relation between microglial activation, NO and neuroinflammation in the human brain. The role of NO in neuroinflammation has been defined in animal models where this neurotransmitter can modulate the inflammatory process acting on key regulatory pathways, such as those associated with excitotoxicity processes induced by glutamate accumulation and microglial activation. Activated glia express inducible NOS and produce NO that triggers calcium mobilization from the endoplasmic reticulum, activating the release of vesicular glutamate from astroglial cells resulting in neuronal death. This change in microglia potentially contributes to the increased age-associated susceptibility and neurodegeneration. In the current review, information is provided about the role of NO, glial activation and age-related processes in the central nervous system (CNS) that may be helpful in the isolation of new therapeutic targets for aging and neurodegenerative diseases. PMID:26347610

  8. Implications of glial nitric oxide in neurodegenerative diseases.

    PubMed

    Yuste, Jose Enrique; Tarragon, Ernesto; Campuzano, Carmen María; Ros-Bernal, Francisco

    2015-01-01

    Nitric oxide (NO) is a pleiotropic janus-faced molecule synthesized by nitric oxide synthases (NOS) which plays a critical role in a number of physiological and pathological processes in humans. The physiological roles of NO depend on its local concentrations, as well as its availability and the nature of downstream target molecules. Its double-edged sword action has been linked to neurodegenerative disorders. Excessive NO production, as the evoked by inflammatory signals, has been identified as one of the major causative reasons for the pathogenesis of several neurodegenerative diseases. Moreover, excessive NO synthesis under neuroinflammation leads to the formation of reactive nitrogen species and neuronal cell death. There is an intimate relation between microglial activation, NO and neuroinflammation in the human brain. The role of NO in neuroinflammation has been defined in animal models where this neurotransmitter can modulate the inflammatory process acting on key regulatory pathways, such as those associated with excitotoxicity processes induced by glutamate accumulation and microglial activation. Activated glia express inducible NOS and produce NO that triggers calcium mobilization from the endoplasmic reticulum, activating the release of vesicular glutamate from astroglial cells resulting in neuronal death. This change in microglia potentially contributes to the increased age-associated susceptibility and neurodegeneration. In the current review, information is provided about the role of NO, glial activation and age-related processes in the central nervous system (CNS) that may be helpful in the isolation of new therapeutic targets for aging and neurodegenerative diseases. PMID:26347610

  9. miRNAs: Key Players in Neurodegenerative Disorders and Epilepsy.

    PubMed

    Karnati, Hanuma Kumar; Panigrahi, Manas Kumar; Gutti, Ravi Kumar; Greig, Nigel H; Tamargo, Ian A

    2015-01-01

    MicroRNAs (miRNAs) are endogenous, ∼22 nucleotide, non-coding RNA molecules that function as post-transcriptional regulators of gene expression. miRNA dysregulation has been observed in cancer and in neurodegenerative disorders such as Alzheimer's, Parkinson's, and Huntington's diseases, amyotrophic lateral sclerosis, and the neurological disorder, epilepsy. Neuronal degradation and death are important hallmarks of neurodegenerative disorders. Additionally, abnormalities in metabolism, synapsis and axonal transport have been associated with Alzheimer's disease, Parkinson's disease, and frontotemporal dementia. A number of recently published studies have demonstrated the importance of miRNAs in the nervous system and have contributed to the growing body of evidence on miRNA dysregulation in neurological disorders. Knowledge of the expressions and activities of such miRNAs may aid in the development of novel therapeutics. In this review, we discuss the significance of miRNA dysregulation in the development of neurodegenerative disorders and the use of miRNAs as targets for therapeutic intervention.

  10. Potential application of lithium in Parkinson's and other neurodegenerative diseases

    PubMed Central

    Lazzara, Carol A.; Kim, Yong-Hwan

    2015-01-01

    Lithium, the long-standing hallmark treatment for bipolar disorder, has recently been identified as a potential neuroprotective agent in neurodegeneration. Here we focus on introducing numerous in vitro and in vivo studies that have shown lithium treatment to be efficacious in reducing oxidative stress and inflammation, increasing autophagy, inhibiting apoptosis, and decreasing the accumulation of α-synulcein, with an emphasis on Parkinson's disease. A number of biological pathways have been shown to be involved in causing these neuroprotective effects. The inhibition of GSK-3β has been the mechanism most studied; however, other modes of action include the regulation of apoptotic proteins and glutamate excitotoxicity as well as down-regulation of calpain. This review provides a framework of the neuroprotective effects of lithium in neurodegenerative diseases and the putative mechanisms by which lithium provides the protection. Lithium-only treatment may not be a suitable therapeutic option for neurodegenerative diseases due to inconsistent efficacy and potential side-effects, however, the use of low dose lithium in combination with other potential or existing therapeutic compounds may be a promising approach to reduce symptoms and disease progression in neurodegenerative diseases. PMID:26578864

  11. Multimodality imaging of Alzheimer disease and other neurodegenerative dementias.

    PubMed

    Nasrallah, Ilya M; Wolk, David A

    2014-12-01

    Neurodegenerative diseases, such as Alzheimer disease, result in cognitive decline and dementia and are a leading cause of mortality in the growing elderly population. These progressive diseases typically have an insidious onset, with overlapping clinical features early in the disease course that make diagnosis challenging. The neurodegenerative diseases are associated with characteristic, although not completely understood, changes in the brain: abnormal protein deposition, synaptic dysfunction, neuronal injury, and neuronal death. Neuroimaging biomarkers-principally regional atrophy on structural MR imaging, patterns of hypometabolism on (18)F-FDG PET, and detection of cerebral amyloid plaque on amyloid PET--are able to evaluate the patterns of these abnormalities in the brain to improve early diagnosis and help predict the disease course. These techniques have unique strengths and synergies in multimodality evaluation of the patient with cognitive decline or dementia. This review discusses the key imaging biomarkers from MR imaging, (18)F-FDG PET, and amyloid PET; the imaging features of the most common neurodegenerative dementias; the role of various neuroimaging studies in differential diagnosis and prognosis; and some promising imaging techniques under development.

  12. ETHICAL AND GENETIC ASPECTS REGARDING PRESYMPTOMATIC TESTING FOR NEURODEGENERATIVE DISEASES.

    PubMed

    Cozaru, Georgeta Camelial; Aşchie, Mariana; Mitroi, Anca Florentina; Poinăreanu, I; Gorduza, E V

    2016-01-01

    Neurodegenerative diseases, such as Alzheimer's dementia, Huntington's chorea, Parkinson's disease or spinocerebellar ataxia, manifests into adulthood with an insidious onset, slowly of progressive symptoms. All of these diseases are characterized by presimptomatic stages that preceded with many years of clinical debut. In Parkinson's disease, more than half of the dopaminergic neurons of the black substance are lost before the advent of motor characteristic manifestations. In Huntington's chorea, the progressive neurodegenerative disease could be diagnose prenatal and presymptomatic by analyse of the number of CAG repeats in exon 1 of the huntingtin gene. A similar mechanism represented by expansion of trinucleotide repeats during hereditary transmission from parents to children was identified in fragile X syndrome, spinocerebellar ataxia, spinal muscular and bulbar atrophy, or myotonic dystrophy. Presymptomatic diagnosis in all these progressive diseases raise many ethical issues, due to the psychological impact that can cause the prediction of a disease for which there is currently no curative treatment. Therefore, a positive result can produce serious psychological trauma and major changes in the lifestyle of the individual, instead, a negative result can bring joy and tranquillity. But the problem arises if presymptomatic testing in these neurodegenerative diseases brings greater benefits compared to the possible psychological damage, which can add the risk of stigmatization or discrimination. PMID:27125067

  13. Neural substrates of spontaneous narrative production in focal neurodegenerative disease.

    PubMed

    Gola, Kelly A; Thorne, Avril; Veldhuisen, Lisa D; Felix, Cordula M; Hankinson, Sarah; Pham, Julie; Shany-Ur, Tal; Schauer, Guido P; Stanley, Christine M; Glenn, Shenly; Miller, Bruce L; Rankin, Katherine P

    2015-12-01

    Conversational storytelling integrates diverse cognitive and socio-emotional abilities that critically differ across neurodegenerative disease groups. Storytelling patterns may have diagnostic relevance and predict anatomic changes. The present study employed mixed methods discourse and quantitative analyses to delineate patterns of storytelling across focal neurodegenerative disease groups, and to clarify the neuroanatomical contributions to common storytelling characteristics. Transcripts of spontaneous social interactions of 46 participants (15 behavioral variant frontotemporal dementia (bvFTD), 7 semantic variant primary progressive aphasia (svPPA), 12 Alzheimer's disease (AD), and 12 healthy older normal controls (NC)) were analyzed for storytelling frequency and characteristics, and videos of the interactions were rated for patients' level of social attentiveness. Compared to controls, svPPAs told more stories and autobiographical stories, and perseverated on aspects of self during the interaction, whereas ADs told fewer autobiographical stories than NCs. svPPAs and bvFTDs were rated as less attentive to social cues. Aspects of storytelling were related to diverse cognitive and socio-emotional functions, and voxel-based anatomic analysis of structural magnetic resonance imaging revealed that temporal organization, narrative evaluations patterns, and social attentiveness correlated with atrophy corresponding to known intrinsic connectivity networks, including the default mode, limbic, salience, and stable task control networks. Differences in spontaneous storytelling among neurodegenerative groups elucidated diverse cognitive, socio-emotional, and neural contributions to narrative production, with implications for diagnostic screening and therapeutic intervention. PMID:26485159

  14. Mesenchymal stem cells: potential in treatment of neurodegenerative diseases.

    PubMed

    Tanna, Tanmay; Sachan, Vatsal

    2014-01-01

    Mesenchymal Stem Cells or Marrow Stromal Cells (MSCs) have long been viewed as a potent tool for regenerative cell therapy. MSCs are easily accessible from both healthy donor and patient tissue and expandable in vitro on a therapeutic scale without posing significant ethical or procedural problems. MSC based therapies have proven to be effective in preclinical studies for graft versus host disease, stroke, myocardial infarction, pulmonary fibrosis, autoimmune disorders and many other conditions and are currently undergoing clinical trials at a number of centers all over the world. MSCs are also being extensively researched as a therapeutic tool against neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS), Huntington's disease (HD) and Multiple Sclerosis (MS). MSCs have been discussed with regard to two aspects in the context of neurodegenerative diseases: their ability to transdifferentiate into neural cells under specific conditions and their neuroprotective and immunomodulatory effects. When transplanted into the brain, MSCs produce neurotrophic and growth factors that protect and induce regeneration of damaged tissue. Additionally, MSCs have also been explored as gene delivery vehicles, for example being genetically engineered to over express glial-derived or brain-derived neurotrophic factor in the brain. Clinical trials involving MSCs are currently underway for MS, ALS, traumatic brain injuries, spinal cord injuries and stroke. In the present review, we explore the potential that MSCs hold with regard to the aforementioned neurodegenerative diseases and the current scenario with reference to the same.

  15. Human-induced pluripotent stem cells: potential for neurodegenerative diseases.

    PubMed

    Ross, Christopher A; Akimov, Sergey S

    2014-09-15

    The cell biology of human neurodegenerative diseases has been difficult to study till recently. The development of human induced pluripotent stem cell (iPSC) models has greatly enhanced our ability to model disease in human cells. Methods have recently been improved, including increasing reprogramming efficiency, introducing non-viral and non-integrating methods of cell reprogramming, and using novel gene editing techniques for generating genetically corrected lines from patient-derived iPSCs, or for generating mutations in control cell lines. In this review, we highlight accomplishments made using iPSC models to study neurodegenerative disorders such as Huntington's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis, Fronto-Temporal Dementia, Alzheimer's disease, Spinomuscular Atrophy and other polyglutamine diseases. We review disease-related phenotypes shown in patient-derived iPSCs differentiated to relevant neural subtypes, often with stressors or cell "aging", to enhance disease-specific phenotypes. We also discuss prospects for the future of using of iPSC models of neurodegenerative disorders, including screening and testing of therapeutic compounds, and possibly of cell transplantation in regenerative medicine. The new iPSC models have the potential to greatly enhance our understanding of pathogenesis and to facilitate the development of novel therapeutics.

  16. Pain in Neurodegenerative Disease: Current Knowledge and Future Perspectives

    PubMed Central

    de Tommaso, Marina; Arendt-Nielsen, Lars; Defrin, Ruth; Kunz, Miriam; Pickering, Gisele; Valeriani, Massimiliano

    2016-01-01

    Neurodegenerative diseases are going to increase as the life expectancy is getting longer. The management of neurodegenerative diseases such as Alzheimer's disease (AD) and other dementias, Parkinson's disease (PD) and PD related disorders, motor neuron diseases (MND), Huntington's disease (HD), spinocerebellar ataxia (SCA), and spinal muscular atrophy (SMA), is mainly addressed to motor and cognitive impairment, with special care to vital functions as breathing and feeding. Many of these patients complain of painful symptoms though their origin is variable, and their presence is frequently not considered in the treatment guidelines, leaving their management to the decision of the clinicians alone. However, studies focusing on pain frequency in such disorders suggest a high prevalence of pain in selected populations from 38 to 75% in AD, 40% to 86% in PD, and 19 to 85% in MND. The methods of pain assessment vary between studies so the type of pain has been rarely reported. However, a prevalent nonneuropathic origin of pain emerged for MND and PD. In AD, no data on pain features are available. No controlled therapeutic trials and guidelines are currently available. Given the relevance of pain in neurodegenerative disorders, the comprehensive understanding of mechanisms and predisposing factors, the application and validation of specific scales, and new specific therapeutic trials are needed. PMID:27313396

  17. Central projections of auditory receptor neurons of crickets.

    PubMed

    Imaizumi, Kazuo; Pollack, Gerald S

    2005-12-19

    We describe the central projections of physiologically characterized auditory receptor neurons of crickets as revealed by confocal microscopy. Receptors tuned to ultrasonic frequencies (similar to those produced by echolocating, insectivorous bats), to a mid-range of frequencies, and a subset of those tuned to low, cricket-like frequencies have similar projections, terminating medially within the auditory neuropile. Quantitative analysis shows that despite the general similarity of these projections they are tonotopic, with receptors tuned to lower frequencies terminating more medially. Another subset of cricket-song-tuned receptors projects more laterally and posteriorly than the other types. Double-fills of receptors and identified interneurons show that the three medially projecting receptor types are anatomically well positioned to provide monosynaptic input to interneurons that relay auditory information to the brain and to interneurons that modify this ascending information. The more laterally and posteriorly branching receptor type may not interact directly with this ascending pathway, but is well positioned to provide direct input to an interneuron that carries auditory information to more posterior ganglia. These results suggest that information about cricket song is segregated into functionally different pathways as early as the level of receptor neurons. Ultrasound-tuned and mid-frequency tuned receptors have approximately twice as many varicosities, which are sites of transmitter release, per receptor as either anatomical type of cricket-song-tuned receptor. This may compensate in part for the numerical under-representation of these receptor types.

  18. Cockroach homologs of praying mantis peripheral auditory system components.

    PubMed

    Yager, David D

    2005-07-01

    This study identifies the cuticular metathoracic structures in earless cockroaches that are the homologs to the peripheral auditory components in their sister taxon, praying mantids, and defines the nature of the cuticular transition from earless to eared in the Dictyoptera. The single, midline ear of mantids comprises an auditory chamber with complex walls that contain the tympana and chordotonal transduction elements. The corresponding area in cockroaches, between the furcasternum and coxae, has many socketed hairs arranged in discrete fields and the Nerve 7 chordotonal organ, the homolog of the mantis tympanal organ. The Nerve 7 chordotonal organ attaches at the apex of the lateral ventropleurite (LVp), which has the same shape and general structure as an auditory chamber wall. High-speed video shows that when the coxa moves toward the midline, the LVp rotates medially to stimulate socketed hairs, and also moves like a triangular hinge giving the chordotonal organ maximal in-out stimulation. Formation of the mantis auditory chamber from the LVp and adjacent structures would involve only enlargement, a shift toward the midline, and a mild rotation. Almost all proprioceptive function would be lost, which may constitute the major cost of building and maintaining the mantis ear. Isolation from leg movement dictates the position of the mantis ear in the midline and the rigid frame, formed by the cuticular knobs, which protects the chordotonal organs. PMID:15887266

  19. Auditory hallucinations inhibit exogenous activation of auditory association cortex.

    PubMed

    David, A S; Woodruff, P W; Howard, R; Mellers, J D; Brammer, M; Bullmore, E; Wright, I; Andrew, C; Williams, S C

    1996-03-22

    Percepts unaccompanied by a veridical stimulus, such as hallucinations, provide an opportunity for mapping the neural correlates of conscious perception. Functional magnetic resonance imaging (fMRI) can reveal localized changes in blood oxygenation in response to actual as well as imagined sensory stimulation. The safe repeatability of fMRI enabled us to study a patient with schizophrenia while he was experiencing auditory hallucinations and when hallucination-free (with supporting data from a second case). Cortical activation was measured in response to periodic exogenous auditory and visual stimulations using time series regression analysis. Functional brain images were obtained in each hallucination condition both while the patient was on and off antipsychotic drugs. The response of the temporal cortex to exogenous auditory stimulation (speech) was markedly reduced when the patient was experiencing hallucinating voices addressing him, regardless of medication. Visual cortical activation (to flashing lights) remained normal over four scans. From the results of this study and previous work on visual hallucinations we conclude that hallucinations coincide with maximal activation of the sensory and association cortex, specific to the modality of the experience. PMID:8724677

  20. Adaptation in the auditory system: an overview

    PubMed Central

    Pérez-González, David; Malmierca, Manuel S.

    2014-01-01

    The early stages of the auditory system need to preserve the timing information of sounds in order to extract the basic features of acoustic stimuli. At the same time, different processes of neuronal adaptation occur at several levels to further process the auditory information. For instance, auditory nerve fiber responses already experience adaptation of their firing rates, a type of response that can be found in many other auditory nuclei and may be useful for emphasizing the onset of the stimuli. However, it is at higher levels in the auditory hierarchy where more sophisticated types of neuronal processing take place. For example, stimulus-specific adaptation, where neurons show adaptation to frequent, repetitive stimuli, but maintain their responsiveness to stimuli with different physical characteristics, thus representing a distinct kind of processing that may play a role in change and deviance detection. In the auditory cortex, adaptation takes more elaborate forms, and contributes to the processing of complex sequences, auditory scene analysis and attention. Here we review the multiple types of adaptation that occur in the auditory system, which are part of the pool of resources that the neurons employ to process the auditory scene, and are critical to a proper understanding of the neuronal mechanisms that govern auditory perception. PMID:24600361

  1. On the externalization of auditory images

    NASA Technical Reports Server (NTRS)

    Durlach, N. I.; Rigopulos, A.; Pang, X. D.; Woods, W. S.; Kulkarni, A.; Colburn, H. S.; Wenzel, E. M.

    1992-01-01

    An acoustic image is said to be 'externalized' if the sound source appears to the listener to lie outside the head. The purpose of the note is to put the phenomenon of externalization of auditory images in proper perspective. It points out that the listener's pinnae (the so-called 'pinna factor') is only one of many factors that determine the extent to which a sound image is externalized and that the relative importance of these factors is not yet clear. The note begins with some general comments on externalization. It then considers the effect of reverberation. It examines head movements, visual effects, and other factors. It concludes with remarks on externalization's relation to head-related transfer functions (HRTFs), the pinna factor, and improved experimental instrumentation.

  2. Stream segregation in the anesthetized auditory cortex

    PubMed Central

    Scholes, Chris; Palmer, Alan R.; Sumner, Christian J.

    2015-01-01

    Auditory stream segregation describes the way that sounds are perceptually segregated into groups or streams on the basis of perceptual attributes such as pitch or spectral content. For sequences of pure tones, segregation depends on the tones' proximity in frequency and time. In the auditory cortex (and elsewhere) responses to sequences of tones are dependent on stimulus conditions in a similar way to the perception of these stimuli. However, although highly dependent on stimulus conditions, perception is also clearly influenced by factors unrelated to the stimulus, such as attention. Exactly how ‘bottom-up’ sensory processes and non-sensory ‘top-down’ influences interact is still not clear. Here, we recorded responses to alternating tones (ABAB …) of varying frequency difference (FD) and rate of presentation (PR) in the auditory cortex of anesthetized guinea-pigs. These data complement previous studies, in that top-down processing resulting from conscious perception should be absent or at least considerably attenuated. Under anesthesia, the responses of cortical neurons to the tone sequences adapted rapidly, in a manner sensitive to both the FD and PR of the sequences. While the responses to tones at frequencies more distant from neuron best frequencies (BFs) decreased as the FD increased, the responses to tones near to BF increased, consistent with a release from adaptation, or forward suppression. Increases in PR resulted in reductions in responses to all tones, but the reduction was greater for tones further from BF. Although asymptotically adapted responses to tones showed behavior that was qualitatively consistent with perceptual stream segregation, responses reached asymptote within 2 s, and responses to all tones were very weak at high PRs (>12 tones per second). A signal-detection model, driven by the cortical population response, made decisions that were dependent on both FD and PR in ways consistent with perceptual stream segregation. This

  3. Testing the dual-pathway model for auditory processing in human cortex.

    PubMed

    Zündorf, Ida C; Lewald, Jörg; Karnath, Hans-Otto

    2016-01-01

    Analogous to the visual system, auditory information has been proposed to be processed in two largely segregated streams: an anteroventral ("what") pathway mainly subserving sound identification and a posterodorsal ("where") stream mainly subserving sound localization. Despite the popularity of this assumption, the degree of separation of spatial and non-spatial auditory information processing in cortex is still under discussion. In the present study, a statistical approach was implemented to investigate potential behavioral dissociations for spatial and non-spatial auditory processing in stroke patients, and voxel-wise lesion analyses were used to uncover their neural correlates. The results generally provided support for anatomically and functionally segregated auditory networks. However, some degree of anatomo-functional overlap between "what" and "where" aspects of processing was found in the superior pars opercularis of right inferior frontal gyrus (Brodmann area 44), suggesting the potential existence of a shared target area of both auditory streams in this region. Moreover, beyond the typically defined posterodorsal stream (i.e., posterior superior temporal gyrus, inferior parietal lobule, and superior frontal sulcus), occipital lesions were found to be associated with sound localization deficits. These results, indicating anatomically and functionally complex cortical networks for spatial and non-spatial auditory processing, are roughly consistent with the dual-pathway model of auditory processing in its original form, but argue for the need to refine and extend this widely accepted hypothesis. PMID:26388552

  4. Asymmetry in primary auditory cortex activity in tinnitus patients and controls.

    PubMed

    Geven, L I; de Kleine, E; Willemsen, A T M; van Dijk, P

    2014-01-01

    Tinnitus is a bothersome phantom sound percept and its neural correlates are not yet disentangled. Previously published papers, using [(18)F]-fluoro-deoxyglucose positron emission tomography (FDG-PET), have suggested an increased metabolism in the left primary auditory cortex in tinnitus patients. This unilateral hyperactivity has been used as a target in localized treatments such as transcranial magnetic stimulation. The purpose of the current study was to test whether left-sided hyperactivity in the auditory cortex is specific to tinnitus or is a general characteristic of the auditory system unrelated to tinnitus. Therefore, FDG-PET was used to measure brain metabolism in 20 tinnitus patients and to compare their results to those in 19 control subjects without tinnitus. In contrast to our expectation, there was no hyperactivity associated with tinnitus. Nevertheless, the activity in the left primary auditory cortex was higher than in the right primary auditory cortex, but this asymmetry was present in both tinnitus patients and control subjects. In contrast, the lateralization in secondary auditory cortex was opposite, with higher activation in the right hemisphere. These data show that hemisphere asymmetries in the metabolic resting activity of the auditory cortex are present, but these are not associated with tinnitus and are a normal characteristic of the normal brain. PMID:24161276

  5. How modality specific is processing of auditory and visual rhythms?

    PubMed

    Pasinski, Amanda C; McAuley, J Devin; Snyder, Joel S

    2016-02-01

    The present study used ERPs to test the extent to which temporal processing is modality specific or modality general. Participants were presented with auditory and visual temporal patterns that consisted of initial two- or three-event beginning patterns. This delineated a constant standard time interval, followed by a two-event ending pattern delineating a variable test interval. Participants judged whether they perceived the pattern as a whole to be speeding up or slowing down. The contingent negative variation (CNV), a negative potential reflecting temporal expectancy, showed a larger amplitude for the auditory modality compared to the visual modality but a high degree of similarity in scalp voltage patterns across modalities, suggesting that the CNV arises from modality-general processes. A late, memory-dependent positive component (P3) also showed similar patterns across modalities.

  6. Adaptation to delayed auditory feedback

    NASA Technical Reports Server (NTRS)

    Katz, D. I.; Lackner, J. R.

    1977-01-01

    Delayed auditory feedback disrupts the production of speech, causing an increase in speech duration as well as many articulatory errors. To determine whether prolonged exposure to delayed auditory feedback (DAF) leads to adaptive compensations in speech production, 10 subjects were exposed in separate experimental sessions to both incremental and constant-delay exposure conditions. Significant adaptation occurred for syntactically structured stimuli in the form of increased speaking rates. After DAF was removed, aftereffects were apparent for all stimulus types in terms of increased speech rates. A carry-over effect from the first to the second experimental session was evident as long as 29 days after the first session. The use of strategies to overcome DAF and the differences between adaptation to DAF and adaptation to visual rearrangement are discussed.

  7. Reality of auditory verbal hallucinations

    PubMed Central

    Valkonen-Korhonen, Minna; Holi, Matti; Therman, Sebastian; Lehtonen, Johannes; Hari, Riitta

    2009-01-01

    Distortion of the sense of reality, actualized in delusions and hallucinations, is the key feature of psychosis but the underlying neuronal correlates remain largely unknown. We studied 11 highly functioning subjects with schizophrenia or schizoaffective disorder while they rated the reality of auditory verbal hallucinations (AVH) during functional magnetic resonance imaging (fMRI). The subjective reality of AVH correlated strongly and specifically with the hallucination-related activation strength of the inferior frontal gyri (IFG), including the Broca's language region. Furthermore, how real the hallucination that subjects experienced was depended on the hallucination-related coupling between the IFG, the ventral striatum, the auditory cortex, the right posterior temporal lobe, and the cingulate cortex. Our findings suggest that the subjective reality of AVH is related to motor mechanisms of speech comprehension, with contributions from sensory and salience-detection-related brain regions as well as circuitries related to self-monitoring and the experience of agency. PMID:19620178

  8. The human auditory evoked response

    NASA Technical Reports Server (NTRS)

    Galambos, R.

    1974-01-01

    Figures are presented of computer-averaged auditory evoked responses (AERs) that point to the existence of a completely endogenous brain event. A series of regular clicks or tones was administered to the ear, and 'odd-balls' of different intensity or frequency respectively were included. Subjects were asked either to ignore the sounds (to read or do something else) or to attend to the stimuli. When they listened and counted the odd-balls, a P3 wave occurred at 300msec after stimulus. When the odd-balls consisted of omitted clicks or tone bursts, a similar response was observed. This could not have come from auditory nerve, but only from cortex. It is evidence of recognition, a conscious process.

  9. Psychophysiological responses to auditory change.

    PubMed

    Chuen, Lorraine; Sears, David; McAdams, Stephen

    2016-06-01

    A comprehensive characterization of autonomic and somatic responding within the auditory domain is currently lacking. We studied whether simple types of auditory change that occur frequently during music listening could elicit measurable changes in heart rate, skin conductance, respiration rate, and facial motor activity. Participants heard a rhythmically isochronous sequence consisting of a repeated standard tone, followed by a repeated target tone that changed in pitch, timbre, duration, intensity, or tempo, or that deviated momentarily from rhythmic isochrony. Changes in all parameters produced increases in heart rate. Skin conductance response magnitude was affected by changes in timbre, intensity, and tempo. Respiratory rate was sensitive to deviations from isochrony. Our findings suggest that music researchers interpreting physiological responses as emotional indices should consider acoustic factors that may influence physiology in the absence of induced emotions. PMID:26927928

  10. Osteoma of the internal auditory canal.

    PubMed

    Kovacić, J; Subarić, M; Lajtman, Z; Curcić, I

    2001-01-01

    Osteomas of the internal auditory canal, inaccesible to clinical examination, are rare lesions. There are only 14 cases of osteomas and exostoses of the internal auditory canal reported in the international medical literature. A patient with an osteoma of the internal auditory canal is presented, along with differential diagnosis and possible etiologic factors for the lesion. The auditory brainsteam evoked response testing showed increased absolute latencies of 1 wave and discrepancy of the wave morphology due to bony compression of the eight nerve in the internal auditory canal. Computed tomography showed a bony growth in the internal auditory canal. Magnetic response showed no abnormalities. No surgery was performed since the symptoms improved by conservative therapy.

  11. Review of auditory subliminal psychodynamic activation experiments.

    PubMed

    Fudin, R; Benjamin, C

    1991-12-01

    Subliminal psychodynamic activation experiments using auditory stimuli have yielded only a modicum of support for the contention that such activation produces predictable behavioral changes. Problems in many auditory subliminal psychodynamic activation experiments indicate that those predictions have not been tested adequately. The auditory mode of presentation, however, has several methodological advantages over the visual one, the method used in the vast majority of subliminal psychodynamic activation experiments. Consequently, it should be considered in subsequent research in this area. PMID:1805167

  12. Biases in Visual, Auditory, and Audiovisual Perception of Space.

    PubMed

    Odegaard, Brian; Wozny, David R; Shams, Ladan

    2015-12-01

    Localization of objects and events in the environment is critical for survival, as many perceptual and motor tasks rely on estimation of spatial location. Therefore, it seems reasonable to assume that spatial localizations should generally be accurate. Curiously, some previous studies have reported biases in visual and auditory localizations, but these studies have used small sample sizes and the results have been mixed. Therefore, it is not clear (1) if the reported biases in localization responses are real (or due to outliers, sampling bias, or other factors), and (2) whether these putative biases reflect a bias in sensory representations of space or a priori expectations (which may be due to the experimental setup, instructions, or distribution of stimuli). Here, to address these questions, a dataset of unprecedented size (obtained from 384 observers) was analyzed to examine presence, direction, and magnitude of sensory biases, and quantitative computational modeling was used to probe the underlying mechanism(s) driving these effects. Data revealed that, on average, observers were biased towards the center when localizing visual stimuli, and biased towards the periphery when localizing auditory stimuli. Moreover, quantitative analysis using a Bayesian Causal Inference framework suggests that while pre-existing spatial biases for central locations exert some influence, biases in the sensory representations of both visual and auditory space are necessary to fully explain the behavioral data. How are these opposing visual and auditory biases reconciled in conditions in which both auditory and visual stimuli are produced by a single event? Potentially, the bias in one modality could dominate, or the biases could interact/cancel out. The data revealed that when integration occurred in these conditions, the visual bias dominated, but the magnitude of this bias was reduced compared to unisensory conditions. Therefore, multisensory integration not only improves the

  13. Biases in Visual, Auditory, and Audiovisual Perception of Space.

    PubMed

    Odegaard, Brian; Wozny, David R; Shams, Ladan

    2015-12-01

    Localization of objects and events in the environment is critical for survival, as many perceptual and motor tasks rely on estimation of spatial location. Therefore, it seems reasonable to assume that spatial localizations should generally be accurate. Curiously, some previous studies have reported biases in visual and auditory localizations, but these studies have used small sample sizes and the results have been mixed. Therefore, it is not clear (1) if the reported biases in localization responses are real (or due to outliers, sampling bias, or other factors), and (2) whether these putative biases reflect a bias in sensory representations of space or a priori expectations (which may be due to the experimental setup, instructions, or distribution of stimuli). Here, to address these questions, a dataset of unprecedented size (obtained from 384 observers) was analyzed to examine presence, direction, and magnitude of sensory biases, and quantitative computational modeling was used to probe the underlying mechanism(s) driving these effects. Data revealed that, on average, observers were biased towards the center when localizing visual stimuli, and biased towards the periphery when localizing auditory stimuli. Moreover, quantitative analysis using a Bayesian Causal Inference framework suggests that while pre-existing spatial biases for central locations exert some influence, biases in the sensory representations of both visual and auditory space are necessary to fully explain the behavioral data. How are these opposing visual and auditory biases reconciled in conditions in which both auditory and visual stimuli are produced by a single event? Potentially, the bias in one modality could dominate, or the biases could interact/cancel out. The data revealed that when integration occurred in these conditions, the visual bias dominated, but the magnitude of this bias was reduced compared to unisensory conditions. Therefore, multisensory integration not only improves the

  14. The Effects of Auditory Stimulation on Auditory Processing Disorder: A Summary of the Findings

    ERIC Educational Resources Information Center

    Ross-Swain, Deborah

    2007-01-01

    The study's purpose is to determine the efficacy of the Tomatis Method of auditory stimulation as a therapeutic intervention for Auditory Processing Disorders (APD). Forty-one subjects (18 females, 23 males; 4.3-19.8 years old) were evaluated for APD. Performance on standardized tests indicated weaknesses with auditory processing skills. Each…

  15. Effects of Methylphenidate (Ritalin) on Auditory Performance in Children with Attention and Auditory Processing Disorders.

    ERIC Educational Resources Information Center

    Tillery, Kim L.; Katz, Jack; Keller, Warren D.

    2000-01-01

    A double-blind, placebo-controlled study examined effects of methylphenidate (Ritalin) on auditory processing in 32 children with both attention deficit hyperactivity disorder and central auditory processing (CAP) disorder. Analyses revealed that Ritalin did not have a significant effect on any of the central auditory processing measures, although…

  16. Auditory, Visual, and Auditory-Visual Perception of Vowels by Hearing-Impaired Children.

    ERIC Educational Resources Information Center

    Hack, Zarita Caplan; Erber, Norman P.

    1982-01-01

    Vowels were presented through auditory, visual, and auditory-visual modalities to 18 hearing impaired children (12 to 15 years old) having good, intermediate, and poor auditory word recognition skills. All the groups had difficulty with acoustic information and visual information alone. The first two groups had only moderate difficulty identifying…

  17. Corticofugal modulation of peripheral auditory responses

    PubMed Central

    Terreros, Gonzalo; Delano, Paul H.

    2015-01-01

    The auditory efferent system originates in the auditory cortex and projects to the medial geniculate body (MGB), inferior colliculus (IC), cochlear nucleus (CN) and superior olivary complex (SOC) reaching the cochlea through olivocochlear (OC) fibers. This unique neuronal network is organized in several afferent-efferent feedback loops including: the (i) colliculo-thalamic-cortico-collicular; (ii) cortico-(collicular)-OC; and (iii) cortico-(collicular)-CN pathways. Recent experiments demonstrate that blocking ongoing auditory-cortex activity with pharmacological and physical methods modulates the amplitude of cochlear potentials. In addition, auditory-cortex microstimulation independently modulates cochlear sensitivity and the strength of the OC reflex. In this mini-review, anatomical and physiological evidence supporting the presence of a functional efferent network from the auditory cortex to the cochlear receptor is presented. Special emphasis is given to the corticofugal effects on initial auditory processing, that is, on CN, auditory nerve and cochlear responses. A working model of three parallel pathways from the auditory cortex to the cochlea and auditory nerve is proposed. PMID:26483647

  18. Bat's auditory system: Corticofugal feedback and plasticity

    NASA Astrophysics Data System (ADS)

    Suga, Nobuo

    2001-05-01

    The auditory system of the mustached bat consists of physiologically distinct subdivisions for processing different types of biosonar information. It was found that the corticofugal (descending) auditory system plays an important role in improving and adjusting auditory signal processing. Repetitive acoustic stimulation, cortical electrical stimulation or auditory fear conditioning evokes plastic changes of the central auditory system. The changes are based upon egocentric selection evoked by focused positive feedback associated with lateral inhibition. Focal electric stimulation of the auditory cortex evokes short-term changes in the auditory cortex and subcortical auditory nuclei. An increase in a cortical acetylcholine level during the electric stimulation changes the cortical changes from short-term to long-term. There are two types of plastic changes (reorganizations): centripetal best frequency shifts for expanded reorganization of a neural frequency map and centrifugal best frequency shifts for compressed reorganization of the map. Which changes occur depends on the balance between inhibition and facilitation. Expanded reorganization has been found in different sensory systems and different species of mammals, whereas compressed reorganization has been thus far found only in the auditory subsystems highly specialized for echolocation. The two types of reorganizations occur in both the frequency and time domains. [Work supported by NIDCO DC00175.

  19. Central auditory function of deafness genes.

    PubMed

    Willaredt, Marc A; Ebbers, Lena; Nothwang, Hans Gerd

    2014-06-01

    The highly variable benefit of hearing devices is a serious challenge in auditory rehabilitation. Various factors contribute to this phenomenon such as the diversity in ear defects, the different extent of auditory nerve hypoplasia, the age of intervention, and cognitive abilities. Recent analyses indicate that, in addition, central auditory functions of deafness genes have to be considered in this context. Since reduced neuronal activity acts as the common denominator in deafness, it is widely assumed that peripheral deafness influences development and function of the central auditory system in a stereotypical manner. However, functional characterization of transgenic mice with mutated deafness genes demonstrated gene-specific abnormalities in the central auditory system as well. A frequent function of deafness genes in the central auditory system is supported by a genome-wide expression study that revealed significant enrichment of these genes in the transcriptome of the auditory brainstem compared to the entire brain. Here, we will summarize current knowledge of the diverse central auditory functions of deafness genes. We furthermore propose the intimately interwoven gene regulatory networks governing development of the otic placode and the hindbrain as a mechanistic explanation for the widespread expression of these genes beyond the cochlea. We conclude that better knowledge of central auditory dysfunction caused by genetic alterations in deafness genes is required. In combination with improved genetic diagnostics becoming currently available through novel sequencing technologies, this information will likely contribute to better outcome prediction of hearing devices.

  20. Models of plasticity in spatial auditory processing.

    PubMed

    Shinn-Cunningham, B

    2001-01-01

    Both psychophysical and physiological studies have examined plasticity of spatial auditory processing. While there is a great deal known about how the system computes basic cues that influence spatial perception, less is known about how these cues are integrated to form spatial percepts and how the auditory system adapts and calibrates in order to maintain accurate spatial perception. After summarizing evidence for plasticity in the spatial auditory pathway, this paper reviews a statistical, decision-theory model of short-term plasticity and a system-level model of the spatial auditory pathway that may help elucidate how long- and short-term experiences influence the computations underlying spatial hearing.

  1. Evaluation of the auditory system: an update.

    PubMed

    Brackmann, D E; Forquer, B D

    1983-01-01

    The purpose of this paper is to describe the audiologic techniques currently used at the Otologic Medical Group, Inc. Auditory threshold in children is determined by a combination of behavioral and objective audiometric techniques. When behavioral techniques fail, auditory brainstem response audiometry combined with impedance audiometry gives a good estimate of hearing thresholds. Impedance audiometry is a valuable addition to the diagnosis of cochlear otosclerosis. This technique is also of benefit in the neurotologic evaluation. Auditory brainstem response audiometry is the most accurate method of detecting an acoustic tumor. We no longer use SISI, tone decay, or Bekesy tests. The newer audiometric studies have greatly improved our evaluation of the auditory system.

  2. Eye closure reduces the cross-modal memory impairment caused by auditory distraction.

    PubMed

    Perfect, Timothy J; Andrade, Jackie; Eagan, Irene

    2011-07-01

    Eyewitnesses instructed to close their eyes during retrieval recall more correct and fewer incorrect visual and auditory details. This study tested whether eye closure causes these effects through a reduction in environmental distraction. Sixty participants watched a staged event before verbally answering questions about it in the presence of auditory distraction or in a quiet control condition. Participants were instructed to close or not close their eyes during recall. Auditory distraction did not affect correct recall, but it increased erroneous recall of visual and auditory details. Instructed eye closure reduced this effect equally for both modalities. The findings support the view that eye closure removes the general resource load of monitoring the environment rather than reducing competition for modality-specific resources. PMID:21417514

  3. Pathogenic protein seeding in Alzheimer disease and other neurodegenerative disorders.

    PubMed

    Jucker, Mathias; Walker, Lary C

    2011-10-01

    The misfolding and aggregation of specific proteins is a seminal occurrence in a remarkable variety of neurodegenerative disorders. In Alzheimer disease (the most prevalent cerebral proteopathy), the two principal aggregating proteins are β-amyloid (Aβ) and tau. The abnormal assemblies formed by conformational variants of these proteins range in size from small oligomers to the characteristic lesions that are visible by optical microscopy, such as senile plaques and neurofibrillary tangles. Pathologic similarities with prion disease suggest that the formation and spread of these proteinaceous lesions might involve a common molecular mechanism-corruptive protein templating. Experimentally, cerebral β-amyloidosis can be exogenously induced by exposure to dilute brain extracts containing aggregated Aβ seeds. The amyloid-inducing agent probably is Aβ itself, in a conformation generated most effectively in the living brain. Once initiated, Aβ lesions proliferate within and among brain regions. The induction process is governed by the structural and biochemical nature of the Aβ seed, as well as the attributes of the host, reminiscent of pathogenically variant prion strains. The concept of prionlike induction and spreading of pathogenic proteins recently has been expanded to include aggregates of tau, α-synuclein, huntingtin, superoxide dismutase-1, and TDP-43, which characterize such human neurodegenerative disorders as frontotemporal lobar degeneration, Parkinson/Lewy body disease, Huntington disease, and amyotrophic lateral sclerosis. Our recent finding that the most effective Aβ seeds are small and soluble intensifies the search in bodily fluids for misfolded protein seeds that are upstream in the proteopathic cascade, and thus could serve as predictive diagnostics and the targets of early, mechanism-based interventions. Establishing the clinical implications of corruptive protein templating will require further mechanistic and epidemiologic investigations

  4. Chronic traumatic encephalopathy pathology in a neurodegenerative disorders brain bank.

    PubMed

    Bieniek, Kevin F; Ross, Owen A; Cormier, Kerry A; Walton, Ronald L; Soto-Ortolaza, Alexandra; Johnston, Amelia E; DeSaro, Pamela; Boylan, Kevin B; Graff-Radford, Neill R; Wszolek, Zbigniew K; Rademakers, Rosa; Boeve, Bradley F; McKee, Ann C; Dickson, Dennis W

    2015-12-01

    Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder linked to repetitive traumatic brain injury (TBI) and characterized by deposition of hyperphosphorylated tau at the depths of sulci. We sought to determine the presence of CTE pathology in a brain bank for neurodegenerative disorders for individuals with and without a history of contact sports participation. Available medical records of 1721 men were reviewed for evidence of past history of injury or participation in contact sports. Subsequently, cerebral cortical samples were processed for tau immunohistochemistry in cases with a documented history of sports exposure as well as age- and disease-matched men and women without such exposure. For cases with available frozen tissue, genetic analysis was performed for variants in APOE, MAPT, and TMEM106B. Immunohistochemistry revealed 21 of 66 former athletes had cortical tau pathology consistent with CTE. CTE pathology was not detected in 198 individuals without exposure to contact sports, including 33 individuals with documented single-incident TBI sustained from falls, motor vehicle accidents, domestic violence, or assaults. Among those exposed to contact sports, those with CTE pathology did not differ from those without CTE pathology with respect to noted clinicopathologic features. There were no significant differences in genetic variants for those with CTE pathology, but we observed a slight increase in MAPT H1 haplotype, and there tended to be fewer homozygous carriers of the protective TMEM106B rs3173615 minor allele in those with sports exposure and CTE pathology compared to those without CTE pathology. In conclusion, this study has identified a small, yet significant, subset of individuals with neurodegenerative disorders and concomitant CTE pathology. CTE pathology was only detected in individuals with documented participation in contact sports. Exposure to contact sports was the greatest risk factor for CTE pathology. Future

  5. How Does Auditory Training Work? Joined-Up Thinking and Listening.

    PubMed

    Ferguson, Melanie; Henshaw, Helen

    2015-11-01

    Auditory training aims to compensate for degradation in the auditory signal and is offered as an intervention to help alleviate the most common complaint in people with hearing loss, understanding speech in a background noise. Yet there remain many unanswered questions. This article reviews some of the key pieces of evidence that assess the evidence for whether, and how, auditory training benefits adults with hearing loss. The evidence supports that improvements occur on the trained task; however, transfer of that learning to generalized real-world benefit is much less robust. For more than a decade, there has been an increasing awareness of the role that cognition plays in listening. But more recently in the auditory training literature, there has been an increased focus on assessing how cognitive performance relevant for listening may improve with training. We argue that this is specifically the case for measures that index executive processes, such as monitoring, attention switching, and updating of working memory, all of which are required for successful listening and communication in challenging or adverse listening conditions. We propose combined auditory-cognitive training approaches, where training interventions develop cognition embedded within auditory tasks, which are most likely to offer generalized benefits to the real-world listening abilities of people with hearing loss. PMID:27587911

  6. Redox Processes in Neurodegenerative Disease Involving Reactive Oxygen Species

    PubMed Central

    Kovacic, Peter; Somanathan, Ratnasamy

    2012-01-01

    Much attention has been devoted to neurodegenerative diseases involving redox processes. This review comprises an update involving redox processes reported in the considerable literature in recent years. The mechanism involves reactive oxygen species and oxidative stress, usually in the brain. There are many examples including Parkinson’s, Huntington’s, Alzheimer’s, prions, Down’s syndrome, ataxia, multiple sclerosis, Creutzfeldt-Jacob disease, amyotrophic lateral sclerosis, schizophrenia, and Tardive Dyskinesia. Evidence indicates a protective role for antioxidants, which may have clinical implications. A multifaceted approach to mode of action appears reasonable. PMID:23730253

  7. Dysphagia in stroke, neurodegenerative disease, and advanced dementia.

    PubMed

    Altman, Kenneth W; Richards, Amanda; Goldberg, Leanne; Frucht, Steven; McCabe, Daniel J

    2013-12-01

    Aspiration risk from dysphagia increases with central and peripheral neurologic disease. Stroke, microvascular ischemic disease, a spectrum of neurodegenerative diseases, and advancing dementia all have unique aspects. However, there are distinct commonalities in this population. Increasing nutritional requirements to stave off oropharyngeal muscular atrophy and a sedentary lifestyle further tax the patient's abilities to safely swallow. This article reviews stroke, muscular dystrophy, myasthenia gravis, multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, and advanced dementia. Approaches to screening and evaluation, recognizing sentinel indicators of decline that increase aspiration risk, and options for managing global laryngeal dysfunction are also presented. PMID:24262965

  8. Mitochondrial quality control: decommissioning power plants in neurodegenerative diseases.

    PubMed

    Mukherjee, Rukmini; Chakrabarti, Oishee

    2013-01-01

    The cell has an intricate quality control system to protect its mitochondria from oxidative stress. This surveillance system is multi-tiered and comprises molecules that are present inside the mitochondria, in the cytosol, and in other organelles like the nucleus and endoplasmic reticulum. These molecules cross talk with each other and protect the mitochondria from oxidative stress. Oxidative stress is a fundamental part of early disease pathogenesis of neurodegenerative diseases. These disorders also damage the cellular quality control machinery that protects the cell against oxidative stress. This exacerbates the oxidative damage and causes extensive neuronal cell death that is characteristic of neurodegeneration. PMID:24288463

  9. [Induced pluripotent stem cells revolutionise research of neurodegenerative diseases].

    PubMed

    Schmidt, Sissel Ida; Knudsen, Matias Jul; Barnkob, Helle Bogetofte; Meyer, Morten

    2016-07-18

    Research into the causes of neurodegenerative diseases like Parkinson's- and Alzheimer's disease has long been hampered by the lack of access to live disease-afflicted neurons for in vitro studies. The introduction of induced pluripotent stem (iPS) cells has made such studies possible. iPS cells can be reprogrammed from somatic patient-derived cells (e.g. skin cells) and differentiated into any cell type of the body. This allows for the production of neurons, which have the genetic background of the patients and show disease-relevant phenotypes.

  10. Corruption and spread of pathogenic proteins in neurodegenerative diseases.

    PubMed

    Walker, Lary C; LeVine, Harry

    2012-09-28

    With advancing age, the brain becomes increasingly susceptible to neurodegenerative diseases, most of which are characterized by the misfolding and errant aggregation of certain proteins. The induction of aggregation involves a crystallization-like seeding mechanism by which a specific protein is structurally corrupted by its misfolded conformer. The latest research indicates that, once formed, proteopathic seeds can spread from one locale to another via cellular uptake, transport, and release. Impeding this process could represent a unified therapeutic strategy for slowing the progression of a wide range of currently intractable disorders.

  11. Dysphagia in stroke, neurodegenerative disease, and advanced dementia.

    PubMed

    Altman, Kenneth W; Richards, Amanda; Goldberg, Leanne; Frucht, Steven; McCabe, Daniel J

    2013-12-01

    Aspiration risk from dysphagia increases with central and peripheral neurologic disease. Stroke, microvascular ischemic disease, a spectrum of neurodegenerative diseases, and advancing dementia all have unique aspects. However, there are distinct commonalities in this population. Increasing nutritional requirements to stave off oropharyngeal muscular atrophy and a sedentary lifestyle further tax the patient's abilities to safely swallow. This article reviews stroke, muscular dystrophy, myasthenia gravis, multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, and advanced dementia. Approaches to screening and evaluation, recognizing sentinel indicators of decline that increase aspiration risk, and options for managing global laryngeal dysfunction are also presented.

  12. Stem cells for the treatment of neurodegenerative diseases.

    PubMed

    Dantuma, Elise; Merchant, Stephanie; Sugaya, Kiminobu

    2010-12-10

    Stem cells offer an enormous pool of resources for the understanding of the human body. One proposed use of stem cells has been as an autologous therapy. The use of stem cells for neurodegenerative diseases has become of interest. Clinical applications of stem cells for Alzheimer disease, Parkinson disease, amyotrophic lateral sclerosis, and multiple sclerosis will increase in the coming years, and although great care will need to be taken when moving forward with prospective treatments, the application of stem cells is highly promising.

  13. Effects of Emotionally Charged Auditory Stimulation on Gait Performance in the Elderly: A Preliminary Study

    PubMed Central

    Rizzo, John-Ross; Raghavan, Preeti; McCrery, J.R.; Oh-Park, Mooyeon; Verghese, Joe

    2015-01-01

    Objectives To evaluate the effect of a novel divided attention task—walking under auditory constraints—on gait performance in older adults and to determine whether this effect was moderated by cognitive status. Design Validation cohort. Setting General community. Participants Ambulatory older adults without dementia (N=104). Interventions Not applicable. Main Outcome Measures In this pilot study, we evaluated walking under auditory constraints in 104 older adults who completed 3 pairs of walking trials on a gait mat under 1 of 3 randomly assigned conditions: 1 pair without auditory stimulation and 2 pairs with emotionally charged auditory stimulation with happy or sad sounds. Results The mean age of subjects was 80.6±4.9 years, and 63% (n=66) were women. The mean velocity during normal walking was 97.9±20.6cm/s, and the mean cadence was 105.1±9.9 steps/min. The effect of walking under auditory constraints on gait characteristics was analyzed using a 2-factorial analysis of variance with a 1-between factor (cognitively intact and minimal cognitive impairment groups) and a 1-within factor (type of auditory stimuli). In both happy and sad auditory stimulation trials, cognitively intact older adults (n=96) showed an average increase of 2.68cm/s in gait velocity (F1.86,191.71=3.99; P=.02) and an average increase of 2.41 steps/min in cadence (F1.75,180.42=10.12; P<.001) as compared with trials without auditory stimulation. In contrast, older adults with minimal cognitive impairment (Blessed test score, 5–10; n=8) showed an average reduction of 5.45cm/s in gait velocity (F1.87,190.83=5.62; P=.005) and an average reduction of 3.88 steps/min in cadence (F1.79,183.10=8.21; P=.001) under both auditory stimulation conditions. Neither baseline fall history nor performance of activities of daily living accounted for these differences. Conclusions Our results provide preliminary evidence of the differentiating effect of emotionally charged auditory stimuli on gait

  14. A Detection-Theoretic Analysis of Auditory Streaming and Its Relation to Auditory Masking

    PubMed Central

    Chang, An-Chieh; Lee, Jungmee; Heo, Inseok

    2016-01-01

    Research on hearing has long been challenged with understanding our exceptional ability to hear out individual sounds in a mixture (the so-called cocktail party problem). Two general approaches to the problem have been taken using sequences of tones as stimuli. The first has focused on our tendency to hear sequences, sufficiently separated in frequency, split into separate cohesive streams (auditory streaming). The second has focused on our ability to detect a change in one sequence, ignoring all others (auditory masking). The two phenomena are clearly related, but that relation has never been evaluated analytically. This article offers a detection-theoretic analysis of the relation between multitone streaming and masking that underscores the expected similarities and differences between these phenomena and the predicted outcome of experiments in each case. The key to establishing this relation is the function linking performance to the information divergence of the tone sequences, DKL (a measure of the statistical separation of their parameters). A strong prediction is that streaming and masking of tones will be a common function of DKL provided that the statistical properties of sequences are symmetric. Results of experiments are reported supporting this prediction. PMID:27641681

  15. A Detection-Theoretic Analysis of Auditory Streaming and Its Relation to Auditory Masking.

    PubMed

    Chang, An-Chieh; Lutfi, Robert; Lee, Jungmee; Heo, Inseok

    2016-01-01

    Research on hearing has long been challenged with understanding our exceptional ability to hear out individual sounds in a mixture (the so-called cocktail party problem). Two general approaches to the problem have been taken using sequences of tones as stimuli. The first has focused on our tendency to hear sequences, sufficiently separated in frequency, split into separate cohesive streams (auditory streaming). The second has focused on our ability to detect a change in one sequence, ignoring all others (auditory masking). The two phenomena are clearly related, but that relation has never been evaluated analytically. This article offers a detection-theoretic analysis of the relation between multitone streaming and masking that underscores the expected similarities and differences between these phenomena and the predicted outcome of experiments in each case. The key to establishing this relation is the function linking performance to the information divergence of the tone sequences, DKL (a measure of the statistical separation of their parameters). A strong prediction is that streaming and masking of tones will be a common function of DKL provided that the statistical properties of sequences are symmetric. Results of experiments are reported supporting this prediction. PMID:27641681

  16. A Detection-Theoretic Analysis of Auditory Streaming and Its Relation to Auditory Masking.

    PubMed

    Chang, An-Chieh; Lutfi, Robert; Lee, Jungmee; Heo, Inseok

    2016-09-18

    Research on hearing has long been challenged with understanding our exceptional ability to hear out individual sounds in a mixture (the so-called cocktail party problem). Two general approaches to the problem have been taken using sequences of tones as stimuli. The first has focused on our tendency to hear sequences, sufficiently separated in frequency, split into separate cohesive streams (auditory streaming). The second has focused on our ability to detect a change in one sequence, ignoring all others (auditory masking). The two phenomena are clearly related, but that relation has never been evaluated analytically. This article offers a detection-theoretic analysis of the relation between multitone streaming and masking that underscores the expected similarities and differences between these phenomena and the predicted outcome of experiments in each case. The key to establishing this relation is the function linking performance to the information divergence of the tone sequences, DKL (a measure of the statistical separation of their parameters). A strong prediction is that streaming and masking of tones will be a common function of DKL provided that the statistical properties of sequences are symmetric. Results of experiments are reported supporting this prediction.

  17. Adenosine and the Auditory System

    PubMed Central

    Vlajkovic, Srdjan M; Housley, Gary D; Thorne, Peter R

    2009-01-01

    Adenosine is a signalling molecule that modulates cellular activity in the central nervous system and peripheral organs via four G protein-coupled receptors designated A1, A2A, A2B, and A3. This review surveys the literature on the role of adenosine in auditory function, particularly cochlear function and its protection from oxidative stress. The specific tissue distribution of adenosine receptors in the mammalian cochlea implicates adenosine signalling in sensory transduction and auditory neurotransmission although functional studies have demonstrated that adenosine stimulates cochlear blood flow, but does not alter the resting and sound-evoked auditory potentials. An interest in a potential otoprotective role for adenosine has recently evolved, fuelled by the capacity of A1 adenosine receptors to prevent cochlear injury caused by acoustic trauma and ototoxic drugs. The balance between A1 and A2A receptors is conceived as critical for cochlear response to oxidative stress, which is an underlying mechanism of the most common inner ear pathologies (e.g. noise-induced and age-related hearing loss, drug ototoxicity). Enzymes involved in adenosine metabolism, adenosine kinase and adenosine deaminase, are also emerging as attractive targets for controlling oxidative stress in the cochlea. Other possible targets include ectonucleotidases that generate adenosine from extracellular ATP, and nucleoside transporters, which regulate adenosine concentrations on both sides of the plasma membrane. Developments of selective adenosine receptor agonists and antagonists that can cross the blood-cochlea barrier are bolstering efforts to develop therapeutic interventions aimed at ameliorating cochlear injury. Manipulations of the adenosine signalling system thus hold significant promise in the therapeutic management of oxidative stress in the cochlea. PMID:20190966

  18. Auditory hallucinations in nonverbal quadriplegics.

    PubMed

    Hamilton, J

    1985-11-01

    When a system for communicating with nonverbal, quadriplegic, institutionalized residents was developed, it was discovered that many were experiencing auditory hallucinations. Nine cases are presented in this study. The "voices" described have many similar characteristics, the primary one being that they give authoritarian commands that tell the residents how to behave and to which the residents feel compelled to respond. Both the relationship of this phenomenon to the theoretical work of Julian Jaynes and its effect on the lives of the residents are discussed.

  19. Active Auditory Mechanics in Insects

    NASA Astrophysics Data System (ADS)

    Robert, D.; Göpfert, M. C.

    2003-02-01

    Evidence is presented that hearing in some insects is an active process. Audition in mosquitoes is used for mate-detection and is supported by antennal receivers, whose sound-induced vibrations are transduced by Johnston's organs. Each of these sensory organs contains ca. 15,000 sensory neurons. As shown by mechanical analysis, a physiologically vulnerable mechanism is at work that nonlinearly enhances the sensitivity and frequency selectivity of antennal hearing. This process of amplification correlates with the electrical activity of the auditory mechanoreceptor units in Johnston's organ.

  20. Creatine for neuroprotection in neurodegenerative disease: end of story?

    PubMed

    Bender, Andreas; Klopstock, Thomas

    2016-08-01

    Creatine (Cr) is a natural compound that plays an important role in cellular energy homeostasis. In addition, it ameliorates oxidative stress, glutamatergic excitotoxicity, and apoptosis in vitro as well as in vivo. Since these pathomechanisms are implicated to play a role in several neurodegenerative diseases, Cr supplementation as a neuroprotective strategy has received a lot of attention with several positive animal studies in models of Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). This has led to a number of randomized clinical trials (RCT) with oral Cr supplementation, with durations up to 5 years. In this paper, we review the evidence and consequences stemming from these trials. In the case of PD, the initial phase II RCT was promising and led to a large and well-designed phase III trial, which, however, turned out to be negative for all outcome measures. None of the RCTs that have examined effects of Cr in ALS patients showed any clinical benefit. In HD, Cr in high doses (up to 30 g/day) was shown to slow down brain atrophy in premanifest Huntingtin mutation carriers. In spite of this, proof is still lacking that Cr can also have beneficial clinical effects in this group of patients, who will go on to develop HD symptoms. Taken together, the use of Cr supplementation has so far proved disappointing in clinical studies with a number of symptomatic neurodegenerative diseases.

  1. Mesenchymal stem cells for the treatment of neurodegenerative disease

    PubMed Central

    Joyce, Nanette; Annett, Geralyn; Wirthlin, Louisa; Olson, Scott; Bauer, Gerhard; Nolta, Jan A

    2010-01-01

    Mesenchymal stem cells/marrow stromal cells (MSCs) present a promising tool for cell therapy, and are currently being tested in US FDA-approved clinical trials for myocardial infarction, stroke, meniscus injury, limb ischemia, graft-versus-host disease and autoimmune disorders. They have been extensively tested and proven effective in preclinical studies for these and many other disorders. There is currently a great deal of interest in the use of MSCs to treat neurodegenerative diseases, in particular for those that are fatal and difficult to treat, such as Huntington's disease and amyotrophic lateral sclerosis. Proposed regenerative approaches to neurological diseases using MSCs include cell therapies in which cells are delivered via intracerebral or intrathecal injection. Upon transplantation into the brain, MSCs promote endogenous neuronal growth, decrease apoptosis, reduce levels of free radicals, encourage synaptic connection from damaged neurons and regulate inflammation, primarily through paracrine actions. MSCs transplanted into the brain have been demonstrated to promote functional recovery by producing trophic factors that induce survival and regeneration of host neurons. Therapies will capitalize on the innate trophic support from MSCs or on augmented growth factor support, such as delivering brain-derived neurotrophic factor or glial-derived neurotrophic factor into the brain to support injured neurons, using genetically engineered MSCs as the delivery vehicles. Clinical trials for MSC injection into the CNS to treat traumatic brain injury and stroke are currently ongoing. The current data in support of applying MSC-based cellular therapies to the treatment of neurodegenerative disorders are discussed. PMID:21082892

  2. Neuroanatomical correlates of cognitive self-appraisal in neurodegenerative disease.

    PubMed

    Rosen, Howard J; Alcantar, Oscar; Rothlind, Johannes; Sturm, Virginia; Kramer, Joel H; Weiner, Michael; Miller, Bruce L

    2010-02-15

    Self-appraisal is a critical cognitive function, which helps us to choose tasks based on an accurate assessment of our abilities. The neural mechanisms of self-appraisal are incompletely understood, although a growing body of literature suggests that several frontal and subcortical regions are important for self-related processing. Anosognosia, or lack of awareness of one's deficits, is common in neurodegenerative dementias, offering an important window onto the brain systems involved in self-appraisal. We examined the neuroanatomical basis of self-appraisal in a mixed group of 39 individuals, including 35 with cognitive impairment due to one of several probable neurodegenerative diseases, using voxel-based morphometry and an objective, neuropsychologically-based measure of self-appraisal accuracy. Self-appraisal accuracy was correlated with tissue content in the right ventromedial prefrontal cortex (vmPFC). We hypothesize that emotional/physiological processing carried out by vmPFC is an important factor mediating self-appraisal accuracy in dementia. PMID:19961939

  3. Neuroanatomical correlates of cognitive self-appraisal in neurodegenerative disease

    PubMed Central

    Rosen, Howard J.; Alcantar, Oscar; Rothlind, Johannes; Sturm, Virginia; Kramer, Joel H.; Weiner, Michael; Miller, Bruce L.

    2009-01-01

    Self-appraisal is a critical cognitive function, which helps us to choose tasks based on an accurate assessment of our abilities. The neural mechanisms of self-appraisal are incompletely understood, although a growing body of literature suggests that several frontal and subcortical regions are important for self-related processing. Anosognosia, or lack of awareness of one's deficits, is common in neurodegenerative dementias, offering an important window onto the brain systems involved in self-appraisal. We examined the neuroanatomical basis of self-appraisal in a mixed group of 39 individuals, including 35 with cognitive impairment due to one of several probable neurodegenerative diseases, using voxel-based morphometry and an objective, neuropsychologically-based measure of self-appraisal accuracy. Self-appraisal accuracy was correlated with tissue content in the right ventromedial prefrontal cortex (vmPFC). We hypothesize that emotional/physiological processing carried out by vmPFC is an important factor mediating self-appraisal accuracy in dementia. PMID:19961939

  4. Creatine for neuroprotection in neurodegenerative disease: end of story?

    PubMed

    Bender, Andreas; Klopstock, Thomas

    2016-08-01

    Creatine (Cr) is a natural compound that plays an important role in cellular energy homeostasis. In addition, it ameliorates oxidative stress, glutamatergic excitotoxicity, and apoptosis in vitro as well as in vivo. Since these pathomechanisms are implicated to play a role in several neurodegenerative diseases, Cr supplementation as a neuroprotective strategy has received a lot of attention with several positive animal studies in models of Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). This has led to a number of randomized clinical trials (RCT) with oral Cr supplementation, with durations up to 5 years. In this paper, we review the evidence and consequences stemming from these trials. In the case of PD, the initial phase II RCT was promising and led to a large and well-designed phase III trial, which, however, turned out to be negative for all outcome measures. None of the RCTs that have examined effects of Cr in ALS patients showed any clinical benefit. In HD, Cr in high doses (up to 30 g/day) was shown to slow down brain atrophy in premanifest Huntingtin mutation carriers. In spite of this, proof is still lacking that Cr can also have beneficial clinical effects in this group of patients, who will go on to develop HD symptoms. Taken together, the use of Cr supplementation has so far proved disappointing in clinical studies with a number of symptomatic neurodegenerative diseases. PMID:26748651

  5. Neural basis of interpersonal traits in neurodegenerative diseases.

    PubMed

    Sollberger, Marc; Stanley, Christine M; Wilson, Stephen M; Gyurak, Anett; Beckman, Victoria; Growdon, Matthew; Jang, Jung; Weiner, Michael W; Miller, Bruce L; Rankin, Katherine P

    2009-11-01

    Several functional and structural imaging studies have investigated the neural basis of personality in healthy adults, but human lesions studies are scarce. Personality changes are a common symptom in patients with neurodegenerative diseases like frontotemporal dementia (FTD) and semantic dementia (SD), allowing a unique window into the neural basis of personality. In this study, we used the Interpersonal Adjective Scales to investigate the structural basis of eight interpersonal traits (dominance, arrogance, coldness, introversion, submissiveness, ingenuousness, warmth, and extraversion) in 257 subjects: 214 patients with neurodegenerative diseases such as FTD, SD, progressive nonfluent aphasia, Alzheimer's disease, amnestic mild cognitive impairment, corticobasal degeneration, and progressive supranuclear palsy and 43 healthy elderly people. Measures of interpersonal traits were correlated with regional atrophy pattern using voxel-based morphometry (VBM) analysis of structural MR images. Interpersonal traits mapped onto distinct brain regions depending on the degree to which they involved agency and affiliation. Interpersonal traits high in agency related to left dorsolateral prefrontal and left lateral frontopolar regions, whereas interpersonal traits high in affiliation related to right ventromedial prefrontal and right anteromedial temporal regions. Consistent with the existing literature on neural networks underlying social cognition, these results indicate that brain regions related to externally focused, executive control-related processes underlie agentic interpersonal traits such as dominance, whereas brain regions related to internally focused, emotion- and reward-related processes underlie affiliative interpersonal traits such as warmth. In addition, these findings indicate that interpersonal traits are subserved by complex neural networks rather than discrete anatomic areas.

  6. MicroRNAs in neurodegenerative diseases and their therapeutic potential.

    PubMed

    Junn, Eunsung; Mouradian, M Maral

    2012-02-01

    MicroRNAs (miRNAs) are abundant, endogenous, short, noncoding RNAs that act as important post-transcriptional regulators of gene expression by base-pairing with their target mRNA. During the last decade, substantial knowledge has accumulated regarding the biogenesis of miRNAs, their molecular mechanisms and functional roles in a variety of cellular contexts. Altered expression of certain miRNA molecules in the brains of patients with neurodegenerative diseases such as Alzheimer and Parkinson suggests that miRNAs could have a crucial regulatory role in these disorders. Polymorphisms in miRNA target sites may also constitute an important determinant of disease risk. Additionally, emerging evidence points to specific miRNAs targeting and regulating the expression of particular proteins that are key to disease pathogenesis. Considering that the amount of these proteins in susceptible neuronal populations appears to be critical to neurodegeneration, miRNA-mediated regulation represents a new target of significant therapeutic prospects. In this review, the implications of miRNAs in several neurodegenerative disorders and their potential as therapeutic interventions are discussed.

  7. MicroRNA in neurodegenerative drug discovery: the way forward?

    PubMed

    Campbell, Kristyn; Booth, Stephanie A

    2015-01-01

    Neurodegenerative diseases occur when neuronal cells in the brain or spinal cord progressively lose function and eventually die. Pathological analysis of these tissues reveals changes that include the loss of synapses, tangles of misfolded protein and immune cell activation, even during very early stages of disease well before debilitating clinical signs are apparent. This suggests that if neurodegeneration is treated early enough, drugs designed to delay the progress of these diseases by either repairing the early damage and loss of neurons, or protecting neuron functionality from further insult, may be efficacious. MicroRNAs (miRNAs) are small non-coding RNAs that can post-transcriptionally regulate gene expression. They are particularly numerous within neurons where many are expressed with high specificity, which suggests that they have important roles in the healthy brain. Indeed, miRNAs are essential for the post-mitotic survival of neurons, implying a crucial role in survival and neuroprotection. This has focused attention on exploring the use of miRNA-based drugs as a means to correct cellular abnormalities and maintain neuronal function in neurodegenerative diseases. These efforts are spurred on by the rapid progress to clinical trials for a number of miRNA-based therapies for other diseases such as cardiovascular diseases, fibrosis and cancer.

  8. Alterations of eye movement control in neurodegenerative movement disorders.

    PubMed

    Gorges, Martin; Pinkhardt, Elmar H; Kassubek, Jan

    2014-01-01

    The evolution of the fovea centralis, the most central part of the retina and the area of the highest visual accuracy, requires humans to shift their gaze rapidly (saccades) to bring some object of interest within the visual field onto the fovea. In addition, humans are equipped with the ability to rotate the eye ball continuously in a highly predicting manner (smooth pursuit) to hold a moving target steadily upon the retina. The functional deficits in neurodegenerative movement disorders (e.g., Parkinsonian syndromes) involve the basal ganglia that are critical in all aspects of movement control. Moreover, neocortical structures, the cerebellum, and the midbrain may become affected by the pathological process. A broad spectrum of eye movement alterations may result, comprising smooth pursuit disturbance (e.g., interrupting saccades), saccadic dysfunction (e.g., hypometric saccades), and abnormal attempted fixation (e.g., pathological nystagmus and square wave jerks). On clinical grounds, videooculography is a sensitive noninvasive in vivo technique to classify oculomotion function alterations. Eye movements are a valuable window into the integrity of central nervous system structures and their changes in defined neurodegenerative conditions, that is, the oculomotor nuclei in the brainstem together with their directly activating supranuclear centers and the basal ganglia as well as cortical areas of higher cognitive control of attention. PMID:24955249

  9. Prions, prion-like prionoids, and neurodegenerative disorders.

    PubMed

    Verma, Ashok

    2016-01-01

    Prion diseases or transmissible spongiform encephalopathies are fatal neurodegenerative diseases characterized by the aggregation and deposition of the misfolded prion protein in the brain. α-synuclein (α-syn)-associated multiple system atrophy has been recently shown to be caused by a bona fide α-syn prion strain. Several other misfolded native proteins such as β-amyloid, tau and TDP-43 share some aspects of prions although none of them is shown to be transmissible in nature or in experimental animals. However, these prion-like "prionoids" are causal to a variety of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. The remarkable recent discovery of at least two new α-syn prion strains and their transmissibility in transgenic mice and in vitro cell models raises a distinct question as to whether some specific strain of other prionoids could have the capability of disease transmission in a manner similar to prions. In this overview, we briefly describe human and other mammalian prion diseases and comment on certain similarities between prion and prionoid and the possibility of prion-like transmissibility of some prionoid strains.

  10. Prions, prion-like prionoids, and neurodegenerative disorders

    PubMed Central

    Verma, Ashok

    2016-01-01

    Prion diseases or transmissible spongiform encephalopathies are fatal neurodegenerative diseases characterized by the aggregation and deposition of the misfolded prion protein in the brain. α-synuclein (α-syn)-associated multiple system atrophy has been recently shown to be caused by a bona fide α-syn prion strain. Several other misfolded native proteins such as β-amyloid, tau and TDP-43 share some aspects of prions although none of them is shown to be transmissible in nature or in experimental animals. However, these prion-like “prionoids” are causal to a variety of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. The remarkable recent discovery of at least two new α-syn prion strains and their transmissibility in transgenic mice and in vitro cell models raises a distinct question as to whether some specific strain of other prionoids could have the capability of disease transmission in a manner similar to prions. In this overview, we briefly describe human and other mammalian prion diseases and comment on certain similarities between prion and prionoid and the possibility of prion-like transmissibility of some prionoid strains. PMID:27293325

  11. Vitagenes, dietary antioxidants and neuroprotection in neurodegenerative diseases.

    PubMed

    Calabrese, Vittorio; Cornelius, Carolin; Mancuso, Cesare; Barone, Eugenio; Calafato, Stella; Bates, Timothy; Rizzarelli, Enrico; Kostova, Albena T Dinkova

    2009-01-01

    The ability of a cell to counteract stressful conditions, known as cellular stress response, requires the activation of pro-survival pathways and the production of molecules with anti-oxidant, anti-apoptotic or pro-apoptotic activities. Among the cellular pathways conferring protection against oxidative stress, a key role is played by vitagenes, which include heat shock proteins (Hsps) heme oxygenase-1 and Hsp70, as well as the thioredoxin/thioredoxin reductase system. Heat shock response contributes to establish a cytoprotective state in a wide variety of human diseases, including inflammation, cancer, aging and neurodegenerative disorders. Given the broad cytoprotective properties of the heat shock response there is now strong interest in discovering and developing pharmacological agents capable of inducing stress responses. Dietary antioxidants, such as curcumin, L-carnitine/acetyl-L-carnitine and carnosine have recently been demonstrated in vitro to be neuroprotective through the activation of hormetic pathways, including vitagenes. In the present review we discuss the importance of vitagenes in the cellular stress response and analyse, from a pharmacological point of view, the potential use of dietary antioxidants in the treatment of neurodegenerative disorders in humans.

  12. The role of the Wnt canonical signaling in neurodegenerative diseases.

    PubMed

    Libro, Rosaliana; Bramanti, Placido; Mazzon, Emanuela

    2016-08-01

    The Wnt/β-catenin or Wnt canonical pathway controls multiple biological processes throughout development and adult life. Growing evidences have suggested that deregulation of the Wnt canonical pathway could be involved in the pathogenesis of neurodegenerative diseases. The Wnt canonical signaling is a pathway tightly regulated, which activation results in the inhibition of the Glycogen Synthase Kinase 3β (GSK-3β) function and in increased β-catenin activity, that migrates into the nucleus, activating the transcription of the Wnt target genes. Conversely, when the Wnt canonical pathway is turned off, increased levels of GSK-3β promote β-catenin degradation. Hence, GSK-3β could be considered as a key regulator of the Wnt canonical pathway. Of note, GSK-3β has also been involved in the modulation of inflammation and apoptosis, determining the delicate balance between immune tolerance/inflammation and neuronal survival/neurodegeneration. In this review, we have summarized the current acknowledgements about the role of the Wnt canonical pathway in the pathogenesis of some neurodegenerative diseases including Alzheimer's disease, cerebral ischemia, Parkinson's disease, Huntington's disease, multiple sclerosis and amyotrophic lateral sclerosis, with particular regard to the main in vitro and in vivo studies in this field, by reviewing 85 research articles about. PMID:27370940

  13. Role of the Retromer Complex in Neurodegenerative Diseases.

    PubMed

    Li, Chaosi; Shah, Syed Zahid Ali; Zhao, Deming; Yang, Lifeng

    2016-01-01

    The retromer complex is a protein complex that plays a central role in endosomal trafficking. Retromer dysfunction has been linked to a growing number of neurological disorders. The process of intracellular trafficking and recycling is crucial for maintaining normal intracellular homeostasis, which is partly achieved through the activity of the retromer complex. The retromer complex plays a primary role in sorting endosomal cargo back to the cell surface for reuse, to the trans-Golgi network (TGN), or alternatively to specialized endomembrane compartments, in which the cargo is not subjected to lysosomal-mediated degradation. In most cases, the retromer acts as a core that interacts with associated proteins, including sorting nexin family member 27 (SNX27), members of the vacuolar protein sorting 10 (VPS10) receptor family, the major endosomal actin polymerization-promoting complex known as Wiskott-Aldrich syndrome protein and scar homolog (WASH), and other proteins. Some of the molecules carried by the retromer complex are risk factors for neurodegenerative diseases. Defects such as haplo-insufficiency or mutations in one or several units of the retromer complex lead to various pathologies. Here, we summarize the molecular architecture of the retromer complex and the roles of this system in intracellular trafficking related the pathogenesis of neurodegenerative diseases.

  14. The Importance of Tau Phosphorylation for Neurodegenerative Diseases

    PubMed Central

    Noble, Wendy; Hanger, Diane P.; Miller, Christopher C. J.; Lovestone, Simon

    2013-01-01

    Fibrillar deposits of highly phosphorylated tau are a key pathological feature of several neurodegenerative tauopathies including Alzheimer’s disease (AD) and some frontotemporal dementias. Increasing evidence suggests that the presence of these end-stage neurofibrillary lesions do not cause neuronal loss, but rather that alterations to soluble tau proteins induce neurodegeneration. In particular, aberrant tau phosphorylation is acknowledged to be a key disease process, influencing tau structure, distribution, and function in neurons. Although typically described as a cytosolic protein that associates with microtubules and regulates axonal transport, several additional functions of tau have recently been demonstrated, including roles in DNA stabilization, and synaptic function. Most recently, studies examining the trans-synaptic spread of tau pathology in disease models have suggested a potential role for extracellular tau in cell signaling pathways intrinsic to neurodegeneration. Here we review the evidence showing that tau phosphorylation plays a key role in neurodegenerative tauopathies. We also comment on the tractability of altering phosphorylation-dependent tau functions for therapeutic intervention in AD and related disorders. PMID:23847585

  15. The role of the Wnt canonical signaling in neurodegenerative diseases.

    PubMed

    Libro, Rosaliana; Bramanti, Placido; Mazzon, Emanuela

    2016-08-01

    The Wnt/β-catenin or Wnt canonical pathway controls multiple biological processes throughout development and adult life. Growing evidences have suggested that deregulation of the Wnt canonical pathway could be involved in the pathogenesis of neurodegenerative diseases. The Wnt canonical signaling is a pathway tightly regulated, which activation results in the inhibition of the Glycogen Synthase Kinase 3β (GSK-3β) function and in increased β-catenin activity, that migrates into the nucleus, activating the transcription of the Wnt target genes. Conversely, when the Wnt canonical pathway is turned off, increased levels of GSK-3β promote β-catenin degradation. Hence, GSK-3β could be considered as a key regulator of the Wnt canonical pathway. Of note, GSK-3β has also been involved in the modulation of inflammation and apoptosis, determining the delicate balance between immune tolerance/inflammation and neuronal survival/neurodegeneration. In this review, we have summarized the current acknowledgements about the role of the Wnt canonical pathway in the pathogenesis of some neurodegenerative diseases including Alzheimer's disease, cerebral ischemia, Parkinson's disease, Huntington's disease, multiple sclerosis and amyotrophic lateral sclerosis, with particular regard to the main in vitro and in vivo studies in this field, by reviewing 85 research articles about.

  16. Endogenously Nitrated Proteins in Mouse Brain: Links To Neurodegenerative Disease

    SciTech Connect

    Sacksteder, Colette A.; Qian, Weijun; Knyushko, Tanya V.; Wang, Haixing H.; Chin, Mark H.; Lacan, Goran; Melega, William P.; Camp, David G.; Smith, Richard D.; Smith, Desmond J.; Squier, Thomas C.; Bigelow, Diana J.

    2006-07-04

    Increased nitrotyrosine modification of proteins has been documented in multiple pathologies in a variety of tissue types; emerging evidence suggests its additional role in redox regulation of normal metabolism. In order to identify proteins sensitive to nitrating conditions in vivo, a comprehensive proteomic dataset identifying 7,792 proteins from whole mouse brain, generated by LC/LC-MS/MS analyses, was used to identify nitrated proteins. This analysis resulted in identification of 31 unique nitrotyrosine sites within 29 different proteins. Over half of the nitrated proteins identified have been reported to be involved in Parkinson's disease, Alzheimer's disease, or other neurodegenerative disorders. Similarly, nitrotyrosine immunoblots of whole brain homogenates show that treatment of mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), an experimental model of Parkinson's disease, induces increased nitration of the same protein bands observed to be nitrated in brains of untreated animals. Comparing sequences and available high resolution structures around nitrated tyrosines with those of unmodified sites indicates a preference of nitration in vivo for surface accessible tyrosines in loops, characteristics consistent with peroxynitrite-induced tyrosine modification. More striking is the five-fold greater nitration of tyrosines having nearby basic sidechains, suggesting electrostatic attraction of basic groups with the negative charge of peroxynitrite. Together, these results suggest that elevated peroxynitrite generation plays a role in neurodegenerative changes in the brain and provides a predictive tool of functionally important sites of nitration.

  17. The role of zinc in neurodegenerative inflammatory pathways in depression.

    PubMed

    Szewczyk, Bernadeta; Kubera, Marta; Nowak, Gabriel

    2011-04-29

    According to new hypothesis, depression is characterized by decreased neurogenesis and enhanced neurodegeneration which, in part, may be caused by inflammatory processes. There is much evidence indicating that depression, age-related changes often associated with impaired brain function and cognitive performances or neurodegenerative processes could be related to dysfunctions affecting the zinc ion availability. Clinical studies revealed that depression is accompanied by serum hypozincemia, which can be normalized by successful antidepressant treatment. In patients with major depression, a low zinc serum level was correlated with an increase in the activation of markers of the immune system, suggesting that this effect may result in part from a depression-related alteration in the immune-inflammatory system. Moreover, a preliminary clinical study demonstrated the benefit of zinc supplementation in antidepressant therapy in both treatment non-resistant and resistant patients. In the preclinical study, the antidepressant activity of zinc was observed in the majority of rodent tests and models of depression and revealed a causative role for zinc deficiency in the induction of depressive-like symptoms, the reduction of neurogenesis and neuronal survival or impaired learning and memory ability. This paper provides an overview of the clinical and experimental evidence that implicates the role of zinc in the pathophysiology and therapy of depression within the context of the inflammatory and neurodegenerative hypothesis of this disease. PMID:20156515

  18. Mitochondrial and Cell Death Mechanisms in Neurodegenerative Diseases

    PubMed Central

    Martin, Lee J.

    2010-01-01

    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 cell death are unresolved. Morphological, biochemical, genetic, as well as cell and animal model studies reveal that mitochondria could have roles in this neurodegeneration. The functions and properties of mitochondria might render subsets of selectively vulnerable neurons intrinsically susceptible to cellular aging and stress and overlying genetic variations, triggering neurodegeneration according to a cell death matrix theory. 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 putative 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 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 review summarizes how mitochondrial pathobiology might contribute to neuronal death in AD, PD, and ALS and could serve as a target for drug therapy. PMID:21258649

  19. Mesenchymal stem cells for the treatment of neurodegenerative disease.

    PubMed

    Joyce, Nanette; Annett, Geralyn; Wirthlin, Louisa; Olson, Scott; Bauer, Gerhard; Nolta, Jan A

    2010-11-01

    Mesenchymal stem cells/marrow stromal cells (MSCs) present a promising tool for cell therapy, and are currently being tested in US FDA-approved clinical trials for myocardial infarction, stroke, meniscus injury, limb ischemia, graft-versus-host disease and autoimmune disorders. They have been extensively tested and proven effective in preclinical studies for these and many other disorders. There is currently a great deal of interest in the use of MSCs to treat neurodegenerative diseases, in particular for those that are fatal and difficult to treat, such as Huntington's disease and amyotrophic lateral sclerosis. Proposed regenerative approaches to neurological diseases using MSCs include cell therapies in which cells are delivered via intracerebral or intrathecal injection. Upon transplantation into the brain, MSCs promote endogenous neuronal growth, decrease apoptosis, reduce levels of free radicals, encourage synaptic connection from damaged neurons and regulate inflammation, primarily through paracrine actions. MSCs transplanted into the brain have been demonstrated to promote functional recovery by producing trophic factors that induce survival and regeneration of host neurons. Therapies will capitalize on the innate trophic support from MSCs or on augmented growth factor support, such as delivering brain-derived neurotrophic factor or glial-derived neurotrophic factor into the brain to support injured neurons, using genetically engineered MSCs as the delivery vehicles. Clinical trials for MSC injection into the CNS to treat traumatic brain injury and stroke are currently ongoing. The current data in support of applying MSC-based cellular therapies to the treatment of neurodegenerative disorders are discussed.

  20. Induced neural stem cells (iNSCs) in neurodegenerative diseases.

    PubMed

    Hermann, Andreas; Storch, Alexander

    2013-09-01

    Recent advances in somatic cell reprogramming is one of the most important developments in neuroscience in the last decades since it offers for the first time the opportunity to work with disease/patient-specific neurons or other neural cell types. Induced pluripotent stem cells (iPSCs) can be differentiated into all cell types of the body enabling investigations not only on neurons but also on muscle or endothelial cells which are cell types often also of great interest in neurodegenerative diseases. The novel technology of direct lineage conversion of somatic cells into neurons (induced neurons; iNs) or into expandable multipotent neural stem cells (induced neural stem cells; iNSCs) provides interesting alternatives to the iPSC technology. These techniques have the advantage of easier cell culture, but only neurons (iNs) or neuroectodermal cells (iNSCs) can be generated. Although there are several open questions coming along with these new neural cell types, they hold great promises for both cell replacement and cell modelling of neurodegenerative diseases.

  1. Human embryonic stem cell therapies for neurodegenerative diseases.

    PubMed

    Tomaskovic-Crook, Eva; Crook, Jeremy M

    2011-06-01

    There is a renewed enthusiasm for the clinical translation of human embryonic stem (hES) cells. This is abetted by putative clinically-compliant strategies for hES cell maintenance and directed differentiation, greater understanding of and accessibility to cells through formal cell registries and centralized cell banking for distribution, the revised US government policy on funding hES cell research, and paradoxically the discovery of induced pluripotent stem (iPS) cells. Additionally, as we consider the constraints (practical and fiscal) of delivering cell therapies for global healthcare, the more efficient and economical application of allogeneic vs autologous treatments will bolster the clinical entry of hES cell derivatives. Neurodegenerative disorders such as Parkinson's disease are primary candidates for hES cell therapy, although there are significant hurdles to be overcome. The present review considers key advances and challenges to translating hES cells into novel therapies for neurodegenerative diseases, with special consideration given to Parkinson's disease and Alzheimer's disease. Importantly, despite the focus on degenerative brain disorders and hES cells, many of the issues canvassed by this review are relevant to systemic application of hES cells and other pluripotent stem cells such as iPS cells.

  2. [Auditory synaptopathy/neuropathy: clinical findings and diagnosis].

    PubMed

    Walger, M; Foerst, A; Beutner, D; Streicher, B; Stürmer, K; Lang-Roth, R

    2011-05-01

    Auditory synaptopathy/neuropathy (AS/AN) is a special subtype of sensorineural hearing disorders with heterogeneous phenotypes and underestimated incidence. AS/AN generally develops in infancy, occasionally in adulthood. Symptoms include fluctuating, mostly bilateral hearing loss and abnormally reduced speech comprehension, especially in noisy environments. Within audiological assessments, patients with AS/AN present otoacoustic emissions (TEOAE; DPOAE) and cochlear microphonics (CM), absence of stapedius reflexes (SR) as well as absent or pathologically altered auditory evoked brainstem potentials (ABR). Children with AS/AN cannot be identified within OAE-based newborn hearing screening programs. Clinical findings, transtympanic electrocochleography (ECoG) and further diagnostic tools permit further identification of individual characteristics. In individual cases conventional amplification and the use of FM systems may improve hearing and communication skills. If these interventions, accompanied by intensive hearing, speech and language therapy are unsuccessful, cochlear implants (CI) or alternative forms of communication may be useful options for rehabilitation. PMID:21505928

  3. Perception of rhythmic grouping depends on auditory experience.

    PubMed

    Iversen, John R; Patel, Aniruddh D; Ohgushi, Kengo

    2008-10-01

    Many aspects of perception are known to be shaped by experience, but others are thought to be innate universal properties of the brain. A specific example comes from rhythm perception, where one of the fundamental perceptual operations is the grouping of successive events into higher-level patterns, an operation critical to the perception of language and music. Grouping has long been thought to be governed by innate perceptual principles established a century ago. The current work demonstrates instead that grouping can be strongly dependent on culture. Native English and Japanese speakers were tested for their perception of grouping of simple rhythmic sequences of tones. Members of the two cultures showed different patterns of perceptual grouping, demonstrating that these basic auditory processes are not universal but are shaped by experience. It is suggested that the observed perceptual differences reflect the rhythms of the two languages, and that native language can exert an influence on general auditory perception at a basic level.

  4. Benign lesions of the external auditory canal.

    PubMed

    Tran, L P; Grundfast, K M; Selesnick, S H

    1996-10-01

    Benign mass lesions of the external auditory canal, such as exostoses and osteomas, are common findings on physical examination but most often do not require treatment. The differential diagnosis of lesions in the external auditory canal, however, should not be limited to those benign processes discussed here, but should also include infectious, dermatologic, congenital, and malignant processes.

  5. Auditory and visual evoked potentials during hyperoxia

    NASA Technical Reports Server (NTRS)

    Smith, D. B. D.; Strawbridge, P. J.

    1974-01-01

    Experimental study of the auditory and visual averaged evoked potentials (AEPs) recorded during hyperoxia, and investigation of the effect of hyperoxia on the so-called contingent negative variation (CNV). No effect of hyperoxia was found on the auditory AEP, the visual AEP, or the CNV. Comparisons with previous studies are discussed.

  6. Changing Auditory Time with Prismatic Goggles

    ERIC Educational Resources Information Center

    Magnani, Barbara; Pavani, Francesco; Frassinetti, Francesca

    2012-01-01

    The aim of the present study was to explore the spatial organization of auditory time and the effects of the manipulation of spatial attention on such a representation. In two experiments, we asked 28 adults to classify the duration of auditory stimuli as "short" or "long". Stimuli were tones of high or low pitch, delivered left or right of the…

  7. Auditory Processing Disorders: An Overview. ERIC Digest.

    ERIC Educational Resources Information Center

    Ciocci, Sandra R.

    This digest presents an overview of children with auditory processing disorders (APDs), children who can typically hear information but have difficulty attending to, storing, locating, retrieving, and/or clarifying that information to make it useful for academic and social purposes. The digest begins by describing central auditory processing and…

  8. Auditory Processing Disorder and Foreign Language Acquisition

    ERIC Educational Resources Information Center

    Veselovska, Ganna

    2015-01-01

    This article aims at exploring various strategies for coping with the auditory processing disorder in the light of foreign language acquisition. The techniques relevant to dealing with the auditory processing disorder can be attributed to environmental and compensatory approaches. The environmental one involves actions directed at creating a…

  9. Auditory-Oral Matching Behavior in Newborns

    ERIC Educational Resources Information Center

    Chen, Xin; Striano, Tricia; Rakoczy, Hannes

    2004-01-01

    Twenty-five newborn infants were tested for auditory-oral matching behavior when presented with the consonant sound /m/ and the vowel sound /a/--a precursor behavior to vocal imitation. Auditory-oral matching behavior by the infant was operationally defined as showing the mouth movement appropriate for producing the model sound just heard (mouth…

  10. Passive Auditory Stimulation Improves Vision in Hemianopia

    PubMed Central

    Lewald, Jörg; Tegenthoff, Martin; Peters, Sören; Hausmann, Markus

    2012-01-01

    Techniques employed in rehabilitation of visual field disorders such as hemianopia are usually based on either visual or audio-visual stimulation and patients have to perform a training task. Here we present results from a completely different, novel approach that was based on passive unimodal auditory stimulation. Ten patients with either left or right-sided pure hemianopia (without neglect) received one hour of unilateral passive auditory stimulation on either their anopic or their intact side by application of repetitive trains of sound pulses emitted simultaneously via two loudspeakers. Immediately before and after passive auditory stimulation as well as after a period of recovery, patients completed a simple visual task requiring detection of light flashes presented along the horizontal plane in total darkness. The results showed that one-time passive auditory stimulation on the side of the blind, but not of the intact, hemifield of patients with hemianopia induced an improvement in visual detections by almost 100% within 30 min after passive auditory stimulation. This enhancement in performance was reversible and was reduced to baseline 1.5 h later. A non-significant trend of a shift of the visual field border toward the blind hemifield was obtained after passive auditory stimulation. These results are compatible with the view that passive auditory stimulation elicited some activation of the residual visual pathways, which are known to be multisensory and may also be sensitive to unimodal auditory stimuli as were used here. Trial Registration DRKS00003577 PMID:22666311

  11. Further Evidence of Auditory Extinction in Aphasia

    ERIC Educational Resources Information Center

    Marshall, Rebecca Shisler; Basilakos, Alexandra; Love-Myers, Kim

    2013-01-01

    Purpose: Preliminary research ( Shisler, 2005) suggests that auditory extinction in individuals with aphasia (IWA) may be connected to binding and attention. In this study, the authors expanded on previous findings on auditory extinction to determine the source of extinction deficits in IWA. Method: Seventeen IWA (M[subscript age] = 53.19 years)…

  12. Auditory Conceptualization: A New Dimension to Phonics.

    ERIC Educational Resources Information Center

    Howard, Marilyn

    A teaching technique that leads to auditory conceptualization--the ability to determine the number and order of sounds embedded within syllables--shows promise of measurably improving the reading proficiency of children of all ability levels. Based on C. and P. Lindamood's published technique, "Auditory Discrimination in Depth," the procedure…

  13. Reactive near field electromagnetic axonal communication channels and their role in neurodegenerative diseases.

    PubMed

    Morgera, Salvatore Domenic

    2015-01-01

    Research focus is on the micron-scale subsystem of the human nervous system known as the axon, or nerve fibre. In studying what has been traditionally treated as an electrochemical subsystem, we find that the axon is both an electrochemical and electromagnetic link in an intricately designed network. This work offers a game changing look at phenomena which enable interaction among millions of fibres tightly packed in bundles and tracts in the human peripheral and central nervous systems, respectively. We maintain that these fibres do not act independently as generally believed, but form intricate spatial and temporal near-field networks. An understanding of these networks will lead to improved diagnostics and therapeutics for neurodegenerative diseases.

  14. A Brain System for Auditory Working Memory

    PubMed Central

    Joseph, Sabine; Gander, Phillip E.; Barascud, Nicolas; Halpern, Andrea R.; Griffiths, Timothy D.

    2016-01-01

    The brain basis for auditory working memory, the process of actively maintaining sounds in memory over short periods of time, is controversial. Using functional magnetic resonance imaging in human participants, we demonstrate that the maintenance of single tones in memory is associated with activation in auditory cortex. In addition, sustained activation was observed in hippocampus and inferior frontal gyrus. Multivoxel pattern analysis showed that patterns of activity in auditory cortex and left inferior frontal gyrus distinguished the tone that was maintained in memory. Functional connectivity during maintenance was demonstrated between auditory cortex and both the hippocampus and inferior frontal cortex. The data support a system for auditory working memory based on the maintenance of sound-specific representations in auditory cortex by projections from higher-order areas, including the hippocampus and frontal cortex. SIGNIFICANCE STATEMENT In this work, we demonstrate a system for maintaining sound in working memory based on activity in auditory cortex, hippocampus, and frontal cortex, and functional connectivity among them. Specifically, our work makes three advances from the previous work. First, we robustly demonstrate hippocampal involvement in all phases of auditory working memory (encoding, maintenance, and retrieval): the role of hippocampus in working memory is controversial. Second, using a pattern classification technique, we show that activity in the auditory cortex and inferior frontal gyrus is specific to the maintained tones in working memory. Third, we show long-range connectivity of auditory cortex to hippocampus and frontal cortex, which may be responsible for keeping such representations active during working memory maintenance. PMID:27098693

  15. Tactile feedback improves auditory spatial localization.

    PubMed

    Gori, Monica; Vercillo, Tiziana; Sandini, Giulio; Burr, David

    2014-01-01

    Our recent studies suggest that congenitally blind adults have severely impaired thresholds in an auditory spatial bisection task, pointing to the importance of vision in constructing complex auditory spatial maps (Gori et al., 2014). To explore strategies that may improve the auditory spatial sense in visually impaired people, we investigated the impact of tactile feedback on spatial auditory localization in 48 blindfolded sighted subjects. We measured auditory spatial bisection thresholds before and after training, either with tactile feedback, verbal feedback, or no feedback. Audio thresholds were first measured with a spatial bisection task: subjects judged whether the second sound of a three sound sequence was spatially closer to the first or the third sound. The tactile feedback group underwent two audio-tactile feedback sessions of 100 trials, where each auditory trial was followed by the same spatial sequence played on the subject's forearm; auditory spatial bisection thresholds were evaluated after each session. In the verbal feedback condition, the positions of the sounds were verbally reported to the subject after each feedback trial. The no feedback group did the same sequence of trials, with no feedback. Performance improved significantly only after audio-tactile feedback. The results suggest that direct tactile feedback interacts with the auditory spatial localization system, possibly by a process of cross-sensory recalibration. Control tests with the subject rotated suggested that this effect occurs only when the tactile and acoustic sequences are spatially congruent. Our results suggest that the tactile system can be used to recalibrate the auditory sense of space. These results encourage the possibility of designing rehabilitation programs to help blind persons establish a robust auditory sense of space, through training with the tactile modality. PMID:25368587

  16. Change Detection in Auditory Textures.

    PubMed

    Boubenec, Yves; Lawlor, Jennifer; Shamma, Shihab; Englitz, Bernhard

    2016-01-01

    Many natural sounds have spectrotemporal signatures only on a statistical level, e.g. wind, fire or rain. While their local structure is highly variable, the spectrotemporal statistics of these auditory textures can be used for recognition. This suggests the existence of a neural representation of these statistics. To explore their encoding, we investigated the detectability of changes in the spectral statistics in relation to the properties of the change. To achieve precise parameter control, we designed a minimal sound texture--a modified cloud of tones--which retains the central property of auditory textures: solely statistical predictability. Listeners had to rapidly detect a change in the frequency marginal probability of the tone cloud occurring at a random time.The size of change as well as the time available to sample the original statistics were found to correlate positively with performance and negatively with reaction time, suggesting the accumulation of noisy evidence. In summary we quantified dynamic aspects of change detection in statistically defined contexts, and found evidence of integration of statistical information.

  17. Vision contingent auditory pitch aftereffects.

    PubMed

    Teramoto, Wataru; Kobayashi, Maori; Hidaka, Souta; Sugita, Yoichi

    2013-08-01

    Visual motion aftereffects can occur contingent on arbitrary sounds. Two circles, placed side by side, were alternately presented, and the onsets were accompanied by tone bursts of high and low frequencies, respectively. After a few minutes of exposure to the visual apparent motion with the tones, a circle blinking at a fixed location was perceived as a lateral motion in the same direction as the previously exposed apparent motion (Teramoto et al. in PLoS One 5:e12255, 2010). In the present study, we attempted to reverse this contingency (pitch aftereffects contingent on visual information). Results showed that after prolonged exposure to the audio-visual stimuli, the apparent visual motion systematically affected the perceived pitch of the auditory stimuli. When the leftward apparent visual motion was paired with the high-low-frequency sequence during the adaptation phase, a test tone sequence was more frequently perceived as a high-low-pitch sequence when the leftward apparent visual motion was presented and vice versa. Furthermore, the effect was specific for the exposed visual field and did not transfer to the other side, thus ruling out an explanation in terms of simple response bias. These results suggest that new audiovisual associations can be established within a short time, and visual information processing and auditory processing can mutually influence each other. PMID:23727883

  18. Auditory free classification of nonnative speech.

    PubMed

    Atagi, Eriko; Bent, Tessa

    2013-11-01

    Through experience with speech variability, listeners build categories of indexical speech characteristics including categories for talker, gender, and dialect. The auditory free classification task-a task in which listeners freely group talkers based on audio samples-has been a useful tool for examining listeners' representations of some of these characteristics including regional dialects and different languages. The free classification task was employed in the current study to examine the perceptual representation of nonnative speech. The category structure and salient perceptual dimensions of nonnative speech were investigated from two perspectives: general similarity and perceived native language background. Talker intelligibility and whether native talkers were included were manipulated to test stimulus set effects. Results showed that degree of accent was a highly salient feature of nonnative speech for classification based on general similarity and on perceived native language background. This salience, however, was attenuated when listeners were listening to highly intelligible stimuli and attending to the talkers' native language backgrounds. These results suggest that the context in which nonnative speech stimuli are presented-such as the listeners' attention to the talkers' native language and the variability of stimulus intelligibility-can influence listeners' perceptual organization of nonnative speech.

  19. A Model of Auditory-Cognitive Processing and Relevance to Clinical Applicability.

    PubMed

    Edwards, Brent

    2016-01-01

    Hearing loss and cognitive function interact in both a bottom-up and top-down relationship. Listening effort is tied to these interactions, and models have been developed to explain their relationship. The Ease of Language Understanding model in particular has gained considerable attention in its explanation of the effect of signal distortion on speech understanding. Signal distortion can also affect auditory scene analysis ability, however, resulting in a distorted auditory scene that can affect cognitive function, listening effort, and the allocation of cognitive resources. These effects are explained through an addition to the Ease of Language Understanding model. This model can be generalized to apply to all sounds, not only speech, representing the increased effort required for auditory environmental awareness and other nonspeech auditory tasks. While the authors have measures of speech understanding and cognitive load to quantify these interactions, they are lacking measures of the effect of hearing aid technology on auditory scene analysis ability and how effort and attention varies with the quality of an auditory scene. Additionally, the clinical relevance of hearing aid technology on cognitive function and the application of cognitive measures in hearing aid fittings will be limited until effectiveness is demonstrated in real-world situations. PMID:27355775

  20. In vivo functional and myeloarchitectonic mapping of human primary auditory areas

    PubMed Central

    Dick, Frederic; Tierney, Adam Taylor; Lutti, Antoine; Josephs, Oliver; Sereno, Martin I.; Weiskopf, Nikolaus

    2012-01-01

    In contrast to vision, where retinotopic mapping alone can define areal borders, primary auditory areas such as A1 are best delineated by combining in vivo tonotopic mapping with post mortem cyto- or myelo-architectonics from the same individual. We combined high-resolution (800 μm) quantitative T1 mapping with phase-encoded tonotopic methods to map primary auditory areas (A1 and R) within the ‘auditory core’ of human volunteers. We first quantitatively characterize the highly myelinated auditory core in terms of shape, area, cortical depth profile, and position, with our data showing considerable correspondence to post-mortem myeloarchitectonic studies, both in cross-participant averages and in individuals. The core region contains two ‘mirror-image‘ tonotopic maps oriented along the same axis as observed in macaque and owl monkey. We suggest that thee two maps within the core are the human analogues of primate auditory areas A1 and R. The core occupies a much smaller portion of tonotopically organized cortex on the superior temporal plane and gyrus than is generally supposed. The multi-modal approach to defining the auditory core will facilitate investigations of structure-function relationships, comparative neuroanatomical studies, and promises new biomarkers for diagnosis and clinical studies. PMID:23152594

  1. A blueprint for vocal learning: auditory predispositions from brains to genomes.

    PubMed

    Wheatcroft, David; Qvarnström, Anna

    2015-08-01

    Memorizing and producing complex strings of sound are requirements for spoken human language. We share these behaviours with likely more than 4000 species of songbirds, making birds our primary model for studying the cognitive basis of vocal learning and, more generally, an important model for how memories are encoded in the brain. In songbirds, as in humans, the sounds that a juvenile learns later in life depend on auditory memories formed early in development. Experiments on a wide variety of songbird species suggest that the formation and lability of these auditory memories, in turn, depend on auditory predispositions that stimulate learning when a juvenile hears relevant, species-typical sounds. We review evidence that variation in key features of these auditory predispositions are determined by variation in genes underlying the development of the auditory system. We argue that increased investigation of the neuronal basis of auditory predispositions expressed early in life in combination with modern comparative genomic approaches may provide insights into the evolution of vocal learning. PMID:26246333

  2. Iron biomineralization of brain tissue and neurodegenerative disorders

    NASA Astrophysics Data System (ADS)

    Mikhaylova (Mikhailova), Albina

    The brain is an organ with a high concentration of iron in specific areas, particularly in the globus pallidus, the substantia nigra, and the red nucleus. In certain pathological states, such as iron overload disease and neurodegenerative disorders, a disturbed iron metabolism can lead to increased accumulation of iron not only in these areas, but also in the brain regions that are typically low in iron content. Recent studies of the physical and magnetic properties of metalloproteins, and in particular the discovery of biogenic magnetite in human brain tissue, have raised new questions about the role of biogenic iron formations in living organisms. Further investigations revealed the presence of magnetite-like crystalline structures in human ferritin, and indicated that released ferritin iron might act as promoter of oxidative damage to tissue, therefore contributing to pathogenesis of neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's diseases. The purpose of this work was to examine the elemental composition and structure of iron deposits in normal brain tissue as well as tissue affected by neurodegenerative disorders. Employing the methods of X-ray microfocus fluorescence mapping, X-ray Absorption Near Edge Structure (XANES), X-ray Absorption Fine Structure spectroscopy (XAFS), and light and electron microscopic examinations allows one to obtain qualitative as well as quantitative data with respect to the cellular distribution and chemical state of iron at levels not detected previously. The described tissue preparation technique allows not only satisfactory XAS iron elemental imaging in situ but also multimodal examination with light and electron microscopes of the same samples. The developed protocol has assured consistent and reproducible results on relatively large sections of flat-embedded tissue. The resulting tissue samples were adequate for XAS examination as well as sufficiently well-preserved for future microscopy studies

  3. Evolutionary adaptations for the temporal processing of natural sounds by the anuran peripheral auditory system.

    PubMed

    Schrode, Katrina M; Bee, Mark A

    2015-03-01

    Sensory systems function most efficiently when processing natural stimuli, such as vocalizations, and it is thought that this reflects evolutionary adaptation. Among the best-described examples of evolutionary adaptation in the auditory system are the frequent matches between spectral tuning in both the peripheral and central auditory systems of anurans (frogs and toads) and the frequency spectra of conspecific calls. Tuning to the temporal properties of conspecific calls is less well established, and in anurans has so far been documented only in the central auditory system. Using auditory-evoked potentials, we asked whether there are species-specific or sex-specific adaptations of the auditory systems of gray treefrogs (Hyla chrysoscelis) and green treefrogs (H. cinerea) to the temporal modulations present in conspecific calls. Modulation rate transfer functions (MRTFs) constructed from auditory steady-state responses revealed that each species was more sensitive than the other to the modulation rates typical of conspecific advertisement calls. In addition, auditory brainstem responses (ABRs) to paired clicks indicated relatively better temporal resolution in green treefrogs, which could represent an adaptation to the faster modulation rates present in the calls of this species. MRTFs and recovery of ABRs to paired clicks were generally similar between the sexes, and we found no evidence that males were more sensitive than females to the temporal modulation patterns characteristic of the aggressive calls used in male-male competition. Together, our results suggest that efficient processing of the temporal properties of behaviorally relevant sounds begins at potentially very early stages of the anuran auditory system that include the periphery.

  4. Evolutionary adaptations for the temporal processing of natural sounds by the anuran peripheral auditory system

    PubMed Central

    Schrode, Katrina M.; Bee, Mark A.

    2015-01-01

    ABSTRACT Sensory systems function most efficiently when processing natural stimuli, such as vocalizations, and it is thought that this reflects evolutionary adaptation. Among the best-described examples of evolutionary adaptation in the auditory system are the frequent matches between spectral tuning in both the peripheral and central auditory systems of anurans (frogs and toads) and the frequency spectra of conspecific calls. Tuning to the temporal properties of conspecific calls is less well established, and in anurans has so far been documented only in the central auditory system. Using auditory-evoked potentials, we asked whether there are species-specific or sex-specific adaptations of the auditory systems of gray treefrogs (Hyla chrysoscelis) and green treefrogs (H. cinerea) to the temporal modulations present in conspecific calls. Modulation rate transfer functions (MRTFs) constructed from auditory steady-state responses revealed that each species was more sensitive than the other to the modulation rates typical of conspecific advertisement calls. In addition, auditory brainstem responses (ABRs) to paired clicks indicated relatively better temporal resolution in green treefrogs, which could represent an adaptation to the faster modulation rates present in the calls of this species. MRTFs and recovery of ABRs to paired clicks were generally similar between the sexes, and we found no evidence that males were more sensitive than females to the temporal modulation patterns characteristic of the aggressive calls used in male–male competition. Together, our results suggest that efficient processing of the temporal properties of behaviorally relevant sounds begins at potentially very early stages of the anuran auditory system that include the periphery. PMID:25617467

  5. Different effects of lesions to auditory core and belt cortex on auditory recognition in dogs.

    PubMed

    Kuśmierek, Paweł; Malinowska, Monika; Kowalska, Danuta M

    2007-07-01

    Auditory recognition memory, in contrast to memory in other modalities, is not affected by damage to the perihinal cortex, and its neural basis remains unknown. In an attempt to elucidate this problem, we investigated the role of canine auditory core and belt areas in auditory recognition. Either core or posterior belt areas were surgically removed. The core and belt regions were defined on the basis of response properties and thalamocortical connectivity established in previous studies. The animals were tested on auditory delayed matching to sample (DMS, a recognition memory task) using complex, trial-unique auditory stimuli. Both core and belt lesions impaired auditory recognition, however, the underlying deficit was different. Lesions to the core areas impaired auditory localization abilities. Lesions to the posterior belt areas did not affect this component of the recognition task, but affected auditory quality discrimination and/or recognition. The deficit following the posterior belt lesion did not increase with retention delay, suggesting that auditory belt areas do not constitute a substrate for auditory recognition memory. Their main function appears to be processing of complex sound patterns, including immediate recognition.

  6. Relationship between Sympathetic Skin Responses and Auditory Hypersensitivity to Different Auditory Stimuli

    PubMed Central

    Kato, Fumi; Iwanaga, Ryoichiro; Chono, Mami; Fujihara, Saori; Tokunaga, Akiko; Murata, Jun; Tanaka, Koji; Nakane, Hideyuki; Tanaka, Goro

    2014-01-01

    [Purpose] Auditory hypersensitivity has been widely reported in patients with autism spectrum disorders. However, the neurological background of auditory hypersensitivity is currently not clear. The present study examined the relationship between sympathetic nervous system responses and auditory hypersensitivity induced by different types of auditory stimuli. [Methods] We exposed 20 healthy young adults to six different types of auditory stimuli. The amounts of palmar sweating resulting from the auditory stimuli were compared between groups with (hypersensitive) and without (non-hypersensitive) auditory hypersensitivity. [Results] Although no group × type of stimulus × first stimulus interaction was observed for the extent of reaction, significant type of stimulus × first stimulus interaction was noted for the extent of reaction. For an 80 dB-6,000 Hz stimulus, the trends for palmar sweating differed between the groups. For the first stimulus, the variance became larger in the hypersensitive group than in the non-hypersensitive group. [Conclusion] Subjects who regularly felt excessive reactions to auditory stimuli tended to have excessive sympathetic responses to repeated loud noises compared with subjects who did not feel excessive reactions. People with auditory hypersensitivity may be classified into several subtypes depending on their reaction patterns to auditory stimuli. PMID:25140103

  7. Relationship between Sympathetic Skin Responses and Auditory Hypersensitivity to Different Auditory Stimuli.

    PubMed

    Kato, Fumi; Iwanaga, Ryoichiro; Chono, Mami; Fujihara, Saori; Tokunaga, Akiko; Murata, Jun; Tanaka, Koji; Nakane, Hideyuki; Tanaka, Goro

    2014-07-01

    [Purpose] Auditory hypersensitivity has been widely reported in patients with autism spectrum disorders. However, the neurological background of auditory hypersensitivity is currently not clear. The present study examined the relationship between sympathetic nervous system responses and auditory hypersensitivity induced by different types of auditory stimuli. [Methods] We exposed 20 healthy young adults to six different types of auditory stimuli. The amounts of palmar sweating resulting from the auditory stimuli were compared between groups with (hypersensitive) and without (non-hypersensitive) auditory hypersensitivity. [Results] Although no group × type of stimulus × first stimulus interaction was observed for the extent of reaction, significant type of stimulus × first stimulus interaction was noted for the extent of reaction. For an 80 dB-6,000 Hz stimulus, the trends for palmar sweating differed between the groups. For the first stimulus, the variance became larger in the hypersensitive group than in the non-hypersensitive group. [Conclusion] Subjects who regularly felt excessive reactions to auditory stimuli tended to have excessive sympathetic responses to repeated loud noises compared with subjects who did not feel excessive reactions. People with auditory hypersensitivity may be classified into several subtypes depending on their reaction patterns to auditory stimuli.

  8. Untangling the brain's neuroinflammatory and neurodegenerative transcriptional responses

    PubMed Central

    Srinivasan, Karpagam; Friedman, Brad A.; Larson, Jessica L.; Lauffer, Benjamin E.; Goldstein, Leonard D.; Appling, Laurie L.; Borneo, Jovencio; Poon, Chungkee; Ho, Terence; Cai, Fang; Steiner, Pascal; van der Brug, Marcel P.; Modrusan, Zora; Kaminker, Joshua S.; Hansen, David V.

    2016-01-01

    A common approach to understanding neurodegenerative disease is comparing gene expression in diseased versus healthy tissues. We illustrate that expression profiles derived from whole tissue RNA highly reflect the degenerating tissues' altered cellular composition, not necessarily transcriptional regulation. To accurately understand transcriptional changes that accompany neuropathology, we acutely purify neurons, astrocytes and microglia from single adult mouse brains and analyse their transcriptomes by RNA sequencing. Using peripheral endotoxemia to establish the method, we reveal highly specific transcriptional responses and altered RNA processing in each cell type, with Tnfr1 required for the astrocytic response. Extending the method to an Alzheimer's disease model, we confirm that transcriptomic changes observed in whole tissue are driven primarily by cell type composition, not transcriptional regulation, and identify hundreds of cell type-specific changes undetected in whole tissue RNA. Applying similar methods to additional models and patient tissues will transform our understanding of aberrant gene expression in neurological disease. PMID:27097852

  9. Nanoparticles and Colloids as Contributing Factors in Neurodegenerative Disease

    PubMed Central

    Bondy, Stephen C.

    2011-01-01

    This review explores the processes underlying the deleterious effects of the presence of insoluble or colloidal depositions within the central nervous system. These materials are chemically unreactive and can have a prolonged residence in the brain. They can be composed of mineral or proteinaceous materials of intrinsic or exogenous origin. Such nanoparticulates and colloids are associated with a range of slow-progressing neurodegenerative states. The potential common basis of toxicity of these materials is discussed. A shared feature of these disorders involves the appearance of deleterious inflammatory changes in the CNS. This may be due to extended and ineffective immune responses. Another aspect is the presence of excess levels of reactive oxygen species within the brain. In addition with their induction by inflammatory events, these may be further heightened by the presence of redox active transition metals to the large surface area afforded by nanoparticles and amphipathic micelles. PMID:21776226

  10. Resting state brain networks and their implications in neurodegenerative disease

    NASA Astrophysics Data System (ADS)

    Sohn, William S.; Yoo, Kwangsun; Kim, Jinho; Jeong, Yong

    2012-10-01

    Neurons are the basic units of the brain, and form network by connecting via synapses. So far, there have been limited ways to measure the brain networks. Recently, various imaging modalities are widely used for this purpose. In this paper, brain network mapping using resting state fMRI will be introduced with several applications including neurodegenerative disease such as Alzheimer's disease, frontotemporal lobar degeneration and Parkinson's disease. The resting functional connectivity using intrinsic functional connectivity in mouse is useful since we can take advantage of perturbation or stimulation of certain nodes of the network. The study of brain connectivity will open a new era in understanding of brain and diseases thus will be an essential foundation for future research.

  11. Mutational Spectrum Analysis of Neurodegenerative Diseases and Its Pathogenic Implication.

    PubMed

    Shen, Liang; Ji, Hong-Fang

    2015-10-14

    One of the most conspicuous features of neurodegenerative diseases (NDs) is the occurrence of dramatic conformation change of individual proteins. We performed a mutational spectrum analysis of disease-causing missense mutations in seven types of NDs at nucleotide and amino acid levels, and compared the results with those of non-NDs. The main findings included: (i) The higher mutation ratio of G:C→T:A transversion to G:C→A:T transition was observed in NDs than in non-NDs, interpreting the excessive guanine-specific oxidative DNA damage in NDs; (ii) glycine and proline had highest mutability in NDs than in non-NDs, which favor the protein conformation change in NDs; (iii) surprisingly low mutation frequency of arginine was observed in NDs. These findings help to understand how mutations may cause NDs.

  12. MicroRNAs: novel therapeutic targets in neurodegenerative diseases.

    PubMed

    Roshan, Reema; Ghosh, Tanay; Scaria, Vinod; Pillai, Beena

    2009-12-01

    The prevalence of neurodegenerative disorders is rising steadily as human life expectancy increases. However, limited knowledge of the molecular basis of disease pathogenesis is a major hurdle in the identification of drug targets and development of therapeutic strategies for these largely incurable disorders. Recently, differential expression of endogenous regulatory small RNAs, known as 'microRNAs' (miRNAs), in patients of Alzheimer's disease, Parkinson's disease and models of ataxia suggest that they might have key regulatory roles in neurodegeneration. miRNAs that can target known mediators of neurodegeneration offer potential therapeutic targets. Our bioinformatic analysis suggests novel miRNA-target interactions that could potentially influence neurodegeneration. The recent development of molecules that alter miRNA expression promises valuable tools that will enhance the therapeutic potential of miRNAs.

  13. Revisiting Metal Toxicity in Neurodegenerative Diseases and Stroke: Therapeutic Potential

    PubMed Central

    Mitra, Joy; Vasquez, Velmarini; Hegde, Pavana M; Boldogh, Istvan; Mitra, Sankar; Kent, Thomas A; Rao, Kosagi S; Hegde, Muralidhar L

    2015-01-01

    Excessive accumulation of pro-oxidant metals, observed in affected brain regions, has consistently been implicated as a contributor to the brain pathology including neurodegenerative diseases and acute injuries such as stroke. Furthermore, the potential interactions between metal toxicity and other commonly associated etiological factors, such as misfolding/aggregation of amyloidogenic proteins or genomic damage, are poorly understood. Decades of research provide compelling evidence implicating metal overload in neurological diseases and stroke. However, the utility of metal toxicity as a therapeutic target is controversial, possibly due to a lack of comprehensive understanding of metal dyshomeostasis-mediated neuronal pathology. In this article, we discuss the current understanding of metal toxicity and the challenges associated with metal-targeted therapies. PMID:25717476

  14. Probing Mechanisms That Underlie Human Neurodegenerative Diseases in Drosophila

    PubMed Central

    Jaiswal, M.; Sandoval, H.; Zhang, K.; Bayat, V.; Bellen, H.J.

    2013-01-01

    The fruit fly, Drosophila melanogaster, is an excellent organism for the study of the genetic and molecular basis of metazoan development. Drosophila provides numerous tools and reagents to unravel the molecular and cellular functions of genes that cause human disease, and the past decade has witnessed a significant expansion of the study of neurodegenerative disease mechanisms in flies. Here we review the interplay between oxidative stress and neuronal toxicity. We cover some of the studies that show how proteasome degradation of protein aggregates, autophagy, mitophagy, and lysosomal function affect the quality control mechanisms required for neuronal survival. We discuss how forward genetic screens in flies have led to the isolation of a few loci that cause neurodegeneration, paving the way for large-scale systematic screens to identify such loci in flies as well as promoting gene discovery in humans. PMID:22974305

  15. Neurodegenerative diseases: quantitative predictions of protein-RNA interactions.

    PubMed

    Cirillo, Davide; Agostini, Federico; Klus, Petr; Marchese, Domenica; Rodriguez, Silvia; Bolognesi, Benedetta; Tartaglia, Gian Gaetano

    2013-02-01

    Increasing evidence indicates that RNA plays an active role in a number of neurodegenerative diseases. We recently introduced a theoretical framework, catRAPID, to predict the binding ability of protein and RNA molecules. Here, we use catRAPID to investigate ribonucleoprotein interactions linked to inherited intellectual disability, amyotrophic lateral sclerosis, Creutzfeuld-Jakob, Alzheimer's, and Parkinson's diseases. We specifically focus on (1) RNA interactions with fragile X mental retardation protein FMRP; (2) protein sequestration caused by CGG repeats; (3) noncoding transcripts regulated by TAR DNA-binding protein 43 TDP-43; (4) autogenous regulation of TDP-43 and FMRP; (5) iron-mediated expression of amyloid precursor protein APP and α-synuclein; (6) interactions between prions and RNA aptamers. Our results are in striking agreement with experimental evidence and provide new insights in processes associated with neuronal function and misfunction.

  16. Targeting New Candidate Genes by Small Molecules Approaching Neurodegenerative Diseases

    PubMed Central

    Fan, Hueng-Chuen; Chi, Ching-Shiang; Cheng, Shin-Nan; Lee, Hsiu-Fen; Tsai, Jeng-Dau; Lin, Shinn-Zong; Harn, Horng-Jyh

    2015-01-01

    Neurodegenerative diseases (NDs) are among the most feared of the disorders that afflict humankind for the lack of specific diagnostic tests and effective treatments. Understanding the molecular, cellular, biochemical changes of NDs may hold therapeutic promise against debilitating central nerve system (CNS) disorders. In the present review, we summarized the clinical presentations and biology backgrounds of NDs, including Parkinson’s disease (PD), Huntington’s disease (HD), and Alzheimer’s disease (AD) and explored the role of molecular mechanisms, including dys-regulation of epigenetic control mechanisms, Ataxia-telangiectasia-mutated protein kinase (ATM), and neuroinflammation in the pathogenesis of NDs. Targeting these mechanisms may hold therapeutic promise against these devastating diseases. PMID:26712747

  17. Nanoparticles and colloids as contributing factors in neurodegenerative disease.

    PubMed

    Bondy, Stephen C

    2011-06-01

    This review explores the processes underlying the deleterious effects of the presence of insoluble or colloidal depositions within the central nervous system. These materials are chemically unreactive and can have a prolonged residence in the brain. They can be composed of mineral or proteinaceous materials of intrinsic or exogenous origin. Such nanoparticulates and colloids are associated with a range of slow-progressing neurodegenerative states. The potential common basis of toxicity of these materials is discussed. A shared feature of these disorders involves the appearance of deleterious inflammatory changes in the CNS. This may be due to extended and ineffective immune responses. Another aspect is the presence of excess levels of reactive oxygen species within the brain. In addition with their induction by inflammatory events, these may be further heightened by the presence of redox active transition metals to the large surface area afforded by nanoparticles and amphipathic micelles.

  18. Opportunities and challenges of pluripotent stem cell neurodegenerative disease models.

    PubMed

    Sandoe, Jackson; Eggan, Kevin

    2013-07-01

    Human neurodegenerative disorders are among the most difficult to study. In particular, the inability to readily obtain the faulty cell types most relevant to these diseases has impeded progress for decades. Recent advances in pluripotent stem cell technology now grant access to substantial quantities of disease-pertinent neurons both with and without predisposing mutations. While this suite of technologies has revolutionized the field of 'in vitro disease modeling', great care must be taken in their deployment if robust, durable discoveries are to be made. Here we review what we perceive to be several of the stumbling blocks in the use of stem cells for the study of neurological disease and offer strategies to overcome them.

  19. Developing neural stem cell-based treatments for neurodegenerative diseases.

    PubMed

    Byrne, James A

    2014-05-30

    Owing to the aging of the population, our society now faces an impending wave of age-related neurodegenerative pathologies, the most significant of which is Alzheimer's disease. Currently, no effective therapies for Alzheimer's disease have been developed. However, recent advances in the fields of neural stem cells and human induced pluripotent stem cells now provide us with the first real hope for a cure. The recent discovery by Blurton-Jones and colleagues that neural stem cells can effectively deliver disease-modifying therapeutic proteins throughout the brains of our best rodent models of Alzheimer's disease, combined with recent advances in human nuclear reprogramming, stem cell research, and highly customized genetic engineering, may represent a potentially revolutionary personalized cellular therapeutic approach capable of effectively curing, ameliorating, and/or slowing the progression of Alzheimer's disease.

  20. Research on neurodegenerative diseases using induced pluripotent stem cells.

    PubMed

    Imamura, Keiko; Inoue, Haruhisa

    2012-06-01

    Induced pluripotent stem cells (iPSC) are derived from somatic cells. These somatic cells have had their gene expression experimentally reprogrammed to an embryonic stem cell-like pluripotent state, gaining the capacity to differentiate various cell types in the three embryonic germ layers. Thus, iPSC technology makes it possible to obtain neuronal cells from any human cells. iPSC can be generated from various kinds of somatic cells and from patients with neurodegenerative diseases. Disease modelling using iPSC technology would elucidate the pathogenesis of such diseases and contribute to related drug discoveries. In this review, we discuss the recent advances in iPSC technology as well as its potential applications.

  1. Untangling the brain's neuroinflammatory and neurodegenerative transcriptional responses.

    PubMed

    Srinivasan, Karpagam; Friedman, Brad A; Larson, Jessica L; Lauffer, Benjamin E; Goldstein, Leonard D; Appling, Laurie L; Borneo, Jovencio; Poon, Chungkee; Ho, Terence; Cai, Fang; Steiner, Pascal; van der Brug, Marcel P; Modrusan, Zora; Kaminker, Joshua S; Hansen, David V

    2016-01-01

    A common approach to understanding neurodegenerative disease is comparing gene expression in diseased versus healthy tissues. We illustrate that expression profiles derived from whole tissue RNA highly reflect the degenerating tissues' altered cellular composition, not necessarily transcriptional regulation. To accurately understand transcriptional changes that accompany neuropathology, we acutely purify neurons, astrocytes and microglia from single adult mouse brains and analyse their transcriptomes by RNA sequencing. Using peripheral endotoxemia to establish the method, we reveal highly specific transcriptional responses and altered RNA processing in each cell type, with Tnfr1 required for the astrocytic response. Extending the method to an Alzheimer's disease model, we confirm that transcriptomic changes observed in whole tissue are driven primarily by cell type composition, not transcriptional regulation, and identify hundreds of cell type-specific changes undetected in whole tissue RNA. Applying similar methods to additional models and patient tissues will transform our understanding of aberrant gene expression in neurological disease. PMID:27097852

  2. Auditory category knowledge in experts and novices

    PubMed Central

    Heald, Shannon L. M.; Van Hedger, Stephen C.; Nusbaum, Howard C.

    2014-01-01

    What do listeners know about sounds that have a systematic organization? Research suggests that listeners store absolute pitch information as part of their representations for specific auditory experiences. It is unclear however, if such knowledge is abstracted beyond these experiences. In two studies we examined this question via a tone adjustment task in which listeners heard one of several target tones to be matched by adjusting the frequency of a subsequent starting tone. In the first experiment listeners estimated tones from one of three distributions differing in frequency range. The effect of tone matching in the three different distributions was then modeled using randomly generated data (RGD) to ascertain the degree to which individuals' estimates are affected by generalized note knowledge. Results showed that while listeners' estimates were similar to the RGD, indicating a central tendency effect reflective of the target tone distribution, listeners were more accurate than the RGD indicating that their estimates were affected by generalized note knowledge. The second experiment tested three groups of listeners who vary in the nature of their note knowledge. Specifically, absolute pitch (AP) possessors, non-AP listeners matched in musical expertise (ME), and non-AP musical novices (MN) adjusted tones from a micro-scale that included only two in-tune notes (B4 and C5). While tone estimates for all groups showed a central tendency effect reflective of the target tone distribution, each groups' estimates were more accurate than the RGD, indicating all listeners' estimates were guided by generalized note knowledge. Further, there was evidence that explicit note knowledge additionally influenced AP possessors' tone estimates, as tones closer to C5 had less error. Results indicate that everyday listeners possess generalized note knowledge that influences the perception of isolated tones and that this effect is made more evident with additional musical experience

  3. Endogenously nitrated proteins in mouse brain: links to neurodegenerative disease.

    PubMed

    Sacksteder, Colette A; Qian, Wei-Jun; Knyushko, Tatyana V; Wang, Haixing; Chin, Mark H; Lacan, Goran; Melega, William P; Camp, David G; Smith, Richard D; Smith, Desmond J; Squier, Thomas C; Bigelow, Diana J

    2006-07-01

    Increased abundance of nitrotyrosine modifications of proteins have been documented in multiple pathologies in a variety of tissue types and play a role in the redox regulation of normal metabolism. To identify proteins sensitive to nitrating conditions in vivo, a comprehensive proteomic data set identifying 7792 proteins from a whole mouse brain, generated by LC/LC-MS/MS analyses, was used to identify nitrated proteins. This analysis resulted in the identification of 31 unique nitrotyrosine sites within 29 different proteins. More than half of the nitrated proteins that have been identified are involved in Parkinson's disease, Alzheimer's disease, or other neurodegenerative disorders. Similarly, nitrotyrosine immunoblots of whole brain homogenates show that treatment of mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), an experimental model of Parkinson's disease, induces an increased level of nitration of the same protein bands observed to be nitrated in brains of untreated animals. Comparing sequences and available high-resolution structures around nitrated tyrosines with those of unmodified sites indicates a preference of nitration in vivo for surface accessible tyrosines in loops, a characteristic consistent with peroxynitrite-induced tyrosine modification. In addition, most sequences contain cysteines or methionines proximal to nitrotyrosines, contrary to suggestions that these amino acid side chains prevent tyrosine nitration. More striking is the presence of a positively charged moiety near the sites of nitration, which is not observed for non-nitrated tyrosines. Together, these observations suggest a predictive tool of functionally important sites of nitration and that cellular nitrating conditions play a role in neurodegenerative changes in the brain.

  4. Staging neurodegenerative disorders: structural, regional, biomarker, and functional progressions.

    PubMed

    Archer, Trevor; Kostrzewa, Richard M; Beninger, Richard J; Palomo, Tomas

    2011-02-01

    The notion of staging in the neurodegenerative disorders is modulated by the constant and progressive loss of several aspects of brain structural integrity, circuitry, and neuronal processes. These destructive processes eventually remove individuals' abilities to perform at sufficient and necessary functional capacity at several levels of disease severity. The classification of (a) patients on the basis of diagnosis, risk prognosis, and intervention outcome, forms the basis of clinical staging, and (b) laboratory animals on the basis of animal model of brain disorder, extent of insult, and dysfunctional expression, provides the components for the clinical staging and preclinical staging, respectively, expressing associated epidemiological, biological, and genetic characteristics. The major focus of clinical staging in the present account stems from the fundamental notions of Braak staging as they describe the course and eventual prognosis for Alzheimer's disease, Lewy Body dementia, and Parkinson's disease. Mild cognitive impairment, which expresses the decline in episodic and semantic memory performance below the age-adjusted normal range without marked loss of global cognition or activities of daily living, and the applications of longitudinal magnetic resonance imaging, major instruments for the monitoring of either disease progression in dementia, present important challenges for staging concepts. Although Braak notions present the essential basis for further developments, current staging conceptualizations seem inadequate to comply with the massive influx of information dealing with neurodegenerative processes in brain, advanced both under clinical realities, and discoveries in the laboratory setting. The contributions of various biomarkers of disease progression, e.g., amyloid precursor protein, and neurotransmitter system imbalances, e.g., dopamine receptor supersensitivity and interactive propensities, await their incorporation into the existing staging

  5. Genetic susceptibility testing for neurodegenerative diseases: Ethical and practice issues

    PubMed Central

    Roberts, J. Scott; Uhlmann, Wendy R.

    2013-01-01

    As the genetics of neurodegenerative disease become better understood, opportunities for genetic susceptibility testing for at-risk individuals will increase. Such testing raises important ethical and practice issues related to test access, informed consent, risk estimation and communication, return of results, and policies to prevent genetic discrimination. The advent of direct-to-consumer genetic susceptibility testing for various neurodegenerative disorders (including Alzheimer’s disease, Parkinson’s disease, and certain prion diseases) means that ethical and practical challenges must be faced not only in traditional research and clinical settings, but also in broader society. This review addresses several topics relevant to the development and implementation of genetic susceptibility tests across research, clinical, and consumer settings; these include appropriate indications for testing, the implications of different methods for disclosing test results, clinical versus personal utility of risk information, psychological and behavioral responses to test results, testing of minors, genetic discrimination, and ethical dilemmas posed by whole-genome sequencing. We also identify future areas of likely growth in the field, including pharmacogenomics and genetic screening for individuals considering or engaged in activities that pose elevated risk of brain injury (e.g., football players, military personnel). APOE gene testing for risk of Alzheimer’s disease is used throughout as an instructive case example, drawing upon the authors’ experience as investigators in a series of multisite randomized clinical trials that have examined the impact of disclosing APOE genotype status to interested individuals (e.g., first-degree relatives, persons with mild cognitive impairment). PMID:23583530

  6. A Comparison of Three Auditory Discrimination-Perception Tests

    ERIC Educational Resources Information Center

    Koenke, Karl

    1978-01-01

    Comparisons were made between scores of 52 third graders on three measures of auditory discrimination: Wepman's Auditory Discrimination Test, the Goldman-Fristoe Woodcock (GFW) Test of Auditory Discrimination, and the Kimmell-Wahl Screening Test of Auditory Perception (STAP). (CL)

  7. Spatial auditory processing in pinnipeds

    NASA Astrophysics Data System (ADS)

    Holt, Marla M.

    Given the biological importance of sound for a variety of activities, pinnipeds must be able to obtain spatial information about their surroundings thorough acoustic input in the absence of other sensory cues. The three chapters of this dissertation address spatial auditory processing capabilities of pinnipeds in air given that these amphibious animals use acoustic signals for reproduction and survival on land. Two chapters are comparative lab-based studies that utilized psychophysical approaches conducted in an acoustic chamber. Chapter 1 addressed the frequency-dependent sound localization abilities at azimuth of three pinniped species (the harbor seal, Phoca vitulina, the California sea lion, Zalophus californianus, and the northern elephant seal, Mirounga angustirostris). While performances of the sea lion and harbor seal were consistent with the duplex theory of sound localization, the elephant seal, a low-frequency hearing specialist, showed a decreased ability to localize the highest frequencies tested. In Chapter 2 spatial release from masking (SRM), which occurs when a signal and masker are spatially separated resulting in improvement in signal detectability relative to conditions in which they are co-located, was determined in a harbor seal and sea lion. Absolute and masked thresholds were measured at three frequencies and azimuths to determine the detection advantages afforded by this type of spatial auditory processing. Results showed that hearing sensitivity was enhanced by up to 19 and 12 dB in the harbor seal and sea lion, respectively, when the signal and masker were spatially separated. Chapter 3 was a field-based study that quantified both sender and receiver variables of the directional properties of male northern elephant seal calls produce within communication system that serves to delineate dominance status. This included measuring call directivity patterns, observing male-male vocally-mediated interactions, and an acoustic playback study

  8. Feature Assignment in Perception of Auditory Figure

    PubMed Central

    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 “objects” (relatively punctate events, such as a dog's bark) and auditory “streams” (sounds involving a pattern over time, such as a galloping rhythm). In Experiments 1 and 2, on each trial two sounds -- an object (a vowel) and a stream (a series of tones) – were presented with one target feature that could be perceptually grouped with either source. In each block of these experiments, listeners were required to attend to one of the two sounds, and report its perceived category. Across several experimental manipulations, listeners were more likely to allocate the feature to an impoverished object if the result of the grouping was a good, identifiable object. Perception of objects was quite sensitive to feature variation (noise masking), whereas perception of streams was more robust to feature variation. In Experiment 3, the number of sound sources competing for the feature was increased to three. This produced a shift toward relying more on spatial cues than on the potential contribution of the feature to an object's perceptual quality. The results support a distinction between auditory objects and streams, and provide new information about the way that the auditory world is parsed. PMID:22288691

  9. Auditory memory function in expert chess players

    PubMed Central

    Fattahi, Fariba; Geshani, Ahmad; Jafari, Zahra; Jalaie, Shohreh; Salman Mahini, Mona

    2015-01-01

    Background: Chess is a game that involves many aspects of high level cognition such as memory, attention, focus and problem solving. Long term practice of chess can improve cognition performances and behavioral skills. Auditory memory, as a kind of memory, can be influenced by strengthening processes following long term chess playing like other behavioral skills because of common processing pathways in the brain. The purpose of this study was to evaluate the auditory memory function of expert chess players using the Persian version of dichotic auditory-verbal memory test. Methods: The Persian version of dichotic auditory-verbal memory test was performed for 30 expert chess players aged 20-35 years and 30 non chess players who were matched by different conditions; the participants in both groups were randomly selected. The performance of the two groups was compared by independent samples t-test using SPSS version 21. Results: The mean score of dichotic auditory-verbal memory test between the two groups, expert chess players and non-chess players, revealed a significant difference (p≤ 0.001). The difference between the ears scores for expert chess players (p= 0.023) and non-chess players (p= 0.013) was significant. Gender had no effect on the test results. Conclusion: Auditory memory function in expert chess players was significantly better compared to non-chess players. It seems that increased auditory memory function is related to strengthening cognitive performances due to playing chess for a long time. PMID:26793666

  10. Auditory Efferent System Modulates Mosquito Hearing.

    PubMed

    Andrés, Marta; Seifert, Marvin; Spalthoff, Christian; Warren, Ben; Weiss, Lukas; Giraldo, Diego; Winkler, Margret; Pauls, Stephanie; Göpfert, Martin C

    2016-08-01

    The performance of vertebrate ears is controlled by auditory efferents that originate in the brain and innervate the ear, synapsing onto hair cell somata and auditory afferent fibers [1-3]. Efferent activity can provide protection from noise and facilitate the detection and discrimination of sound by modulating mechanical amplification by hair cells and transmitter release as well as auditory afferent action potential firing [1-3]. Insect auditory organs are thought to lack efferent control [4-7], but when we inspected mosquito ears, we obtained evidence for its existence. Antibodies against synaptic proteins recognized rows of bouton-like puncta running along the dendrites and axons of mosquito auditory sensory neurons. Electron microscopy identified synaptic and non-synaptic sites of vesicle release, and some of the innervating fibers co-labeled with somata in the CNS. Octopamine, GABA, and serotonin were identified as efferent neurotransmitters or neuromodulators that affect auditory frequency tuning, mechanical amplification, and sound-evoked potentials. Mosquito brains thus modulate mosquito ears, extending the use of auditory efferent systems from vertebrates to invertebrates and adding new levels of complexity to mosquito sound detection and communication. PMID:27476597

  11. Auditory Evoked Bursts in Mouse Visual Cortex during Isoflurane Anesthesia

    PubMed Central

    Land, Rüdiger; Engler, Gerhard

    2012-01-01

    General anesthesia is not a uniform state of the brain. Ongoing activity differs between light and deep anesthesia and cortical response properties are modulated in dependence of anesthetic dosage. We investigated how anesthesia level affects cross-modal interactions in primary sensory cortex. To examine this, we continuously measured the effects of visual and auditory stimulation during increasing and decreasing isoflurane level in the mouse visual cortex and the subiculum (from baseline at 0.7 to 2.5 vol % and reverse). Auditory evoked burst activity occurred in visual cortex after a transition during increase of anesthesia level. At the same time, auditory and visual evoked bursts occurred in the subiculum, even though the subiculum was unresponsive to both stimuli previous to the transition. This altered sensory excitability was linked to the presence of burst suppression activity in cortex, and to a regular slow burst suppression rhythm (∼0.2 Hz) in the subiculum. The effect disappeared during return to light anesthesia. The results show that pseudo-heteromodal sensory burst responses can appear in brain structures as an effect of an anesthesia induced state change. PMID:23185462

  12. Wiring of Divergent Networks in the Central Auditory System

    PubMed Central

    Lee, Charles C.; Kishan, Amar U.; Winer, Jeffery A.

    2011-01-01

    Divergent axonal projections are found throughout the central auditory system. Here, we evaluate these branched projections in terms of their types, distribution, and putative physiological roles. In general, three patterns of axon collateralization are found: intricate local branching, long-distance collaterals, and branched axons (BAs) involved in feedback-control loops. Local collaterals in the auditory cortex may be involved in local processing and modulation of neuronal firing, while long-range collaterals are optimized for wide-dissemination of information. Rarely do axons branch to both ascending and descending targets. Branched projections to two or more widely separated nuclei or areas are numerically sparse but widespread. Finally, branching to contralateral targets is evident at multiple levels of the auditory pathway and may enhance binaural computations for sound localization. These patterns of axonal branching are comparable to those observed in other modalities. We conclude that the operations served by BAs are area- and nucleus-specific and may complement the divergent unbranched projections of local neuronal populations. PMID:21847372

  13. Feedback delays eliminate auditory-motor learning in speech production.

    PubMed

    Max, Ludo; Maffett, Derek G

    2015-03-30

    Neurologically healthy individuals use sensory feedback to alter future movements by updating internal models of the effector system and environment. For example, when visual feedback about limb movements or auditory feedback about speech movements is experimentally perturbed, the planning of subsequent movements is adjusted - i.e., sensorimotor adaptation occurs. A separate line of studies has demonstrated that experimentally delaying the sensory consequences of limb movements causes the sensory input to be attributed to external sources rather than to one's own actions. Yet similar feedback delays have remarkably little effect on visuo-motor adaptation (although the rate of learning varies, the amount of adaptation is only moderately affected with delays of 100-200ms, and adaptation still occurs even with a delay as long as 5000ms). Thus, limb motor learning remains largely intact even in conditions where error assignment favors external factors. Here, we show a fundamentally different result for sensorimotor control of speech articulation: auditory-motor adaptation to formant-shifted feedback is completely eliminated with delays of 100ms or more. Thus, for speech motor learning, real-time auditory feedback is critical. This novel finding informs theoretical models of human motor control in general and speech motor control in particular, and it has direct implications for the application of motor learning principles in the habilitation and rehabilitation of individuals with various sensorimotor speech disorders.

  14. Does visual experience influence the spatial distribution of auditory attention?

    PubMed

    Lerens, Elodie; Renier, Laurent

    2014-02-01

    Sighted individuals are less accurate and slower to localize sounds coming from the peripheral space than sounds coming from the frontal space. This specific bias in favour of the frontal auditory space seems reduced in early blind individuals, who are particularly better than sighted individuals at localizing sounds coming from the peripheral space. Currently, it is not clear to what extent this bias in the auditory space is a general phenomenon or if it applies only to spatial processing (i.e. sound localization). In our approach we compared the performance of early blind participants with that of sighted subjects during a frequency discrimination task with sounds originating either from frontal or peripheral locations. Results showed that early blind participants discriminated faster than sighted subjects both peripheral and frontal sounds. In addition, sighted subjects were faster at discriminating frontal sounds than peripheral ones, whereas early blind participants showed equal discrimination speed for frontal and peripheral sounds. We conclude that the spatial bias observed in sighted subjects reflects an unbalance in the spatial distribution of auditory attention resources that is induced by visual experience. PMID:24378238

  15. K-means clustering method for auditory evoked potentials selection.

    PubMed

    Gourevitch, B; Le Bouquin-Jeannes, R

    2003-07-01

    Surface auditory evoked potentials are generally recorded using a headset of 32, 64 or 128 electrodes, but the quality of the responses is quite heterogeneous on the scalp surface. In some contexts, such as the analysis of auditory evoked potentials recorded in radio-frequency fields, the signal quality is essential, and it appears pertinent to consider only a limited number of electrodes. Therefore, before analysing signals influenced by radio-frequency fields, it is necessary to consider the preliminary step of selecting the channels where auditory activity is strong. This step is often realised by human visual selection and can take a considerable time. In this paper, a simple k-means clustering method is proposed, to select automatically the important channels, and the results are compared with traditional methods of selection. The method detected channels that showed a concordance rate of 86.5% with the visual selection (performed by five individuals) and gave the same final selection (only two extra electrodes in the automatic case). Moreover, the time needed for this automatic selection was 100 times less than that for the visual selection, and also human variability was avoided.

  16. Auditory connections and functions of prefrontal cortex

    PubMed Central

    Plakke, Bethany; Romanski, Lizabeth M.

    2014-01-01

    The functional auditory system extends from the ears to the frontal lobes with successively more complex functions occurring as one ascends the hierarchy of the nervous system. Several areas of the frontal lobe receive afferents from both early and late auditory processing regions within the temporal lobe. Afferents from the early part of the cortical auditory system, the auditory belt cortex, which are presumed to carry information regarding auditory features of sounds, project to only a few prefrontal regions and are most dense in the ventrolateral prefrontal cortex (VLPFC). In contrast, projections from the parabelt and the rostral superior temporal gyrus (STG) most likely convey more complex information and target a larger, widespread region of the prefrontal cortex. Neuronal responses reflect these anatomical projections as some prefrontal neurons exhibit responses to features in acoustic stimuli, while other neurons display task-related responses. For example, recording studies in non-human primates indicate that VLPFC is responsive to complex sounds including vocalizations and that VLPFC neurons in area 12/47 respond to sounds with similar acoustic morphology. In contrast, neuronal responses during auditory working memory involve a wider region of the prefrontal cortex. In humans, the frontal lobe is involved in auditory detection, discrimination, and working memory. Past research suggests that dorsal and ventral subregions of the prefrontal cortex process different types of information with dorsal cortex processing spatial/visual information and ventral cortex processing non-spatial/auditory information. While this is apparent in the non-human primate and in some neuroimaging studies, most research in humans indicates that specific task conditions, stimuli or previous experience may bias the recruitment of specific prefrontal regions, suggesting a more flexible role for the frontal lobe during auditory cognition. PMID:25100931

  17. Adaptation in the auditory space map of the barn owl.

    PubMed

    Gutfreund, Yoram; Knudsen, Eric I

    2006-08-01

    Auditory neurons in the owl's external nucleus of the inferior colliculus (ICX) integrate information across frequency channels to create a map of auditory space. This study describes a powerful, sound-driven adaptation of unit responsiveness in the ICX and explores the implications of this adaptation for sensory processing. Adaptation in the ICX was analyzed by presenting lightly anesthetized owls with sequential pairs of dichotic noise bursts. Adaptation occurred in response even to weak, threshold-level sounds and remained strong for more than 100 ms after stimulus offset. Stimulation by one range of sound frequencies caused adaptation that generalized across the entire broad range of frequencies to which these units responded. Identical stimuli were used to test adaptation in the lateral shell of the central nucleus of the inferior colliculus (ICCls), which provides input directly to the ICX. Compared with ICX adaptation, adaptation in the ICCls was substantially weaker, shorter lasting, and far more frequency specific, suggesting that part of the adaptation observed in the ICX was attributable to processes resident to the ICX. The sharp tuning of ICX neurons to space, along with their broad tuning to frequency, allows ICX adaptation to preserve a representation of stimulus location, regardless of the frequency content of the sound. The ICX is known to be a site of visually guided auditory map plasticity. ICX adaptation could play a role in this cross-modal plasticity by providing a short-term memory of the representation of auditory localization cues that could be compared with later-arriving, visual-spatial information from bimodal stimuli. PMID:16707713

  18. Persistent Fluctuations in Stride Intervals under Fractal Auditory Stimulation

    PubMed Central

    Marmelat, Vivien; Torre, Kjerstin; Beek, Peter J.; Daffertshofer, Andreas

    2014-01-01

    Stride sequences of healthy gait are characterized by persistent long-range correlations, which become anti-persistent in the presence of an isochronous metronome. The latter phenomenon is of particular interest because auditory cueing is generally considered to reduce stride variability and may hence be beneficial for stabilizing gait. Complex systems tend to match their correlation structure when synchronizing. In gait training, can one capitalize on this tendency by using a fractal metronome rather than an isochronous one? We examined whether auditory cues with fractal variations in inter-beat intervals yield similar fractal inter-stride interval variability as isochronous auditory cueing in two complementary experiments. In Experiment 1, participants walked on a treadmill while being paced by either an isochronous or a fractal metronome with different variation strengths between beats in order to test whether participants managed to synchronize with a fractal metronome and to determine the necessary amount of variability for participants to switch from anti-persistent to persistent inter-stride intervals. Participants did synchronize with the metronome despite its fractal randomness. The corresponding coefficient of variation of inter-beat intervals was fixed in Experiment 2, in which participants walked on a treadmill while being paced by non-isochronous metronomes with different scaling exponents. As expected, inter-stride intervals showed persistent correlations similar to self-paced walking only when cueing contained persistent correlations. Our results open up a new window to optimize rhythmic auditory cueing for gait stabilization by integrating fractal fluctuations in the inter-beat intervals. PMID:24651455

  19. Persistent fluctuations in stride intervals under fractal auditory stimulation.

    PubMed

    Marmelat, Vivien; Torre, Kjerstin; Beek, Peter J; Daffertshofer, Andreas

    2014-01-01

    Stride sequences of healthy gait are characterized by persistent long-range correlations, which become anti-persistent in the presence of an isochronous metronome. The latter phenomenon is of particular interest because auditory cueing is generally considered to reduce stride variability and may hence be beneficial for stabilizing gait. Complex systems tend to match their correlation structure when synchronizing. In gait training, can one capitalize on this tendency by using a fractal metronome rather than an isochronous one? We examined whether auditory cues with fractal variations in inter-beat intervals yield similar fractal inter-stride interval variability as isochronous auditory cueing in two complementary experiments. In Experiment 1, participants walked on a treadmill while being paced by either an isochronous or a fractal metronome with different variation strengths between beats in order to test whether participants managed to synchronize with a fractal metronome and to determine the necessary amount of variability for participants to switch from anti-persistent to persistent inter-stride intervals. Participants did synchronize with the metronome despite its fractal randomness. The corresponding coefficient of variation of inter-beat intervals was fixed in Experiment 2, in which participants walked on a treadmill while being paced by non-isochronous metronomes with different scaling exponents. As expected, inter-stride intervals showed persistent correlations similar to self-paced walking only when cueing contained persistent correlations. Our results open up a new window to optimize rhythmic auditory cueing for gait stabilization by integrating fractal fluctuations in the inter-beat intervals.

  20. Causal contribution of primate auditory cortex to auditory perceptual decision-making

    PubMed Central

    Tsunada, Joji; Liu, Andrew S.K.; Gold, Joshua I.; Cohen, Yale E.

    2015-01-01

    Auditory perceptual decisions are thought to be mediated by the ventral auditory pathway. However, the specific and causal contributions of different brain regions in this pathway, including the middle-lateral (ML) and anterolateral (AL) belt regions of the auditory cortex, to auditory decisions have not been fully identified. To identify these contributions, we recorded from and microstimulated ML and AL sites while monkeys decided whether an auditory stimulus contained more low-frequency or high-frequency tone bursts. Both ML and AL neural activity was modulated by the frequency content of the stimulus. However, only the responses of the most stimulus-sensitive AL neurons were systematically modulated by the monkeys’ choices. Consistent with this observation, microstimulation of AL—but not ML—systematically biased the monkeys’ behavior toward the choice associated with the preferred frequency of the stimulated site. Together, these findings suggest that AL directly and causally contributes sensory evidence used to form this auditory decision. PMID:26656644

  1. Auditory Neuropathy/Dyssynchrony in Biotinidase Deficiency

    PubMed Central

    Yaghini, Omid

    2016-01-01

    Biotinidase deficiency is a disorder inherited autosomal recessively showing evidence of hearing loss and optic atrophy in addition to seizures, hypotonia, and ataxia. In the present study, a 2-year-old boy with Biotinidase deficiency is presented in which clinical symptoms have been reported with auditory neuropathy/auditory dyssynchrony (AN/AD). In this case, transient-evoked otoacoustic emissions showed bilaterally normal responses representing normal function of outer hair cells. In contrast, acoustic reflex test showed absent reflexes bilaterally, and visual reinforcement audiometry and auditory brainstem responses indicated severe to profound hearing loss in both ears. These results suggest AN/AD in patients with Biotinidase deficiency. PMID:27144235

  2. Survival of auditory hair cells.

    PubMed

    Seymour, Michelle L; Pereira, Fred A

    2015-07-01

    The inability of mammals to regenerate auditory hair cells creates a pressing need to understand the means of enhancing hair cell survival following insult or injury. Hair cells are easily damaged by noise exposure, by ototoxic medications and as a consequence of aging processes, all of which lead to progressive and permanent hearing impairment as hair cells are lost. Significant efforts have been invested in designing strategies to prevent this damage from occurring since permanent hearing loss has a profound impact on communication and quality of life for patients. In this mini-review, we discuss recent progress in the use of antioxidants, anti-inflammatories and apoptosis inhibitors to enhance hair cell survival. We conclude by clarifying the distinction between protection and rescue strategies and by highlighting important areas of future research.

  3. Auditory display for the blind

    NASA Technical Reports Server (NTRS)

    Fish, R. M. (Inventor)

    1974-01-01

    A system for providing an auditory display of two-dimensional patterns as an aid to the blind is described. It includes a scanning device for producing first and second voltages respectively indicative of the vertical and horizontal positions of the scan and a further voltage indicative of the intensity at each point of the scan and hence of the presence or absence of the pattern at that point. The voltage related to scan intensity controls transmission of the sounds to the subject so that the subject knows that a portion of the pattern is being encountered by the scan when a tone is heard, the subject determining the position of this portion of the pattern in space by the frequency and interaural difference information contained in the tone.

  4. Auditory, visual, and auditory-visual processing performance in typically developing children: modality independence versus dependence.

    PubMed

    Pillai, Roshni; Yathiraj, Asha

    2015-02-01

    The study was carried out to determine whether cross-modal interactions occur during processing of auditory and/or visual signals that require separation/closure, integration, and duration pattern perception in typically developing children. Thirty typically developing children were evaluated on three auditory processing tests (speech-in-noise test in Indian-English, dichotic-consonant vowel test, and duration pattern test) that tapped separation/closure, integration and duration pattern perception. The children were also evaluated on the visual and auditory-visual analogues of the auditory tests. Differences in modality were found in each of the processes that were tested. The performance when the auditory and visual modalities were tested simultaneously was significantly higher than the auditory or visual modality for tests that involved separation/closure and integration. In contrast, scores on the analogous auditory-visual duration pattern test were significantly higher than the auditory test but not the visual analogous test. Further, the scores of the auditory modality were significantly poorer than the visual modality for separation/closure and duration patterning but not for integration. Findings of the study indicate that performance on higher level processing varies depending on the modality that is assessed and supports the presence of cross-modality interactions.

  5. Visually induced auditory expectancy in music reading: a behavioral and electrophysiological study.

    PubMed

    Schön, Daniele; Besson, Mireille

    2005-04-01

    The general aim of this experiment was to investigate the processes involved in reading musical notation and to study the relationship between written music and its auditory representation. It was of main interest to determine whether musicians are able to develop expectancies for specific tonal or atonal auditory events based on visual score alone. Can musicians expect an "atonal" event or will it always sound odd? Moreover, it was of interest to determine whether the modulations in amplitude of a late positive component (P600) described in previous studies are linked to a general mismatch detection process or to specific musical expectancies. Results showed clearly that musicians are able to expect tonal auditory endings based on visual information and are also able to do so for atonal endings, although to a smaller extent. Strong interactions seem to exist between visual and auditory musical codes and visual information seems to influence auditory processing as early as 100 msec. These results are directly relevant for the question of whether music reading is actually music perception.

  6. Osteoma of the external auditory canal.

    PubMed

    Ohtani, I; Aikawa, T; Honda, M; Ouchi, J

    1984-01-01

    A case of osteoma of the external auditory canal in a 19-year-old male patient was reported. The differentiation between osteoma and exostosis was discussed clinically, histopathologically and scanning electron microscopically.

  7. Auditory evoked potentials and transcendental meditation.

    PubMed

    Barwood, T J; Empson, J A; Lister, S G; Tilley, A J

    1978-11-01

    Auditory evoked potentials to tone stimuli were recorded from 8 practised meditators before, during, and after meditation, and also during light sleep. No consistent changes were noted between baseline and meditating AEPs, or between meditating and sleep AEPs.

  8. Sexual Orientation and the Auditory System

    PubMed Central

    McFadden, Dennis

    2011-01-01

    The auditory system exhibits differences by sex and by sexual orientation, and the implication is that relevant auditory structures are altered during prenatal development, possibly by exposure to androgens. The otoacoustic emissions (OAEs) of newborn male infants are weaker than those of newborn females, and these sex differences persist through the lifespan. The OAEs of nonheterosexual females also are weaker than those of heterosexual females, suggesting an atypically strong exposure to androgens some time early in development. Auditory evoked potentials (AEPs) also exhibit sex differences beginning early in life. Some AEPs are different for heterosexual and nonheterosexual females, and other AEPs are different for heterosexual and nonheterosexual males. Research on non-humans treated with androgenic or anti-androgenic agents also suggests that OAEs are masculinized by prenatal exposure to androgens late in gestation. Collectively, the evidence suggests that prenatal androgens, acting globally or locally, affect both nonheterosexuality and the auditory system. PMID:21310172

  9. Auditory pathways: are 'what' and 'where' appropriate?

    PubMed

    Hall, Deborah A

    2003-05-13

    New evidence confirms that the auditory system encompasses temporal, parietal and frontal brain regions, some of which partly overlap with the visual system. But common assumptions about the functional homologies between sensory systems may be misleading. PMID:12747854

  10. Auditory perception modulated by word reading.

    PubMed

    Cao, Liyu; Klepp, Anne; Schnitzler, Alfons; Gross, Joachim; Biermann-Ruben, Katja

    2016-10-01

    Theories of embodied cognition positing that sensorimotor areas are indispensable during language comprehension are supported by neuroimaging and behavioural studies. Among others, the auditory system has been suggested to be important for understanding sound-related words (visually presented) and the motor system for action-related words. In this behavioural study, using a sound detection task embedded in a lexical decision task, we show that in participants with high lexical decision performance sound verbs improve auditory perception. The amount of modulation was correlated with lexical decision performance. Our study provides convergent behavioural evidence of auditory cortex involvement in word processing, supporting the view of embodied language comprehension concerning the auditory domain. PMID:27324193

  11. Hemodynamic imaging of the auditory cortex.

    PubMed

    Deborah, Ann Hall; Karima, Susi

    2015-01-01

    Over the past 20 years or so, functional magnetic resonance imaging (fMRI) has proven to be an influential tool for measuring perceptual and cognitive processing non-invasively in the human brain. This article provides a brief yet comprehensive overview of this dominant method for human auditory neuroscience, providing the reader with knowledge about the practicalities of using this technique to assess central auditory coding. Key learning objectives include developing an understanding of the basic MR physics underpinning the technique, the advantage of auditory fMRI over other current neuroimaging alternatives, and highlighting some of the practical considerations involved in setting up, running, and analyzing an auditory fMRI experiment. The future utility of fMRI and anticipated technical developments is also briefly evaluated. Throughout the review, key concepts are illustrated using specific author examples, with particular emphasis on fMRI findings that address questions pertaining to basic sound coding (such as frequency and pitch).

  12. Auditory-visual spatial interaction and modularity

    PubMed

    Radeau, M

    1994-02-01

    The results of dealing with the conditions for pairing visual and auditory data coming from spatially separate locations argue for cognitive impenetrability and computational autonomy, the pairing rules being the Gestalt principles of common fate and proximity. Other data provide evidence for pairing with several properties of modular functioning. Arguments for domain specificity are inferred from comparison with audio-visual speech. Suggestion of innate specification can be found in developmental data indicating that the grouping of visual and auditory signals is supported very early in life by the same principles that operate in adults. Support for a specific neural architecture comes from neurophysiological studies of the bimodal (auditory-visual) neurons of the cat superior colliculus. Auditory-visual pairing thus seems to present the four main properties of the Fodorian module.

  13. The Goldilocks effect in infant auditory attention.

    PubMed

    Kidd, Celeste; Piantadosi, Steven T; Aslin, Richard N

    2014-01-01

    Infants must learn about many cognitive domains (e.g., language, music) from auditory statistics, yet capacity limits on their cognitive resources restrict the quantity that they can encode. Previous research has established that infants can attend to only a subset of available acoustic input. Yet few previous studies have directly examined infant auditory attention, and none have directly tested theorized mechanisms of attentional selection based on stimulus complexity. This work utilizes model-based behavioral methods that were recently developed to examine visual attention in infants (e.g., Kidd, Piantadosi, & Aslin, 2012). The present results demonstrate that 7- to 8-month-old infants selectively attend to nonsocial auditory stimuli that are intermediately predictable/complex with respect to their current implicit beliefs and expectations. These findings provide evidence of a broad principle of infant attention across modalities and suggest that sound-to-sound transitional statistics heavily influence the allocation of auditory attention in human infants.

  14. Auditory Cortex Mapmaking: Principles, Projections, and Plasticity

    PubMed Central

    Schreiner, Christoph E.; Winer, Jeffery A.

    2008-01-01

    Maps of sensory receptor epithelia and of derived or computed features of the sensory environment are a common feature of auditory, visual, and somatic sensory representations from the periphery to the cerebral cortex. Maps enhance the understanding of normal neural organization and its modification by pathology and experience. They underlie the derivation of the computational principles that govern sensory processing and the generation of perception. Despite their intuitive explanatory power, the functio of and rules for organizing maps and their plasticity are not well understood. Some puzzles of auditory cortical map organization are that only a few complete receptor maps are available, and that even fewer computational maps have been identified beyond primary cortical areas. Neuroanatomical evidence suggests equally organized connectional patterns throughout the cortical hierarchy that might nerlie map stability. Here we consider the implications of auditory cortical map organization and its plasticity and evaluate the complementary role of maps in representation and computation from an auditory perspective. PMID:17964251

  15. Auditory scene analysis by echolocation in bats.

    PubMed

    Moss, C F; Surlykke, A

    2001-10-01

    Echolocating bats transmit ultrasonic vocalizations and use information contained in the reflected sounds to analyze the auditory scene. Auditory scene analysis, a phenomenon that applies broadly to all hearing vertebrates, involves the grouping and segregation of sounds to perceptually organize information about auditory objects. The perceptual organization of sound is influenced by the spectral and temporal characteristics of acoustic signals. In the case of the echolocating bat, its active control over the timing, duration, intensity, and bandwidth of sonar transmissions directly impacts its perception of the auditory objects that comprise the scene. Here, data are presented from perceptual experiments, laboratory insect capture studies, and field recordings of sonar behavior of different bat species, to illustrate principles of importance to auditory scene analysis by echolocation in bats. In the perceptual experiments, FM bats (Eptesicus fuscus) learned to discriminate between systematic and random delay sequences in echo playback sets. The results of these experiments demonstrate that the FM bat can assemble information about echo delay changes over time, a requirement for the analysis of a dynamic auditory scene. Laboratory insect capture experiments examined the vocal production patterns of flying E. fuscus taking tethered insects in a large room. In each trial, the bats consistently produced echolocation signal groups with a relatively stable repetition rate (within 5%). Similar temporal patterning of sonar vocalizations was also observed in the field recordings from E. fuscus, thus suggesting the importance of temporal control of vocal production for perceptually guided behavior. It is hypothesized that a stable sonar signal production rate facilitates the perceptual organization of echoes arriving from objects at different directions and distances as the bat flies through a dynamic auditory scene. Field recordings of E. fuscus, Noctilio albiventris, N

  16. Contribution of auditory nerve fibers to compound action potential of the auditory nerve.

    PubMed

    Bourien, Jérôme; Tang, Yong; Batrel, Charlène; Huet, Antoine; Lenoir, Marc; Ladrech, Sabine; Desmadryl, Gilles; Nouvian, Régis; Puel, Jean-Luc; Wang, Jing

    2014-09-01

    Sound-evoked compound action potential (CAP), which captures the synchronous activation of the auditory nerve fibers (ANFs), is commonly used to probe deafness in experimental and clinical settings. All ANFs are believed to contribute to CAP threshold and amplitude: low sound pressure levels activate the high-spontaneous rate (SR) fibers, and increasing levels gradually recruit medium- and then low-SR fibers. In this study, we quantitatively analyze the contribution of the ANFs to CAP 6 days after 30-min infusion of ouabain into the round window niche. Anatomic examination showed a progressive ablation of ANFs following increasing concentration of ouabain. CAP amplitude and threshold plotted against loss of ANFs revealed three ANF pools: 1) a highly ouabain-sensitive pool, which does not participate in either CAP threshold or amplitude, 2) a less sensitive pool, which only encoded CAP amplitude, and 3) a ouabain-resistant pool, required for CAP threshold and amplitude. Remarkably, distribution of the three pools was similar to the SR-based ANF distribution (low-, medium-, and high-SR fibers), suggesting that the low-SR fiber loss leaves the CAP unaffected. Single-unit recordings from the auditory nerve confirmed this hypothesis and further showed that it is due to the delayed and broad first spike latency distribution of low-SR fibers. In addition to unraveling the neural mechanisms that encode CAP, our computational simulation of an assembly of guinea pig ANFs generalizes and extends our experimental findings to different species of mammals. Altogether, our data demonstrate that substantial ANF loss can coexist with normal hearing threshold and even unchanged CAP amplitude. PMID:24848461

  17. A neurodegenerative vascular burden index and the impact on cognition.

    PubMed

    Heinzel, Sebastian; Liepelt-Scarfone, Inga; Roeben, Benjamin; Nasi-Kordhishti, Isabella; Suenkel, Ulrike; Wurster, Isabel; Brockmann, Kathrin; Fritsche, Andreas; Niebler, Raphael; Metzger, Florian G; Eschweiler, Gerhard W; Fallgatter, Andreas J; Maetzler, Walter; Berg, Daniela

    2014-01-01

    A wide range of vascular burden factors has been identified to impact vascular function and structure as indicated by carotid intima-media thickness (IMT). On the basis of their impact on IMT, vascular factors may be selected and clustered in a vascular burden index (VBI). Since many vascular factors increase the risk of Alzheimer's disease (AD), a multifactorial neurodegenerative VBI may be related to early pathological processes in AD and cognitive decline in its preclinical stages. We investigated an elderly cohort at risk for neurodegeneration (TREND study, n = 1102) for the multifactorial influence of vascular burden factors on IMT measured by ultrasound. To create a VBI for this cohort, vascular factors and their definitions (considering medical history, medication, and/or blood marker data) were selected based on their statistical effects on IMT in multiple regressions including age and sex. The impact of the VBI on cognitive performance was assessed using the Trail-Making Test (TMT) and the consortium to establish a registry for Alzheimer's disease (CERAD) neuropsychological battery. IMT was significantly predicted by age (standardized β = 0.26), sex (0.09; males > females) and the factors included in the VBI: obesity (0.18), hypertension (0.14), smoking (0.08), diabetes (0.07), and atherosclerosis (0.05), whereas other cardiovascular diseases or hypercholesterolemia were not significant. Individuals with 2 or more VBI factors compared to individuals without had an odds ratio of 3.17 regarding overly increased IMT ( ≥ 1.0 mm). The VBI showed an impact on executive control [log(TMT B-A), p = 0.047] and a trend toward decreased global cognitive function (CERAD total score, p = 0.057) independent of age, sex, and education. A VBI established on the basis of IMT may help to identify individuals with overly increased vascular burden linked to decreased cognitive function indicating neurodegenerative processes. The longitudinal study of

  18. Characterizing a neurodegenerative syndrome: primary progressive apraxia of speech

    PubMed Central

    Duffy, Joseph R.; Strand, Edythe A.; Machulda, Mary M.; Senjem, Matthew L.; Master, Ankit V.; Lowe, Val J.; Jack, Clifford R.; Whitwell, Jennifer L.

    2012-01-01

    Apraxia of speech is a disorder of speech motor planning and/or programming that is distinguishable from aphasia and dysarthria. It most commonly results from vascular insults but can occur in degenerative diseases where it has typically been subsumed under aphasia, or it occurs in the context of more widespread neurodegeneration. The aim of this study was to determine whether apraxia of speech can present as an isolated sign of neurodegenerative disease. Between July 2010 and July 2011, 37 subjects with a neurodegenerative speech and language disorder were prospectively recruited and underwent detailed speech and language, neurological, neuropsychological and neuroimaging testing. The neuroimaging battery included 3.0 tesla volumetric head magnetic resonance imaging, [18F]-fluorodeoxyglucose and [11C] Pittsburg compound B positron emission tomography scanning. Twelve subjects were identified as having apraxia of speech without any signs of aphasia based on a comprehensive battery of language tests; hence, none met criteria for primary progressive aphasia. These subjects with primary progressive apraxia of speech included eight females and four males, with a mean age of onset of 73 years (range: 49–82). There were no specific additional shared patterns of neurological or neuropsychological impairment in the subjects with primary progressive apraxia of speech, but there was individual variability. Some subjects, for example, had mild features of behavioural change, executive dysfunction, limb apraxia or Parkinsonism. Voxel-based morphometry of grey matter revealed focal atrophy of superior lateral premotor cortex and supplementary motor area. Voxel-based morphometry of white matter showed volume loss in these same regions but with extension of loss involving the inferior premotor cortex and body of the corpus callosum. These same areas of white matter loss were observed with diffusion tensor imaging analysis, which also demonstrated reduced fractional anisotropy

  19. Optogenetic stimulation of the auditory pathway

    PubMed Central

    Hernandez, Victor H.; Gehrt, Anna; Reuter, Kirsten; Jing, Zhizi; Jeschke, Marcus; Mendoza Schulz, Alejandro; Hoch, Gerhard; Bartels, Matthias; Vogt, Gerhard; Garnham, Carolyn W.; Yawo, Hiromu; Fukazawa, Yugo; Augustine, George J.; Bamberg, Ernst; Kügler, Sebastian; Salditt, Tim; de Hoz, Livia; Strenzke, Nicola; Moser, Tobias

    2014-01-01

    Auditory prostheses can partially restore speech comprehension when hearing fails. Sound coding with current prostheses is based on electrical stimulation of auditory neurons and has limited frequency resolution due to broad current spread within the cochlea. In contrast, optical stimulation can be spatially confined, which may improve frequency resolution. Here, we used animal models to characterize optogenetic stimulation, which is the optical stimulation of neurons genetically engineered to express the light-gated ion channel channelrhodopsin-2 (ChR2). Optogenetic stimulation of spiral ganglion neurons (SGNs) activated the auditory pathway, as demonstrated by recordings of single neuron and neuronal population responses. Furthermore, optogenetic stimulation of SGNs restored auditory activity in deaf mice. Approximation of the spatial spread of cochlear excitation by recording local field potentials (LFPs) in the inferior colliculus in response to suprathreshold optical, acoustic, and electrical stimuli indicated that optogenetic stimulation achieves better frequency resolution than monopolar electrical stimulation. Virus-mediated expression of a ChR2 variant with greater light sensitivity in SGNs reduced the amount of light required for responses and allowed neuronal spiking following stimulation up to 60 Hz. Our study demonstrates a strategy for optogenetic stimulation of the auditory pathway in rodents and lays the groundwork for future applications of cochlear optogenetics in auditory research and prosthetics. PMID:24509078

  20. Long Latency Auditory Evoked Potentials during Meditation.

    PubMed

    Telles, Shirley; Deepeshwar, Singh; Naveen, Kalkuni Visweswaraiah; Pailoor, Subramanya

    2015-10-01

    The auditory sensory pathway has been studied in meditators, using midlatency and short latency auditory evoked potentials. The present study evaluated long latency auditory evoked potentials (LLAEPs) during meditation. Sixty male participants, aged between 18 and 31 years (group mean±SD, 20.5±3.8 years), were assessed in 4 mental states based on descriptions in the traditional texts. They were (a) random thinking, (b) nonmeditative focusing, (c) meditative focusing, and (d) meditation. The order of the sessions was randomly assigned. The LLAEP components studied were P1 (40-60 ms), N1 (75-115 ms), P2 (120-180 ms), and N2 (180-280 ms). For each component, the peak amplitude and peak latency were measured from the prestimulus baseline. There was significant decrease in the peak latency of the P2 component during and after meditation (P<.001; analysis of variance and post hoc analysis with Bonferroni adjustment). The P1, P2, and N2 components showed a significant decrease in peak amplitudes during random thinking (P<.01; P<.001; P<.01, respectively) and nonmeditative focused thinking (P<.01; P<.01; P<.05, respectively). The results suggest that meditation facilitates the processing of information in the auditory association cortex, whereas the number of neurons recruited was smaller in random thinking and non-meditative focused thinking, at the level of the secondary auditory cortex, auditory association cortex and anterior cingulate cortex.