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Purpose: Amplitude modulations (AMs) are important for speech intelligibility, and deficits in speech intelligibility are a leading source of impairment in childhood listening difficulties (LiD). The present study aimed to explore the relationships between AM perception and speech-in-noise (SiN) comprehension in children and to determine whether deficits in AM processing contribute to childhood LiD. Evoked responses were used to parse the neural origins of AM processing. Method: Forty-one children with LiD and 44 typically developing children, ages 8-16 years, participated in the study. Behavioral AM depth thresholds were measured at 4 and 40 Hz. SiN tasks included the Listening in Spatialized Noise–Sentences Test (LiSN-S) and a coordinate response measure (CRM)-based task. Evoked responses were obtained during an AM change detection task using alternations between 4 and 40 Hz, including the N1 of the acoustic change complex, auditory steady-state response (ASSR), P300, and a late positive response (late potential [LP]). Maturational effects were explored via age correlations. Results: Age correlated with 4-Hz AM thresholds, CRM separated talker scores, and N1 amplitude. Age-normed LiSN-S scores obtained without spatial or talker cues correlated with age-corrected 4-Hz AM thresholds and area under the LP curve. CRM separated talker scores correlated with AM thresholds and area under the LP curve. Most behavioral measures of AM perception correlated with the signal-to-noise ratio and phase coherence of the 40-Hz ASSR. AM change response time also correlated with area under the LP curve. Children with LiD exhibited deficits with respect to 4-Hz thresholds, AM change accuracy, and area under the LP curve. Conclusions: The observed relationships between AM perception and SiN performance extend the evidence that modulation perception is important for understanding SiN in childhood. In line with this finding, children with LiD demonstrated poorer performance on some measures of AM perception, but their evoked responses implicated a primarily cognitive deficit. [ABSTRACT FROM AUTHOR]

Purpose: The study explored whether visual information improves speech identification in typically developing children with normal hearing when the auditory signal is spectrally degraded. Method: Children (n = 69) and adults (n = 15) were presented with noise-vocoded sentences from the Children's Co-ordinate Response Measure (Rosen, 2011) in auditory-only or audiovisual conditions. The number of bands was adaptively varied to modulate the degradation of the auditory signal, with the number of bands required for approximately 79% correct identification calculated as the threshold. Results: The youngest children (4- to 5-year-olds) did not benefit from accompanying visual information, in comparison to 6- to 11-year-old children and adults. Audiovisual gain also increased with age in the child sample. Conclusions: The current data suggest that children younger than 6 years of age do not fully utilize visual speech cues to enhance speech perception when the auditory signal is degraded. This evidence not only has implications for understanding the development of speech perception skills in children with normal hearing but may also inform the development of new treatment and intervention strategies that aim to remediate speech perception difficulties in pediatric cochlear implant users.

Selective attention to sound object features such as pitch and location is associated with enhanced brain activity in ventral and dorsal streams, respectively. We examined the role of these pathways in involuntary orienting and conflict resolution using fMRI. Participants were presented with two tones that may, or may not, share the same nonspatial (frequency) or spatial (location) auditory features. In separate blocks of trials, participants were asked to attend to sound frequency or sound location and ignore the change in the task-irrelevant feature. In both attend-frequency and attend-location tasks, RTs were slower when the task-irrelevant feature changed than when it stayed the same (involuntary orienting). This behavioral cost coincided with enhanced activity in the pFC and superior temporal gyrus. Conflict resolution was examined by comparing situations where the change in stimulus features was congruent (both features changed) and incongruent (only one feature changed). Participants were slower and less accurate for incongruent than congruent sound features. This congruency effect was associated with enhanced activity in the pFC and was greater in the right superior temporal gyrus and medial frontal cortex during the attend-location task than during the attend-frequency task. Together, these findings do not support a strict division of "labor" into ventral and dorsal streams but rather suggest interactions between these pathways in situations involving changes in task-irrelevant sound feature and conflict resolution. These findings also validate the Test of Attention in Listening task by revealing distinct neural correlates for involuntary orienting and conflict resolution. [ABSTRACT FROM AUTHOR]

Listening difficulties (LiD) are common in children with and without hearing loss. Impaired interactions between the two ears have been proposed as an important component of LiD when there is no hearing loss, also known as auditory processing disorder (APD). We examined the ability of 6–13 year old (y.o.) children with normal audiometric thresholds to identify and selectively attend to dichotically presented CV syllables using the Bergen Dichotic Listening Test (BDLT; www.dichoticlistening.com). Children were recruited as typically developing (TD; n = 39) or having LiD (n = 35) based primarily on composite score of the ECLiPS caregiver report. Different single syllables (ba, da, ga, pa, ta, ka) were presented simultaneously to each ear (6 × 36 trials). Children reported the syllable heard most clearly (non-forced, NF) or the syllable presented to the right [forced right (FR)] or left [forced left (FL)] ear. Interaural level differences (ILDs) manipulated bottom-up perceptual salience. Dichotic listening (DL) data [correct responses, laterality index (LI)] were analyzed initially by group (LiD, TD), age, report method (NF, FR, FL), and ILD (0, ± 15 dB) and compared with speech-in-noise thresholds (LiSN-S) and cognitive performance (NIH Toolbox). fMRI measured brain activation produced by a receptive speech task that segregated speech, phonetic, and intelligibility components. Some activated areas [planum temporale (PT), inferior frontal gyrus (IFG), and orbitofrontal cortex (OFC)] were correlated with dichotic results in TD children only. Neither group, age, nor report method affected the LI of right/left recall. However, a significant interaction was found between ear, group, and ILD. Laterality indices were small and tended to increase with age, as previously reported. Children with LiD had significantly larger mean LIs than TD children for stimuli with ILDs, especially those favoring the left ear. Neural activity associated with Speech, Phonetic, and Intelligibility sentence cues did not differ significantly between groups. Significant correlations between brain activity level and BDLT were found in several frontal and temporal locations for the TD but not for the LiD group. Overall, the children with LiD had only subtle differences from TD children in the BDLT, and correspondingly minor changes in brain activation. [ABSTRACT FROM AUTHOR]

Objective: To establish the modality specificity and generality of selective attention networks. Method: Forty-eight young adults completed a battery of four auditory and visual selective attention tests based upon the Attention Network framework: the visual and auditory Attention Network Tests (vANT, aANT), the Test of Everyday Attention (TEA), and the Test of Attention in Listening (TAiL). These provided independent measures for auditory and visual alerting, orienting, and conflict resolution networks. The measures were subjected to an exploratory factor analysis to assess underlying attention constructs. Results: The analysis yielded a four-component solution. The first component comprised of a range of measures from the TEA and was labeled "general attention." The third component was labeled "auditory attention," as it only contained measures from the TAiL using pitch as the attended stimulus feature. The second and fourth components were labeled as "spatial orienting" and "spatial conflict," respectively-they were comprised of orienting and conflict resolution measures from the vANT, aANT, and TAiL attend-location task-all tasks based upon spatial judgments (e.g., the direction of a target arrow or sound location). Conclusions: These results do not support our a-priori hypothesis that attention networks are either modality specific or supramodal. Auditory attention separated into selectively attending to spatial and non-spatial features, with the auditory spatial attention loading onto the same factor as visual spatial attention, suggesting spatial attention is supramodal. However, since our study did not include a non-spatial measure of visual attention, further research will be required to ascertain whether non-spatial attention is modality-specific. [ABSTRACT FROM AUTHOR]

Imitation is a potentially crucial aspect of social cognitive development. Although deficits in imitation ability have been widely demonstrated in autism spectrum disorder ( ASD), the specificity and significance of the findings is unclear, due largely to methodological limitations. We developed a novel assessment of imitation ability, using objective movement parameters (path length and action duration) derived from a touch-sensitive tablet laptop during drawing actions on an identical tablet. By direct comparison of the kinematics of a model's actions with those of the participant who observed them, measures of imitation accuracy were obtained. By replaying the end-point of the movement as a spot on the screen, imitation accuracy was compared against a 'ghost control' condition, with no human actor but only the end-point of the movement seen [object movement reenactment ( OMR)]. Hence, demands of the control task were closely matched to the experimental task with respect to motor, memory, and attentional abilities. Adolescents with ASD showed poorer accuracy for copying object size and action duration on both the imitation and OMR tasks, but were significantly more impaired for imitation of object size. Our results provide evidence that some of the imitation deficit in ASD is specific to a self-other mapping problem, and cannot be explained by general factors such as memory, spatial reasoning, motor control, or attention, nor related to the social demands of the testing situation. Autism Res 2013, 6: 522-530. © 2013 International Society for Autism Research, Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Purpose: Amplitude modulations (AM) are important for speech intelligibility, and deficits in speech intelligibility are a leading source of impairment in childhood listening difficulties (LiD). The present study aimed to explore the relationships between AM perception and speech-in-noise (SiN) comprehension in children and to determine whether deficits in AM processing contribute to childhood LiD. Evoked responses were used to parse the neural origin of AM processing., Method: Forty-one children with LiD and forty-four typically-developing children, ages 8-16 y.o., participated in the study. Behavioral AM depth thresholds were measured at 4 and 40 Hz. SiN tasks included the LiSN-S and a Coordinate Response Measure (CRM)-based task. Evoked responses were obtained during an AM Change detection task using alternations between 4 and 40 Hz, including the N1 of the acoustic change complex, auditory steady-state response (ASSR), P300, and a late positive response (LP). Maturational effects were explored via age correlations., Results: Age correlated with 4 Hz AM thresholds, CRM Separated Talker scores, and N1 amplitude. Age-normed LiSN-S scores obtained without spatial or talker cues correlated with age-corrected 4 Hz AM thresholds and area under the LP curve. CRM Separated Talker scores correlated with AM thresholds and area under the LP curve. Most behavioral measures of AM perception correlated with the SNR and phase coherence of the 40 Hz ASSR. AM Change RT also correlated with area under the LP curve. Children with LiD exhibited deficits with respect to 4 Hz thresholds, AM Change accuracy, and area under the LP curve., Conclusions: The observed relationships between AM perception and SiN performance extend the evidence that modulation perception is important for understanding SiN in childhood. In line with this finding, children with LiD demonstrated poorer performance on some measures of AM perception, but their evoked responses implicated a primarily cognitive deficit.

Purpose This exploratory study assessed the perceptual, cognitive, and academic learning effects of an adaptive, integrated, directionality, and noise reduction hearing aid program in pediatric users. Method Fifteen pediatric hearing aid users (6-12 years old) received new bilateral, individually fitted Oticon Opn hearing aids programmed with OpenSound Navigator (OSN) processing. Word recognition in noise, sentence repetition in quiet, nonword repetition, vocabulary learning, selective attention, executive function, memory, and reading and mathematical abilities were measured within 1 week of the initial hearing aid fitting and 2 months post fit. Caregivers completed questionnaires assessing their child's listening and communication abilities prior to study enrollment and after 2 months of using the study hearing aids. Results Caregiver reporting indicated significant improvements in speech and sound perception, spatial sound awareness, and the ability to participate in conversations. However, there was no positive change in performance in any of the measured skills. Mathematical scores significantly declined after 2 months. Conclusions OSN provided a perceived improvement in functional benefit, compared to their previous hearing aids, as reported by caregivers. However, there was no positive change in listening skills, cognition, and academic success after 2 months of using OSN. Findings may have been impacted by reporter bias, limited sample size, and a relatively short trial period. This study took place during the summer when participants were out of school, which may have influenced the decline in mathematical scores. The results support further exploration with age- and audiogram-matched controls, larger sample sizes, and longer test-retest intervals that correspond to the academic school year.

In everyday situations auditory selective attention requires listeners to suppress task-irrelevant stimuli and to resolve conflicting information in order to make appropriate goal-directed decisions. Traditionally, these two processes (i.e. distractor suppression and conflict resolution) have been studied separately. In the present study we measured neuroelectric activity while participants performed a new paradigm in which both processes are quantified. In separate block of trials, participants indicate whether two sequential tones share the same pitch or location depending on the block's instruction. For the distraction measure, a positive component peaking at ~250 ms was found - a distraction positivity. Brain electrical source analysis of this component suggests different generators when listeners attended to frequency and location, with the distraction by location more posterior than the distraction by frequency, providing support for the dual-pathway theory. For the conflict resolution measure, a negative frontocentral component (270-450 ms) was found, which showed similarities with that of prior studies on auditory and visual conflict resolution tasks. The timing and distribution are consistent with two distinct neural processes with suppression of task-irrelevant information occurring before conflict resolution. This new paradigm may prove useful in clinical populations to assess impairments in filtering out task-irrelevant information and/or resolving conflicting information.

Pharmacological dopamine replacement therapies provide the most well-established treatments for Parkinson's disease (PD). However, these long-term treatments can lead to motor complications and off-target effects. ProSavin(®), a lentiviral vector (LV)-based gene therapy approach aimed at restoring local and continuous dopamine production, through delivery of three enzymes in the dopamine biosynthesis pathway, was demonstrated to be safe and well-tolerated in a phase I/II clinical study of patients with advanced PD. Although improvements in motor behaviour were observed, the data indicated that higher levels of dopamine replacement might be required to maximize benefit. We attempted to increase production of dopamine, and its precursor L-Dopa in LV-transduced cells, by optimizing the gene order in the ProSavin expression cassette, and by creating fusions of two or three of the transgenes, using linker sequences. In vitro analysis showed that several gene arrangements provided significantly increased dopamine and/or L-Dopa production compared with ProSavin, and that LV titers and transgene expression were not affected by introducing gene fusions. One vector, equine infectious anemia virus (EIAV)-TCiA, was selected for further characterization and showed significant improvements in dopamine and L-Dopa production compared with ProSavin, in human neuronal cells. Further characterization of EIAV-TCiA demonstrated expression of all three dopamine enzymes in vivo and faithful delivery and integration of the expected gene expression cassette within the genome of target cells, as assessed by Northern and Southern blotting. In conclusion, we have developed a novel LV vector with an increased capacity for L-Dopa and dopamine production compared with the current ProSavin vector. Clinical evaluation of this vector will be performed to assess the benefits in patients with PD.

Imitation is a potentially crucial aspect of social cognitive development. Although deficits in imitation ability have been widely demonstrated in autism spectrum disorder (ASD), the specificity and significance of the findings is unclear, due largely to methodological limitations. We developed a novel assessment of imitation ability, using objective movement parameters (path length and action duration) derived from a touch-sensitive tablet laptop during drawing actions on an identical tablet. By direct comparison of the kinematics of a model's actions with those of the participant who observed them, measures of imitation accuracy were obtained. By replaying the end-point of the movement as a spot on the screen, imitation accuracy was compared against a "ghost control" condition, with no human actor but only the end-point of the movement seen [object movement reenactment (OMR)]. Hence, demands of the control task were closely matched to the experimental task with respect to motor, memory, and attentional abilities. Adolescents with ASD showed poorer accuracy for copying object size and action duration on both the imitation and OMR tasks, but were significantly more impaired for imitation of object size. Our results provide evidence that some of the imitation deficit in ASD is specific to a self-other mapping problem, and cannot be explained by general factors such as memory, spatial reasoning, motor control, or attention, nor related to the social demands of the testing situation., (© 2013 International Society for Autism Research, Wiley Periodicals, Inc.)

ProSavin is an equine infectious anemia virus vector-based gene therapy for Parkinson's disease for which inducible HEK293T-based producer cell lines (PCLs) have been developed. These cell lines demonstrate stringent tetracycline-regulated expression of the packaging components and yield titers comparable to the established transient production system. A prerequisite for the use of PCL-derived lentiviral vectors (LVs) in clinical applications is the thorough characterization of both the LV and respective PCL with regard to identity and genetic stability. We describe the detailed characterization of two ProSavin PCLs (PS5.8 and PS46.2) and resultant ProSavin vector. The two cell lines demonstrate stable production of vector over a time period sufficient to allow generation of master and working cell banks, and subsequent large-scale vector production. ProSavin generated from the PCLs performs comparably in vivo to that produced by the standard transient transfection process with respect to transduction efficiency and immunogenicity. The development of ProSavin PCLs, and the detailed characterization described here, will aid the advancement of ProSavin for clinical application.