Altered structural connectome of children with auditory processing disorder: a diffusion MRI study.

Auditory processing disorder (APD) is a listening impairment that some school-aged children may experience despite having normal peripheral hearing. Recent resting-state functional magnetic resonance imaging (MRI) has revealed an alteration in regional functional brain topology in children with APD. However, little is known about the structural organization in APD. We used diffusion MRI data to investigate the structural connectome of 58 children from 8 to 14 years old diagnosed with APD (n = 29) and children without hearing complaints (healthy controls, HC; n = 29). We investigated the rich-club organization and structural connection differences between groups. The APD group showed similar rich-club organization and edge-wise connection compared with the HC group. However, at the regional level, we observed increased average path length (APL) and betweenness centrality in the right inferior parietal lobule and inferior precentral gyrus, respectively, in the APD group. Only HCs demonstrated a positive association between APL and the listening-in-spatialized-noise-sentences task in the left orbital gyrus. In line with previous findings, the current results provide evidence for altered structural networks at the regional level in the APD group, suggesting the involvement of multimodal deficits and a role for structure-function alteration in the listening difficulties of children with APD.

[Congenital amusia and its effects on non-musical skills]. / Amusia congénita y sus efectos en habilidades no musicales.

INTRODUCTION: Congenital amusia is a specific condition in which the individual is unable to recognise tonal variations in a piece of musical. This cannot be explained by a previous brain injury, hearing loss, cognitive deficit, socio-affective disorder or lack of environmental stimulation. The current estimated prevalence is 1.5% of the world population, with a significant genetic component among those who suffer from it. It has been claimed that certain cognitive abilities in the emotional, spatial and language fields may be affected in people with amusia. AIM: To review the literature describing the effects on non-musical skills that may coexist in individuals with congenital amusia. DEVELOPMENT: Several neuroimaging studies have observed morphological and functional changes in the temporal lobe, as well as in the white matter connections between the superior temporal gyrus and the inferior frontal gyrus. From these affected regions, there may be a deficit in cognitive skills related to adjacent areas. CONCLUSIONS: Congenital amusia has been associated with poor performance in different non-musical cognitive skills, such as visuospatial processing, language processing, reading difficulties, face recognition and emotional aspects.

TITLE: Amusia congénita y sus efectos en habilidades no musicales.Introducción. La amusia congénita es una condición específica en la que el individuo afectado es incapaz de reconocer variaciones tonales en las piezas musicales. Esto no puede explicarse por una lesión encefálica previa, una pérdida auditiva, un déficit cognitivo, un trastorno socioafectivo o una falta de estimulación ambiental. Actualmente se estima una prevalencia del 1,5% de la población mundial, con un importante componente genético entre los afectados. Se ha descrito que en las personas con amusia puede haber afectación de ciertas habilidades cognitivas en el campo emocional, espacial y del lenguaje. Objetivo. Revisar la bibliografía donde se describen los efectos en las habilidades no musicales que pueden coexistir en individuos con amusia congénita. Desarrollo. Varios estudios de neuroimagen han permitido observar cambios morfológicos y funcionales en el lóbulo temporal, así como en las conexiones de la sustancia blanca entre el giro temporal superior y el giro frontal inferior. Partiendo de estas regiones afectadas, podría existir un déficit en habilidades cognitivas relacionadas con áreas adyacentes. Conclusiones. La amusia congénita se ha relacionado con un pobre desempeño en diferentes habilidades cognitivas no musicales, como el procesamiento visuoespacial, el procesamiento del lenguaje, alteraciones de la lectura, el reconocimiento de rostros y aspectos emocionales.

Deficits in auditory sensory discrimination among children with attention-deficit/hyperactivity disorder.

Research into children with attention-deficit/hyperactivity disorder (ADHD) has focused on complex cognitive dysfunction, but less attention has been paid to sensory perception processes underlying the symptoms of ADHD. Based on signal detection theory, the present study compared the sensory discrimination ability and decision bias of children with and without ADHD. It also investigated the differences between ADHD with predominantly inattentive (ADHDi) and combined presentations (ADHDc). The sample of 75 children and adolescents with ADHD (24 ADHDi, 51 ADHDc) (16 females and 59 males) and 22 typical developing controls (TD) (8 females and 14 males) completed an auditory signal detection task. Participants were asked to detect signals against levels of transient background noise (35, 45, 55, and 65 dB). The results showed that with the increase of noise levels, both the ADHD and TD groups demonstrated decreased sensory discrimination. Although both groups successfully detected signal against noise levels from 35 to 55 dB, the ADHD group showed lower discrimination ability than that of the TD group. For decision bias, no group difference was found. Further comparisons regarding the predominant symptom presentation of ADHD sub-groups showed no differences. Current research has suggested that the deficit in ADHD people's signal detection performance can be attributed to sensory discrimination rather than decision bias. We suggest that background noise should be taken into account when using auditory stimuli to investigate cognitive functions in people with ADHD.

Parental perception of listening difficulties: an interaction between weaknesses in language processing and ability to sustain attention.

(Central) auditory processing disorder ((C)APD) is a controversial diagnostic category which may be an artefact of referral route. Yet referral route must, to some extent, be influenced by a child's profile of presenting symptoms. This study tested the hypothesis that parental perception of listening difficulty is associated with weaknesses in ability to sustain attention while listening to speech. Forty-four children (24 with listening difficulties) detected targets embedded in a 16-minute story. The targets were either mispronunciations or nonsense words. Sentence context was modulated to separate out effects due to deficits in language processing from effects due to deficits in attention. Children with listening difficulties missed more targets than children with typical listening abilities. Both groups of children were initially sensitive to sentence context, but this declined over time in the children with listening difficulties. A report-based measure of language abilities captured the majority of variance in a measure capturing time-related changes in sensitivity to context. Overall, the findings suggest parents perceive children to have listening, not language difficulties, because weaknesses in language processing only emerge when stressed by the additional demands associated with attending to, and processing, speech over extended periods of time.

Musical deficits and cortical thickness in people with schizophrenia.

Investigation of acquired amusia caused by brain damage suggested that cortical lesions of the right hemisphere contributed to musical deficits. We previously reported reduced musical ability in schizophrenia; these deficits were correlated with clinical manifestations such as cognitive dysfunction and negative symptoms. However, the neural substrate underlying the musical disability in schizophrenia remains unclear. We investigated the relationship between musical deficits and cortical thickness in patients with schizophrenia using structural MRI. We recruited 24 patients (13 males; age mean=45.9years old), and 22 controls (14 males, age mean=43.5years old). Musical ability was assessed with the Montreal Battery for Evaluation of Amusia (MBEA), cognitive function with the Brief Assessment of Cognition in Schizophrenia (BACS) and clinical features of illness with the Positive and Negative Syndrome Scale (PANSS). MRI Images were acquired and processed using FreeSurfer. Surface-based analysis showed that thinner cortex in left temporal and inferior frontal region was associated with lower musical ability in schizophrenia. In contrast, in controls thicker cortex in the left supramarginal region was correlated with lower musical ability. These results shed light on the clinical pathology underlying the associations of musical ability, cognitive dysfunction and negative symptoms in patients with schizophrenia.

The lateralized arcuate fasciculus in developmental pitch disorders among mandarin amusics: left for speech and right for music.

The arcuate fasciculus (AF) is a neural fiber tract that is critical to speech and music development. Although the predominant role of the left AF in speech development is relatively clear, how the AF engages in music development is not understood. Congenital amusia is a special neurodevelopmental condition, which not only affects musical pitch but also speech tone processing. Using diffusion tensor tractography, we aimed at understanding the role of AF in music and speech processing by examining the neural connectivity characteristics of the bilateral AF among thirty Mandarin amusics. Compared to age- and intelligence quotient (IQ)-matched controls, amusics demonstrated increased connectivity as reflected by the increased fractional anisotropy in the right posterior AF but decreased connectivity as reflected by the decreased volume in the right anterior AF. Moreover, greater fractional anisotropy in the left direct AF was correlated with worse performance in speech tone perception among amusics. This study is the first to examine the neural connectivity of AF in the neurodevelopmental condition of amusia as a result of disrupted music pitch and speech tone processing. We found abnormal white matter structural connectivity in the right AF for the amusic individuals. Moreover, we demonstrated that the white matter microstructural properties of the left direct AF is modulated by lexical tone deficits among the amusic individuals. These data support the notion of distinctive pitch processing systems between music and speech.

Neural differences between the processing of musical meaning conveyed by direction of pitch change and natural music in congenital amusia.

Music is a unique communication system for human beings. Iconic musical meaning is one dimension of musical meaning, which emerges from musical information resembling sounds of objects, qualities of objects, or qualities of abstract concepts. The present study investigated whether congenital amusia, a disorder of musical pitch perception, impacts the processing of iconic musical meaning. With a cross-modal semantic priming paradigm, target images were primed by semantically congruent or incongruent musical excerpts, which were characterized by direction (upward or downward) of pitch change (Experiment 1), or were selected from natural music (Experiment 2). Twelve Mandarin-speaking amusics and 12 controls performed a recognition (implicit) and a semantic congruency judgment (explicit) task while their EEG waveforms were recorded. Unlike controls, amusics failed to elicit an N400 effect when musical meaning was represented by direction of pitch change, regardless of the nature of the tasks (implicit versus explicit). However, the N400 effect in response to musical meaning in natural musical excerpts was observed for both the groups in both types of tasks. These results indicate that amusics are able to process iconic musical meaning through multiple acoustic cues in natural musical excerpts, but not through the direction of pitch change. This is the first study to investigate the processing of musical meaning in congenital amusia, providing evidence in support of the "melodic contour deafness hypothesis" with regard to iconic musical meaning processing in this disorder.

Neurobiology of Congenital Amusia.

The past decade of research has provided compelling evidence that musical engagement is a fundamental human trait, and its biological basis is increasingly scrutinized. In this endeavor, the detailed study of individuals who have musical deficiencies is instructive because of likely neurogenetic underpinnings. Such individuals have 'congenital amusia', an umbrella term for lifelong musical disabilities that cannot be attributed to intellectual disability, lack of exposure, or brain damage after birth. Key points are reviewed here that have emerged during recent years regarding the neurobiology of the disorder, focusing on the importance of recurrent processing between the right inferior frontal cortex and the auditory cortex for conscious monitoring of musical pitch, and how this relates to developmental cognitive disorders in general.

Abnormal topological organization of the white matter network in Mandarin speakers with congenital amusia.

Congenital amusia is a neurogenetic disorder that mainly affects the processing of musical pitch. Brain imaging evidence indicates that it is associated with abnormal structural and functional connections in the fronto-temporal region. However, a holistic understanding of the anatomical topology underlying amusia is still lacking. Here, we used probabilistic diffusion tensor imaging tractography and graph theory to examine whole brain white matter structural connectivity in 31 Mandarin-speaking amusics and 24 age- and IQ-matched controls. Amusics showed significantly reduced global connectivity, as indicated by the abnormally decreased clustering coefficient (Cp) and increased normalized shortest path length (λ) compared to the controls. Moreover, amusics exhibited enhanced nodal strength in the right inferior parietal lobule relative to controls. The co-existence of the lexical tone deficits was associated with even more deteriorated global network efficiency in amusics, as suggested by the significant correlation between the increments in normalized shortest path length (λ) and the insensitivity in lexical tone perception. Our study is the first to reveal reduced global connectivity efficiency in amusics as well as an increase in the global connectivity cost due to the co-existed lexical tone deficits. Taken together these results provide a holistic perspective on the anatomical substrates underlying congenital amusia.

Pitch-Responsive Cortical Regions in Congenital Amusia.

Congenital amusia is a lifelong deficit in music perception thought to reflect an underlying impairment in the perception and memory of pitch. The neural basis of amusic impairments is actively debated. Some prior studies have suggested that amusia stems from impaired connectivity between auditory and frontal cortex. However, it remains possible that impairments in pitch coding within auditory cortex also contribute to the disorder, in part because prior studies have not measured responses from the cortical regions most implicated in pitch perception in normal individuals. We addressed this question by measuring fMRI responses in 11 subjects with amusia and 11 age- and education-matched controls to a stimulus contrast that reliably identifies pitch-responsive regions in normal individuals: harmonic tones versus frequency-matched noise. Our findings demonstrate that amusic individuals with a substantial pitch perception deficit exhibit clusters of pitch-responsive voxels that are comparable in extent, selectivity, and anatomical location to those of control participants. We discuss possible explanations for why amusics might be impaired at perceiving pitch relations despite exhibiting normal fMRI responses to pitch in their auditory cortex: (1) individual neurons within the pitch-responsive region might exhibit abnormal tuning or temporal coding not detectable with fMRI, (2) anatomical tracts that link pitch-responsive regions to other brain areas (e.g., frontal cortex) might be altered, and (3) cortical regions outside of pitch-responsive cortex might be abnormal. The ability to identify pitch-responsive regions in individual amusic subjects will make it possible to ask more precise questions about their role in amusia in future work.

Importance of a multidisciplinary approach and monitoring in fetal warfarin syndrome.

Warfarin is a synthetic oral anticoagulant that crosses the placenta and can lead to a number of congenital abnormalities known as fetal warfarin syndrome. Our aim is to report on the follow-up from birth to age 8 years of a patient with fetal warfarin syndrome. He presented significant respiratory dysfunction, as well as dental and speech and language complications. The patient was the second child of a mother who took warfarin during pregnancy due to a metallic heart valve. The patient had respiratory dysfunction at birth. On physical examination, he had a hypoplastic nose, pectus excavatum, and clubbing of the fingers. Nasal fibrobronchoscopy showed upper airway obstruction due to narrowing of the nasal cavities. He underwent surgical correction with Max Pereira graft, zetaplasty, and osteotomies for the piriform aperture. At dental evaluation, he had caries and delayed eruption of the upper incisors. Speech and language assessment revealed high palate, mouth breathing, little nasal patency, and shortened upper lip. Auditory long latency and cognitive-related potential to auditory stimuli demonstrated functional changes in the cortical auditory pathways. We believe that the frequency of certain findings observed in our patient may be higher in fetal warfarin syndrome than is appreciated, since a significant number result in abortions, stillbirths, or children evaluated in the first year of life without a follow-up. Thus, a multidisciplinary approach and long-term monitoring of these patients may be necessary.

Palinacousis.

Palinacousis is derived from the Greek words palin, which means again or anew, and acousis, meaning hearing. It was first described by Jacobs et al. (1971), who defined the phenomenon as "an auditory illusion of perseveration or persistence of sound impressions for seconds, minutes, or hours after the cessation of auditory stimulation." The auditory perseveration does not occur spontaneously but is triggered by something in the environment. A limited number of cases have been described in the literature. This chapter describes the anatomic abnormalities that may cause this phenomenon, the clinical characteristics that define palinacousis, differential diagnosis and potential etiologies.

Auditory neglect and related disorders.

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.

Congenital amusias.

In contrast to the sophisticated music processing reported in the general population, individuals with congenital amusia show deficits in music perception and production. Congenital amusia occurs without brain damage, sensory or cognitive deficits, and has been suggested as a lifelong deficit with genetic origin. Even though recognized for a long time, this disorder has been systematically studied only relatively recently for its behavioral and neural correlates. The currently most investigated hypothesis about the underlying deficits concerns the pitch dimension, notably with impaired pitch discrimination and memory. Anatomic and functional investigations of pitch processing revealed that the amusic brain presents abnormalities in the auditory and inferior frontal cortices, associated with decreased connectivity between these structures. The deficit also impairs processing of pitch in speech material and processing of the time dimension in music for some of the amusic individuals, but does not seem to affect spatial processing. Some studies suggest at least partial dissociation in the disorder between perception and production. Recent studies revealed spared implicit pitch perception in congenital amusia, supporting the power of implicit cognition in the music domain. Current challenges consist in defining different subtypes of congenital amusia as well as developing rehabilitation programs for this "musical handicap."

Sources of pathology underlying listening disorders in children.

Some children referred to audiology and developmental disability services have listening difficulties, despite normal audiograms. These children may be tested for 'auditory processing disorder' (APD), a controversial construct suggesting that neural dysfunction in the central auditory system leads to impaired auditory perception. An important question, not currently tested in clinical evaluation, is whether listening difficulties result from problems with bottom-up auditory sensory processing or top-down modulating cognition. Perceptual variability and poor performance on standardized tests suggest that listening difficulties are primarily cognitive in origin. However, evidence for impaired olivocochlear function and temporal processing deficits may implicate peripheral or central auditory dysfunction in some cases. Wide-spread, top-down modulation of auditory cortical, brainstem and ear function suggests that afferent and efferent control systems may not be simple to segregate. During normal maturation, hearing appears to develop in proportion to the complexity of both stimuli and tasks. But some younger individuals have mature hearing, highlighting individual differences that suggest APD may be due to a generalized developmental delay. Recent studies have investigated specific hypotheses showing, for example, that spatial hearing and executive function are compromised in some children with listening difficulties. Using speech stimuli (e.g. consonant-vowel syllables) to examine auditory brainstem responses, and psychophysiological relations between dichotic hearing and cortical physiology, various effects of auditory experience and development point the way to promising approaches for further studies of APD. Newer technology, from genetic sequencing to MRI, may have the sensitivity to test whether and how frequently APD is associated with impaired processing in the auditory system.

Impaired development and competitive refinement of the cortical frequency map in tumor necrosis factor-α-deficient mice.

Early experience shapes sensory representations in a critical period of heightened plasticity. This adaptive process is thought to involve both Hebbian and homeostatic synaptic plasticity. Although Hebbian plasticity has been investigated as a mechanism for cortical map reorganization, less is known about the contribution of homeostatic plasticity. We investigated the role of homeostatic synaptic plasticity in the development and refinement of frequency representations in the primary auditory cortex using the tumor necrosis factor-α (TNF-α) knockout (KO), a mutant mouse with impaired homeostatic but normal Hebbian plasticity. Our results indicate that these mice develop weaker tonal responses and incomplete frequency representations. Rearing in a single-frequency revealed a normal expansion of cortical representations in KO mice. However, TNF-α KOs lacked homeostatic adjustments of cortical responses following exposure to multiple frequencies. Specifically, while this sensory over-stimulation resulted in competitive refinement of frequency tuning in wild-type controls, it broadened frequency tuning in TNF-α KOs. Our results suggest that homeostatic plasticity plays an important role in gain control and competitive interaction in sensory cortical development.

Damage to left anterior temporal cortex predicts impairment of complex syntactic processing: a lesion-symptom mapping study.

Sentence processing problems form a common consequence of left-hemisphere brain injury, in some patients to such an extent that their pattern of language performance is characterized as "agrammatic". However, the location of left-hemisphere damage that causes such problems remains controversial. It has been suggested that the critical site for syntactic processing is Broca's area of the frontal cortex or, alternatively, that a more widely distributed network is responsible for syntactic processing. The aim of this study was to identify brain regions that are required for successful sentence processing. Voxel-based lesion-symptom mapping (VLSM) was used to identify brain regions where injury predicted impaired sentence processing in 50 native speakers of Icelandic with left-hemisphere stroke. Sentence processing was assessed by having individuals identify which picture corresponded to a verbally presented sentence. The VLSM analysis revealed that impaired sentence processing was best predicted by damage to a large left-hemisphere temporo-parieto-occipital area. This is likely due to the multimodal nature of the sentence processing task, which involves auditory and visual analysis, as well as lexical and syntactic processing. Specifically impaired processing of noncanonical sentence types, when compared with canonical sentence processing, was associated with damage to the left-hemisphere anterior superior and middle temporal gyri and the temporal pole. Anterior temporal cortex, therefore, appears to play a crucial role in syntactic processing, and patients with brain damage to this area are more likely to present with receptive agrammatism than patients in which anterior temporal cortex is spared.

Auditory and visual temporal processing disruption in open angle glaucoma.

PURPOSE: Open angle glaucoma (OAG) is increasingly being viewed as an age-related neurodegenerative condition that may occur in individuals who are innately susceptible to global (autonomic) neural injury. Recent data support the plausibility of auditory neural impairment in a proportion of individuals with OAG, with results showing a key disruption to processing temporal properties of sound. This study tested the hypothesis that temporal processing deficits consistent with central (cortical) processing abnormalities are present in both the visual and auditory domains in individuals with glaucoma. METHODS: A series of tasks designed to test progressively more complex aspects of temporal processing were conducted in 25 OAG individuals and 25 age- and sex-matched controls. For audition, baseline measurement of hearing sensitivity was followed by functional assessment of amplitude modulation detection, frequency discrimination at two reference levels, and speech perception. For vision, measures of foveal temporal contrast detection at two flicker rates, speed discrimination at two reference velocities, and coherent global motion detection were assessed. RESULTS: A significant proportion of the OAG cohort displayed an impairment in auditory low-frequency discrimination, speech perception, visual speed discrimination for slow velocities and/or visual global motion detection, compared to controls (36%, 25%, 39%, and 34% respectively, were outside the 90th percentile of control performance; P < 0.05). CONCLUSIONS: A subgroup of individuals with OAG displayed impaired auditory temporal processing concurrent with signs of visual temporal processing impairment. These temporal processing deficits were in the presence of normal sound detection and normal central luminance increment thresholds.

Co-localisation of abnormal brain structure and function in specific language impairment.

We assessed the relationship between brain structure and function in 10 individuals with specific language impairment (SLI), compared to six unaffected siblings, and 16 unrelated control participants with typical language. Voxel-based morphometry indicated that grey matter in the SLI group, relative to controls, was increased in the left inferior frontal cortex and decreased in the right caudate nucleus and superior temporal cortex bilaterally. The unaffected siblings also showed reduced grey matter in the caudate nucleus relative to controls. In an auditory covert naming task, the SLI group showed reduced activation in the left inferior frontal cortex, right putamen, and in the superior temporal cortex bilaterally. Despite spatially coincident structural and functional abnormalities in frontal and temporal areas, the relationships between structure and function in these regions were different. These findings suggest multiple structural and functional abnormalities in SLI that are differently associated with receptive and expressive language processing.