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.

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.

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.

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.

Impaired auditory temporal selectivity in the inferior colliculus of aged Mongolian gerbils.

Aged humans show severe difficulties in temporal auditory processing tasks (e.g., speech recognition in noise, low-frequency sound localization, gap detection). A degradation of auditory function with age is also evident in experimental animals. To investigate age-related changes in temporal processing, we compared extracellular responses to temporally variable pulse trains and human speech in the inferior colliculus of young adult (3 month) and aged (3 years) Mongolian gerbils. We observed a significant decrease of selectivity to the pulse trains in neuronal responses from aged animals. This decrease in selectivity led, on the population level, to an increase in signal correlations and therefore a decrease in heterogeneity of temporal receptive fields and a decreased efficiency in encoding of speech signals. A decrease in selectivity to temporal modulations is consistent with a downregulation of the inhibitory transmitter system in aged animals. These alterations in temporal processing could underlie declines in the aging auditory system, which are unrelated to peripheral hearing loss. These declines cannot be compensated by traditional hearing aids (that rely on amplification of sound) but may rather require pharmacological treatment.

Functional MRI evidence of an abnormal neural network for pitch processing in congenital amusia.

Congenital amusia (tone deafness) is a lifelong disorder that prevents typically developing individuals from acquiring basic musical skills. Electrophysiological evidence indicates that congenital amusia is related to a musical pitch deficit that does not seem to arise from a dysfunction of the auditory cortex but rather from an anomaly along a frontotemporal auditory pathway. In order to better localize the neural basis of this pitch disorder, here we conducted a functional magnetic resonance imaging (fMRI) study. Congenital amusic adults and "musically intact" controls were scanned while passively listening to pure-tone melodic-like sequences in which the pitch distance between consecutive tones was varied parametrically. In both amusics and controls, brain activity increased as a function of increasing pitch distance, even for fine pitch changes, in both the left and right auditory cortices. These results support prior electrophysiological work showing that the auditory cortex of amusic individuals responds normally to pitch. In contrast, the right inferior frontal gyrus showed an abnormal deactivation in the amusic group, as well as reduced connectivity with the auditory cortex as compared with controls. These fMRI data are highly consistent with previous gray and white matter anomalies found in amusics in the auditory and inferior frontal cortices, as well as reduced white matter connections between these 2 regions.

[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.

Morphological features of the medial superior olive in autism.

Autism is a psychosocial disorder clinically characterized by social difficulties, impairment in communication skills and repetitive behavioral patterns. Despite the increasing reported incidence of autism, the neurobiology of this disorder is poorly understood. However, researchers have uncovered numerous structural anomalies in the brainstem, cerebellum and forebrain of autistic individuals and there is substantial support for the association of hearing deficits with autism. In an effort to discover an anatomical correlate for the functional auditory deficits found in autism, we examined the SOC, a group of brainstem nuclei that function in sound source localization, in post-mortem brain tissue from autistic individuals. The neurons of the medial superior olive (MSO), an SOC nucleus, display a precise geometric organization essential for detection of timing differences between the two ears. We examined the architecture of the MSO in five autistic brains (ages 8 to 32 years) and two age-matched controls (ages 26 and 29 years) and found a significant disruption in the morphology of MSO neurons in autistic brains, involving cell body shape and orientation. The results from this study provide evidence on the cellular level that may help to explain the hearing difficulties associated with autism.

Family-based association analysis of a statistically derived quantitative traits for ADHD reveal an association in DRD4 with inattentive symptoms in ADHD individuals.

The objective of this study was to determine whether single nucleotide polymorphisms (SNPs) within candidate genes for ADHD are associated with quantitative phenotypes generated from inattentive and hyperactive-impulsive symptoms. One hundred forty-three SNPs were genotyped in and around five ADHD candidate genes. A highly heritable quantitative phenotype was generated at each SNP by weighting inattentive and hyperactive-impulsive symptoms. Once these phenotypes were generated, a screening procedure was used to select and test the five SNP/phenotype combinations with the greatest power to detect an association for each candidate gene. Adjacent SNPs in the promoter region of DRD4, hCV26775267 and hCV26775266, were associated with the quantitative phenotypes generated from the ADHD symptoms (corrected P-values = 0.012 for both SNPs). The correlations between the ADHD symptoms and quantitative phenotype revealed that inattentive symptoms had a strong influence on the generated phenotype. Subsequent family-based association test-principal components (FBAT-PC) analyses using inattentive symptoms only also had significant associations. SNPs in the promoter region of DRD4 are associated with the phenotypes generated from ADHD symptoms. The strong correlation of the inattentive symptoms with these quantitative phenotypes and the subsequent FBAT-PC analyses suggest this region is primarily associated with inattentive symptoms. This analysis adds to previous findings by suggesting that variants at these loci may be specifically associated with inattentive symptoms.

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.

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.

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.

Morphometry of the amusic brain: a two-site study.

Congenital amusia (or tone deafness) is a lifelong disability that prevents otherwise normal-functioning individuals from developing basic musical skills. Behavioural evidence indicates that congenital amusia is due to a severe deficit in pitch processing, but very little is known about the neural correlates of this condition. The objective of the present study was to investigate the structural neural correlates of congenital amusia. To this aim, voxel-based morphometry was used to detect brain anatomical differences in amusic individuals relative to musically intact controls, by analysing T1-weighted magnetic resonance images from two independent samples of subjects. The results were consistent across samples in highlighting a reduction in white matter concentration in the right inferior frontal gyrus of amusic individuals. This anatomical anomaly was correlated with performance on pitch-based musical tasks. The results are consistent with neuroimaging findings implicating right inferior frontal regions in musical pitch encoding and melodic pitch memory. We conceive the present results as a consequence of an impoverished communication in a right-hemisphere-based network involving the inferior frontal cortex and the right auditory cortex. Moreover, the data point to the integrity of white matter tracts in right frontal brain areas as being key in acquiring normal musical competence.

Approaches to the cortical analysis of auditory objects.

We describe work that addresses the cortical basis for the analysis of auditory objects using 'generic' sounds that do not correspond to any particular events or sources (like vowels or voices) that have semantic association. The experiments involve the manipulation of synthetic sounds to produce systematic changes of stimulus features, such as spectral envelope. Conventional analyses of normal functional imaging data demonstrate that the analysis of spectral envelope and perceived timbral change involves a network consisting of planum temporale (PT) bilaterally and the right superior temporal sulcus (STS). Further analysis of imaging data using dynamic causal modelling (DCM) and Bayesian model selection was carried out in the right hemisphere areas to determine the effective connectivity between these auditory areas. Specifically, the objective was to determine if the analysis of spectral envelope in the network is done in a serial fashion (that is from HG to PT to STS) or parallel fashion (that is PT and STS receives input from HG simultaneously). Two families of models, serial and parallel (16 in total) that represent different hypotheses about the connectivity between HG, PT and STS were selected. The models within a family differ with respect to the pathway that is modulated by the analysis of spectral envelope. After the models are identified, Bayesian model selection procedure is then used to select the 'optimal' model from the specified models. The data strongly support a particular serial model containing modulation of the HG to PT effective connectivity during spectral envelope variation. Parallel work in neurological subjects addresses the effect of lesions to different parts of this network. We have recently studied in detail subjects with 'dystimbria': an alteration in the perceived quality of auditory objects distinct from pitch or loudness change. The subjects have lesions of the normal network described above with normal perception of pitch strength but abnormal perception of the analysis of spectral envelope change.

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.

Do you hear what I hear? Neural correlates of thought disorder during listening to speech in schizophrenia.

Thought disorder is a fundamental symptom of schizophrenia, observable as irregularities in speech. It has been associated with functional and structural abnormalities in brain regions involved in language processing, including left temporal regions, during language production tasks. We were interested in the neural correlates of thought disorder during receptive language processing, as this function is relatively preserved despite relying on the same brain regions as expressive language. Twelve patients with schizophrenia and 11 controls listened to 30-s speech samples while undergoing fMRI scanning. Thought disorder and global symptom ratings were obtained for each patient. Thought disorder but not global symptomatology correlated positively with the BOLD response in the left posterior superior temporal lobe while listening to comprehensible speech (cluster-level corrected p=.023). The pattern of brain activity associated with thought disorder during listening to comprehensible speech differs from that seen during language generation tasks, where a reduction of the leftward laterality of language has often been observed. As receptive language is spared in thought disorder, we propose that the increase in activation reflects compensatory processing allowing for normal performance.

Developmental timeframes for induction of microgyria and rapid auditory processing deficits in the rat.

Induction of a focal freeze lesion to the skullcap of a 1-day-old rat pup leads to the formation of microgyria similar to those identified postmortem in human dyslexics. Rats with microgyria exhibit rapid auditory processing deficits similar to those seen in language-impaired (LI) children, and infants at risk for LI and these effects are particularly marked in juvenile as compared to adult subjects. In the current study, a startle response paradigm was used to investigate gap detection in juvenile and adult rats that received bilateral freezing lesions or sham surgery on postnatal day (P) 1, 3 or 5. Microgyria were confirmed in P1 and 3 lesion rats, but not in the P5 lesion group. We found a significant reduction in brain weight and neocortical volume in P1 and 3 lesioned brains relative to shams. Juvenile (P27-39) behavioral data indicated significant rapid auditory processing deficits in all three lesion groups as compared to sham subjects, while adult (P60+) data revealed a persistent disparity only between P1-lesioned rats and shams. Combined results suggest that generalized pathology affecting neocortical development is responsible for the presence of rapid auditory processing deficits, rather than factors specific to the formation of microgyria per se. Finally, results show that the window for the induction of rapid auditory processing deficits through disruption of neurodevelopment appears to extend beyond the endpoint for cortical neuronal migration, although, the persistent deficits exhibited by P1 lesion subjects suggest a secondary neurodevelopmental window at the time of cortical neuromigration representing a peak period of vulnerability.