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.

Music perception in acquired prosopagnosia.

BACKGROUND: Acquired prosopagnosia is often associated with other deficits such as dyschromatopsia and topographagnosia, from damage to adjacent perceptual networks. A recent study showed that some subjects with developmental prosopagnosia also have congenital amusia, but problems with music perception have not been described with the acquired variant. OBJECTIVE: Our goal was to determine if music perception was also impaired in subjects with acquired prosopagnosia, and if so, its anatomic correlate. METHOD: We studied eight subjects with acquired prosopagnosia, all of whom had extensive neuropsychological and neuroimaging testing. They performed a battery of tests evaluating pitch and rhythm processing, including the Montréal Battery for the Evaluation of Amusia. RESULTS: At the group level, subjects with anterior temporal lesions were impaired in pitch perception relative to the control group, but not those with occipitotemporal lesions. Three of eight subjects with acquired prosopagnosia had impaired musical pitch perception while rhythm perception was spared. Two of the three also showed reduced musical memory. These three reported alterations in their emotional experience of music: one reported music anhedonia and aversion, while the remaining two had changes consistent with musicophilia. The lesions of these three subjects affected the right or bilateral temporal poles as well as the right amygdala and insula. None of the three prosopagnosic subjects with lesions limited to the inferior occipitotemporal cortex exhibited impaired pitch perception or musical memory, or reported changes in music appreciation. CONCLUSION: Together with the results of our previous studies of voice recognition, these findings indicate an anterior ventral syndrome that can include the amnestic variant of prosopagnosia, phonagnosia, and various alterations in music perception, including acquired amusia, reduced musical memory, and subjective reports of altered emotional experience of music.

Altered brain network topology in children with auditory processing disorder: A resting-state multi-echo fMRI study.

Children with auditory processing disorder (APD) experience hearing difficulties, particularly in the presence of competing sounds, despite having normal audiograms. There is considerable debate on whether APD symptoms originate from bottom-up (e.g., auditory sensory processing) and/or top-down processing (e.g., cognitive, language, memory). A related issue is that little is known about whether functional brain network topology is altered in APD. Therefore, we used resting-state functional magnetic resonance imaging data to investigate the functional brain network organization of 57 children from 8 to 14 years old, diagnosed with APD (n = 28) and without hearing difficulties (healthy control, HC; n = 29). We applied complex network analysis using graph theory to assess the whole-brain integration and segregation of functional networks and brain hub architecture. Our results showed children with APD and HC have similar global network properties -i.e., an average of all brain regions- and modular organization. Still, the APD group showed different hub architecture in default mode-ventral attention, somatomotor and frontoparietal-dorsal attention modules. At the nodal level -i.e., single-brain regions-, we observed decreased participation coefficient (PC - a measure quantifying the diversity of between-network connectivity) in auditory cortical regions in APD, including bilateral superior temporal gyrus and left middle temporal gyrus. Beyond auditory regions, PC was also decreased in APD in bilateral posterior temporo-occipital cortices, left intraparietal sulcus, and right posterior insular cortex. Correlation analysis suggested a positive association between PC in the left parahippocampal gyrus and the listening-in-spatialized-noise -sentences task where APD children were engaged in auditory perception. In conclusion, our findings provide evidence of altered brain network organization in children with APD, specific to auditory networks, and shed new light on the neural systems underlying children's listening difficulties.

Impaired face recognition is associated with abnormal gray matter volume in the posterior cingulate cortex in congenital amusia.

Congenital amusia is as a neurodevelopment disorder primarily defined by impairment in pitch discrimination and pitch memory. Interestingly, it has been reported that individuals with congenital amusia also exhibit deficits in face recognition (prosopagnosia). One explanation of such comorbidity is that the neural substrates of pitch recognition and face recognition may be similar. To test this hypothesis, face recognition ability was assessed using the Cambridge Face Memory Test (CFMT) and gray matter volume was determined through voxel-based morphometry (VBM) among participants with and without congenital amusia. As expected, participants with amusia performed worse on the CFMT test and showed reduced gray matter volume (GMV) in the middle temporal gyrus (MTG), the superior temporal gyrus (STG), and the posterior cingulate cortex (PCC) in the right hemisphere, when compared with matched controls. Furthermore, correlation analyses demonstrated that the CFMT score was positively related to MTG, STG, and PCC GMV in all participants, while separate analyses of each group found a positive correlation of CFMT score and PCC GMV in amusics. These findings suggest that face recognition is associated with a widely distributed microstructural network in the human brain and the PCC plays an important role in both pitch recognition and face recognition in amusics. In addition, neurodevelopmental disorders such as congenital amusia and prosopagnosia may share a common neural substrate.

[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.

Neural architectures of music - Insights from acquired amusia.

The ability to perceive and produce music is a quintessential element of human life, present in all known cultures. Modern functional neuroimaging has revealed that music listening activates a large-scale bilateral network of cortical and subcortical regions in the healthy brain. Even the most accurate structural studies do not reveal which brain areas are critical and causally linked to music processing. Such questions may be answered by analysing the effects of focal brain lesions in patients´ ability to perceive music. In this sense, acquired amusia after stroke provides a unique opportunity to investigate the neural architectures crucial for normal music processing. Based on the first large-scale longitudinal studies on stroke-induced amusia using modern multi-modal magnetic resonance imaging (MRI) techniques, such as advanced lesion-symptom mapping, grey and white matter morphometry, tractography and functional connectivity, we discuss neural structures critical for music processing, consider music processing in light of the dual-stream model in the right hemisphere, and propose a neural model for acquired amusia.

The neural basis for understanding imitation-induced musical meaning: The role of the human mirror system.

Music can convey meanings by imitating phenomena of the extramusical world, and these imitation-induced musical meanings can be understood by listeners. Although the human mirror system (HMS) is implicated in imitation, little is known about the HMS's role in making sense of meaning that derives from musical imitation. To answer this question, we used fMRI to examine listeners' brain activities during the processing of imitation-induced musical meaning with a cross-modal semantic priming paradigm. Eleven normal individuals and 11 individuals with congenital amusia, a neurodevelopmental disorder of musical processing, participated in the experiment. Target pictures with either an upward or downward movement were primed by semantically congruent or incongruent melodic sequences characterized by the direction of pitch change (upward or downward). When contrasting the incongruent with the congruent condition between the two groups, we found greater activations in the left supramarginal gyrus/inferior parietal lobule and inferior frontal gyrus in normals but not in amusics. The implications of these findings in terms of the role of the HMS in understanding imitation-induced musical meaning are discussed.

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.

Reduced auditory segmentation potentials in first-episode schizophrenia.

Auditory scene analysis (ASA) dysfunction is likely an important component of the symptomatology of schizophrenia. Auditory object segmentation, the grouping of sequential acoustic elements into temporally-distinct auditory objects, can be assessed with electroencephalography through measurement of the auditory segmentation potential (ASP). Further, N2 responses to the initial and final elements of auditory objects are enhanced relative to medial elements, which may indicate auditory object edge detection (initiation and termination). Both ASP and N2 modulation are impaired in long-term schizophrenia. To determine whether these deficits are present early in disease course, we compared ASP and N2 modulation between individuals at their first episode of psychosis within the schizophrenia spectrum (FE, N=20) and matched healthy controls (N=24). The ASP was reduced by >40% in FE; however, N2 modulation was not statistically different from HC. This suggests that auditory segmentation (ASP) deficits exist at this early stage of schizophrenia, but auditory edge detection (N2 modulation) is relatively intact. In a subset of subjects for whom structural MRIs were available (N=14 per group), ASP sources were localized to midcingulate cortex (MCC) and temporal auditory cortex. Neurophysiological activity in FE was reduced in MCC, an area linked to aberrant perceptual organization, negative symptoms, and cognitive dysfunction in schizophrenia, but not temporal auditory cortex. This study supports the validity of the ASP for measurement of auditory object segmentation and suggests that the ASP may be useful as an early index of schizophrenia-related MCC dysfunction. Further, ASP deficits may serve as a viable biomarker of disease presence.

Tracting the neural basis of music: Deficient structural connectivity underlying acquired amusia.

Acquired amusia provides a unique opportunity to investigate the fundamental neural architectures of musical processing due to the transition from a functioning to defective music processing system. Yet, the white matter (WM) deficits in amusia remain systematically unexplored. To evaluate which WM structures form the neural basis for acquired amusia and its recovery, we studied 42 stroke patients longitudinally at acute, 3-month, and 6-month post-stroke stages using DTI [tract-based spatial statistics (TBSS) and deterministic tractography (DT)] and the Scale and Rhythm subtests of the Montreal Battery of Evaluation of Amusia (MBEA). Non-recovered amusia was associated with structural damage and subsequent degeneration in multiple WM tracts including the right inferior fronto-occipital fasciculus (IFOF), arcuate fasciculus (AF), inferior longitudinal fasciculus (ILF), uncinate fasciculus (UF), and frontal aslant tract (FAT), as well as in the corpus callosum (CC) and its posterior part (tapetum). In a linear regression analysis, the volume of the right IFOF was the main predictor of MBEA performance across time. Overall, our results provide a comprehensive picture of the large-scale deficits in intra- and interhemispheric structural connectivity underlying amusia, and conversely highlight which pathways are crucial for normal music perception.

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.

Classifying song and speech: effects of focal temporal lesions and musical disorder.

Song and speech represent two auditory categories the brain usually classifies fairly easily. Functionally, this classification ability may depend to a great extent on characteristic features of pitch patterns present in song melody and speech prosody. Anatomically, the temporal lobe (TL) has been discussed as playing a prominent role in the processing of both. Here we tested individuals with congenital amusia and patients with unilateral left and right TL lesions in their ability to categorize song and speech. In a forced-choice paradigm, specifically designed auditory stimuli representing sung, spoken and "ambiguous" stimuli (being perceived as "halfway between" song and speech), had to be classified as either "song" or "speech". Congenital amusics and TL patients, contrary to controls, exhibited a surprising bias to classifying the ambiguous stimuli as "song" despite their apparent deficit to correctly process features typical for song. This response bias possibly reflects a strategy where, based on available context information (here: forced choice for either speech or song), classification of non-processable items may be achieved through elimination of processable classes. This speech-based strategy masks the pitch processing deficit in congenital amusics and TL lesion patients.

Neural Basis of Acquired Amusia and Its Recovery after Stroke.

UNLABELLED: Although acquired amusia is a relatively common disorder after stroke, its precise neuroanatomical basis is still unknown. To evaluate which brain regions form the neural substrate for acquired amusia and its recovery, we performed a voxel-based lesion-symptom mapping (VLSM) and morphometry (VBM) study with 77 human stroke subjects. Structural MRIs were acquired at acute and 6 month poststroke stages. Amusia and aphasia were behaviorally assessed at acute and 3 month poststroke stages using the Scale and Rhythm subtests of the Montreal Battery of Evaluation of Amusia (MBEA) and language tests. VLSM analyses indicated that amusia was associated with a lesion area comprising the superior temporal gyrus, Heschl's gyrus, insula, and striatum in the right hemisphere, clearly different from the lesion pattern associated with aphasia. Parametric analyses of MBEA Pitch and Rhythm scores showed extensive lesion overlap in the right striatum, as well as in the right Heschl's gyrus and superior temporal gyrus. Lesions associated with Rhythm scores extended more superiorly and posterolaterally. VBM analysis of volume changes from the acute to the 6 month stage showed a clear decrease in gray matter volume in the right superior and middle temporal gyri in nonrecovered amusic patients compared with nonamusic patients. This increased atrophy was more evident in anterior temporal areas in rhythm amusia and in posterior temporal and temporoparietal areas in pitch amusia. Overall, the results implicate right temporal and subcortical regions as the crucial neural substrate for acquired amusia and highlight the importance of different temporal lobe regions for the recovery of amusia after stroke. SIGNIFICANCE STATEMENT: Lesion studies are essential in uncovering the brain regions causally linked to a given behavior or skill. For music perception ability, previous lesion studies of amusia have been methodologically limited in both spatial accuracy and time domain as well as by small sample sizes, providing coarse and equivocal information about which brain areas underlie amusia. By using longitudinal MRI and behavioral data from a large sample of stroke patients coupled with modern voxel-based analyses methods, we were able provide the first systematic evidence for the causal role of right temporal and striatal areas in music perception. Clinically, these results have important implications for the diagnosis and prognosis of amusia after stroke and for rehabilitation planning.

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.

Altered intrinsic connectivity of the auditory cortex in congenital amusia.

Congenital amusia, a neurodevelopmental disorder of music perception and production, has been associated with abnormal anatomical and functional connectivity in a right frontotemporal pathway. To investigate whether spontaneous connectivity in brain networks involving the auditory cortex is altered in the amusic brain, we ran a seed-based connectivity analysis, contrasting at-rest functional MRI data of amusic and matched control participants. Our results reveal reduced frontotemporal connectivity in amusia during resting state, as well as an overconnectivity between the auditory cortex and the default mode network (DMN). The findings suggest that the auditory cortex is intrinsically more engaged toward internal processes and less available to external stimuli in amusics compared with controls. Beyond amusia, our findings provide new evidence for the link between cognitive deficits in pathology and abnormalities in the connectivity between sensory areas and the DMN at rest.

Neuropsychological and neuroradiologic correlates of emotional prosody comprehension.

We examined a series of 59 patients with acute stroke lesions for the presence of comprehension emotional aprosody. Based on a standardized assessment of comprehension of emotional intonation, 29 patients (49%) showed emotional aprosody (17% "mild" aprosody [n = 10] and 32% "severe" aprosody [n = 19]). Patients with comprehension emotional aprosody showed a higher frequency of extinction on double-simultaneous stimulation, anosognosia, and deficits in facial emotion comprehension. Patients with comprehension emotional aprosody also showed a higher frequency of right-hemisphere lesions involving the basal ganglia and the temporoparietal cortex and more severe frontal and diencephalic atrophy. Comprehension emotional aprosody was not necessarily associated with poststroke depression (PSD) since patients with and without PSD showed similar impairments in emotional prosody comprehension.

Toward a brain map of auditory hallucinations.

OBJECTIVE: This study asks whether auditory hallucinations are reflected in a distinctive metabolic map of the brain. METHOD: Regional brain metabolism was measured by positron emission tomography with [18F]-fluorodeoxyglucose in 12 DSM-III schizophrenic patients who experienced auditory hallucinations during glucose uptake and 10 who did not. All patients were free of neuroleptics and 19 had never been treated with neuroleptics. Nine patients were reexamined after 1 year to assess effects of neuroleptic treatment. RESULTS: Compared with the patients who did not experience hallucinations, the patients who did experience hallucinations had significantly lower relative metabolism in auditory and Wernicke's regions and a trend toward higher metabolism in the right hemisphere homologue of Broca's region. Hallucination scores correlated positively and significantly with relative metabolism in the striatum and anterior cingulate regions. Neuroleptic treatment resulted in a significant increase in striatal metabolism and a reduced frontal-parietal ratio, which was significantly correlated with a decrease in hallucination scores. CONCLUSIONS: Auditory hallucinations involve language regions of the cortex in a pattern similar to that seen in normal subjects listening to their own voices but different in that left prefrontal regions are not activated. The striatum plays a critical role in auditory hallucinations.

The potential value of serial cerebral SPECT scanning in the evaluation of psychiatric illness.

Cerebral SPECT imaging has the potential to make an important contribution to clinical psychiatry. Cerebral SPECT scanning, stimulated by the work with PET, is readily available and much less expensive than PET. This paper reports a case demonstrating the potential value of cerebral SPECT scanning with I-123 IMP, specifically in the serial evaluation of a schizophrenic patient with auditory hallucinations. The initial scan revealed focal areas of increased uptake in the caudate nuclei of the basal ganglia, and in the right temporal lobe. After pharmacological treatment with clinical improvement, the follow-up SPECT scan demonstrated significant improvement in the distribution of the radiopharmaceutical.