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.

Alterations of functional connectivity in auditory and sensorimotor neural networks: A case report in a patient with cortical deafness after bilateral putaminal hemorrhagic stroke.

RATIONALE: Cortical deafness is a rare auditory dysfunction caused by damage to brain auditory networks. The aim was to report alterations of functional connectivity in intrinsic auditory, motor, and sensory networks in a cortical deafness patient. PATIENT CONCERNS: A 41-year-old woman suffered a right putaminal hemorrhage. Eight years earlier, she had suffered a left putaminal hemorrhage and had minimal sequelae. She had quadriparesis, imbalance, hypoesthesia, and complete hearing loss. DIAGNOSES: She was diagnosed with cortical deafness. After 6 months, resting-state functional magnetic resonance imaging (rs-fMRI) and diffuse tensor imaging (DTI) were performed. DTI revealed that the acoustic radiation was disrupted while the corticospinal tract and somatosensory track were intact using deterministic tracking methods. Furthermore, the patient showed decreased functional connectivity between auditory and sensorimotor networks. INTERVENTIONS: The patient underwent in-patient stroke rehabilitation therapy for 2 months. OUTCOMES: Gait function and ability for activities of daily living were improved. However, complete hearing impairment persisted in 6 months after bilateral putaminal hemorrhagic stroke. LESSONS: Our case report seems to suggest that functional alterations of spontaneous neuronal activity in auditory and sensorimotor networks are related to motor and sensory impairments in a patient with cortical deafness.

Structural and Functional Aberrations of the Auditory Brainstem in Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental condition associated with difficulties in the social, communicative, and behavioral domains. Most cases of ASD arise from an unknown etiologic process, but there are numerous risk factors, including comorbidities and maternal exposures. Although it is not part of the diagnostic criteria, hearing difficulties ranging from deafness to hyperacusis are present in the majority of persons with ASD. High-functioning children with ASD have been found to have significantly slower and asymmetric auditory brainstem reflexes. Additionally, histopathological studies of postmortem brainstems in decedents who had ASD have consistently revealed significantly fewer neurons in auditory nuclei compared with those in people who did not have ASD. The authors review the literature implicating auditory dysfunction in ASD along with results from human study participants and postmortem human brain tissue. Together, these results implicate significant structural and functional abnormalities in the auditory brainstem in ASD and support the utility of auditory testing to screen for ASD.

Detection of silent gaps in white noise following cortical deactivation in rats.

Rodent studies using cortical removal techniques, ranging from transient deactivation to surgical ablation of cortex, reveal the importance of auditory cortical integrity in detecting short silent gaps in white noise (2-15 ms). Processing limits for longer gaps under decorticate conditions in rats remain unknown. Determining the temporal threshold for subcortical resolution of gaps in noise could, however, shed light on both normal hierarchical processing of acoustic temporal stimuli, as well as the etiology of processing anomalies following developmental cortical disruption. To address these important issues, we assessed whether intact rats, as well as those with induced developmental cortical disruptions (microgyria) could resolve silent gaps of 20-100 ms in duration when embedded in white noise, during functional deactivation of auditory cortex. Results showed that both intact rats, as well as those with cortical malformations resulting from early focal disruptions of neuronal migration could resolve silent gaps of 100-ms duration under cortical deactivation (KCl). However, only intact rats could reliably detect 75-ms gaps, suggesting possible subcortical anomalies in subjects with early cortical disturbances.

Enhancement of sound motion detection in acallosal individuals.

It has been proposed that the corpus callosum may play an important role in spectral cue processing that allows vertical auditory movement perception. The purpose of the present study was to assess the contribution of the corpus callosum to this type of auditory processing. Noise bursts were presented to 10 control and two callosal agenesis individuals from different positions located within midsagittal and coronal planes. Although acallosal participants were comparable with controls in their ability to correctly identify the trajectory direction or its length, they showed greater capability in detecting motion per se when the task was difficult. These results suggest that in the absence of the corpus callosum, compensatory reorganization of the brain allowed for superior auditory spectral cue processing.

Variations of planum temporale asymmetries with Heschl's Gyri duplications and association with cognitive abilities: MRI investigation of 428 healthy volunteers.

In a large sample of 428 healthy adults balanced for gender and manual preference (MP), we investigated planum temporale (PT) surface area variability in relation with Heschl's gyrus (HG) duplication pattern, MP, and familial sinistrality (FS), considering different PT definitions. In a sub-sample of 362 participants, we also investigated whether variability of PT asymmetry was associated with differences in verbal abilities. On each participant brain hemisphere MRI, we delineated a posterior PT area (PTpost), excluding the second Heschl gyrus in case of either complete posterior duplication (CPD) or common stem partial duplication (CSD). We then defined a total PT area (PTtot) as the union of PTpost and of the second HG when present, and a HGPT area as the union of PTtot and of the first HG. The HG duplication pattern of one hemisphere was found to significantly affect the PTpost surface area of the same hemisphere, a larger reduction being present in case of CPD than in case of CSD, leading to a strong impact of both left and right HG duplication patterns on PTpost asymmetry. The HG duplication pattern had no effect on PTtot surface areas, while a significant effect of the left HG duplication was present on PTtot asymmetry that was larger in case of a CSD as compared to a single HG. By contrast, the type of HG duplication did not affect HGPT and neither left nor right HG duplication pattern had an effect on HGPT asymmetry. Meanwhile, MP had no effect on PTpost, PTtot, HGPT, or their asymmetries. The absence of a left PTpost was associated with existence of FS (FS+) (7FS+ among nine without PTpost). Removing the nine individuals lacking PTpost, a lower left PTpost surface area was observed in FS+ participants with left CPD. In the sub-sample of 362 participants, we observed a significant interaction between PTpost asymmetry and cognitive abilities due to poorer lexical performances in individuals having a symmetric PTpost as compared to individuals having either a leftward or a rightward asymmetric PTpost. By contrast, there was no significant effect of PTtot or HGPT asymmetry on cognitive abilities. This study shows that HG duplication pattern mainly affects the surface area of the most posterior part of PT and its asymmetry, this PTpost area being specifically associated with variability in verbal performances. This study also shows, for the first time, an association between decreased performances and lack of PTpost anatomical asymmetry, being rightward asymmetrical having no deleterious effect on verbal abilities, thereby supporting the idea that anatomical lateralization is necessary for optimal verbal performances.

Reduced auditory M100 asymmetry in schizophrenia and dyslexia: applying a developmental instability approach to assess atypical brain asymmetry.

Although atypical structural and functional superior temporal gyrus (STG) asymmetries are frequently observed in patients with schizophrenia and individuals with dyslexia, their significance is unclear. One possibility is that atypical asymmetries reflect a general risk factor that can be seen across multiple neurodevelopmental conditions--a risk factor whose origins are best understood in the context of Developmental Instability (DI) theory. DI measures (minor physical anomalies (MPAs) and fluctuating asymmetries (FAs)) reflect perturbation of the genetic plan. The present study sought to assess whether the presence of peripheral indices of DI predicts anomalous functional auditory cortex asymmetry in schizophrenia patients and dyslexia subjects. The location of the auditory M100 response was used as a measure of functional STG asymmetry, as it has been reported that in controls (but not in subjects with schizophrenia or dyslexia) the M100 source location in the right hemisphere is shifted anterior to that seen for the left hemisphere. Whole-brain auditory evoked magnetic field data were successfully recorded from 14 male schizophrenia patients, 21 male subjects with dyslexia, and 16 normal male control subjects. MPA and FA measures were also obtained. Replicating previous studies, both schizophrenia and dyslexia groups showed less M100 asymmetry than did controls. Schizophrenia and dyslexia subjects also had higher MPA scores than normal controls. Although neither total MPA nor FA measures predicted M100 asymmetry, analyses on individual MPA items revealed a relationship between high palate and M100 asymmetry. Findings suggest that M100 positional asymmetry is not a diagnostically specific feature in several neurodevelopmental conditions. Continued research examining DI and brain asymmetry relationships is warranted.

Auditory event-related responses in children with semi-lobar holoprosencephaly.

The purpose of this study was to evaluate auditory sensory and discrimination responses in children with semi-lobar holoprosencephaly (HPE). Event-related potential (ERP) signals were recorded to tone pair stimuli at 62 electrode sites from the scalp using an oddball paradigm (a two-block design, inter-stimulus interval=70 or 300 ms; frequency of tone pair=100 vs. 100 Hz for the frequent and 100 vs. 300 Hz for the infrequent). Latencies and amplitudes of P150, N250, and mismatch negativity (MMN)-like components were compared between children with HPE and controls. Our results revealed less organized ERP waveforms to both stimuli in children with HPE, with diminished P150 and N250 components across brain area. Robust and delayed MMN-like responses were elicited from the children with HPE, with decreased MMN amplitudes in the central, parietal, occipital, and posterior temporal areas. Our results suggest that while brain sensory responses to auditory tones may be impaired in children with semi-lobar HPE, subcomponents of auditory discrimination processes remain functional.

Cortical intercorrelations of temporal area volumes in schizophrenia.

BACKGROUND: Abnormal temporal connections with other cortical areas may underlie some of the most prominent cognitive deficits described in schizophrenia. In order to evaluate the relationship between temporal and other cortical regions in schizophrenia, we examined the intercorrelations of volumetric measures of gray and white matter for each Brodmann's area of the temporal lobe with volumes in the rest of the cortex in patients with schizophrenia and normal comparison subjects. METHODS: MR images were acquired in normal subjects (n=46) and patients with schizophrenia (n=106), divided into good-outcome (n=52) and poor-outcome (Kraepelinian; n=54) subtypes; and correlational patterns between the volumes of individual Brodmann's areas were compared and examined in relation to outcome. RESULTS: Positive frontotemporal intercorrelations were significantly stronger while negative frontotemporal intercorrelations were weaker in schizophrenia patients as compared to normal subjects. Correlations between the right temporal pole and other temporal regions were significantly weaker in schizophrenia patients than in controls. When compared to normal controls and good-outcome patients, schizophrenia patients with poor outcomes showed a selective pattern of stronger gray matter correlations between the medial temporal vs. primary visual and between primary auditory vs. dorsolateral prefrontal cortices, all in the left hemisphere. CONCLUSIONS: Strengthening of positive associations among the temporal and extratemporal (mainly frontal and occipital) regions as well as weakening of regional intercorrelations within the temporal lobe in patients appear to constitute the major differences of correlational patterns in schizophrenia patients and normal subjects. Present findings may be implicated in object recognition deficits seen in patients with schizophrenia, as well as in purportedly deficient spatial and semantic processing of both auditory and visual information that may be associated with poor outcome.

Planum temporale volume in children and adolescents with autism.

Previous research has revealed a lack of planum temporale (PT) asymmetry in adults with autism. This finding is now extended to children and adolescents with the disorder. MRI scans were obtained from 12 children with autism and 12 gender, handedness and age-matched comparison participants. The volume of gray matter in the PT and Heschl's gyrus (HG) in both hemispheres was measured. PT volume was larger in the left hemisphere than in the right in the comparison, but not the autism group. This specifically reflected reduced volume of the left PT in the autism group. There were noted differences in the overall morphological appearance of the right Sylvian fissure in the autism group, but no volumetric difference in the right PT. No differences in HG volumes were observed between the two groups. Lack of PT asymmetry may suggest an early neurodevelopmental disturbance in autism.

Abnormal thalamocortical pathfinding and terminal arbors lead to enlarged barrels in neonatal GAP-43 heterozygous mice.

GAP-43 has been implicated in axonal pathfinding and sprouting, synaptic plasticity, and neurotransmitter release. However, its effect on cortical development in vivo is poorly understood. We have previously shown that GAP-43 knockout (-/-) mice fail to develop whisker-related barrels or an ordered whisker map in the cortex. Here we used cytochrome oxidase (CO) histochemistry to demonstrate that GAP-43 heterozygous (+/-) mice develop larger than normal barrels at postnatal day 7 (P7), despite normal body and brain weight. Using serotonin transporter (5HT-T) histochemistry to label thalamocortical afferents (TCAs), we found no obvious abnormalities in other somatosensory areas or primary visual cortex of GAP-43 (+/-) mice. However, TCA projections to (+/-) primary auditory cortex were not as clearly defined. To clarify the mechanism underlying the large-barrel phenotype, we used lipophilic (DiI) axon labeling. We found evidence for multiple pathfinding abnormalities among GAP-43 (+/-) TCAs. These axons show increased fasciculation within the internal capsule, as well as abnormal turning and branching in the subcortical white matter. These pathfinding errors most likely reflect failures of signal recognition and/or transduction by ingrowing TCAs. In addition, many DiI-labeled (+/-) TCAs exhibit widespread, sparsely branched terminal arbors in layer IV, reflecting the large-barrel phenotype. They also resemble those found in rat barrel cortex deprived of whisker inputs from birth, suggesting a failure of activity-dependent synaptogenesis and/or synaptic stabilization in (+/-) cortex. Our findings suggest that reduced GAP-43 expression can alter the fine-tuning of a cortical map through a combination of pathfinding and synaptic plasticity mechanisms.

Atypical organisation of the auditory cortex in dyslexia as revealed by MEG.

Neuroanatomical and -radiological studies have converged to suggest an atypical organisation in the temporal bank of the left-hemispheric Sylvian fissure for dyslexia. Against the background of this finding, we applied high temporal resolution magnetoencephalography (MEG) to investigate functional aspects of the left-hemispheric auditory cortex in 11 right-handed dyslexic children (aged 8-13 years) and nine matched normal subjects (aged 8-14 years). Event-related field components during a passive oddball paradigm with pure tones and consonant-vowel syllables were evaluated. The first major peak of the auditory evoked response, the M80, showed identical topographical distributions in both groups. In contrast, the generating brain structures of the later M210 component were located more anterior to the earlier response in children with dyslexia only. Control children exhibited the expected activation of more posterior source locations of the component that appeared later in the processing stream. Since the group difference in the relative location of the M210 source seemed to be independent of stimulus category, it is concluded that dyslexics and normally literate children differ as to the organisation of their left-hemispheric auditory cortex.

Differential metabolic rates in prefrontal and temporal Brodmann areas in schizophrenia and schizotypal personality disorder.

In an exploration of the schizophrenia spectrum, we compared cortical metabolic rates in unmedicated patients with schizophrenia and schizotypal personality disorder (SPD) with findings in age- and sex-matched normal volunteers. Coregistered magnetic resonance imaging (MRI) and positron emission tomography (PET) scans were obtained in 27 schizophrenic, 13 SPD, and 32 normal volunteers who performed a serial verbal learning test during tracer uptake. A template of Brodmann areas derived from a whole brain histological section atlas was used to analyze PET findings. Significantly lower metabolic rates were found in prefrontal areas 44-46 in schizophrenic patients than in normal volunteers. SPD patients did not differ from normal volunteers in most lateral frontal regions, but they had values intermediate between those of normal volunteers and schizophrenic patients in lateral temporal regions. SPD patients showed higher than normal metabolic rates in both medial frontal and medial temporal areas. Metabolic rates in Brodmann area 10 were distinctly higher in SPD patients than in either normal volunteers or schizophrenic patients.

Morphological brain differences between adult stutterers and non-stutterers.

BACKGROUND: The neurophysiological and neuroanatomical foundations of persistent developmental stuttering (PDS) are still a matter of dispute. A main argument is that stutterers show atypical anatomical asymmetries of speech-relevant brain areas, which possibly affect speech fluency. The major aim of this study was to determine whether adults with PDS have anomalous anatomy in cortical speech-language areas. METHODS: Adults with PDS (n = 10) and controls (n = 10) matched for age, sex, hand preference, and education were studied using high-resolution MRI scans. Using a new variant of the voxel-based morphometry technique (augmented VBM) the brains of stutterers and non-stutterers were compared with respect to white matter (WM) and grey matter (GM) differences. RESULTS: We found increased WM volumes in a right-hemispheric network comprising the superior temporal gyrus (including the planum temporale), the inferior frontal gyrus (including the pars triangularis), the precentral gyrus in the vicinity of the face and mouth representation, and the anterior middle frontal gyrus. In addition, we detected a leftward WM asymmetry in the auditory cortex in non-stutterers, while stutterers showed symmetric WM volumes. CONCLUSIONS: These results provide strong evidence that adults with PDS have anomalous anatomy not only in perisylvian speech and language areas but also in prefrontal and sensorimotor areas. Whether this atypical asymmetry of WM is the cause or the consequence of stuttering is still an unanswered question.

Congenital structural brain defects in the deaf dalmatian.

Deafness in dalmatian dogs in known to be congenital. It has been reported that the condition is manifested in structural defects of the sensitive lamina of the organ of Corti. In a study of deaf puppies, examined as they became available, this was found to be in doubt. Moreover, a characteristic gross reduction of area was found in the structure of the acoustic cortex in affected puppies. Extension of the morphometric studies further showed that the acoustic pathways were generally attenuated in keeping with the changes in the cortex. Consideration is given to the probability that the condition develops centrally rather than peripherally. Thus instead of the central components failing to develop because of lack of evocative stimulus from the end organ it is envisaged that the peripheral organ regresses because of incomplete innervation by central outgrowth.

Impact of auditory cortical asymmetry in cochlear implantation.

OBJECTIVE: Is there a cochlear implant ear advantage for speech perception? Patients A total number of 68 cochlear implant recipients were evaluated retrospectively. They were 20 adults implanted in right ear, 20 matched adults implanted in left ear while 14 children implanted in right ear and 14 matched children implanted in left ear. METHODS: Behavioral responses & age based speech perception tests were evaluated at 6 months and 1 year post implantation. RESULTS: Adult showed no statistical difference in all tests at 6 months evaluation while 1 year evaluation showed significant better performance for right implanted group in monosyllabic discrimination test. Children showed statistical significant performance in monosyllabic identification and minimal pairs testes at 6 months evaluation; and in monosyllabic identification only at 1 year evaluation. CONCLUSION: The present data support that right ear implantation would fasten the development of auditory skills especially in young children, an issue to be considered in unilateral implantation.

Pyramidal neuron number in layer 3 of primary auditory cortex of subjects with schizophrenia.

Individuals with schizophrenia demonstrate impairments of sensory processing within primary auditory cortex. We have previously identified lower densities of dendritic spines and axon boutons, and smaller mean pyramidal neuron somal volume, in layer 3 of the primary auditory cortex in subjects with schizophrenia, all of which might reflect fewer layer 3 pyramidal neurons in schizophrenia. To examine this hypothesis, we developed a robust stereological method based upon unbiased principles for estimation of total volume and pyramidal neuron numbers for each layer of a cortical area. Our method generates both a systematic, uniformly random set of mapping sections as well as a set of randomly rotated sections cut orthogonal to the pial surface, within the region of interest. We applied our approach in twelve subjects with schizophrenia, each matched to a normal comparison subject. Primary auditory cortex volume was assessed using Cavalieri's method. The relative and absolute volume of each cortical layer and, within layer 3, the number and density of pyramidal neurons were estimated using our novel approach. Subject groups did not differ in regional volume, layer volumes, or pyramidal neuron number, although pyramidal neuron density was significantly greater in subjects with schizophrenia. These findings suggest that previously observed lower densities of dendritic spines and axon boutons reflect fewer numbers per neuron, and contribute to greater neuronal density via a reduced neuropil. Our approach represents a powerful new method for stereologic estimation of features of interest within individual layers of cerebral cortex, with applications beyond the current study.

Chronic auditory hallucinations in schizophrenic patients: MR analysis of the coincidence between functional and morphologic abnormalities.

PURPOSE: To prospectively evaluate if functional magnetic resonance (MR) imaging abnormalities associated with auditory emotional stimuli coexist with focal brain reductions in schizophrenic patients with chronic auditory hallucinations. MATERIALS AND METHODS: Institutional review board approval was obtained and all participants gave written informed consent. Twenty-one right-handed male patients with schizophrenia and persistent hallucinations (started to hear hallucinations at a mean age of 23 years +/- 10, with 15 years +/- 8 of mean illness duration) and 10 healthy paired participants (same ethnic group [white], age, and education level [secondary school]) were studied. Functional echo-planar T2*-weighted (after both emotional and neutral auditory stimulation) and morphometric three-dimensional gradient-recalled echo T1-weighted MR images were analyzed using Statistical Parametric Mapping (SPM2) software. Brain activation images were extracted by subtracting those with emotional from nonemotional words. Anatomic differences were explored by optimized voxel-based morphometry. The functional and morphometric MR images were overlaid to depict voxels statistically reported by both techniques. A coincidence map was generated by multiplying the emotional subtracted functional MR and volume decrement morphometric maps. Statistical analysis used the general linear model, Student t tests, random effects analyses, and analysis of covariance with a correction for multiple comparisons following the false discovery rate method. RESULTS: Large coinciding brain clusters (P < .005) were found in the left and right middle temporal and superior temporal gyri. Smaller coinciding clusters were found in the left posterior and right anterior cingular gyri, left inferior frontal gyrus, and middle occipital gyrus. CONCLUSION: The middle and superior temporal and the cingular gyri are closely related to the abnormal neural network involved in the auditory emotional dysfunction seen in schizophrenic patients.

Planum temporale asymmetry and ear advantage in dichotic listening in Developmental Dyslexia and Attention-Deficit/Hyperactivity Disorder (ADHD).

The planum temporale is clearly involved in language processing, for it serves as the auditory association cortex. Research has consistently demonstrated that 60 to 70% of the population has leftward asymmetry of the planum temporale. Research has also suggested that dyslexic individuals tend to have either rightward asymmetry or symmetrical plana. Moreover, many studies have found a relationship between the presence of dyslexia and/or language impairment and deficits in the normal right ear advantage found in dichotic listening paradigms. In this context, this study examined the relationship between planum temporale asymmetry and ear preference in dichotic listening performance in children with Developmental Dyslexia and Attention-Deficit/Hyperactivity Disorder (ADHD). Subjects included 19 children with dyslexia (10 of whom had a comorbid diagnosis of ADHD), 23 children with ADHD, and 12 diagnosed normal control children. Dichotic listening data were not collected for 8 of the 12 normal control children and for 3 of the 23 ADHD children. Results revealed no significant difference between ADHD and dyslexic subjects in regard to ear advantage on the free recall dichotic listening task. In addition, although the directed dichotic listening tasks were not related to degree of planum asymmetry, as predicted, results indicated that subjects who consistently displayed an atypical left ear advantage tended to have larger right bank lengths than those who consistently displayed a typical right ear advantage. These findings support the notion that some individuals with dyslexia or language deficits tend to have a larger right planum temporale and that performance on dichotic listening tasks may reflect this relatively unusual pattern.

Absence of cross-modal reorganization in the primary auditory cortex of congenitally deaf cats.

To investigate possible cross-modal reorganization of the primary auditory cortex (field A1) in congenitally deaf cats, after years of auditory deprivation, multiunit activity and local field potentials were recorded in lightly anesthetized animals and compared with responses obtained in hearing cats. Local field potentials were also used for current source-density analyses. For visual stimulation, phase-reversal gratings of three to five different spatial frequencies and three to five different orientations were presented at the point of central vision. Peripheral visual field was tested using hand-held stimuli (light bar-shaped stimulus of different orientations, moved in different directions and flashed) typically used for neurophysiological characterization of visual fields. From 200 multiunit recordings, no response to visual stimuli could be found in A1 of any of the investigated animals. Using the current source-density analysis of local field potentials, no local generators of field potentials could be found within A1, despite of the presence of small local field potentials. No multiunit responses to somatosensory stimulation (whiskers, face, pinna, head, neck, all paws, back, tail) could be obtained. In conclusion, there were no indications for a cross-modal reorganization (visual, somatosensory) of area A1 in congenitally deaf cats.