Cortical deafness of following bilateral temporal lobe stroke.

Cortical deafness is an extremely rare clinical manifestation that originates mainly from bilateral cortical lesions in the primary auditory cortex. Its main clinical manifestation is the bilateral sudden loss of hearing. Diagnosis is difficulty due to its rarity and similarity with other language and communication disorders, such as Wernicke's aphasia, auditory agnosia or verbal deafness. Herein, we present a case report of a young woman with a sudden bilateral loss of auditory comprehension. Initially, a psychiatric nature of the disorder was considered, but the persistence of the symptoms, lead to the diagnosis of cortical deafness secondary to bilateral ischemic lesions in both temporal lobes. Progressive improvement occurred and three months after the initial manifestations she manifested pure verbal deafness. Cortical deafness usually has a poor functional prognosis, with limited therapeutic options. Rehabilitation and speech therapy is recommended to improve the chance of patients achieving communication skills.

Tonotopic maps in human auditory cortex using arterial spin labeling.

A tonotopic organization of the human auditory cortex (AC) has been reliably found by neuroimaging studies. However, a full characterization and parcellation of the AC is still lacking. In this study, we employed pseudo-continuous arterial spin labeling (pCASL) to map tonotopy and voice selective regions using, for the first time, cerebral blood flow (CBF). We demonstrated the feasibility of CBF-based tonotopy and found a good agreement with BOLD signal-based tonotopy, despite the lower contrast-to-noise ratio of CBF. Quantitative perfusion mapping of baseline CBF showed a region of high perfusion centered on Heschl's gyrus and corresponding to the main high-low-high frequency gradients, co-located to the presumed primary auditory core and suggesting baseline CBF as a novel marker for AC parcellation. Furthermore, susceptibility weighted imaging was employed to investigate the tissue specificity of CBF and BOLD signal and the possible venous bias of BOLD-based tonotopy. For BOLD only active voxels, we found a higher percentage of vein contamination than for CBF only active voxels. Taken together, we demonstrated that both baseline and stimulus-induced CBF is an alternative fMRI approach to the standard BOLD signal to study auditory processing and delineate the functional organization of the auditory cortex. Hum Brain Mapp 38:1140-1154, 2017. © 2016 Wiley Periodicals, Inc.

Klinefelter syndrome has increased brain responses to auditory stimuli and motor output, but not to visual stimuli or Stroop adaptation.

Klinefelter syndrome (47, XXY) (KS) is a genetic syndrome characterized by the presence of an extra X chromosome and low level of testosterone, resulting in a number of neurocognitive abnormalities, yet little is known about brain function. This study investigated the fMRI-BOLD response from KS relative to a group of Controls to basic motor, perceptual, executive and adaptation tasks. Participants (N: KS = 49; Controls = 49) responded to whether the words "GREEN" or "RED" were displayed in green or red (incongruent versus congruent colors). One of the colors was presented three times as often as the other, making it possible to study both congruency and adaptation effects independently. Auditory stimuli saying "GREEN" or "RED" had the same distribution, making it possible to study effects of perceptual modality as well as Frequency effects across modalities. We found that KS had an increased response to motor output in primary motor cortex and an increased response to auditory stimuli in auditory cortices, but no difference in primary visual cortices. KS displayed a diminished response to written visual stimuli in secondary visual regions near the Visual Word Form Area, consistent with the widespread dyslexia in the group. No neural differences were found in inhibitory control (Stroop) or in adaptation to differences in stimulus frequencies. Across groups we found a strong positive correlation between age and BOLD response in the brain's motor network with no difference between groups. No effects of testosterone level or brain volume were found. In sum, the present findings suggest that auditory and motor systems in KS are selectively affected, perhaps as a compensatory strategy, and that this is not a systemic effect as it is not seen in the visual system.

Decoding four different sound-categories in the auditory cortex using functional near-infrared spectroscopy.

The ability of the auditory cortex in the brain to distinguish different sounds is important in daily life. This study investigated whether activations in the auditory cortex caused by different sounds can be distinguished using functional near-infrared spectroscopy (fNIRS). The hemodynamic responses (HRs) in both hemispheres using fNIRS were measured in 18 subjects while exposing them to four sound categories (English-speech, non-English-speech, annoying sounds, and nature sounds). As features for classifying the different signals, the mean, slope, and skewness of the oxy-hemoglobin (HbO) signal were used. With regard to the language-related stimuli, the HRs evoked by understandable speech (English) were observed in a broader brain region than were those evoked by non-English speech. Also, the magnitudes of the HbO signals evoked by English-speech were higher than those of non-English speech. The ratio of the peak values of non-English and English speech was 72.5%. Also, the brain region evoked by annoying sounds was wider than that by nature sounds. However, the signal strength for nature sounds was stronger than that for annoying sounds. Finally, for brain-computer interface (BCI) purposes, the linear discriminant analysis (LDA) and support vector machine (SVM) classifiers were applied to the four sound categories. The overall classification performance for the left hemisphere was higher than that for the right hemisphere. Therefore, for decoding of auditory commands, the left hemisphere is recommended. Also, in two-class classification, the annoying vs. nature sounds comparison provides a higher classification accuracy than the English vs. non-English speech comparison. Finally, LDA performs better than SVM.

Functional Topography of Human Auditory Cortex.

Functional and anatomical studies have clearly demonstrated that auditory cortex is populated by multiple subfields. However, functional characterization of those fields has been largely the domain of animal electrophysiology, limiting the extent to which human and animal research can inform each other. In this study, we used high-resolution functional magnetic resonance imaging to characterize human auditory cortical subfields using a variety of low-level acoustic features in the spectral and temporal domains. Specifically, we show that topographic gradients of frequency preference, or tonotopy, extend along two axes in human auditory cortex, thus reconciling historical accounts of a tonotopic axis oriented medial to lateral along Heschl's gyrus and more recent findings emphasizing tonotopic organization along the anterior-posterior axis. Contradictory findings regarding topographic organization according to temporal modulation rate in acoustic stimuli, or "periodotopy," are also addressed. Although isolated subregions show a preference for high rates of amplitude-modulated white noise (AMWN) in our data, large-scale "periodotopic" organization was not found. Organization by AM rate was correlated with dominant pitch percepts in AMWN in many regions. In short, our data expose early auditory cortex chiefly as a frequency analyzer, and spectral frequency, as imposed by the sensory receptor surface in the cochlea, seems to be the dominant feature governing large-scale topographic organization across human auditory cortex. SIGNIFICANCE STATEMENT: In this study, we examine the nature of topographic organization in human auditory cortex with fMRI. Topographic organization by spectral frequency (tonotopy) extended in two directions: medial to lateral, consistent with early neuroimaging studies, and anterior to posterior, consistent with more recent reports. Large-scale organization by rates of temporal modulation (periodotopy) was correlated with confounding spectral content of amplitude-modulated white-noise stimuli. Together, our results suggest that the organization of human auditory cortex is driven primarily by its response to spectral acoustic features, and large-scale periodotopy spanning across multiple regions is not supported. This fundamental information regarding the functional organization of early auditory cortex will inform our growing understanding of speech perception and the processing of other complex sounds.

Deciphering phonemes from syllables in blood oxygenation level-dependent signals in human superior temporal gyrus.

Linguistic units such as phonemes and syllables are important for speech perception. How the brain encodes these units is not well understood. Many neuroimaging studies have found distinct representations of consonant-vowel syllables that shared one phoneme and differed in the other phoneme (e.g. /ba/ and /da/), but it is unclear whether this discrimination ability is due to the neural coding of phonemes or syllables. We combined functional magnetic resonance imaging with multivariate pattern analysis to explore this question. Subjects listened to nine Mandarin syllables in a consonant-vowel form. We successfully decoded phonemes from the syllables based on the blood oxygenation level-dependent signals in the superior temporal gyrus (STG). Specifically, a classifier trained on the cortical patterns elicited by a set of syllables, which contained two phonemes, could distinguish the cortical patterns elicited by other syllables that contained the two phonemes. The results indicated that phonemes have unique representations in the STG. In addition, there was a categorical effect, i.e. the cortical patterns of consonants were similar, and so were the cortical patterns of vowels. Further analysis showed that phonemes exhibited stronger encoding specificity in the mid-STG than in the anterior STG.

Hemodynamic imaging of the auditory cortex.

Over the past 20 years or so, functional magnetic resonance imaging (fMRI) has proven to be an influential tool for measuring perceptual and cognitive processing non-invasively in the human brain. This article provides a brief yet comprehensive overview of this dominant method for human auditory neuroscience, providing the reader with knowledge about the practicalities of using this technique to assess central auditory coding. Key learning objectives include developing an understanding of the basic MR physics underpinning the technique, the advantage of auditory fMRI over other current neuroimaging alternatives, and highlighting some of the practical considerations involved in setting up, running, and analyzing an auditory fMRI experiment. The future utility of fMRI and anticipated technical developments is also briefly evaluated. Throughout the review, key concepts are illustrated using specific author examples, with particular emphasis on fMRI findings that address questions pertaining to basic sound coding (such as frequency and pitch).

An fMRI Study of the Ventriloquism Effect.

In spatial perception, visual information has higher acuity than auditory information and we often misperceive sound-source locations when spatially disparate visual stimuli are presented simultaneously. Ventriloquists make good use of this auditory illusion. In this study, we investigated neural substrates of the ventriloquism effect to understand the neural mechanism of multimodal integration. This study was performed in 2 steps. First, we investigated how sound locations were represented in the auditory cortex. Secondly, we investigated how simultaneous presentation of spatially disparate visual stimuli affects neural processing of sound locations. Based on the population rate code hypothesis that assumes monotonic sensitivity to sound azimuth across populations of broadly tuned neurons, we expected a monotonic increase of blood oxygenation level-dependent (BOLD) signals for more contralateral sounds. Consistent with this hypothesis, we found that BOLD signals in the posterior superior temporal gyrus increased monotonically as a function of sound azimuth. We also observed attenuation of the monotonic azimuthal sensitivity by spatially disparate visual stimuli. The alteration of the neural pattern was considered to reflect the neural mechanism of the ventriloquism effect. Our findings indicate that conflicting audiovisual spatial information of an event is associated with an attenuation of neural processing of auditory spatial localization.

Deficits in predictive coding underlie hallucinations in schizophrenia.

The neural mechanisms that produce hallucinations and other psychotic symptoms remain unclear. Previous research suggests that deficits in predictive signals for learning, such as prediction error signals, may underlie psychotic symptoms, but the mechanism by which such deficits produce psychotic symptoms remains to be established. We used model-based fMRI to study sensory prediction errors in human patients with schizophrenia who report daily auditory verbal hallucinations (AVHs) and sociodemographically matched healthy control subjects. We manipulated participants' expectations for hearing speech at different periods within a speech decision-making task. Patients activated a voice-sensitive region of the auditory cortex while they experienced AVHs in the scanner and displayed a concomitant deficit in prediction error signals in a similar portion of auditory cortex. This prediction error deficit correlated strongly with increased activity during silence and with reduced volumes of the auditory cortex, two established neural phenotypes of AVHs. Furthermore, patients with more severe AVHs had more deficient prediction error signals and greater activity during silence within the region of auditory cortex where groups differed, regardless of the severity of psychotic symptoms other than AVHs. Our findings suggest that deficient predictive coding accounts for the resting hyperactivity in sensory cortex that leads to hallucinations.

Functional imaging of auditory cortex in adult cats using high-field fMRI.

Current knowledge of sensory processing in the mammalian auditory system is mainly derived from electrophysiological studies in a variety of animal models, including monkeys, ferrets, bats, rodents, and cats. In order to draw suitable parallels between human and animal models of auditory function, it is important to establish a bridge between human functional imaging studies and animal electrophysiological studies. Functional magnetic resonance imaging (fMRI) is an established, minimally invasive method of measuring broad patterns of hemodynamic activity across different regions of the cerebral cortex. This technique is widely used to probe sensory function in the human brain, is a useful tool in linking studies of auditory processing in both humans and animals and has been successfully used to investigate auditory function in monkeys and rodents. The following protocol describes an experimental procedure for investigating auditory function in anesthetized adult cats by measuring stimulus-evoked hemodynamic changes in auditory cortex using fMRI. This method facilitates comparison of the hemodynamic responses across different models of auditory function thus leading to a better understanding of species-independent features of the mammalian auditory cortex.

Task-dependent decoding of speaker and vowel identity from auditory cortical response patterns.

Selective attention to relevant sound properties is essential for everyday listening situations. It enables the formation of different perceptual representations of the same acoustic input and is at the basis of flexible and goal-dependent behavior. Here, we investigated the role of the human auditory cortex in forming behavior-dependent representations of sounds. We used single-trial fMRI and analyzed cortical responses collected while subjects listened to the same speech sounds (vowels /a/, /i/, and /u/) spoken by different speakers (boy, girl, male) and performed a delayed-match-to-sample task on either speech sound or speaker identity. Univariate analyses showed a task-specific activation increase in the right superior temporal gyrus/sulcus (STG/STS) during speaker categorization and in the right posterior temporal cortex during vowel categorization. Beyond regional differences in activation levels, multivariate classification of single trial responses demonstrated that the success with which single speakers and vowels can be decoded from auditory cortical activation patterns depends on task demands and subject's behavioral performance. Speaker/vowel classification relied on distinct but overlapping regions across the (right) mid-anterior STG/STS (speakers) and bilateral mid-posterior STG/STS (vowels), as well as the superior temporal plane including Heschl's gyrus/sulcus. The task dependency of speaker/vowel classification demonstrates that the informative fMRI response patterns reflect the top-down enhancement of behaviorally relevant sound representations. Furthermore, our findings suggest that successful selection, processing, and retention of task-relevant sound properties relies on the joint encoding of information across early and higher-order regions of the auditory cortex.

Auditory neuroimaging with fMRI and PET.

For much of the past 30 years, investigations of auditory perception and language have been enhanced or even driven by the use of functional neuroimaging techniques that specialize in localization of central responses. Beginning with investigations using positron emission tomography (PET) and gradually shifting primarily to usage of functional magnetic resonance imaging (fMRI), auditory neuroimaging has greatly advanced our understanding of the organization and response properties of brain regions critical to the perception of and communication with the acoustic world in which we live. As the complexity of the questions being addressed has increased, the techniques, experiments and analyses applied have also become more nuanced and specialized. A brief review of the history of these investigations sets the stage for an overview and analysis of how these neuroimaging modalities are becoming ever more effective tools for understanding the auditory brain. We conclude with a brief discussion of open methodological issues as well as potential clinical applications for auditory neuroimaging. This article is part of a Special Issue entitled Human Auditory Neuroimaging.

Hemodynamic responses to speech and music in preverbal infants.

Numerous studies have provided clues about the ontogeny of lateralization of auditory processing in humans, but most have employed specific subtypes of stimuli and/or have assessed responses in discrete temporal windows. The present study used near-infrared spectroscopy (NIRS) to establish changes in hemodynamic activity in the neocortex of preverbal infants (aged 4-11 months) while they were exposed to two distinct types of complex auditory stimuli (full sentences and musical phrases). Measurements were taken from bilateral temporal regions, including both anterior and posterior superior temporal gyri. When the infant sample was treated as a homogenous group, no significant effects emerged for stimulus type. However, when infants' hemodynamic responses were categorized according to their overall changes in volume, two very clear neurophysiological patterns emerged. A high-responder group showed a pattern of early and increasing activation, primarily in the left hemisphere, similar to that observed in comparable studies with adults. In contrast, a low-responder group showed a pattern of gradual decreases in activation over time. Although age did track with responder type, no significant differences between these groups emerged for stimulus type, suggesting that the high- versus low-responder characterization generalizes across classes of auditory stimuli. These results highlight a new way to conceptualize the variable cortical blood flow patterns that are frequently observed across infants and stimuli, with hemodynamic response volumes potentially serving as an early indicator of developmental changes in auditory-processing sensitivity.

Developmental changes in resting and functional cerebral blood flow and their relationship to the BOLD response.

Our understanding of cerebral blood flow (CBF) in the healthy developing brain has been limited due to the invasiveness of methods historically available for CBF measurement. Clinically based studies using radioactive tracers with children have focused on resting state CBF. Yet potential age-related changes in flow during stimulation may affect the blood oxygenation level dependent (BOLD) response used to investigate cognitive neurodevelopment. This study used noninvasive arterial spin labeling magnetic resonance imaging to compare resting state and stimulus-driven CBF between typically developing children 8 years of age, 12 years of age, and adults. Further, we acquired functional CBF and BOLD images simultaneously to examine their relationship during sensory stimulation. Analyses revealed age-related CBF differences during rest; the youngest group showed greater CBF than 12-year-olds or adults. During stimulation of the auditory cortex, younger children also showed a greater absolute increase in CBF than adults. However, the magnitude of CBF response above baseline was comparable between groups. Similarly, the amplitude of the BOLD response was stable across age. The combination of the 8 year olds' elevated CBF, both at rest and in response to stimulation, without elevation in the BOLD response suggests that additional physiological factors that also play a role in the BOLD effect, such as metabolic processes that are also elevated in this period, may offset the increased CBF in these children. Thus, CBF measurements reveal maturational differences in the hemodynamics underlying the BOLD effect in children despite the resemblance of the BOLD response between children and adults.

Preattentive mechanisms of change detection in early auditory cortex: a 7 Tesla fMRI study.

The auditory system continuously monitors the environment for irregularities in an automatic, preattentive fashion. This is presumably accomplished by two mechanisms: a sensory mechanism detects a deviant sound on the basis of differential refractoriness of neural populations sensitive to the standard and deviant sounds, whereas the cognitive mechanism reveals deviance by comparing incoming auditory information with a template derived from previous input. Using fast event-related high-resolution functional magnetic resonance imaging at 7 Tesla we show that both mechanisms can be mapped to different parts of the auditory cortex both at the group level and the single-subject level. The sensory mechanism is supported by primary auditory areas in Heschl's gyrus whereas the cognitive mechanism is implemented in more anterior secondary auditory areas. Both mechanisms are equally engaged by simple sine-wave tones and speech-related phonemes indicating that streams of speech and non-speech stimuli are processed in a similar fashion.

Perceptual demand modulates activation of human auditory cortex in response to task-irrelevant sounds.

In the visual modality, perceptual demand on a goal-directed task has been shown to modulate the extent to which irrelevant information can be disregarded at a sensory-perceptual stage of processing. In the auditory modality, the effect of perceptual demand on neural representations of task-irrelevant sounds is unclear. We compared simultaneous ERPs and fMRI responses associated with task-irrelevant sounds across parametrically modulated perceptual task demands in a dichotic-listening paradigm. Participants performed a signal detection task in one ear (Attend ear) while ignoring task-irrelevant syllable sounds in the other ear (Ignore ear). Results revealed modulation of syllable processing by auditory perceptual demand in an ROI in middle left superior temporal gyrus and in negative ERP activity 130-230 msec post stimulus onset. Increasing the perceptual demand in the Attend ear was associated with a reduced neural response in both fMRI and ERP to task-irrelevant sounds. These findings are in support of a selection model whereby ongoing perceptual demands modulate task-irrelevant sound processing in auditory cortex.

Corticostriatal contributions to musical expectancy perception.

This study investigates the functional neuroanatomy of harmonic music perception with fMRI. We presented short pieces of Western classical music to nonmusicians. The ending of each piece was systematically manipulated in the following four ways: Standard Cadence (expected resolution), Deceptive Cadence (moderate deviation from expectation), Modulated Cadence (strong deviation from expectation but remaining within the harmonic structure of Western tonal music), and Atonal Cadence (strongest deviation from expectation by leaving the harmonic structure of Western tonal music). Music compared with baseline broadly recruited regions of the bilateral superior temporal gyrus (STG) and the right inferior frontal gyrus (IFG). Parametric regressors scaled to the degree of deviation from harmonic expectancy identified regions sensitive to expectancy violation. Areas within the BG were significantly modulated by expectancy violation, indicating a previously unappreciated role in harmonic processing. Expectancy violation also recruited bilateral cortical regions in the IFG and anterior STG, previously associated with syntactic processing in other domains. The posterior STG was not significantly modulated by expectancy. Granger causality mapping found functional connectivity between IFG, anterior STG, posterior STG, and the BG during music perception. Our results imply the IFG, anterior STG, and the BG are recruited for higher-order harmonic processing, whereas the posterior STG is recruited for basic pitch and melodic processing.

Reduced neuronal activity in language-related regions after transcranial magnetic stimulation therapy for auditory verbal hallucinations.

BACKGROUND: Transcranial magnetic stimulation (TMS) is a novel therapeutic approach, used in patients with pharmacoresistant auditory verbal hallucinations (AVH). To investigate the neurobiological effects of TMS on AVH, we measured cerebral blood flow with pseudo-continuous magnetic resonance-arterial spin labeling 20 ± 6 hours before and after TMS treatment. METHODS: Thirty patients with schizophrenia or schizoaffective disorder were investigated. Fifteen patients received a 10-day TMS treatment to the left temporoparietal cortex, and 15 received the standard treatment. The stimulation location was chosen according to an individually determined language region determined by a functional magnetic resonance imaging language paradigm, which identified the sensorimotor language area, area Spt (sylvian parietotemporal), as the target region. RESULTS: TMS-treated patients showed positive clinical effects, which were indicated by a reduction in AVH scores (p ≤ .001). Cerebral blood flow was significantly decreased in the primary auditory cortex (p ≤ .001), left Broca's area (p ≤ .001), and cingulate gyrus (p ≤ .001). In control subjects, neither positive clinical effects nor cerebral blood flow decreases were detected. The decrease in cerebral blood flow in the primary auditory cortex correlated with the decrease in AVH scores (p ≤ .001). CONCLUSIONS: TMS reverses hyperactivity of language regions involved in the emergence of AVH. Area Spt acts as a gateway to the hallucination-generating cerebral network. Successful therapy corresponded to decreased cerebral blood flow in the primary auditory cortex, supporting its crucial role in triggering AVH and contributing to the physical quality of the false perceptions.

Segregating the neural correlates of physical and perceived change in auditory input using the change deafness effect.

Psychophysical experiments show that auditory change detection can be disturbed in situations in which listeners have to monitor complex auditory input. We made use of this change deafness effect to segregate the neural correlates of physical change in auditory input from brain responses related to conscious change perception in an fMRI experiment. Participants listened to two successively presented complex auditory scenes, which consisted of six auditory streams, and had to decide whether scenes were identical or whether the frequency of one stream was changed between presentations. Our results show that physical changes in auditory input, independent of successful change detection, are represented at the level of auditory cortex. Activations related to conscious change perception, independent of physical change, were found in the insula and the ACC. Moreover, our data provide evidence for significant effective connectivity between auditory cortex and the insula in the case of correctly detected auditory changes, but not for missed changes. This underlines the importance of the insula/anterior cingulate network for conscious change detection.

Learning of new sound categories shapes neural response patterns in human auditory cortex.

The formation of new sound categories is fundamental to everyday goal-directed behavior. Categorization requires the abstraction of discrete classes from continuous physical features as required by context and task. Electrophysiology in animals has shown that learning to categorize novel sounds alters their spatiotemporal neural representation at the level of early auditory cortex. However, functional magnetic resonance imaging (fMRI) studies so far did not yield insight into the effects of category learning on sound representations in human auditory cortex. This may be due to the use of overlearned speech-like categories and fMRI subtraction paradigms, leading to insufficient sensitivity to distinguish the responses to learning-induced, novel sound categories. Here, we used fMRI pattern analysis to investigate changes in human auditory cortical response patterns induced by category learning. We created complex novel sound categories and analyzed distributed activation patterns during passive listening to a sound continuum before and after category learning. We show that only after training, sound categories could be successfully decoded from early auditory areas and that learning-induced pattern changes were specific to the category-distinctive sound feature (i.e., pitch). Notably, the similarity between fMRI response patterns for the sound continuum mirrored the sigmoid shape of the behavioral category identification function. Our results indicate that perceptual representations of novel sound categories emerge from neural changes at early levels of the human auditory processing hierarchy.