Abnormally increased vocal responses to pitch feedback perturbations in patients with cerebellar degeneration.

Cerebellar degeneration (CD) has deleterious effects on speech motor behavior. Recently, a dissociation between feedback and feedforward control of speaking was observed in CD: Whereas CD patients exhibited reduced adaptation across trials to consistent formant feedback alterations, they showed enhanced within-trial compensation for unpredictable formant feedback perturbations. In this study, it was found that CD patients exhibit abnormally increased within-trial vocal compensation responses to unpredictable pitch feedback perturbations. Taken together with recent findings, the results indicate that CD is associated with a general hypersensitivity to auditory feedback during speaking.

Investigating the Neural Basis of Theta Burst Stimulation to Premotor Cortex on Emotional Vocalization Perception: A Combined TMS-fMRI Study.

Previous studies have established a role for premotor cortex in the processing of auditory emotional vocalizations. Inhibitory continuous theta burst transcranial magnetic stimulation (cTBS) applied to right premotor cortex selectively increases the reaction time to a same-different task, implying a causal role for right ventral premotor cortex (PMv) in the processing of emotional sounds. However, little is known about the functional networks to which PMv contribute across the cortical hemispheres. In light of these data, the present study aimed to investigate how and where in the brain cTBS affects activity during the processing of auditory emotional vocalizations. Using functional neuroimaging, we report that inhibitory cTBS applied to the right premotor cortex (compared to vertex control site) results in three distinct response profiles: following stimulation of PMv, widespread frontoparietal cortices, including a site close to the target site, and parahippocampal gyrus displayed an increase in activity, whereas the reverse response profile was apparent in a set of midline structures and right IFG. A third response profile was seen in left supramarginal gyrus in which activity was greater post-stimulation at both stimulation sites. Finally, whilst previous studies have shown a condition specific behavioral effect following cTBS to premotor cortex, we did not find a condition specific neural change in BOLD response. These data demonstrate a complex relationship between cTBS and activity in widespread neural networks and are discussed in relation to both emotional processing and the neural basis of cTBS.

Impaired Feedforward Control and Enhanced Feedback Control of Speech in Patients with Cerebellar Degeneration.

The cerebellum has been hypothesized to form a crucial part of the speech motor control network. Evidence for this comes from patients with cerebellar damage, who exhibit a variety of speech deficits, as well as imaging studies showing cerebellar activation during speech production in healthy individuals. To date, the precise role of the cerebellum in speech motor control remains unclear, as it has been implicated in both anticipatory (feedforward) and reactive (feedback) control. Here, we assess both anticipatory and reactive aspects of speech motor control, comparing the performance of patients with cerebellar degeneration and matched controls. Experiment 1 tested feedforward control by examining speech adaptation across trials in response to a consistent perturbation of auditory feedback. Experiment 2 tested feedback control, examining online corrections in response to inconsistent perturbations of auditory feedback. Both male and female patients and controls were tested. The patients were impaired in adapting their feedforward control system relative to controls, exhibiting an attenuated anticipatory response to the perturbation. In contrast, the patients produced even larger compensatory responses than controls, suggesting an increased reliance on sensory feedback to guide speech articulation in this population. Together, these results suggest that the cerebellum is crucial for maintaining accurate feedforward control of speech, but relatively uninvolved in feedback control.SIGNIFICANCE STATEMENT Speech motor control is a complex activity that is thought to rely on both predictive, feedforward control as well as reactive, feedback control. While the cerebellum has been shown to be part of the speech motor control network, its functional contribution to feedback and feedforward control remains controversial. Here, we use real-time auditory perturbations of speech to show that patients with cerebellar degeneration are impaired in adapting feedforward control of speech but retain the ability to make online feedback corrections; indeed, the patients show an increased sensitivity to feedback. These results indicate that the cerebellum forms a crucial part of the feedforward control system for speech but is not essential for online, feedback control.

You talkin' to me? Communicative talker gaze activates left-lateralized superior temporal cortex during perception of degraded speech.

Neuroimaging studies of speech perception have consistently indicated a left-hemisphere dominance in the temporal lobes' responses to intelligible auditory speech signals (McGettigan and Scott, 2012). However, there are important communicative cues that cannot be extracted from auditory signals alone, including the direction of the talker's gaze. Previous work has implicated the superior temporal cortices in processing gaze direction, with evidence for predominantly right-lateralized responses (Carlin & Calder, 2013). The aim of the current study was to investigate whether the lateralization of responses to talker gaze differs in an auditory communicative context. Participants in a functional MRI experiment watched and listened to videos of spoken sentences in which the auditory intelligibility and talker gaze direction were manipulated factorially. We observed a left-dominant temporal lobe sensitivity to the talker's gaze direction, in which the left anterior superior temporal sulcus/gyrus and temporal pole showed an enhanced response to direct gaze - further investigation revealed that this pattern of lateralization was modulated by auditory intelligibility. Our results suggest flexibility in the distribution of neural responses to social cues in the face within the context of a challenging speech perception task.

Cohesion and Joint Speech: Right Hemisphere Contributions to Synchronized Vocal Production.

UNLABELLED: Synchronized behavior (chanting, singing, praying, dancing) is found in all human cultures and is central to religious, military, and political activities, which require people to act collaboratively and cohesively; however, we know little about the neural underpinnings of many kinds of synchronous behavior (e.g., vocal behavior) or its role in establishing and maintaining group cohesion. In the present study, we measured neural activity using fMRI while participants spoke simultaneously with another person. We manipulated whether the couple spoke the same sentence (allowing synchrony) or different sentences (preventing synchrony), and also whether the voice the participant heard was "live" (allowing rich reciprocal interaction) or prerecorded (with no such mutual influence). Synchronous speech was associated with increased activity in posterior and anterior auditory fields. When, and only when, participants spoke with a partner who was both synchronous and "live," we observed a lack of the suppression of auditory cortex, which is commonly seen as a neural correlate of speech production. Instead, auditory cortex responded as though it were processing another talker's speech. Our results suggest that detecting synchrony leads to a change in the perceptual consequences of one's own actions: they are processed as though they were other-, rather than self-produced. This may contribute to our understanding of synchronized behavior as a group-bonding tool. SIGNIFICANCE STATEMENT: Synchronized human behavior, such as chanting, dancing, and singing, are cultural universals with functional significance: these activities increase group cohesion and cause participants to like each other and behave more prosocially toward each other. Here we use fMRI brain imaging to investigate the neural basis of one common form of cohesive synchronized behavior: joint speaking (e.g., the synchronous speech seen in chants, prayers, pledges). Results showed that joint speech recruits additional right hemisphere regions outside the classic speech production network. Additionally, we found that a neural marker of self-produced speech, suppression of sensory cortices, did not occur during joint synchronized speech, suggesting that joint synchronized behavior may alter self-other distinctions in sensory processing.

Getting the Cocktail Party Started: Masking Effects in Speech Perception.

Spoken conversations typically take place in noisy environments, and different kinds of masking sounds place differing demands on cognitive resources. Previous studies, examining the modulation of neural activity associated with the properties of competing sounds, have shown that additional speech streams engage the superior temporal gyrus. However, the absence of a condition in which target speech was heard without additional masking made it difficult to identify brain networks specific to masking and to ascertain the extent to which competing speech was processed equivalently to target speech. In this study, we scanned young healthy adults with continuous fMRI, while they listened to stories masked by sounds that differed in their similarity to speech. We show that auditory attention and control networks are activated during attentive listening to masked speech in the absence of an overt behavioral task. We demonstrate that competing speech is processed predominantly in the left hemisphere within the same pathway as target speech but is not treated equivalently within that stream and that individuals who perform better in speech in noise tasks activate the left mid-posterior superior temporal gyrus more. Finally, we identify neural responses associated with the onset of sounds in the auditory environment; activity was found within right lateralized frontal regions consistent with a phasic alerting response. Taken together, these results provide a comprehensive account of the neural processes involved in listening in noise.

Feel the Noise: Relating Individual Differences in Auditory Imagery to the Structure and Function of Sensorimotor Systems.

Humans can generate mental auditory images of voices or songs, sometimes perceiving them almost as vividly as perceptual experiences. The functional networks supporting auditory imagery have been described, but less is known about the systems associated with interindividual differences in auditory imagery. Combining voxel-based morphometry and fMRI, we examined the structural basis of interindividual differences in how auditory images are subjectively perceived, and explored associations between auditory imagery, sensory-based processing, and visual imagery. Vividness of auditory imagery correlated with gray matter volume in the supplementary motor area (SMA), parietal cortex, medial superior frontal gyrus, and middle frontal gyrus. An analysis of functional responses to different types of human vocalizations revealed that the SMA and parietal sites that predict imagery are also modulated by sound type. Using representational similarity analysis, we found that higher representational specificity of heard sounds in SMA predicts vividness of imagery, indicating a mechanistic link between sensory- and imagery-based processing in sensorimotor cortex. Vividness of imagery in the visual domain also correlated with SMA structure, and with auditory imagery scores. Altogether, these findings provide evidence for a signature of imagery in brain structure, and highlight a common role of perceptual-motor interactions for processing heard and internally generated auditory information.

Exploring the roles of spectral detail and intonation contour in speech intelligibility: an FMRI study.

The melodic contour of speech forms an important perceptual aspect of tonal and nontonal languages and an important limiting factor on the intelligibility of speech heard through a cochlear implant. Previous work exploring the neural correlates of speech comprehension identified a left-dominant pathway in the temporal lobes supporting the extraction of an intelligible linguistic message, whereas the right anterior temporal lobe showed an overall preference for signals clearly conveying dynamic pitch information [Johnsrude, I. S., Penhune, V. B., & Zatorre, R. J. Functional specificity in the right human auditory cortex for perceiving pitch direction. Brain, 123, 155-163, 2000; Scott, S. K., Blank, C. C., Rosen, S., & Wise, R. J. Identification of a pathway for intelligible speech in the left temporal lobe. Brain, 123, 2400-2406, 2000]. The current study combined modulations of overall intelligibility (through vocoding and spectral inversion) with a manipulation of pitch contour (normal vs. falling) to investigate the processing of spoken sentences in functional MRI. Our overall findings replicate and extend those of Scott et al. [Scott, S. K., Blank, C. C., Rosen, S., & Wise, R. J. Identification of a pathway for intelligible speech in the left temporal lobe. Brain, 123, 2400-2406, 2000], where greater sentence intelligibility was predominately associated with increased activity in the left STS, and the greatest response to normal sentence melody was found in right superior temporal gyrus. These data suggest a spatial distinction between brain areas associated with intelligibility and those involved in the processing of dynamic pitch information in speech. By including a set of complexity-matched unintelligible conditions created by spectral inversion, this is additionally the first study reporting a fully factorial exploration of spectrotemporal complexity and spectral inversion as they relate to the neural processing of speech intelligibility. Perhaps surprisingly, there was little evidence for an interaction between the two factors-we discuss the implications for the processing of sound and speech in the dorsolateral temporal lobes.

T'ain't what you say, it's the way that you say it--left insula and inferior frontal cortex work in interaction with superior temporal regions to control the performance of vocal impersonations.

Historically, the study of human identity perception has focused on faces, but the voice is also central to our expressions and experiences of identity [Belin, P., Fecteau, S., & Bedard, C. Thinking the voice: Neural correlates of voice perception. Trends in Cognitive Sciences, 8, 129-135, 2004]. Our voices are highly flexible and dynamic; talkers speak differently, depending on their health, emotional state, and the social setting, as well as extrinsic factors such as background noise. However, to date, there have been no studies of the neural correlates of identity modulation in speech production. In the current fMRI experiment, we measured the neural activity supporting controlled voice change in adult participants performing spoken impressions. We reveal that deliberate modulation of vocal identity recruits the left anterior insula and inferior frontal gyrus, supporting the planning of novel articulations. Bilateral sites in posterior superior temporal/inferior parietal cortex and a region in right middle/anterior STS showed greater responses during the emulation of specific vocal identities than for impressions of generic accents. Using functional connectivity analyses, we describe roles for these three sites in their interactions with the brain regions supporting speech planning and production. Our findings mark a significant step toward understanding the neural control of vocal identity, with wider implications for the cognitive control of voluntary motor acts.

Dissociating object directed and non-object directed action in the human mirror system; implications for theories of motor simulation.

Mirror neurons are single cells found in macaque premotor and parietal cortices that are active during action execution and observation. In non-human primates, mirror neurons have only been found in relation to object-directed movements or communicative gestures, as non-object directed actions of the upper limb are not well characterized in non-human primates. Mirror neurons provide important evidence for motor simulation theories of cognition, sometimes referred to as the direct matching hypothesis, which propose that observed actions are mapped onto associated motor schemata in a direct and automatic manner. This study, for the first time, directly compares mirror responses, defined as the overlap between action execution and observation, during object directed and meaningless non-object directed actions. We present functional MRI data that demonstrate a clear dissociation between object directed and non-object directed actions within the human mirror system. A premotor and parietal network was preferentially active during object directed actions, whether observed or executed. Moreover, we report spatially correlated activity across multiple voxels for observation and execution of an object directed action. In contrast to predictions made by motor simulation theory, no similar activity was observed for non-object directed actions. These data demonstrate that object directed and meaningless non-object directed actions are subserved by different neuronal networks and that the human mirror response is significantly greater for object directed actions. These data have important implications for understanding the human mirror system and for simulation theories of motor cognition. Subsequent theories of motor simulation must account for these differences, possibly by acknowledging the role of experience in modulating the mirror response.

An application of univariate and multivariate approaches in FMRI to quantifying the hemispheric lateralization of acoustic and linguistic processes.

The question of hemispheric lateralization of neural processes is one that is pertinent to a range of subdisciplines of cognitive neuroscience. Language is often assumed to be left-lateralized in the human brain, but there has been a long running debate about the underlying reasons for this. We addressed this problem with fMRI by identifying the neural responses to amplitude and spectral modulations in speech and how these interact with speech intelligibility to test previous claims for hemispheric asymmetries in acoustic and linguistic processes in speech perception. We used both univariate and multivariate analyses of the data, which enabled us to both identify the networks involved in processing these acoustic and linguistic factors and to test the significance of any apparent hemispheric asymmetries. We demonstrate bilateral activation of superior temporal cortex in response to speech-derived acoustic modulations in the absence of intelligibility. However, in a contrast of amplitude-modulated and spectrally modulated conditions that differed only in their intelligibility (where one was partially intelligible and the other unintelligible), we show a left dominant pattern of activation in STS, inferior frontal cortex, and insula. Crucially, multivariate pattern analysis showed that there were significant differences between the left and the right hemispheres only in the processing of intelligible speech. This result shows that the left hemisphere dominance in linguistic processing does not arise because of low-level, speech-derived acoustic factors and that multivariate pattern analysis provides a method for unbiased testing of hemispheric asymmetries in processing.

Discriminating between auditory and motor cortical responses to speech and nonspeech mouth sounds.

Several perspectives on speech perception posit a central role for the representation of articulations in speech comprehension, supported by evidence for premotor activation when participants listen to speech. However, no experiments have directly tested whether motor responses mirror the profile of selective auditory cortical responses to native speech sounds or whether motor and auditory areas respond in different ways to sounds. We used fMRI to investigate cortical responses to speech and nonspeech mouth (ingressive click) sounds. Speech sounds activated bilateral superior temporal gyri more than other sounds, a profile not seen in motor and premotor cortices. These results suggest that there are qualitative differences in the ways that temporal and motor areas are activated by speech and click sounds: Anterior temporal lobe areas are sensitive to the acoustic or phonetic properties, whereas motor responses may show more generalized responses to the acoustic stimuli.

Naturalistic stimulus trains evoke reproducible subicular responses both within and between animals in vivo.

Previous investigation of CA1-evoked subicular responses has used either single low-frequency pulses (LF), paired-pulses (PP), or high-frequency bursts. Here we test for the first time how subiculum responds to naturalistic stimulation trains (NSTs). We recorded CA1-evoked field potentials from dorsal rat subiculum in response to LF, PP, and two NST patterns. The latter were derived from CA1 place cell activity; NST1 contained bursts of stimuli presented in two main episodes, while the burst-patterned stimuli in NST2 were spaced more evenly. NSTs generated significantly greater field responses compared with LF or PP patterns. Response patterns to either NST were significantly correlated across trial repeats in 9 out of 10 rats, supporting a robust postsynaptic encoding of CA1 input by subiculum. Correlations between NST responses were also observed across experiments; however, these were more variable than those within experiments. The relationship between response magnitude and activation history revealed a strong correlation between magnitude and NST instantaneous frequency for NST1 but was weaker for NST2. In addition, the number of stimuli within a prior 500 ms window was a determining factor for response magnitude for both NSTs. Overall, the robust reproducibility in subicular responses within rats suggests that information within NSTs is faithfully transmitted through the CA1-subiculum axis. However, variation in response sequences across rats suggests that encoding patterns to the same input differ across the subiculum. Changes in the ratio of target bursting and regularly spiking neurons along the subicular proximodistal axis may account for this variation. The activation history of this connection also appears to be a strong determining factor for response magnitude.

Separate areas for mirror responses and agency within the parietal operculum.

There is common neural activity in parietal and premotor cortex when executing and observing goal-directed movements: the "mirror" response. In addition, active and passive limb movements cause overlapping activity in premotor and somatosensory cortex. This association of motor and sensory activity cannot ascribe agency, the ability to discriminate between self- and non-self-generated events. This requires that some signals accompanying self-initiated limb movement dissociate from those evoked by observing the action of another or by movement imposed on oneself by external force. We demonstrated associated activity within the medial parietal operculum in response to feedforward visual or somatosensory information accompanying observed and imposed finger movements. In contrast, the response to motor and somatosensory information during self-initiated finger and observed movements resulted in activity localized to the lateral parietal operculum. This ascribes separate functions to medial and lateral second-order somatosensory cortex, anatomically dissociating the agent and the mirror response, demonstrating how executed and observed events are distinguished despite common activity in widespread sensorimotor cortices.

The human mirror system: a motor resonance theory of mind-reading.

Electrophysiological data confirm the existence of neurons that respond to both motor and sensory events in the macaque brain. These mirror neurons respond to execution and observation of goal-orientated actions. It has been suggested that they comprise a neural basis for encoding an internal representation of action. In this paper the evidence for a parallel system in humans is reviewed and the implications for human theory of mind processing are discussed. Different components of theory of mind are discussed; the evidence for mirror activity within subtypes is addressed. While there is substantial evidence for a human mirror system, there are weaknesses in the attempts to localize such a system in the brain. Preliminary evidence indicates that mirror neurons may be involved in theory of mind; however, these data by their very nature are reliant on the presence, and precise characterization, of the human mirror system.