Kristina Simonyan

Neuroanatomical Changes due to Hearing Loss and Chronic Tinnitus: A Combined VBM and DTI Study

Subjective tinnitus is the perception of sound in the absence of an external source. Tinnitus is often accompanied by hearing loss but not everyone with hearing loss experiences tinnitus. We examined neuroanatomical alterations associated with hearing loss and tinnitus in three groups of subjects: those with hearing loss with tinnitus, those with hearing loss without tinnitus and normal hearing controls without tinnitus. To examine changes in gray matter we used structural MRI scans and voxel-based morphometry (VBM) and to identify changes in white matter tract orientation we used diffusion tensor imaging (DTI). A major finding of our study was that there were both gray and white matter changes in the vicinity of the auditory cortex for subjects with hearing loss alone relative to those with tinnitus and those with normal hearing. We did not find significant changes in gray or white matter in subjects with tinnitus and hearing loss compared to normal hearing controls. VBM analysis revealed that individuals with hearing loss without tinnitus had gray matter decreases in anterior cingulate and superior and medial frontal gyri relative to those with hearing loss and tinnitus. Region-of-interest analysis revealed additional decreases in superior temporal gyrus for the hearing loss group compared to the tinnitus group. Investigating effects of hearing loss alone, we found gray matter decreases in superior and medial frontal gyri in participants with hearing loss compared to normal hearing controls. DTI analysis showed decreases in fractional anisotropy values in the right superior and inferior longitudinal fasciculi, corticospinal tract, inferior fronto-occipital tract, superior occipital fasciculus, and anterior thalamic radiation for the hearing loss group relative to normal hearing controls. In attempting to dissociate the effect of tinnitus from hearing loss, we observed that hearing loss rather than tinnitus had the greatest influence on gray and white matter alterations.

Laryngeal Motor Cortex and Control of Speech in Humans

Speech production is one of the most complex and rapid motor behaviors, and it involves a precise coordination of more than 100 laryngeal, orofacial, and respiratory muscles. Yet we lack a complete understanding of laryngeal motor cortical control during production of speech and other voluntary laryngeal behaviors. In recent years, a number of studies have confirmed the laryngeal motor cortical representation in humans and have provided some information about its interactions with other cortical and subcortical regions that are principally involved in vocal motor control of speech production. In this review, the authors discuss the organization of the peripheral and central laryngeal control based on neuroimaging and electrical stimulation studies in humans and neuroanatomical tracing studies in nonhuman primates. It is hypothesized that the location of the laryngeal motor cortex in the primary motor cortex and its direct connections with the brain stem laryngeal motoneurons in humans, as opposed to its location in the premotor cortex with only indirect connections to the laryngeal motoneurons in nonhuman primates, may represent one of the major evolutionary developments in humans toward the ability to speak and vocalize voluntarily.

Sensory stimulation activates both motor and sensory components of the swallowing system

Volitional swallowing in humans involves the coordination of both brainstem and cerebral swallowing control regions. Peripheral sensory inputs are necessary for safe and efficient swallowing, and their importance to the patterned components of swallowing has been demonstrated. However, the role of sensory inputs to the cerebral system during volitional swallowing is less clear. We used four conditions applied during functional magnetic resonance imaging to differentiate between sensory, motor planning, and motor execution components for cerebral control of swallowing. Oral air pulse stimulation was used to examine the effect of sensory input, covert swallowing was used to engage motor planning for swallowing, and overt swallowing was used to activate the volitional swallowing system. Breath-holding was also included to determine whether its effects could account for the activation seen during overt swallowing. Oral air pulse stimulation, covert swallowing and overt swallowing all produced activation in the primary motor cortex, cingulate cortex, putamen and insula. Additional regions of the swallowing cerebral system that were activated by the oral air pulse stimulation condition included the primary and secondary somatosensory cortex and thalamus. Although air pulse stimulation was on the right side only, bilateral cerebral activation occurred. On the other hand, covert swallowing minimally activated sensory regions, but did activate the supplementary motor area and other motor regions. Breath-holding did not account for the activation during overt swallowing. The effectiveness of oral-sensory stimulation for engaging both sensory and motor components of the cerebral swallowing system demonstrates the importance of sensory input in cerebral swallowing control.

Whispering dysphonia (DYT4 dystonia) is caused by a mutation in the TUBB4 gene

A study was undertaken to identify the gene underlying DYT4 dystonia, a dominantly inherited form of spasmodic dysphonia combined with other focal or generalized dystonia and a characteristic facies and body habitus, in an Australian family.

Human Brain Activation during Phonation and Exhalation: Common Volitional Control for Two Upper Airway Functions

Phonation is defined as a laryngeal motor behavior used for speech production, which involves a highly specialized coordination of laryngeal and respiratory neuromuscular control. During speech, brief periods of vocal fold vibration for vowels are interspersed by voiced and unvoiced consonants, glottal stops and glottal fricatives (/h/). It remains unknown whether laryngeal/respiratory coordination of phonation for speech relies on separate neural systems from respiratory control or whether a common system controls both behaviors. To identify the central control system for human phonation, we used event-related fMRI to contrast brain activity during phonation with activity during prolonged exhalation in healthy adults. Both whole-brain analyses and region of interest comparisons were conducted. Production of syllables containing glottal stops and vowels was accompanied by activity in left sensorimotor, bilateral temporoparietal and medial motor areas. Prolonged exhalation similarly involved activity in left sensorimotor and temporoparietal areas but not medial motor areas. Significant differences between phonation and exhalation were found primarily in the bilateral auditory cortices with whole-brain analysis. The ROI analysis similarly indicated task differences in the auditory cortex with differences also detected in the inferolateral motor cortex and dentate nucleus of the cerebellum. A second experiment confirmed that activity in the auditory cortex only occurred during phonation for speech and did not depend upon sound production. Overall, a similar central neural system was identified for both speech phonation and voluntary exhalation that primarily differed in auditory monitoring.

Abnormal Activation of the Primary Somatosensory Cortex in Spasmodic Dysphonia: An fMRI Study

Spasmodic dysphonia (SD) is a task-specific focal dystonia of unknown pathophysiology, characterized by involuntary spasms in the laryngeal muscles during speaking. Our aim was to identify symptom-specific functional brain activation abnormalities in adductor spasmodic dysphonia (ADSD) and abductor spasmodic dysphonia (ABSD). Both SD groups showed increased activation extent in the primary sensorimotor cortex, insula, and superior temporal gyrus during symptomatic and asymptomatic tasks and decreased activation extent in the basal ganglia, thalamus, and cerebellum during asymptomatic tasks. Increased activation intensity in SD patients was found only in the primary somatosensory cortex during symptomatic voice production, which showed a tendency for correlation with ADSD symptoms. Both SD groups had lower correlation of activation intensities between the primary motor and sensory cortices and additional correlations between the basal ganglia, thalamus, and cerebellum during symptomatic and asymptomatic tasks. Compared with ADSD patients, ABSD patients had larger activation extent in the primary sensorimotor cortex and ventral thalamus during symptomatic task and in the inferior temporal cortex and cerebellum during symptomatic and asymptomatic voice production. The primary somatosensory cortex shows consistent abnormalities in activation extent, intensity, correlation with other brain regions, and symptom severity in SD patients and, therefore, may be involved in the pathophysiology of SD.

Functional but not structural networks of the human laryngeal motor cortex show left hemispheric lateralization during syllable but not breathing production

The laryngeal motor cortex (LMC) is indispensible for the vocal motor control of speech and song production. Patients with bilateral lesions in this region are unable to speak and sing, although their nonverbal vocalizations, such as laughter and cry, are preserved. Despite the importance of the LMC in the control of voluntary voice production in humans, the literature describing its connections remains sparse. We used diffusion tensor probabilistic tractography and functional magnetic resonance imaging-based functional connectivity analysis to identify LMC networks controlling two tasks necessary for speech production: voluntary voice as repetition of two different syllables and voluntary breathing as controlled inspiration and expiration. Peaks of activation during all tasks were found in the bilateral ventral primary motor cortex in close proximity to each other. Functional networks of the LMC during voice production but not during controlled breathing showed significant left-hemispheric lateralization (p < 0.0005). However, structural networks of the LMC associated with both voluntary voice production and controlled breathing had bilateral hemispheric organization. Our findings indicate the presence of a common bilateral structural network of the LMC, upon which different functional networks are built to control various voluntary laryngeal tasks. Bilateral organization of functional LMC networks during controlled breathing supports its indispensible role in all types of laryngeal behaviors. Significant left-hemispheric lateralization of functional networks during simple but highly learned voice production suggests the readiness of the LMC network for production of a complex voluntary behavior, such as human speech.

Functional neuroanatomy of human voluntary cough and sniff production

Cough and sniff are both spontaneous respiratory behaviors that can be initiated voluntarily in humans. Disturbances of cough may be life threatening, while inability to sniff impairs the sense of smell in neurological patients. Cortical mechanisms of voluntary cough and sniff production have been predicted to exist; however, the localization and function of supramedullary areas responsible for these behaviors are poorly understood. We used functional magnetic resonance imaging to identify the central control of voluntary cough and sniff compared with breathing. We determined that both voluntary cough and sniff require a widespread pattern of sensorimotor activation along the Sylvian fissure convergent with voluntary breathing. Task-specific activation occurred in a pontomesencephalic region during voluntary coughing and in the hippocampus and piriform cortex during voluntary sniffing. Identification of the localization of cortical activation for cough control in humans may help potential drug development to target these regions in patients with chronic cough. Understanding the sensorimotor sniff control mechanisms may provide a new view on the cerebral functional reorganization of olfactory control in patients with neurological disorders.

Abnormal Structure–Function Relationship in Spasmodic Dysphonia

Spasmodic dysphonia (SD) is a primary focal dystonia characterized by involuntary spasms in the laryngeal muscles during speech production. Although recent studies have found abnormal brain function and white matter organization in SD, the extent of gray matter alterations, their structure-function relationships, and correlations with symptoms remain unknown. We compared gray matter volume (GMV) and cortical thickness (CT) in 40 SD patients and 40 controls using voxel-based morphometry and cortical distance estimates. These measures were examined for relationships with blood oxygen level-dependent signal change during symptomatic syllable production in 15 of the same patients. SD patients had increased GMV, CT, and brain activation in key structures of the speech control system, including the laryngeal sensorimotor cortex, inferior frontal gyrus (IFG), superior/middle temporal and supramarginal gyri, and in a structure commonly abnormal in other primary dystonias, the cerebellum. Among these regions, GMV, CT and activation of the IFG and cerebellum showed positive relationships with SD severity, while CT of the IFG correlated with SD duration. The left anterior insula was the only region with decreased CT, which also correlated with SD symptom severity. These findings provide evidence for coupling between structural and functional abnormalities at different levels within the speech production system in SD.

Dopamine regulation of human speech and bird song: A critical review

To understand the neural basis of human speech control, extensive research has been done using a variety of methodologies in a range of experimental models. Nevertheless, several critical questions about learned vocal motor control still remain open. One of them is the mechanism(s) by which neurotransmitters, such as dopamine, modulate speech and song production. In this review, we bring together the two fields of investigations of dopamine action on voice control in humans and songbirds, who share similar behavioral and neural mechanisms for speech and song production. While human studies investigating the role of dopamine in speech control are limited to reports in neurological patients, research on dopaminergic modulation of bird song control has recently expanded our views on how this system might be organized. We discuss the parallels between bird song and human speech from the perspective of dopaminergic control as well as outline important differences between these species.