Investigating the human sensory brainstem with MRI
Auditory decision making critically depends upon structural connections between superior temporal cortex and dorsal striatum. Auditory corticostriatal connections have been mapped in animal models including non-human primates, where primary auditory cortex preferentially connects to putamen while caudate head receives most of its inputs from anterior superior temporal cortex. Using a publicly available high-quality, high-resolution human diffusion-weighted MRI dataset, we identified structural connectivity streamlines between auditory cortical regions and dorsal striatal regions that suggest a privileged route from speech-related auditory cortex to posterior putamen (Sitek, Helou, and Chandrasekaran, 2022 preprint).
Dorsal striatum has a clear role for auditory behavior in animal models, but its involvement in human communication is poorly understood. Using ultra-high field 7T MRI, we are acquiring 1.5 mm isotropic resolution BOLD functional MRI from participants who categorized Mandarin speech stimuli on the basis of dynamically varying pitch patterns. With multivariate pattern analysis, we find that dorsal striatum strongly predicts the stimulus category in native Mandarin speakers but is less accurate in Mandarin-naive participants. Overall, our work demonstrates prioritized connectivity between superior temporal cortex and putamen and is highly suggestive of distinct functional roles for striatal subdivisions in auditory speech categorization.
The computational power of the brain comes from its incredible interconnectedness. To study brain connectivity in living humans, we can estimate structural connectivity using diffusion-weighted MRI tractography, and we can estimate functional connectivity using functional MRI. I used tractography to map the subcortical auditory system in both typical participants and in a post mortem sample (Sitek & Gulban et al., 2019).
To study whole-brain connectivity in persistent developmental stuttering, I used both tractography and functional connectivity and found that long-range functional connectivity between orbitofrontal cortex and cerebellum was strongly negatively correlated with stuttering severity in adults (Sitek et al., 2016).
Much of our knowledge of the brainstem comes from research conducted in animal models. While a lot of brainstem anatomy is the same across mammals, there are species-specific anatomy features that are difficult to study in humans due to technical challenges. I have used state-of-the-art imaging techniques of post mortem human brains to bridge the gap between animal models and research with typical human participants. With Faruk Gulban and others, I published the first publicly available 3-D atlases of human auditory brainstem structures based on post mortem MRI and histology (Sitek & Gulban et al., 2019).
We are currently examining vasculature in the human dorsal midbrain (superior colliculus and inferior colliculus) to better understand how vasculature may influence the functional MRI signal.
To learn more about brainstem anatomy in living humans, I have used “quantitative” MRI methods to estimate specific brain tissue properties (Sitek & Ghosh, 2020 OHBM poster). Tissue characteristics were consistent across individuals and within individuals across different sessions, demonstrating the applicability of quantitative MRI in studying the human brainstem.
In future work, I will quantify anatomical tissue properties in human brainstem within individual structures (for instance, in the layers of the superior colliculus).
While we speak, our brains are not only generating the motor commands for speech—they’re also listening to the sounds we’re creating to make sure we’re saying what we intended to say. This processing is accentuated when the auditory feedback given to the participant is altered to be different from what was produced, but we wanted to know if it varies based on the natural variability of speech production. I looked at the brain’s natural electrical signals using EEG during speech production and playback and found that auditory cortex is more active when a repeated utterance is very different from the previous example of that utterance (Sitek et al., 2013).
Speech production is affected by a variety of factors, including a speaker’s mental state. Using functional MRI, I investigated how emotional speech is processed in the brains of typical individuals and in those with major depressive disorder (MDD) (Sitek et al., 2017 SNL poster). Depressed individuals showed greater activation of motor and limbic cortical regions and altered connectivity of the right insula, a major cortical hub.
Researching the human brainstem is challenging due to the small size of specific structures, their close proximity, and their location deep within the brain. In collaboration with Faruk Gulban (Sitek & Gulban et al., 2019), we identified the major subcortical auditory structures in each individual participant using functional MRI, providing methods for future investigations into more specific auditory processing and how it’s affected by hearing disorders.
The superior colliculus is an important subcortical structure for creating visual maps of the world, incorporating information from multiple sensory modalities, including hearing and touch. In collaboration with the Max Planck Institute for Biological Cybernetics in Tübingen, Germany, I investigated somatovisual processing in human superior colliculus with ultra-high field 9.4 Tesla functional MRI (Sitek et al., 2020 OHBM poster). I found that visual attention in superior colliculus is modulated by tactile information (air puffs to the fingers), and that multisensory information may be represented deeper in colliculus. I will next investigate auditory–visual processing in superior colliculus to find out how these sensory modalities interact.