The overall goal of this research is to investigate the nature of cerebellar involvement in cognitive function, using functional MRI (fMRI), transcranial magnetic stimulation (TMS), and concurrent TMS/fMRI. Cerebellar activation has been found in a wide variety of cognitive tasks, including verbal fluency, conceptual reasoning, planning, and theory of mind. Although a number of theories of cerebellar involvement in cognition have been proposed, there is no consensus to date on a specific operation that is provided by the cerebellum that contributes to cognitive function. In addition some cerebellar researchers question whether cognitive-related cerebellar activations are contaminated by incidental motor movements, e.g., movements of the eyes, or movements of articulation. In this project we address these issues using verbal working memory, which reliably and robustly elicits cerebellar activation, as a model cognitive system. Verbal working memory is a fundamental cognitive function with a strong theoretical framework. We propose that the cerebellum can be integrated into this framework: Our studies to date have supported a cerebro-cerebellar verbal working memory model that emphasizes a functional link between neocortical articulatory control regions, such as premotor cortex/Broca's Area, to the superior cerebellum, and a second network that links neocortical substrates of phonological storage, located in inferior parietal regions, to the inferior cerebellum. Our first specific aim is to test these circuitry assumptions using novel concurrent TMS/fMRI investigations that employ our newly developed and published methods for precisely identifying in the scanner the stimulation site and TMS trajectory in the brain. Our second specific aim is to assess the contribution of incidental motor function to cerebellar activation during verbal working memory by systematically varying the eye movement, articulatory movement, and finger movement requirements during verbal working memory to determine if these motor functions can explain working memory-load-dependent activations in the cerebellum.
Our third aim i s to evaluate alternative theoretical explanations of the fundamental computation underlying cerebellar cognitive activations, using verbal working memory as our model system. Our verbal working memory protocol, the Sternberg Task, contains a number of components that have been theorized by different researchers to be fundamental to cerebellar function. These components include sensory acquisition, timing, sequence deviation detection, and forward modeling/error correction. The experiments in this project will examine the contribution of these different components to verbal working memory elicited cerebellar activations. The impact of this project is that the results will help us understand the fundamental functions(s) that the cerebellum provides in cognition. This understanding is essential for interpreting both the numerous functional neuroimaging studies that show cerebellar activation in well controlled cognitive tasks, as well as the patterns of cognitive deficits observed in cerebellar patients.

Public Health Relevance

Both patient and neuroimaging studies suggest involvement of the cerebellum in cognition, but there is no consensus on what function the cerebellum might be performing. The experiments in this proposal will use advanced neuroimaging methods and a fundamental cognitive task, verbal working memory, to evaluate different theories of cerebellar function. The results will enhance understanding of how the cerebellum supports cognition, and will provide insight on possible rehabilitation strategies for cerebellar patients.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Neurobiology of Learning and Memory Study Section (LAM)
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Rossi, Andrew
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Johns Hopkins University
Schools of Medicine
United States
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Rentiya, Zubir; Khan, Noore-Sabah; Ergun, Ezgi et al. (2017) Distinct cerebellar regions related to motor and cognitive performance in SCA6 patients. Neuropsychologia 107:25-30
Peterburs, Jutta; Cheng, Dominic T; Desmond, John E (2016) The Association Between Eye Movements and Cerebellar Activation in a Verbal Working Memory Task. Cereb Cortex 26:3802-13
Peterburs, Jutta; Desmond, John E (2016) The role of the human cerebellum in performance monitoring. Curr Opin Neurobiol 40:38-44