The fluid, seemingly effortless execution of sequences of movements is a ubiquitous feature of everyday motor skills. Ample evidence for their importance comes from the common human neuropathologies (Parkinson's disease, in particular) in which sequential skills are especially impaired. Long-term motor sequencing skills are formed, most likely, across multiple time scales in associative, premotor, and motor circuits of the brain. Recent evidence suggests that for each of these brain circuits, a sub-cortical loop through the basal ganglia (BG) contributes selectively to reinforcement-driven modulation of thalamo-cortical plasticity. These findings lead to the hypothesis that BG loops play central roles in the acquisition of sequence information, but are less important in the recall or use of already-learned sequences.
The specific aims (SAs) of this proposal will test that general hypothesis by using non-human primates: 1) to determine if neurons in the globus pallidus interna (GPi, the primary BG output nucleus for skeletomotor function) preferentially encode sequence information during new learning;and 2) to test whether intact BG circuits are necessary for new sequence learning. Associative loops through the BG may play a greater role in the fast acquisition of flexible goal-directed representations of sequence information while the premotor and motor loops may mediate slow acquisition of habit-like effector-specific representations. We will infer the circuit membership of individual GPi neurons by stimulating different cortical areas and observing the orthodromic inhibitory effects. Animals will perform a discrete sequence production task using novel, familiar and over-trained sequences. SAl will test if neuronal encoding of sequence-specific information in associative, premotor, and motor circuits of GPi reflects the predicted roles of these circuits in learning novel, familiar, and over-trained sequences. SA2 will determine if an interruption of BG output (i.e., GPi inactivation or lesion) selectively impairs training-related improvements in sequence performance. The prediction is that inactivations or lesions in the associative BG circuit will impair novel sequence learning whereas lesions in premotor and motor circuits will block the further refinement and solidification of performance of already-familiar sequences. Results from these experiments will aid in understanding the physiological basis for

Public Health Relevance

TThe proposed work is central to the problem of understanding the mechansims where practice leads to to reorganization of the human motor system in the face of aging, neurodeneration, stroke or brain injury. Understanding these mechansims has an impact on the design of therapies directed at preserving function, developing compensator movements and ultimately, developing novel motor capacity.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
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National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
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University of California Santa Barbara
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Soto, Fabian A; Vucovich, Lauren; Musgrave, Robert et al. (2015) General recognition theory with individual differences: a new method for examining perceptual and decisional interactions with an application to face perception. Psychon Bull Rev 22:88-111
Lawlor, Patrick Nathan; Kalisky, Tomer; Rosner, Robert et al. (2014) Conceptualizing cancer drugs as classifiers. PLoS One 9:e106444
Ashby, F Gregory (2014) Is state-trace analysis an appropriate tool for assessing the number of cognitive systems? Psychon Bull Rev 21:935-46
Devarajan, Karthik; Cheung, Vincent C K (2014) On nonnegative matrix factorization algorithms for signal-dependent noise with application to electromyography data. Neural Comput 26:1128-68
Smith, J David; Johnston, Jennifer J R; Musgrave, Robert D et al. (2014) Cross-modal information integration in category learning. Atten Percept Psychophys 76:1473-84
Acuna, Daniel E; Wymbs, Nicholas F; Reynolds, Chelsea A et al. (2014) Multifaceted aspects of chunking enable robust algorithms. J Neurophysiol 112:1849-56
Fernandes, Hugo L; Stevenson, Ian H; Vilares, Iris et al. (2014) The generalization of prior uncertainty during reaching. J Neurosci 34:11470-84
Klimm, Florian; Bassett, Danielle S; Carlson, Jean M et al. (2014) Resolving structural variability in network models and the brain. PLoS Comput Biol 10:e1003491
Smith, J David; Boomer, Joseph; Zakrzewski, Alexandria C et al. (2014) Deferred feedback sharply dissociates implicit and explicit category learning. Psychol Sci 25:447-57
Barany, Deborah A; Della-Maggiore, Valeria; Viswanathan, Shivakumar et al. (2014) Feature interactions enable decoding of sensorimotor transformations for goal-directed movement. J Neurosci 34:6860-73

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