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NEURAL SUBSTRATES ASSOCIATED WITH CONTEXT-DEPENDENT LEARNING by Ya-Yun (Alice) Lee A Dissertation Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (BIOKINESIOLOGY) December 2013 Copyright 2013 Ya-Yun (Alice) Lee
|Title||Neural substrates associated with context-dependent learning|
|Author||Lee, Ya-Yun (Alice)|
|Degree||Doctor of Philosophy|
|Degree program||Biokinesiology and Physical Therapy|
|School||School of Dentistry|
|Advisor (committee chair)||Fisher, Beth E.|
|Advisor (committee member)||
Winstein, Carolee J.
Gordon, James G.
Petzinger, Giselle M.
Zelinski, Elizabeth M.
|Abstract||This dissertation is designed to investigate neural substrates associated with context-dependent learning. Context-dependent learning is a phenomenon in which people demonstrate superior performance in the environmental context where they originally learned a motor task and conversely, do not perform as well if the task is carried out in a novel context. While context-dependent learning has been mostly established in healthy young adults, it has not been systematically investigated in people with neurological disorders or non-disabled older adults. In addition, the neural substrates associated with context-dependent learning for motor skill acquisition are not well understood. One neural network that could potentially be associated with context-dependent learning is the frontostriatal circuit – recurrent neural connections between the dorsolateral prefrontal cortex (DLPFC) and the dorsal striatum. Animal and computer simulation studies have suggested that the frontostriatal circuit is important for selecting an appropriate movement plan according to environmental stimuli. While the DLPFC encodes all contextual information associated with a task, the dorsal striatum selects and filters task relevant information in order to generate the most appropriate action plan. Based on this proposed function of the frontostriatal circuit in processing contextual information, we hypothesized that the neuronal interactions between the DLPFC and dorsal striatum within the frontostriatal circuit could be important for mediating context-dependent learning. Therefore, three studies were designed in this dissertation to test this hypothesis. ❧ In the first study, we recruited individuals with Parkinson’s disease (PD), known to have striatum impairments, to test the hypothesis that striatum is a potential neural substrate for context-dependent learning. Ten individuals with PD and 10 age-matched non-disabled adults were recruited into the PD group and the Control group. The study was conducted over two consecutive days approximately 24 hours apart. On the first day, participants practiced a finger sequence task consisting of 3 numerical sequences. Unknown to the participants, each sequence was embedded within a specific colored circle and a specific location on the computer screen. On the second day, the participants were tested under two testing conditions: SWITCH and SAME conditions. Under the SWITCH condition, the context associated with each sequence was changed from that of practice; while under the SAME condition, the sequence-context association remained the same as practice. The primary outcome measure was total time accuracy cost (TTAC), which took both movement speed and accuracy into account. From the second day testing conditions, switch cost was calculated to indicate context-dependent learning. Switch cost was the TTAC performance difference between the SWITCH and SAME conditions normalized by the SAME condition (100 % × [SWITCH − SAME] / SAME). A larger switch cost value would indicate greater context-dependent learning. The results showed that individuals with PD and non-disabled adults demonstrated comparable learning of the finger sequence task when tested under the SAME condition. When tested under the SWITCH condition, participants in both groups showed a decrement in motor performance. However, individuals with PD demonstrated a significantly greater decrement in motor performance than the control participants, leading to a higher TTAC switch cost. Additional analysis of the switch cost showed that when the sequence-context association was switched, participants with PD engaged in additional planning while executing subsequent finger presses. ❧ Study 2 was designed to investigate whether the frontostriatal circuit is associated with context-dependent learning. To indicate the integrity of the frontostriatal circuit, set-shifting ability was tested. The participants in Study 1 also participated in this study. After completion of the finger sequence task on the second day, the participants were given the trail making test (TMT) to assess their set-shifting ability. The result of the TMT was correlated with the TTAC switch cost obtained from Study 1. Findings from Study 2 showed that TTAC switch cost was positively correlated with the result of the TMT in people with PD, suggesting that an individual with PD who had greater difficulty performing set-shifting also demonstrated greater context-dependency. However, this relationship was not observed in non-disabled adults. The results of Study 2 suggested that context-dependent learning could be related to the integrity of the frontostriatal circuit. ❧ To test the hypothesis that the DLPFC plays a specific role in context-dependent learning, 30 non-disabled adults (age-matched to the participants with PD in Study 1) were recruited for Study 3. The participants were recruited into the Control group, the rTMS DLPFC group and rTMS Vertex group. The participants in the Control group were the same participants in Study 1. Similar to the procedures of Study 1, all participants practiced the finger sequence task on the first day. Before the SWITCH and SAME testing conditions on the second day, the participants in the rTMS DLPFC and rTMS Vertex groups received 1 Hz rTMS over the left DLPFC or the Vertex for 20 minutes. The rTMS DLPFC group demonstrated a reduced TTAC switch cost when compared to the Control group or the rTMS Vertex group, suggesting that perturbation to the DLPFC reduced context-dependent learning compared to the control conditions. ❧ Overall, findings from these three studies suggest that the neuronal interaction between the DLPFC and the striatum within the frontostriatal circuit have specific roles in context-dependent learning. While impairment of the striatum as exists in PD leads to a heightened context-dependent learning, decreased neuronal excitability of the DLPFC reduces context-dependency. Given these results, it is reasonable to hypothesize that the DLPFC is relatively over-activated in people with PD in order to compensate for the impaired striatum. This over-activation of the DLPFC with excessive encoding may be the cause of greater context-dependency observed in PD. ❧ This dissertation work is clinically relevant. First, the findings from Study 1 suggest that training environment is important for people with PD. When designing a rehabilitation program for individuals with PD, clinicians should consider the training context for the specific motor task. Second, the results of the third study suggest that context-dependent learning could be reduced with low frequency rTMS applied over the DLPFC in non-disabled adults. One interesting future study is to investigate the influence of low frequency rTMS over the DLPFC on context-dependent learning in people with PD.|
|Keyword||context-dependent learning; Parkinson's disease; dorsolateral prefrontal cortex; transcranial magnetic stimulation|
|Part of collection||University of Southern California dissertations and theses|
|Publisher (of the original version)||University of Southern California|
|Place of publication (of the original version)||Los Angeles, California|
|Publisher (of the digital version)||University of Southern California. Libraries|
|Provenance||Electronically uploaded by the author|
|Legacy record ID||usctheses-m|
|Contributing entity||University of Southern California|
|Rights||Lee, Ya-Yun (Alice)|
|Physical access||The author retains rights to his/her dissertation, thesis or other graduate work according to U.S. copyright law. Electronic access is being provided by the USC Libraries in agreement with the author, as the original true and official version of the work, but does not grant the reader permission to use the work if the desired use is covered by copyright. It is the author, as rights holder, who must provide use permission if such use is covered by copyright. The original signature page accompanying the original submission of the work to the USC Libraries is retained by the USC Libraries and a copy of it may be obtained by authorized requesters contacting the repository e-mail address given.|
|Repository name||University of Southern California Digital Library|
|Repository address||USC Digital Library, University of Southern California, University Park Campus MC 7002, 106 University Village, Los Angeles, California 90089-7002, USA|
|Full text||NEURAL SUBSTRATES ASSOCIATED WITH CONTEXT-DEPENDENT LEARNING by Ya-Yun (Alice) Lee A Dissertation Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (BIOKINESIOLOGY) December 2013 Copyright 2013 Ya-Yun (Alice) Lee|