Objective: To investigate the role of the amygdala in motor program selection and timing in Parkinson disease.

Background: PD is characterized by considerable heterogeneity, which might be partially explained by varying capacities for compensation. While increased activation observed in the cerebellum in PD has frequently been considered compensatory, the role of other brain regions, such as the amygdala, has been less frequently explored, despite evidence that the amygdala undergoes significant change in PD [3].

Method: Task-based fMRI data was obtained from 9 healthy subjects and 9 Parkinson patients. Subjects were asked to squeeze a rubber bulb to keep a bar within two parallel “tracks” that were scrolling downward. Squeezing increased the width of a bar. Normally, 10% of the maximum voluntary contraction (MVC) was required to keep the bar within the tracks. Approximately every 10s, there were bifurcations of each track and the subject had to follow either the inside or outside track necessitating squeezing to 5% or 15% of MVC respectively. During the control condition (C), subjects were instructed to simply follow the inside and outside tracks alternately, and the bifurcations came at constant (10s) intervals. In the Timing task (T), the time between bifurcations was jittered randomly. Finally, in the selection task (S), the bifurcations again were constant, but the colour of the bar changed 1s before the bifurcation, which instructed the subject as to what track to take (red=inside, green=outside). We determined which Regions of Interest (ROIs) were robustly activated at the time of bifurcations, contrasting (S-C) and (T-C) tasks. We also used connectivity measures to assess relative connection strengths between ROIs as well as assessed the timing of activation.

Results: All subjects activated the caudate and putamen in both (S-C) and (T-C) contrasts, however only in PD subjects was the amygdala significantly activated. Comparison of ROIs’ time of maximum activation also revealed that amygdala was activated faster in S and T conditions compared to the C task in PD subjects. Similarly in PD, the greatest connectivity was seen to/from amygdala, while in HC the strongest edges were to/from caudate and putamen.

Conclusion: We suggest that PD subjects recruit the amygdala to maintain performance in motor timing and motor program selection.

References: [1] Zetusky, Walter J., Joseph Jankovic, and Francis J. Pirozzolo. “The heterogeneity of Parkinson’s disease: clinical and prognostic implications.” Neurology 35.4 (1985): 522-522. [2] Palmer, Samantha J., et al. “Motor reserve and novel area recruitment: amplitude and spatial characteristics of compensation in Parkinson’s disease.” European Journal of Neuroscience 29.11 (2009): 2187-2196. [3] Braak, H., Braak, E., Yilmazer, D., de Vos, R. A., Jansen, E. N., Bohl, J., & Jellinger, K. (1994). Amygdala pathology in Parkinson’s disease. Acta neuropathologica, 88(6), 493-500. [4] Frank, Michael J., Lauren C. Seeberger, and Randall C. O’reilly. “By carrot or by stick: cognitive reinforcement learning in parkinsonism.” Science 306.5703 (2004): 1940-1943. [5] Tessitore, A., Hariri, A. R., Fera, F., Smith, W. G., Chase, T. N., Hyde, T. M., … & Mattay, V. S. (2002). Dopamine modulates the response of the human amygdala: a study in Parkinson’s disease. Journal of Neuroscience, 22(20), 9099-9103.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/compensatory-amygdala-activity-during-motor-timing-and-selection-in-pd/