Post on 22-Jan-2016
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J. Vincent Filoteo 1,2, W. Todd Maddox3, David P. Salmon3, Stephanie L. Lessig 1,2, and David D. Song1,2
1VA San Diego Healthcare System; 2University of California San Diego; 3University of Texas at Austin
Apathy and Perceptual Category Learning in Parkinson's Disease: Possible Role of the Ventral Striatum
Apathy is significantly associated with Apathy is significantly associated with cognitive deficits in patients with cognitive deficits in patients with Parkinson's disease (PD) and results in Parkinson's disease (PD) and results in greater impairment than depression alonegreater impairment than depression alone..(1,2)(1,2)
Apathy in PD is also associated with ventral Apathy in PD is also associated with ventral striatal dysfunctionstriatal dysfunction(3)(3), a region known to be , a region known to be involved in reinforcement-based learning.involved in reinforcement-based learning.(4)(4)
No study, however, has examined whether No study, however, has examined whether PD patients with high levels of apathy are PD patients with high levels of apathy are impaired on such tasks.impaired on such tasks.
We examines reinforcement-based learning We examines reinforcement-based learning in high apathy PD patients using an implicit in high apathy PD patients using an implicit category learning task that is believed to category learning task that is believed to rely on striatal dopamine and has been rely on striatal dopamine and has been shown to be sensitive to the cognitive shown to be sensitive to the cognitive deficits observed in PD patients. deficits observed in PD patients. (5) (5)
BACKGROUND
PARTICIPANTS
Sixty seven nondemented PD patients were Sixty seven nondemented PD patients were classified as either having clinical levels of classified as either having clinical levels of apathy (high apathy PD, or PD-HA; n=31) or apathy (high apathy PD, or PD-HA; n=31) or low apathy (low apathy PD, or PD-LA; low apathy (low apathy PD, or PD-LA; n=36) using a cut-off score (n=36) using a cut-off score (>>14) from the 14) from the Apathy Scale (AS) Apathy Scale (AS) (6)(6). Forty four normal . Forty four normal controls (NC) also participated.controls (NC) also participated.
The mean (SD) for age, years of education The mean (SD) for age, years of education (ED), total scores on the Mattis Dementia (ED), total scores on the Mattis Dementia Rating Scale (MDRS) Rating Scale (MDRS) (7)(7) , the AS, and the , the AS, and the Geriatric Depression Scale (GDS) Geriatric Depression Scale (GDS) (8)(8), for the , for the PD-HA, PD-LA, and NC groups are PD-HA, PD-LA, and NC groups are displayed below.displayed below.
PD-HAPD-HA PD-LAPD-LA NCNC
AgeAge 69.669.6 66.266.2 66.766.7(8.0)(8.0) (6.1)(6.1) (8.8)(8.8)
EDED 16.616.6 16.116.1 16.216.2(2.7)(2.7) (2.8)(2.8) (2.5)(2.5)
MDRSMDRS 137.3137.3 138.1138.1 140.3140.3(4.9)(4.9) (3.9)(3.9) (3.6)(3.6)
ASAS 17.317.3 8.78.7 9.09.0(3.2)(3.2) (3.3)(3.3) (5.1)(5.1)
GDSGDS 9.49.4 4.34.3 3.03.0(5.6)(5.6) (4.2)(4.2) (4.1)(4.1)
The reinforcement-based learning task The reinforcement-based learning task administered was an implicit learning task administered was an implicit learning task developed by Ashby and Gott. developed by Ashby and Gott. (9)(9)
Participants were shown stimuli consisting Participants were shown stimuli consisting of Gabor patches (see below) and were of Gabor patches (see below) and were asked to classify each into one of two asked to classify each into one of two categories by pressing one of two computer categories by pressing one of two computer keys. Six, 80 trial blocks were presented.keys. Six, 80 trial blocks were presented.
Following each response, participants were Following each response, participants were given corrective feedback.given corrective feedback.
A sample trial is displayed below.A sample trial is displayed below.
REINFORCEMENT-BASEDLEARNING TASK
1. Aarsland, D., Marsh, L. and Schrag, A. (2009). Neuropsychiatric symptoms in Parkinson's disease. Mov Disord, 24(15): 2175-86.
2. Zgaljardic, D.J., Borod, J.C. , Foldi, N.S. , Rocco, M., Mattis, P.J. , Gordon, M.F., Feigin, A.S. , and Eidelberg, D. (2007). Relationship between self-reported apathy and executive dysfunction in nondemented patients with Parkinson disease. Cogn Behav Neurol, 20(3): 184-92.
3. Remy, P., Doder, M., Lees, A., Turjanski, N. and Brooks, D. (2005). Depression in Parkinson's disease: loss of dopamine and noradrenaline innervation in the limbic system. Brain, 128(Pt 6): 1314-22.
4. Haber, S.N. and Knutson, B. (2010). The reward circuit: linking primate anatomy and human imaging. Neuropsychopharmacology. 35(1): 4-26.
5. Filoteo, J.V., Maddox, W.T., Salmon, D.P., & Song, D.D. (2005). Information integration category learning in patients with striatal dysfunction. Neuropsychology, 19, 212-222.
6. Starkstein, S.E., Mayberg, H.S., Preziosi, T.J. , Andrezejewski, P., Leiguarda, R., and Robinson, R.G. (1992) Reliability, validity, and clinical correlates of apathy in Parkinson's disease. J
Neuropsychiatry Clin Neurosci, 4(2): 134-9.7. Mattis, S., Dementia Rating Scale. 1988, Odessa, FL: Psychological Assessment Resources.8. Yesavage, J.A., Brink, T.L., Rose, T.L., Lum, O., Huang, V., Adey, M., & Leirer, V.O.. (1982). Development and
validation of a geriatic depression screening scale: A preliminary report . J Psychiatr Res, 17(1): 37-39.9. Ashby, F. G., & Gott, R. E. (1988). Decision rules in the perception and categorization of multidimensional stimuli .
Journal of Experimental Psychology: Learning, Memory, and Cognition, 14, 33-53.
REFERENCES
REGRESSION ANALYSES
CONCLUSIONS
The rule that dictated category membership The rule that dictated category membership was a nonlinear relationship between the was a nonlinear relationship between the width and orientation of the bars width and orientation of the bars comprising the Gabor patch.comprising the Gabor patch.
The distribution of stimuli is displayed The distribution of stimuli is displayed below. Open circles represent Category A below. Open circles represent Category A exemplars, and closed circles represent exemplars, and closed circles represent Category B exemplars. Category B exemplars.
AorB?
ResponseCorrect
orWrong
Ori
enta
tion
Spatial Frequency
REINFORCEMENT-BASEDLEARNING RESULTS
Accuracy results are displayed below for Accuracy results are displayed below for the three groups.the three groups.
PD-HA patients were significantly PD-HA patients were significantly impaired in reinforcement-based learning impaired in reinforcement-based learning relative to both PD-LA and NCs, whereas relative to both PD-LA and NCs, whereas the latter two groups did not differ.the latter two groups did not differ.
Several regression analyses indicated that Several regression analyses indicated that apathy levels, but not depression levels, apathy levels, but not depression levels, predicted performance on the predicted performance on the reinforcement-based learning task.reinforcement-based learning task.
Neither apathy or depression predicted Neither apathy or depression predicted performance on the rule-based taskperformance on the rule-based task
PD patients with apathy are impaired in PD patients with apathy are impaired in reinforcement-based learning, but not rule-reinforcement-based learning, but not rule-based learning.based learning.
Although PD patients with apathy also report Although PD patients with apathy also report greater symptoms of depression, depression is greater symptoms of depression, depression is not associated with impaired reinforcement-not associated with impaired reinforcement-based or rule-based learning.based or rule-based learning.
Apathy and impaired reinforcement based Apathy and impaired reinforcement based learning may share the same neural substrate learning may share the same neural substrate and could be due to dysfunction within the and could be due to dysfunction within the ventral striatum.ventral striatum.
Groups did not differ in Age or ED, but PD-Groups did not differ in Age or ED, but PD-HA and PD-LA groups had lower MDRS HA and PD-LA groups had lower MDRS scores than NCs.scores than NCs.
PD-HA had greater AS scores than PD-LA PD-HA had greater AS scores than PD-LA and NCs, whereas both PD groups had and NCs, whereas both PD groups had greater GDS scores than NCs.greater GDS scores than NCs.
RULE-BASED LEARNING TASK
To examine the specificity of the PD-HA To examine the specificity of the PD-HA patients’ deficit, we administered a second patients’ deficit, we administered a second category learning task where subjects had category learning task where subjects had to categorize single line that varied in to categorize single line that varied in length and orientation into one of 4 length and orientation into one of 4 categories. The rule that dictated category categories. The rule that dictated category membership depended on the length of the membership depended on the length of the line and orientation was irrelevant. The line and orientation was irrelevant. The figure below displays the category figure below displays the category exemplars, with squares representing exemplars, with squares representing Category A exemplars, circles Category A exemplars, circles representing Category B exemplars, representing Category B exemplars, closed triangles representing Category C closed triangles representing Category C exemplars, and open triangles exemplars, and open triangles representing Category D exemplars.representing Category D exemplars.
RULE-BASED LEARNING RESULTS
PD-HA and PD-LA differed from controls PD-HA and PD-LA differed from controls but not from one another.but not from one another.