Biomedical subjects

David D Song

Publications and source records attributed to David D Song.

4 recordsLinked to original sources

PubMed2006

Characterizing rule-based category learning deficits in patients with Parkinson's disease.

Parkinson's disease (PD) patients and normal controls were tested in three category learning experiments to determine if previously observed rule-based category learning impairments in PD patients were due to deficits in selective attention or working memory. In Experiment 1, optimal categorization required participants to base their decision on a single stimulus dimension and ignore irrelevant variation on another dimension, thus emphasizing selective attention processes. In Experiment 2, optimal categorization required participants to base their decision on both stimulus dimensions using a conjunction of unidimensional decisions. Thus, this task placed less emphasis on selective attention and more on working memory. In Experiment 3, optimal categorization again required participants to base their decision on both stimulus dimensions using a disjunction of two unidimensional decisions in which an additional verbal operation was needed, thereby placing even greater emphasis on working memory. Results indicated that PD patients were impaired in the unidimensional rule-based condition, but not the other two rule-based conditions. These results are consistent with previous studies that demonstrate that PD patients are impaired in learning rule-based categories when selective attention demands are greatest, whereas these patients are normal in learning rule-based tasks when working memory demands are emphasized. Overall, these findings help to delineate the conditions under which PD patients display rule-based category learning deficits.

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PubMed2005

The impact of irrelevant dimensional variation on rule-based category learning in patients with Parkinson's disease.

This study examined the impact of irrelevant dimensional variation on rule-based category learning in patients with Parkinson's disease (PD), older controls (OC), and younger controls (YC). Participants were presented with 4-dimensional, binary-valued stimuli and were asked to categorize each into 1 of 2 categories. Category membership was based on the value of a single dimension. Four experimental conditions were administered in which there were zero, 1, 2, or 3 randomly varying irrelevant dimensions. Results indicated that patients with PD were impacted to a greater extent than both the OC and YC participants when the number of randomly varying irrelevant dimensions increased. These results suggest that the degree of working memory and selective attention requirements of a categorization task will impact whether PD patients are impaired in rule-based category learning, and help to clarify recent discrepancies in the literature.

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PubMed2005

Information-integration category learning in patients with striatal dysfunction.

Information-integration category learning was examined in patients with Parkinson's disease (PD) and in healthy control participants in 2 different conditions. In the linear condition, optimal categorization required a nonverbalizable linear integration of information from the 2 stimulus dimensions, whereas in the nonlinear condition, a nonlinear integration of information was required. Each participant completed 600 trials in each condition and was given corrective feedback following each trial. Results indicated that PD patients were not impaired in the linear condition across all trials, whereas the same patients were impaired in the nonlinear condition, but only later in training. The authors conducted model-based analyses to identify participants who used an information-integration approach, and a comparison of the accuracy rates of those individuals further revealed a specific deficit in information-integration category learning in patients with PD. These findings suggest that the striatum may be particularly involved in information-integration category learning when the rule is highly complex.

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PubMed2004

Enhanced substantia nigra mitochondrial pathology in human alpha-synuclein transgenic mice after treatment with MPTP.

Recent studies have implicated alpha-synuclein (alpha-S) in the pathogenesis of Parkinson's disease (PD). The mechanisms underlying PD are not completely understood; however, mitochondrial complex I inhibition and oxidative injury may be involved. Because the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a potent complex I inhibitor that can cause oxidative injury and mimic many aspects of PD in treated animals, we sought to determine whether the overexpression of alpha-S in transgenic (tg) mice (alpha-S-tg) would enhance the substantia nigra (SN) pathology resulting from treatment with MPTP. For this purpose, alpha-S-tg mice were produced expressing high levels of wild-type (wt) human alpha-S under the control of the neuron-specific Thy-1 promoter. Alpha-S-tg mice and non-tg controls were treated with MPTP (15 mg/kg ip, twice a week for 2 weeks) or saline (Sal) and then examined 2 weeks after completion of treatment by transmission electron microscopy (EM). We found that alpha-S-tg mice treated with MPTP had extensive mitochondrial alterations, increases in mitochondrial size, filamentous neuritic aggregations, axonal degeneration, and formation of electron dense perinuclear cytoplasmic inclusions in the SN that did not occur in the hippocampus or neocortex, nor in MPTP-treated non-tg mice or Sal-treated alpha-S-tg mice. These findings support the potential involvement of alpha-S expression in the vulnerability of SN neurons to toxicity from mitochondrial complex I inhibitors and the subsequent development of neurodegenerative pathology.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗