New on Pubmed this Week

1: J Neurosci Methods. 2009 Feb 15;177(1):20-9. Epub 2008 Sep 26.Click here to read Links
Objective quantification of arm rigidity in MPTP-treated primates.
Mera TO, Johnson MD, Rothe D, Zhang J, Xu W, Ghosh D, Vitek J, Alberts JL.

Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, United States.

Rigidity is a cardinal symptom of Parkinson's disease and is frequently used as an outcome measure in clinical and non-human primate studies examining the effects of medication or surgical intervention. A limitation of current rigidity assessment methods is that they are inherently subjective. To better understand the physiological mechanisms of rigidity and how various therapeutic approaches work, a more objective and quantitative method is needed. In this study, an automated arm rigidity testing (ART) system was developed to objectively quantify rigidity while the primate's limb was moved between two user-specified angles. Recordings of normal force versus elbow-angle were categorized according to area and slope. These quantitative measures of rigidity were investigated in three rhesus macaque monkeys treated with 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine and compared with clinical assessment methods. The ART system incorporates electromyographical recordings that can detect and differentiate active from actual resistance. The ART system detected significant changes in rigidity measures following administration of apomorphine or deep brain stimulation of the globus pallidus internus. The most sensitive measures were total area, extension slope, and flexion slope. The ART system provides precise and reliable measures of rigidity that are objective and quantitative.

2: Synapse. 2009 Feb;63(2):136-46.Links
Subthalamic nucleus stimulation and lesioning have distinct state-dependent effects upon striatal dopamine metabolism.
Walker RH, Koch RJ, Moore C, Meshul CK.

Department of Neurology, James J. Peters Veterans Affairs Medical Center, Bronx, New York.

The mechanism by which deep brain stimulation (DBS) of the subthalamic nucleus (STN) achieves its effects in Parkinson's disease (PD) is not known. In animal models of PD, stimulation and lesioning of the STN have some effects which are the same, but others which differ, in reversing cellular and behavioral changes induced by dopamine depletion. We compared the effects of short-term STN stimulation and lesions upon extracellular levels of dopamine and metabolites using in vivo microdialysis of the dorsal striatum of awake, intact and unilateral 6-hydroxydopamine (6OHDA)-lesioned rats. STN stimulation in control rats decreased striatal dopamine levels and caused a relative increase in dopamine metabolism, as expressed by HVA/dopamine and DOPAC/dopamine ratios. This suggests an increase in both vesicular dopamine release (metabolized to HVA), and release from the cytoplasmic dopamine pool (metabolized to DOPAC). STN lesions in control rats increased the HVA/dopamine ratio, also suggesting a relative increase in vesicular dopamine release. These results indicate that STN stimulation and lesioning can affect striatal dopamine metabolism in the intact system. In 6OHDA-lesioned rats at baseline, metabolic ratios were markedly decreased as compared with controls. STN lesions of 6OHDA-lesioned rats did not affect relative metabolic ratios as compared with baseline levels. In 6-OHDA-lesioned rats, STN stimulation decreased extracellular levels of dopamine, and, to a greater extent, metabolites, resulting in a decrease in metabolic ratios. This further decrease in dopamine turnover with STN stimulation would serve to maintain dopamine levels in the dopamine-depleted striatum, and may account for the therapeutic benefit of DBS in Parkinson's disease. Synapse 63:136-146, 2009. Published 2008 Wiley-Liss, Inc.

PMID: 19021215 [PubMed - in process]

3: Neurosci Lett. 2009 Jan 16;449(3):161-3. Epub 2008 Oct 30.Click here to read Links
Changes of procedural learning in Chinese patients with non-demented Parkinson disease.
Wang XP, Sun BM, Ding HL.

Department of Neurology, Shanghai First People's Hospital, Shanghai Jiao-Tong University, Shanghai 200080, China.

To study procedural learning changes in patients with non-demented Parkinson disease (PD) but without depression. The Nissen serial reaction time task (SRTT) software version II (as a task of procedural learning), the Wechsler Memory Scale-Chinese version (WMS-CR), and two tasks of implicit memory were applied to 20 PD patients with a Hoehn-Yahr score at I-II degrees and 20 matched healthy controls were enrolled for the Nissen Version test. In the explicit WMS-CR and the implicit (word stem completion and degraded picture naming) tasks, the patients' scores fell within normal limits. In the SRTT, healthy controls displayed significantly reduced response times and error rates across the blocks of repeated sequence trials. In contrast, PD patients only showed a reduction in error rates but no change in response times. Impairment of nigrostriatal pathways selectively affects the performance in visuo-motor learning tasks such as the SRTT, but not in both the explicit tasks of WMS-CR and the implicit tasks.