Motor Skill Learning, Retention, and Control Deficits in Parkinson's Disease

Parkinson's disease, which affects the basal ganglia, is known to lead to various impairments of motor control. Since the basal ganglia have also been shown to be involved in learning processes, motor learning has frequently been investigated in this group of patients. However, results are still inconsistent, mainly due to skill levels and time scales of testing. To bridge across the time scale problem, the present study examined de novo skill learning over a long series of practice sessions that comprised early and late learning stages as well as retention. 19 non-demented, medicated, mild to moderate patients with Parkinson's disease and 19 healthy age and gender matched participants practiced a novel throwing task over five days in a virtual environment where timing of release was a critical element. Six patients and seven control participants came to an additional long-term retention testing after seven to nine months. Changes in task performance were analyzed by a method that differentiates between three components of motor learning prominent in different stages of learning: Tolerance, Noise and Covariation. In addition, kinematic analysis related the influence of skill levels as affected by the specific motor control deficits in Parkinson patients to the process of learning. As a result, patients showed similar learning in early and late stages compared to the control subjects. Differences occurred in short-term retention tests; patients' performance constantly decreased after breaks arising from poorer release timing. However, patients were able to overcome the initial timing problems within the course of each practice session and could further improve their throwing performance. Thus, results demonstrate the intact ability to learn a novel motor skill in non-demented, medicated patients with Parkinson's disease and indicate confounding effects of motor control deficits on retention performance

The relationship of quantitative brain magnetic resonance imaging measures to neuropathologic indexes of human immunodeficiency virus infection.

ObjectiveTo directly examine the relationship between magnetic resonance imaging (MRI) abnormalities and neuropathologic changes in the brains of patients with the acquired immunodeficiency syndrome.DesignA total of 17 brains from patients with acquired immunodeficiency syndrome for which postmortem MRI scans were available were used in this study. Volumes of cortical gray matter, deep gray matter, and abnormal white matter were estimated from the MRIs of the left hemispheres of the formalin-fixed brains from patients with acquired immunodeficiency syndrome using quantitative morphometric techniques. Quantitative estimates of human immunodeficiency virus, gliosis, and neocortical synaptic and dendritic density were obtained from the corresponding right hemispheres. Quantification of human immunodeficiency virus and gliosis was performed on all 17 specimens, while quantification of synaptic and dendritic density was performed on 10 of the 17 specimens.SettingAll specimens were obtained from patients with the acquired immunodeficiency syndrome who underwent autopsy between 1990 and 1992 at the University of California-San Diego Medical Center and the San Diego (Calif) Department of Veterans Affairs Hospital.ResultsNo association was found between MRI volumes and gliosis, a nonspecific marker of central nervous system damage. Significant and regionally specific relationships were obtained, however, between the severity of central nervous system human immunodeficiency virus infection and the MRI volume estimates of gray matter and abnormal white matter. In addition, a significant association was observed between cortical gray matter volumes and cortical synaptic density.ConclusionThese findings indicate that the quantitative morphometric analysis of MRIs in patients may provide sensitive in vivo markers of neuropathologic changes associated with human immunodeficiency virus infection of the brain

The relationship of quantitative brain magnetic resonance imaging measures to neuropathologic indexes of human immunodeficiency virus infection.

ObjectiveTo directly examine the relationship between magnetic resonance imaging (MRI) abnormalities and neuropathologic changes in the brains of patients with the acquired immunodeficiency syndrome.DesignA total of 17 brains from patients with acquired immunodeficiency syndrome for which postmortem MRI scans were available were used in this study. Volumes of cortical gray matter, deep gray matter, and abnormal white matter were estimated from the MRIs of the left hemispheres of the formalin-fixed brains from patients with acquired immunodeficiency syndrome using quantitative morphometric techniques. Quantitative estimates of human immunodeficiency virus, gliosis, and neocortical synaptic and dendritic density were obtained from the corresponding right hemispheres. Quantification of human immunodeficiency virus and gliosis was performed on all 17 specimens, while quantification of synaptic and dendritic density was performed on 10 of the 17 specimens.SettingAll specimens were obtained from patients with the acquired immunodeficiency syndrome who underwent autopsy between 1990 and 1992 at the University of California-San Diego Medical Center and the San Diego (Calif) Department of Veterans Affairs Hospital.ResultsNo association was found between MRI volumes and gliosis, a nonspecific marker of central nervous system damage. Significant and regionally specific relationships were obtained, however, between the severity of central nervous system human immunodeficiency virus infection and the MRI volume estimates of gray matter and abnormal white matter. In addition, a significant association was observed between cortical gray matter volumes and cortical synaptic density.ConclusionThese findings indicate that the quantitative morphometric analysis of MRIs in patients may provide sensitive in vivo markers of neuropathologic changes associated with human immunodeficiency virus infection of the brain

Effects of acute administration of d-amphetamine and haloperidol on procedural learning in man

The effects of an indirect dopamine-agonist, d-amphetamine, and a non-selective dopamine receptor antagonist, haloperidol, were investigated in normal male volunteers using a between-subjects double-blind design in a procedural learning task, thought mainly to involve unconscious/automatic learning. The results showed: (1) d-amphetamine facilitated response speed, whereas haloperidol inhibited it, in comparison to placebo; (2) the linear increase in procedural learning corresponded with pharmacological manipulation of degree of dopaminergic activity, i.e. subjects given haloperidol showed the least, and subjects given d-amphetamine the greatest, procedural learning. The implications of these findings are discussed in relation to investigation of abnormalities of procedural learning processes in schizophrenia