Principal component analysis of PiB distribution in Parkinson and Alzheimer diseases.

Objective: To use principal component analyses (PCA) of Pittsburgh compound B (PiB) PET imaging to determine whether the pattern of in vivo β-amyloid (Aβ) in Parkinson disease (PD) with cognitive impairment is similar to the pattern found in symptomatic Alzheimer disease (AD).

Methods: PiB PET scans were obtained from participants with PD with cognitive impairment (n = 53), participants with symptomatic AD (n = 35), and age-matched controls (n = 67). All were assessed using the Clinical Dementia Rating and APOE genotype was determined in 137 participants.

A pilot study of basal ganglia and thalamus structure by high dimensional mapping in children with Tourette syndrome.

Background: Prior brain imaging and autopsy studies have suggested that structural abnormalities of the basal ganglia (BG) nuclei may be present in Tourette Syndrome (TS). These studies have focused mainly on the volume differences of the BG structures and not their anatomical shapes.  Shape differences of various brain structures have been demonstrated in other neuropsychiatric disorders using large-deformation, high dimensional brain mapping (HDBM-LD).

A fixed-dose randomized controlled trial of olanzapine for psychosis in Parkinson disease.

Background: Psychosis is a common and debilitating side effect of long-term dopaminergic treatment of Parkinson disease (PD). While clozapine is an effective treatment, the need for blood monitoring has limited its first-line use. 

Objective: Since olanzapine shows similar receptor affinity to clozapine, we hypothesized that it might be an effective alternative to clozapine for treatment of drug-induced psychosis (DIP) in PD, and that lower doses than usual might make it tolerable.

Validity of large-deformation high dimensional brain mapping of the basal ganglia in adults with Tourette syndrome.

The basal ganglia and thalamus may play a critical role for behavioral inhibition mediated by prefrontal, parietal, temporal, and cingulate cortices. The cortico-basal ganglia-thalamo-cortical loop with projections from frontal cortex to striatum, then to globus pallidus or to substantia nigra pars reticulata, to thalamus and back to cortex, provides the anatomical substrate for this function. In-vivo neuroimaging studies have reported reduced volumes in the thalamus and basal ganglia in individuals with Tourette Syndrome (TS) when compared with healthy controls.

Intravenous levodopa administration in humans based on a two-compartment kinetic model.

Levodopa, when combined with a decarboxylase inhibitor, essentially delivers dopamine directly to the brain, with no net effect on brain blood vessels. For future neuroimaging studies of Parkinson disease and Tourette syndrome, we sought to rapidly produce a biologically relevant levodopa concentration in plasma and then maintain that concentration long enough to assess motor, cognitive, emotional, and neuroimaging responses, while minimizing side effects in levodopa-naive individuals. Based on available pharmacokinetic data and a two-compartment model, we designed a decreasing-exponential-rate infusion to meet these goals.

Levodopa challenge neuroimaging of levodopa-related mood fluctuations in Parkinson's disease.

Some patients with advanced Parkinson's disease (PD) develop dose-related fluctuations in mood. This may reflect alterations in dopamine-influenced brain circuits that mediate emotion. However, there is no available information to localize which dopamine-influenced neurons may be most affected.

Cognitive-pharmacologic functional magnetic resonance imaging in tourette syndrome: a pilot study.

Background: Dopamine agonists and antagonists can reduce abnormal movements and vocalizations (tics) in Tourette syndrome (TS); however, dopamine-responsive abnormal function in specific brain regions has not been directly demonstrated in TS. We sought to identify dopamine-modulated brain regions that function abnormally in TS by combining functional magnetic resonance imaging (fMRI), a working memory (WM) task, and infusion of the dopamine prodrug levodopa (while blocking dopamine production outside the brain).

Methods: We obtained complete fMRI data in 8 neuroleptic-naive adults with a chronic tic disorder and in 10 well-matched tic-free control subjects.

Rapid intravenous loading of levodopa for human research: clinical results.

Levodopa has several advantages as a pharmacological challenge agent for human neuroscience research. Exogenous levodopa changes striatal neuronal activity and increases extracellular dopamine concentrations, and with adequate inhibition of peripheral metabolism levodopa does not change mean cerebral blood flow. For neuroimaging studies of Parkinson disease (PD) and Tourette syndrome, we sought to rapidly produce a biologically relevant steady-state levodopa concentration and then maintain that concentration for at least an hour.

Clinical features and comorbidity of mood fluctuations in Parkinson's disease.

Parkinson's disease (PD) patients commonly develop fluctuations in their motor responses to levodopa within several years of initiation of treatment; some also develop nonmotor fluctuations. The authors performed a case-control study comparing the frequency of comorbid symptoms in 70 PD patients who experienced clinically apparent mood changes during their motor "on" or "off" states with two control groups with no mood fluctuations. Mood fluctuators had significantly younger age at onset and longer disease duration and were significantly more likely to have dementia, psychosis, clinical depression, and motor complications.