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author:("hartlin, J.")
1.  Cerebral blood flow responses to dorsal and ventral STN DBS correlate with gait and balance responses in Parkinson disease 
Experimental neurology  2012;241:105-112.
Objectives
The effects of subthalamic nucleus (STN) deep brain stimulation (DBS) on gait and balance vary and the underlying mechanisms remain unclear. DBS location may alter motor benefit due to anatomical heterogeneity in STN. The purposes of this study were to (1) compare effects of DBS of dorsal (D-STN) versus ventral (V-STN) regions on gait, balance and regional cerebral blood flow (rCBF) and (2) examine relationships between changes in rCBF and changes in gait and balance induced by D-STN or V-STN DBS.
Methods
We used a validated atlas registration to locate and stimulate through electrode contacts in D-STN and V-STN regions of 37 people with Parkinson disease. In a within-subjects, double-blind and counterbalanced design controlled for DBS settings, we measured PET rCBF responses in a priori regions of interest and quantified gait and balance during DBS Off, unilateral D-STN DBS and unilateral V-STN DBS.
Results
DBS of either site increased stride length without producing significant group-level changes in gait velocity, cadence or balance. Both sites increased rCBF in subcortical regions and produced variable changes in cortical and cerebellar regions. DBS-induced changes in gait velocity related to premotor cortex rCBF changes during V-STN DBS (r = −0.40, p = 0.03) and to rCBF changes in the cerebellum anterior lobe during D-STN DBS (r = −0.43, p = 0.02).
Conclusions
DBS-induced changes in gait corresponded to rCBF responses in selected cortical and cerebellar regions. These relationships differed during D-STN versus V-STN DBS, suggesting DBS acts through distinct neuronal pathways dependent on DBS location.
doi:10.1016/j.expneurol.2012.12.003
PMCID: PMC3570746  PMID: 23262122
deep brain stimulation; gait; positron emission tomography; Parkinson disease; subthalamic nucleus
2.  Amyloid imaging of Lewy body-associated disorders 
Background
Clinicopathologic studies of Parkinson disease dementia (PDD) and dementia with Lewy bodies (DLB) commonly reveal abnormal β-amyloid deposition in addition to diffuse Lewy bodies (α-synuclein aggregates), but the relationship among these neuropathologic features and the development of dementia in these disorders remains uncertain.
Objective
To determine whether amyloid-βdeposition detected by PET imaging with Pittsburgh Compound B (PIB) distinguishes clinical subtypes of Lewy body-associated disorders.
Methods
Nine healthy controls (HC), eight PD with no cognitive impairment (PD-noCI), nine PD with mild cognitive impairment (PD-MCI), six dementia with Lewy bodies (DLB) and fifteen PD with dementia (PDD) patients underwent [11C]-PIB PET imaging, clinical examination, and cognitive testing. The binding potential (BP) of PIB for predefined regions and the mean cortical BP (MCBP) were calculated for each participant. Annual longitudinal follow-up and postmortem examinations were performed on a subset of participants.
Results
Regional PIB BPs and the proportion of individuals with abnormally elevated MCBP were not significantly different across participant groups. Elevated PIB binding was associated with worse global cognitive impairment in participants with Lewy body disorders but was not associated with any other clinical or neuropsychological features, including earlier onset or faster rate of progression of cognitive impairment.
Conclusions
These results suggest that the presence of fibrillar amyloid-βdoes not distinguish between clinical subtypes of Lewy body-associated disorders, although larger numbers are needed to more definitively rule out this association. Amyloid-βmay modify the severity of global cognitive impairment in individuals with Lewy body-associated dementia.
doi:10.1002/mds.23393
PMCID: PMC2978796  PMID: 20922808
Parkinson’s disease; Parkinson’s disease with dementia; Dementia with Lewy bodies; PET
3.  In vivo amyloid imaging in autopsy-confirmed Parkinson disease with dementia 
Neurology  2010;74(1):77-84.
Objective:
To investigate the specificity of in vivo amyloid imaging with [11C]–Pittsburgh Compound B (PIB) in Parkinson disease dementia (PDD).
Methods:
We performed detailed neuropathologic examination for 3 individuals with PDD who had PIB PET imaging within 15 months of death.
Results:
We observed elevated cortical uptake of [11C]-PIB on in vivo PET imaging in 2 of the 3 cases. At autopsy, all 3 individuals had abundant cortical Lewy bodies (Braak PD stage 6), and were classified as low-probability Alzheimer disease (AD) based on NIA-Reagan criteria. The 2 PIB-positive individuals had abundant diffuse Aβ plaques but only sparse neuritic plaques and intermediate neurofibrillary tangle pathology. The PIB-negative individual had rare diffuse plaques, no neuritic plaques, and low neurofibrillary tangle burden.
Conclusions:
[11C]–Pittsburgh Compound B (PIB) PET is specific for fibrillar Aβ molecular pathology but not for pathologic diagnosis of comorbid Alzheimer disease in individuals with Parkinson disease dementia. The ability to specifically identify fibrillar Aβ amyloid in the setting of α-synucleinopathy makes [11C]-PIB PET a valuable tool for prospectively evaluating how the presence of Aβ amyloid influences the clinical course of dementia in patients with Lewy body disorders.
GLOSSARY
= Alzheimer disease;
= binding potentials;
= Clinical Dementia Rating;
= dementia of the Alzheimer type;
= dementia with Lewy bodies;
= distribution volume;
= Mental State Examination;
= Neuropsychiatric Inventory Questionnaire;
= Parkinson disease dementia;
= Pittsburgh Compound B;
= Unified Parkinson's Disease Rating Scale.
doi:10.1212/WNL.0b013e3181c7da8e
PMCID: PMC2809026  PMID: 20038776
4.  Subthalamic nucleus stimulation-induced regional blood flow responses correlate with improvement of motor signs in Parkinson disease 
Brain  2008;131(10):2710-2719.
Deep brain stimulation of the subthalamic nucleus (STN DBS) improves motor symptoms in idiopathic Parkinson's disease, yet the mechanism of action remains unclear. Previous studies indicate that STN DBS increases regional cerebral blood flow (rCBF) in immediate downstream targets but does not reveal which brain regions may have functional changes associated with improved motor manifestations. We studied 48 patients with STN DBS who withheld medication overnight and underwent PET scans to measure rCBF responses to bilateral STN DBS. PET scans were performed with bilateral DBS OFF and ON in a counterbalanced order followed by clinical ratings of motor manifestations using Unified Parkinson Disease Rating Scale 3 (UPDRS 3). We investigated whether improvement in UPDRS 3 scores in rigidity, bradykinesia, postural stability and gait correlate with rCBF responses in a priori determined regions. These regions were selected based on a previous study showing significant STN DBS-induced rCBF change in the thalamus, midbrain and supplementary motor area (SMA). We also chose the pedunculopontine nucleus region (PPN) due to mounting evidence of its involvement in locomotion. In the current study, bilateral STN DBS improved rigidity (62%), bradykinesia (44%), gait (49%) and postural stability (56%) (paired t-tests: P < 0.001). As expected, bilateral STN DBS also increased rCBF in the bilateral thalami, right midbrain, and decreased rCBF in the right premotor cortex (P < 0.05, corrected). There were significant correlations between improvement of rigidity and decreased rCBF in the SMA (rs = –0.4, P < 0.02) and between improvement in bradykinesia and increased rCBF in the thalamus (rs = 0.31, P < 0.05). In addition, improved postural reflexes correlated with decreased rCBF in the PPN (rs = –0.38, P < 0.03). These modest correlations between selective motor manifestations and rCBF in specific regions suggest possible regional selectivity for improvement of different motor signs of Parkinson's disease.
doi:10.1093/brain/awn179
PMCID: PMC2724898  PMID: 18697909
Parkinson's disease; deep brain stimulation; subthalamic nucleus; pedunculopontine nucleus; positron emission tomography

Results 1-4 (4)