Parkinson’s Disease as a Disconnection Syndrome

Department of Psychology, Boston University, 648 Beacon Street, Boston, MA 02215, USA.
Neuropsychology Review (Impact Factor: 4.59). 04/2010; 20(2):191-208. DOI: 10.1007/s11065-010-9128-8
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Parkinson's disease (PD) is a major neurodegenerative disorder that is usually considered in terms of midbrain and basal ganglia dysfunction. Regarding PD instead as a disconnection syndrome may prove beneficial to understanding aspects of cognition, perception, and other neuropsychological domains in the disease. PD is usually of unilateral onset, providing evidence of intrahemispheric dissociations and an imbalance in the usual relative strengths of the right and left hemispheres. Hence, in order to appreciate the neuropsychology of PD, it is important to apply to this disease our understanding of hemispheric lateralization effects and within-hemisphere circuitry from brainstem to higher-order association cortex. The focus of this review is on the relevance of PD-related disconnections among subcortical and cortical structures to cognition, perception, emotion, and associated brainstem-based domains such as sleep and mood disturbance. Besides providing information on disease characteristics, regarding PD as a disconnection syndrome allows us to more completely understand normal brain-behavior relations in general.

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    • "However, the inter-hemispheric coordination in PD is still an unexplored field. PD is usually of unilateral onset, providing evidence of inter-hemispheric dissociations and an imbalance between activity of the left and right hemisphere [9]. Abnormalities in the corpus callosum and widely impaired white matter integrity in the frontal, temporal, and parietal lobes have been reported in PD patients, which may affect inter-hemispheric functional coordination [10] [11] [12]. "
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    ABSTRACT: Background. Abnormalities in white matter integrity and specific functional network alterations have been increasingly reported in patients with Parkinson’s disease (PD). However, little is known about the inter-hemispheric interaction in PD. Methods. Fifty-one drug naive patients with PD and 51 age- and gender-matched healthy subjects underwent resting-state functional magnetic resonance imaging (rs-fMRI) scans. We compared the inter-hemispheric resting-state functional connectivity between patients with PD and healthy controls, using the voxel-mirrored homotopic connectivity (VMHC) approach. Then, we correlated the results from VMHC and clinical features in PD patients. Results. Relative to healthy subject, patients exhibited significantly lower VMHC in putamen and cortical regions associated with sensory processing and motor control (involving sensorimotor and supramarginal cortex), which have been verified to play a critical role in PD. In addition, there were inverse relationships between the UPDRS motor scores and VMHC in the sensorimotor, and between the illness duration and VMHC in the supramarginal gyrus in PD patients. Conclusions. Our results suggest that the functional coordination between homotopic brain regions is impaired in PD patients, extending previous notions about the disconnection of corticostriatal circuit by providing new evidence supporting a disturbance in inter-hemispheric connections in PD.
    07/2015; 2015:1-8. DOI:10.1155/2015/692684
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    • "Therefore, an asymmetrical depletion of dopamine in the substantia nigra lead to asymmetrical dysregulation of the striatum , which may in turn lead to asymmetrical dysfunction of cortical-subcortical circuits. Specific cognitive and neuropsychiatric problems are reported as consequence of side of initial motor onset [25]. Two previous studies showed that PD patients with right onset had higher odds of developing apathy and showed more severe apathy than PD patients with left onset [26] [27]. "
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    ABSTRACT: Apathy is a neuropsychiatric symptom in Parkinson's Disease (PD) which has a negative impact on quality of life and might be related in part to damage of presynaptic dopaminergic system. Little is known about relationship between striatal dopamine levels and apathy in PD patients without dementia and/or depression. The aim of the present study was to investigate the relationship between "pure apathy" and striatal dopamine uptake in untreated, drug-naïve PD patients without clinically significant dementia and/or depression. Fourteen PD patients with pure apathy and 14 PD patients without apathy, matched for age, side of motor symptoms at onset, motor disability and disease duration, underwent both neuropsychological and behavioral examination including self-rated version of the Apathy Evaluation Scale (AES-S). All patients underwent 123 I-FP-CIT (DaT-SCAN) SPECT to assess dopamine transporter (DAT) striatal uptake. PD patients with apathy showed lower DAT levels in the striatum than non-apathetic patients. After Bonferroni correction the difference between groups was significant in the right caudate. Apathy is associated with reduced striatal dopamine transporter levels, independent of motor disability and depression in non-demented PD patients. These findings suggest that dysfunction of dopaminergic innervation in the striatum and particularly in the right caudate may contribute to development of apathy in early PD. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Parkinsonism & Related Disorders 02/2015; 21(5). DOI:10.1016/j.parkreldis.2015.02.015 · 3.97 Impact Factor
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    • "Similarly, a recent cross-sectional study showed that compared to healthy controls and PD patients without cognitive symptoms, PD-MCI patients showed more distributed WM abnormalities in anterior and posterior parts of the brain (e.g., the corona radiata and the uncinated fasciculus) [15]. Given these findings, PD may be considered a disconnection syndrome, implying axonal dysfunction of white matter [16], which however, has not been adequately investigated [17]. Previous neuroimaging studies mainly were cross-sectional without follow-up scans, therefore determining if volumetric reduction is a stable hallmark or only a manifestation of late stage of disease, could not be elucidated. "
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    ABSTRACT: Existing literature on brain volumetric alterations in patients with Parkinson's disease (PD) have mainly focused on gray matter (GM) and are largely cross-sectional. Little is known about white matter (WM) volumetric features and their impact on cognitive symptoms in PD. Therefore, the present study aims to examine both GM and WM volumes of cognitively asymptomatic PD patients with a longitudinal design. A total of 42 cognitively asymptomatic patients with early stage PD were recruited and followed up for 1.5 years. At follow-up, 12 patients progressed to mild cognitive impairment (MCI) and were classified as "converters" while the remaining 30 patients remained cognitively asymptomatic and were classified as "non-converters". All patients underwent clinical and neuropsychological assessments as well as MRI scans at baseline and at follow-up. At baseline, non-converters and converters had comparable cognitive scores. At follow-up, converters showed more deficits in frontal-related cognitive function than non-converters. Volumetric analyses revealed that converters had more longitudinal reduction in WM, but not GM, volume compared to non-converters. The decreased volumes among converters were mainly localized in the frontal areas. Moreover, baseline global WM volume significantly predicted conversion to PD-MCI, while baseline GM and WM volumes of the frontal and parietal regions were associated with frontal cognitive changes across time. PD patients who develop MCI demonstrate longitudinal reduction in WM volume, especially in the frontal areas. While both regional GM and WM volumes associate with frontal cognitive decline, baseline global WM volume may be a neuroimaging marker of conversion to PD-MCI. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Parkinsonism & Related Disorders 02/2015; 21(5). DOI:10.1016/j.parkreldis.2015.02.014 · 3.97 Impact Factor
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