Mesolimbic dopaminergic dysfunction in Parkinson’s disease depression: evidence from a 123I-FP-CIT SPECT investigation

Frosini, Daniela; Unti, Elisa; Guidoccio, Federica; Gamba, Claudia Del; Puccini, Giulia; Volterrani, Duccio; Bonuccelli, Ubaldo; Ceravolo, Roberto

doi:10.1007/s00702-015-1370-z

Cited by 29 publications

(19 citation statements)

References 19 publications

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“…First of all, 123 I-FP-CIT imaging was able to explore molecular fronto-striatal connectivity, as previously reported 22, 23 . As already mentioned, voxels carrying similar information were grouped by ICA in sources that can be considered as “metabolic” pattern, reflecting a similar 123 I-FP-CIT binding in the different 29 .…”

Section: Discussionmentioning

confidence: 58%

Source-Based Morphometry Multivariate Approach to Analyze [123I]FP-CIT SPECT Imaging

et al. 2017

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Background 123I-FP-CIT (DaTSCAN®) SPECT imaging is widely used to study neurodegenerative parkinsonism, with the evaluation of presynaptic dopamine transporter (DAT) in striatal regions. Beyond DAT, 123I-FP-CIT may be also considered for other monoaminergic systems, in particular serotonin transporter (SERT). Independent Component Analysis (ICA) implemented in Source-Based Morphometry (SBM), a multivariate approach, represents an alternative method to explore monoaminergic neurotransmission, studying the relationship among voxels, and grouping them into “metabolic” neural networks. Methods One-hundred forty-three subjects (84 with Parkinson’s disease (PD) and 59 control individuals (CG)) underwent DATSCAN® imaging. The 123I-FP-CIT binding was evaluated by the multivariate SBM approach, as well as by region-of-interest (ROI) (caudate/putamen) (BRASS software) and whole-brain voxelwise univariate (Statistical Parametric Mapping, SPM) approaches. Results As compared to univariate approaches (BRASS and SPM), which only demonstrated striatal 123I-FP-CIT binding reduction in the PD group, SBM identified six sources of non-artifactual origin, including basal ganglia and cortical regions as well as brainstem. Among them, three sources (basal ganglia and cortical regions) presented loading scores (as index of 123I-FP-CIT binding) significantly different between PD and CG. Notably, even though not significantly different between PD and CG, the remaining three non-artifactual sources were characterized by a predominant frontal, brainstem and occipito-temporal involvement. Discussion The concept of source blind separation by the application of ICA (as implemented in SBM) represents a feasible approach to be considered in 123I-FP-CIT (DaTSCAN®) SPECT imaging. Taking advantage of this multivariate analysis, specific patterns of variance can be identified (involving either striatal or extrastriatal regions) that could be useful in differentiating neurodegenerative parkinsonisms.

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Section: Discussionmentioning

confidence: 58%

Source-Based Morphometry Multivariate Approach to Analyze [123I]FP-CIT SPECT Imaging

et al. 2017

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“…For instance, previous PET studies revealed ACC hypometabolism associated with depression in PD 46, 56 . Depressed PD patients exhibited a specific loss of dopamine and noradrenaline innervation in the ACC 6, 57 . In addition, microstructural changes in the ACC bundles were related to dPD patients 58, 59 .…”

Section: Discussionmentioning

confidence: 99%

Aberrant Intra- and Internetwork Functional Connectivity in Depressed Parkinson’s Disease

Wei

Zhu

et al. 2017

Sci Rep

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Much is known concerning the underlying mechanisms of Parkinson’s disease (PD) with depression, but our understanding of this disease at the neural-system level remains incomplete. This study used resting-state functional MRI (rs-fMRI) and independent component analysis (ICA) to investigate intrinsic functional connectivity (FC) within and between large-scale neural networks in 20 depressed PD (dPD) patients, 35 non-depressed PD (ndPD) patients, and 34 healthy controls (HC). To alleviate the influence caused by ICA model order selection, this work reported results from analyses at 2 levels (low and high model order). Within these two analyses, similar results were obtained: 1) dPD and ndPD patients relative to HC had reduced FC in basal ganglia network (BGN); 2) dPD compared with ndPD patients exhibited increased FC in left frontoparietal network (LFPN) and salience network (SN), and decreased FC in default-mode network (DMN); 3) dPD patients compared to HC showed increased FC between DMN and LFPN. Additionally, connectivity anomalies in the DMN, LFPN and SN correlated with the depression severity in patients with PD. Our findings confirm the involvement of BGN, DMN, LFPN and SN in depression in PD, facilitating the development of more detailed and integrative neural models of PD with depression.

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“…Similarly, PD patients demonstrating executive impairments exhibited lower prefrontal cortex activity as measured by fMRI during a working memory task [42]. An idea that grows out of this insight is that VTA dopamine loss contributes to non-motor symptoms such as depression [43]. Many of the PD patients in pathological studies in the literature, in this and previous studies, die before non-motor symptoms are routinely investigated, thus rendering it impossible to assess the significance of VTA cell loss in PD.…”

Section: Discussionmentioning

confidence: 99%

“…Neuroimaging studies, however have shed some light on this question by documenting abnormalities in mesocortical and mesolimbic circuits. For instance, Frosini et al demonstrated decreased dopaminergic innervation of the anterior cingulate cortex in PD patients with depression as compared to PD patients without depression, measured by dopamine transporter density [43]. Moreover, extensive animal work has indicated that dopamine dysfunction in mesocortical and mesolimbic pathways can consistently impair behaviors that are impaired in PD patients [44].…”

Section: Discussionmentioning

confidence: 99%

The vulnerable ventral tegmental area in Parkinson’s disease

2015

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Introduction The involvement of dopaminergic neurons in the ventral tegmental area (VTA) in Parkinson’s disease (PD) has not been universally recognized by neuroscientists and neurologists. Here, we conduct a review of previous research documenting dopaminergic neuronal loss in both the substantia nigra pars compacta (SNpc) and VTA and add three new post-mortem PD cases to the literature. Methods PD and control brains were sectioned, stained for tyrosine hydroxylase, and cells in the SNpc and VTA were counted. Results Based on the review, we report two main results: 1) the VTA does degenerate in PD, and 2) the VTA degenerates less than the SNpc. Conclusion Inconsistent clinical information about these cases limits our ability to interpret how the VTA contributes to PD symptoms. However, our data in combination with prior PD neuropathological cases in the literature unequivocally establish that the VTA is involved in PD, and could be relevant for future investigation of non-motor symptoms in PD.

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Mesolimbic dopaminergic dysfunction in Parkinson’s disease depression: evidence from a 123I-FP-CIT SPECT investigation

Cited by 29 publications

References 19 publications

Source-Based Morphometry Multivariate Approach to Analyze [123I]FP-CIT SPECT Imaging

Source-Based Morphometry Multivariate Approach to Analyze [123I]FP-CIT SPECT Imaging

Aberrant Intra- and Internetwork Functional Connectivity in Depressed Parkinson’s Disease

The vulnerable ventral tegmental area in Parkinson’s disease

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