Publications

@article{Hoenig2022b,

title = {Clear‐headed into old age: Resilience and resistance against brain aging—A <scp>PET</scp> imaging perspective},

author = {Merle C. Hoenig and Alexander Drzezga},

doi = {10.1111/jnc.15598},

issn = {1471-4159},

year  = {2023},

date = {2023-02-00},

urldate = {2023-02-00},

journal = {Journal of Neurochemistry},

volume = {164},

number = {3},

pages = {325--345},

publisher = {Wiley},

abstract = {<jats:title>Abstract</jats:title><jats:p>With the advances in modern medicine and the adaptation towards healthier lifestyles, the average life expectancy has doubled since the 1930s, with individuals born in the millennium years now carrying an estimated life expectancy of around 100 years. And even though many individuals around the globe manage to age successfully, the prevalence of aging‐associated neurodegenerative diseases such as sporadic Alzheimer’s disease has never been as high as nowadays. The prevalence of Alzheimer’s disease is anticipated to triple by 2050, increasing the societal and economic burden tremendously. Despite all efforts, there is still no available treatment defeating the accelerated aging process as seen in this disease. Yet, given the advances in neuroimaging techniques that are discussed in the current Review article, such as in positron emission tomography (PET) or magnetic resonance imaging (MRI), pivotal insights into the heterogenous effects of aging‐associated processes and the contribution of distinct lifestyle and risk factors already have and are still being gathered. In particular, the concepts of resilience (i.e. coping with brain pathology) and resistance (i.e. avoiding brain pathology) have more recently been discussed as they relate to mechanisms that are associated with the prolongation and/or even stop of the progressive brain aging process. Better understanding of the underlying mechanisms of resilience and resistance may one day, hopefully, support the identification of defeating mechanism against accelerating aging.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36345092,

title = {The Concept of Motor Reserve in Parkinson's Disease: New Wine in Old Bottles?},

author = {Merle C Hoenig and Verena Dzialas and Alexander Drzezga and Thilo van Eimeren},

doi = {10.1002/mds.29266},

issn = {1531-8257},

year  = {2023},

date = {2023-01-01},

journal = {Mov Disord},

volume = {38},

number = {1},

pages = {16--20},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Hoenig2022,

title = {The Concept of Motor Reserve in Parkinson's Disease: New Wine in Old Bottles?},

author = {Merle C. Hoenig and Verena Dzialas and Alexander Drzezga and Thilo van Eimeren},

doi = {10.1002/mds.29266},

issn = {1531-8257},

year  = {2023},

date = {2023-01-00},

urldate = {2023-01-00},

journal = {Movement Disorders},

volume = {38},

number = {1},

pages = {16--20},

publisher = {Wiley},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Katzdobler2022,

title = {Additive value of [18F]PI-2620 perfusion imaging in progressive supranuclear palsy and corticobasal syndrome},

author = {Sabrina Katzdobler and Alexander Nitschmann and Henryk Barthel and Gerard Bischof and Leonie Beyer and Ken Marek and Mengmeng Song and Olivia Wagemann and Carla Palleis and Endy Weidinger and Anne Nack and Urban Fietzek and Carolin Kurz and Jan Häckert and Theresa Stapf and Christian Ferschmann and Maximilian Scheifele and Florian Eckenweber and Gloria Biechele and Nicolai Franzmeier and Anna Dewenter and Sonja Schönecker and Dorothee Saur and Matthias L. Schroeter and Jost-Julian Rumpf and Michael Rullmann and Andreas Schildan and Marianne Patt and Andrew W. Stephens and Thilo van Eimeren and Bernd Neumaier and Alexander Drzezga and Adrian Danek and Joseph Classen and Katharina Bürger and Daniel Janowitz and Boris-Stephan Rauchmann and Sophia Stöcklein and Robert Perneczky and Florian Schöberl and Andreas Zwergal and Günter U. Höglinger and Peter Bartenstein and Victor Villemagne and John Seibyl and Osama Sabri and Johannes Levin and Matthias Brendel and },

doi = {10.1007/s00259-022-05964-w},

issn = {1619-7089},

year  = {2023},

date = {2023-01-00},

journal = {Eur J Nucl Med Mol Imaging},

volume = {50},

number = {2},

pages = {423--434},

publisher = {Springer Science and Business Media LLC},

abstract = {Abstract



                Purpose

                Early after [18F]PI-2620 PET tracer administration, perfusion imaging has potential for regional assessment of neuronal injury in neurodegenerative diseases. This is while standard late-phase [18F]PI-2620 tau-PET is able to discriminate the 4-repeat tauopathies progressive supranuclear palsy and corticobasal syndrome (4RTs) from disease controls and healthy controls. Here, we investigated whether early-phase [18F]PI-2620 PET has an additive value for biomarker based evaluation of 4RTs.

              

                Methods

                Seventy-eight patients with 4RTs (71 ± 7 years, 39 female), 79 patients with other neurodegenerative diseases (67 ± 12 years, 35 female) and twelve age-matched controls (69 ± 8 years, 8 female) underwent dynamic (0–60 min) [18F]PI-2620 PET imaging. Regional perfusion (0.5–2.5 min p.i.) and tau load (20–40 min p.i.) were measured in 246 predefined brain regions [standardized-uptake-value ratios (SUVr), cerebellar reference]. Regional SUVr were compared between 4RTs and controls by an ANOVA including false-discovery-rate (FDR, p < 0.01) correction. Hypoperfusion in resulting 4RT target regions was evaluated at the patient level in all patients (mean value − 2SD threshold). Additionally, perfusion and tau pattern expression levels were explored regarding their potential discriminatory value of 4RTs against other neurodegenerative disorders, including validation in an independent external dataset (n = 37), and correlated with clinical severity in 4RTs (PSP rating scale, MoCA, activities of daily living).

              

                Results

                Patients with 4RTs had significant hypoperfusion in 21/246 brain regions, most dominant in thalamus, caudate nucleus, and anterior cingulate cortex, fitting to the topology of the 4RT disease spectrum. However, single region hypoperfusion was not specific regarding the discrimination of patients with 4RTs against patients with other neurodegenerative diseases. In contrast, perfusion pattern expression showed promise for discrimination of patients with 4RTs from other neurodegenerative diseases (AUC: 0.850). Discrimination by the combined perfusion-tau pattern expression (AUC: 0.903) exceeded that of the sole tau pattern expression (AUC: 0.864) and the discriminatory power of the combined perfusion-tau pattern expression was replicated in the external dataset (AUC: 0.917). Perfusion but not tau pattern expression was associated with PSP rating scale (R = 0.402; p = 0.0012) and activities of daily living (R =  − 0.431; p = 0.0005).

              

                Conclusion

                [18F]PI-2620 perfusion imaging mirrors known topology of regional hypoperfusion in 4RTs. Single region hypoperfusion is not specific for 4RTs, but perfusion pattern expression may provide an additive value for the discrimination of 4RTs from other neurodegenerative diseases and correlates closer with clinical severity than tau pattern expression.

              },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Steidel2022,

title = {Longitudinal trimodal imaging of midbrain-associated network degeneration in Parkinson’s disease},

author = {Kenan Steidel and Marina C. Ruppert and Andrea Greuel and Masoud Tahmasian and Franziska Maier and Jochen Hammes and Thilo van Eimeren and Lars Timmermann and Marc Tittgemeyer and Alexander Drzezga and David J. Pedrosa and Carsten Eggers},

doi = {10.1038/s41531-022-00341-8},

issn = {2373-8057},

year  = {2022},

date = {2022-12-00},

journal = {npj Parkinsons Dis.},

volume = {8},

number = {1},

publisher = {Springer Science and Business Media LLC},

abstract = {AbstractThe prevailing network perspective of Parkinson’s disease (PD) emerges not least from the ascending neuropathology traceable in histological studies. However, whether longitudinal in vivo correlates of network degeneration in PD can be observed remains unresolved. Here, we applied a trimodal imaging protocol combining 18F-fluorodeoxyglucose (FDG)- and 18F-fluoro-L-Dopa- (FDOPA)-PET with resting-state functional MRI to assess longitudinal changes in midbrain metabolism, striatal dopamine depletion and striatocortical dysconnectivity in 17 well-characterized PD patients. Whole-brain (un)paired-t-tests with focus on midbrain or striatum were performed between visits and in relation to 14 healthy controls (HC) in PET modalities. Resulting clusters of FDOPA-PET comparisons provided volumes for seed-based functional connectivity (FC) analyses between visits and in relation to HC. FDG metabolism in the left midbrain decreased compared to baseline along with caudatal FDOPA-uptake. This caudate cluster exhibited a longitudinal FC decrease to sensorimotor and frontal areas. Compared to healthy subjects, dopamine-depleted putamina indicated stronger decline in striatocortical FC at follow-up with respect to baseline. Increasing nigrostriatal deficits and striatocortical decoupling were associated with deterioration in motor scores between visits in repeated-measures correlations. In summary, our results demonstrate the feasibility of in-vivo tracking of progressive network degeneration using a multimodal imaging approach. Specifically, our data suggest advancing striatal and widespread striatocortical dysfunction via an anterior-posterior gradient originating from a hypometabolic midbrain cluster within a well-characterized and only mild to moderately affected PD cohort during a relatively short period.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35943058,

title = {Gray Matter Volume Loss in Proposed Brain-First and Body-First Parkinson's Disease Subtypes},

author = {Magdalena Banwinkler and Verena Dzialas and  and Merle C Hoenig and Thilo van Eimeren},

doi = {10.1002/mds.29172},

issn = {1531-8257},

year  = {2022},

date = {2022-10-01},

journal = {Mov Disord},

volume = {37},

number = {10},

pages = {2066--2074},

abstract = {BACKGROUND: α-Synuclein pathology is associated with neuronal degeneration in Parkinson's disease (PD) and considered to sequentially spread across the brain (Braak stages). According to a new hypothesis of distinct α-synuclein spreading directions based on the initial site of pathology, the "brain-first" spreading subtype would be associated with a more asymmetric cerebral and nigrostriatal pathology than the "body-first" subtype.nnOBJECTIVE: Here, we tested if proposed markers of brain-first PD (ie, higher dopamine transporter [DaT] asymmetry; absence of rapid eye movement sleep behavior disorder [RBD]) are associated with a greater or more asymmetric reduction in gray matter volume (GMV) in comparison to body-first PD.nnMETHODS: Data of 255 de novo PD patients and 110 healthy controls (HCs) were retrieved from the Parkinson's Progression Markers Initiative. Structural magnetic resonance images were preprocessed, and GMVs and their hemispherical asymmetry were obtained for each of the neuropathologically defined Braak stages. Group and correlation comparisons were performed to assess differences in GMV and GMV asymmetry between PD subtypes.nnRESULTS: PD patients demonstrated significantly smaller bilateral GMVs compared to HCs, in a pattern denoting stage-dependent disease-related brain atrophy. However, the degree of putaminal DaT asymmetry was not associated with reduced GMV or higher GMV asymmetry. Furthermore, RBD-negative and RBD-positive patients did not demonstrate a significant difference in GMV or GMV asymmetry.nnCONCLUSIONS: Our findings suggest that putative brain-first and body-first patients do not present diverging brain atrophy patterns. Although certainly not disproving the brain-first/body-first spreading hypothesis, this study fails to provide evidence in support of it. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Banwinkler2022b,

title = {Gray Matter Volume Loss in Proposed <scp>Brain‐First</scp> and <scp>Body‐First</scp> Parkinson's Disease Subtypes},

author = {Magdalena Banwinkler and Verena Dzialas and and Merle C. Hoenig and Thilo van Eimeren},

doi = {10.1002/mds.29172},

issn = {1531-8257},

year  = {2022},

date = {2022-10-00},

urldate = {2022-10-00},

journal = {Movement Disorders},

volume = {37},

number = {10},

pages = {2066--2074},

publisher = {Wiley},

abstract = {<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>α‐Synuclein pathology is associated with neuronal degeneration in Parkinson's disease (PD) and considered to sequentially spread across the brain (Braak stages). According to a new hypothesis of distinct α‐synuclein spreading directions based on the initial site of pathology, the “brain‐first” spreading subtype would be associated with a more asymmetric cerebral and nigrostriatal pathology than the “body‐first” subtype.</jats:p></jats:sec><jats:sec><jats:title>Objective</jats:title><jats:p>Here, we tested if proposed markers of brain‐first PD (ie, higher dopamine transporter [DaT] asymmetry; absence of rapid eye movement sleep behavior disorder [RBD]) are associated with a greater or more asymmetric reduction in gray matter volume (GMV) in comparison to body‐first PD.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Data of 255 de novo PD patients and 110 healthy controls (HCs) were retrieved from the Parkinson's Progression Markers Initiative. Structural magnetic resonance images were preprocessed, and GMVs and their hemispherical asymmetry were obtained for each of the neuropathologically defined Braak stages. Group and correlation comparisons were performed to assess differences in GMV and GMV asymmetry between PD subtypes.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>PD patients demonstrated significantly smaller bilateral GMVs compared to HCs, in a pattern denoting stage‐dependent disease‐related brain atrophy. However, the degree of putaminal DaT asymmetry was not associated with reduced GMV or higher GMV asymmetry. Furthermore, RBD‐negative and RBD‐positive patients did not demonstrate a significant difference in GMV or GMV asymmetry.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Our findings suggest that putative brain‐first and body‐first patients do not present diverging brain atrophy patterns. Although certainly not disproving the brain‐first/body‐first spreading hypothesis, this study fails to provide evidence in support of it. © 2022 The Authors. <jats:italic>Movement Disorders</jats:italic> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society</jats:p></jats:sec>},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36138984,

title = {Imaging the Limbic System in Parkinson's Disease-A Review of Limbic Pathology and Clinical Symptoms},

author = {Magdalena Banwinkler and Hendrik Theis and Stéphane Prange and Thilo van Eimeren},

doi = {10.3390/brainsci12091248},

issn = {2076-3425},

year  = {2022},

date = {2022-09-01},

journal = {Brain Sci},

volume = {12},

number = {9},

abstract = {The limbic system describes a complex of brain structures central for memory, learning, as well as goal directed and emotional behavior. In addition to pathological studies, recent findings using in vivo structural and functional imaging of the brain pinpoint the vulnerability of limbic structures to neurodegeneration in Parkinson's disease (PD) throughout the disease course. Accordingly, dysfunction of the limbic system is critically related to the symptom complex which characterizes PD, including neuropsychiatric, vegetative, and motor symptoms, and their heterogeneity in patients with PD. The aim of this systematic review was to put the spotlight on neuroimaging of the limbic system in PD and to give an overview of the most important structures affected by the disease, their function, disease related alterations, and corresponding clinical manifestations. PubMed was searched in order to identify the most recent studies that investigate the limbic system in PD with the help of neuroimaging methods. First, PD related neuropathological changes and corresponding clinical symptoms of each limbic system region are reviewed, and, finally, a network integration of the limbic system within the complex of PD pathology is discussed.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Banwinkler2022,

title = {Imaging the Limbic System in Parkinson’s Disease—A Review of Limbic Pathology and Clinical Symptoms},

author = {Magdalena Banwinkler and Hendrik Theis and Stéphane Prange and Thilo van Eimeren},

doi = {10.3390/brainsci12091248},

issn = {2076-3425},

year  = {2022},

date = {2022-09-00},

journal = {Brain Sciences},

volume = {12},

number = {9},

publisher = {MDPI AG},

abstract = {The limbic system describes a complex of brain structures central for memory, learning, as well as goal directed and emotional behavior. In addition to pathological studies, recent findings using in vivo structural and functional imaging of the brain pinpoint the vulnerability of limbic structures to neurodegeneration in Parkinson’s disease (PD) throughout the disease course. Accordingly, dysfunction of the limbic system is critically related to the symptom complex which characterizes PD, including neuropsychiatric, vegetative, and motor symptoms, and their heterogeneity in patients with PD. The aim of this systematic review was to put the spotlight on neuroimaging of the limbic system in PD and to give an overview of the most important structures affected by the disease, their function, disease related alterations, and corresponding clinical manifestations. PubMed was searched in order to identify the most recent studies that investigate the limbic system in PD with the help of neuroimaging methods. First, PD related neuropathological changes and corresponding clinical symptoms of each limbic system region are reviewed, and, finally, a network integration of the limbic system within the complex of PD pathology is discussed.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Prange2022,

title = {Molecular Imaging in Parkinsonian Disorders—What’s New and Hot?},

author = {Stéphane Prange and Hendrik Theis and Magdalena Banwinkler and Thilo van Eimeren},

doi = {10.3390/brainsci12091146},

issn = {2076-3425},

year  = {2022},

date = {2022-09-00},

journal = {Brain Sciences},

volume = {12},

number = {9},

publisher = {MDPI AG},

abstract = {Neurodegenerative parkinsonian disorders are characterized by a great diversity of clinical symptoms and underlying neuropathology, yet differential diagnosis during lifetime remains probabilistic. Molecular imaging is a powerful method to detect pathological changes in vivo on a cellular and molecular level with high specificity. Thereby, molecular imaging enables to investigate functional changes and pathological hallmarks in neurodegenerative disorders, thus allowing to better differentiate between different forms of degenerative parkinsonism, improve the accuracy of the clinical diagnosis and disentangle the pathophysiology of disease-related symptoms. The past decade led to significant progress in the field of molecular imaging, including the development of multiple new and promising radioactive tracers for single photon emission computed tomography (SPECT) and positron emission tomography (PET) as well as novel analytical methods. Here, we review the most recent advances in molecular imaging for the diagnosis, prognosis, and mechanistic understanding of parkinsonian disorders. First, advances in imaging of neurotransmission abnormalities, metabolism, synaptic density, inflammation, and pathological protein aggregation are reviewed, highlighting our renewed understanding regarding the multiplicity of neurodegenerative processes involved in parkinsonian disorders. Consequently, we review the role of molecular imaging in the context of disease-modifying interventions to follow neurodegeneration, ensure stratification, and target engagement in clinical trials.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36138882,

title = {Molecular Imaging in Parkinsonian Disorders-What's New and Hot?},

author = {Stéphane Prange and Hendrik Theis and Magdalena Banwinkler and Thilo van Eimeren},

doi = {10.3390/brainsci12091146},

issn = {2076-3425},

year  = {2022},

date = {2022-08-01},

journal = {Brain Sci},

volume = {12},

number = {9},

abstract = {Neurodegenerative parkinsonian disorders are characterized by a great diversity of clinical symptoms and underlying neuropathology, yet differential diagnosis during lifetime remains probabilistic. Molecular imaging is a powerful method to detect pathological changes in vivo on a cellular and molecular level with high specificity. Thereby, molecular imaging enables to investigate functional changes and pathological hallmarks in neurodegenerative disorders, thus allowing to better differentiate between different forms of degenerative parkinsonism, improve the accuracy of the clinical diagnosis and disentangle the pathophysiology of disease-related symptoms. The past decade led to significant progress in the field of molecular imaging, including the development of multiple new and promising radioactive tracers for single photon emission computed tomography (SPECT) and positron emission tomography (PET) as well as novel analytical methods. Here, we review the most recent advances in molecular imaging for the diagnosis, prognosis, and mechanistic understanding of parkinsonian disorders. First, advances in imaging of neurotransmission abnormalities, metabolism, synaptic density, inflammation, and pathological protein aggregation are reviewed, highlighting our renewed understanding regarding the multiplicity of neurodegenerative processes involved in parkinsonian disorders. Consequently, we review the role of molecular imaging in the context of disease-modifying interventions to follow neurodegeneration, ensure stratification, and target engagement in clinical trials.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35763033,

title = {Inhibitory framing in hypersexual patients with Parkinson's disease. An fMRI pilot study},

author = {Hendrik Theis and Catharina Probst and Anna Campabadal and Katharina S Goerlich and Oliver Granert and Stephan Wolff and Karsten Witt and Günther Deuschl and Thilo van Eimeren},

doi = {10.1007/s00221-022-06397-5},

issn = {1432-1106},

year  = {2022},

date = {2022-08-01},

journal = {Exp Brain Res},

volume = {240},

number = {7-8},

pages = {2097--2107},

abstract = {Hypersexuality in medicated patients with PD is caused by an increased influence of motivational drive areas and a decreased influence of inhibitory control areas due to dopaminergic medication. In this pilot study, we test a newly developed paradigm investigating the influence of dopaminergic medication on brain activation elicited by sexual pictures with and without inhibitory contextual framing. Twenty PD patients with and without hypersexuality were examined with fMRI either OFF or ON standardized dopaminergic medication. The paradigm consisted of a priming phase where either a neutral context or an inhibitory context was presented. This priming phase was either followed by a sexual or a neutral target. Sexual, compared to neutral pictures resulted in a BOLD activation of various brain regions implicated in sexual processing. Hypersexual PD patients showed increased activity compared to PD controls in these regions. There was no relevant effect of medication between the two groups. The inhibitory context elicited less activation in inhibition-related areas in hypersexual PD, but had no influence on the perception of sexual cues. The paradigm partially worked: reactivity of motivational brain areas to sexual cues was increased in hypersexual PD and inhibitory contextual framing lead to decreased activation of inhibitory control areas in PD. We could not find a medication effect and the length of the inhibitory stimulus was not optimal to suppress reactivity to sexual cues. Our data provide new insights into the mechanisms of hypersexuality and warrant a replication with a greater cohort and an optimized stimulus length in the future.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Theis2022,

title = {Inhibitory framing in hypersexual patients with Parkinson’s disease. An fMRI pilot study},

author = {Hendrik Theis and Catharina Probst and Anna Campabadal and Katharina S. Goerlich and Oliver Granert and Stephan Wolff and Karsten Witt and Günther Deuschl and Thilo van Eimeren},

doi = {10.1007/s00221-022-06397-5},

issn = {1432-1106},

year  = {2022},

date = {2022-08-00},

journal = {Exp Brain Res},

volume = {240},

number = {7-8},

pages = {2097--2107},

publisher = {Springer Science and Business Media LLC},

abstract = {AbstractHypersexuality in medicated patients with PD is caused by an increased influence of motivational drive areas and a decreased influence of inhibitory control areas due to dopaminergic medication. In this pilot study, we test a newly developed paradigm investigating the influence of dopaminergic medication on brain activation elicited by sexual pictures with and without inhibitory contextual framing. Twenty PD patients with and without hypersexuality were examined with fMRI either OFF or ON standardized dopaminergic medication. The paradigm consisted of a priming phase where either a neutral context or an inhibitory context was presented. This priming phase was either followed by a sexual or a neutral target. Sexual, compared to neutral pictures resulted in a BOLD activation of various brain regions implicated in sexual processing. Hypersexual PD patients showed increased activity compared to PD controls in these regions. There was no relevant effect of medication between the two groups. The inhibitory context elicited less activation in inhibition-related areas in hypersexual PD, but had no influence on the perception of sexual cues. The paradigm partially worked: reactivity of motivational brain areas to sexual cues was increased in hypersexual PD and inhibitory contextual framing lead to decreased activation of inhibitory control areas in PD. We could not find a medication effect and the length of the inhibitory stimulus was not optimal to suppress reactivity to sexual cues. Our data provide new insights into the mechanisms of hypersexuality and warrant a replication with a greater cohort and an optimized stimulus length in the future.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ophey2022,

title = {Cognitive Performance and Learning Parameters Predict Response to Working Memory Training in Parkinson’s Disease},

author = {Anja Ophey and Julian Wenzel and Riya Paul and Kathrin Giehl and Sarah Rehberg and Carsten Eggers and Paul Reker and Thilo van Eimeren and Elke Kalbe and Lana Kambeitz-Ilankovic},

doi = {10.3233/jpd-223448},

issn = {1877-718X},

year  = {2022},

date = {2022-07-12},

journal = {Journal of Parkinson’s Disease},

volume = {12},

number = {7},

pages = {2235--2247},

publisher = {SAGE Publications},

abstract = {Background: Working memory (WM) training (WMT) is a popular intervention approach against cognitive decline in patients with Parkinson’s disease (PD). However, heterogeneity in WM responsiveness suggests that WMT may not be equally efficient for all patients. Objective: The present study aims to evaluate a multivariate model to predict post-intervention verbal WM in patients with PD using a supervised machine learning approach. We test the predictive potential of novel learning parameters derived from the WMT and compare their predictiveness to other more commonly used domains including demographic, clinical, and cognitive data. Methods: 37 patients with PD (age: 64.09±8.56, 48.6% female, 94.7% Hoehn & Yahr stage 2) participated in a 5-week WMT. Four random forest regression models including 1) cognitive variables only, 2) learning parameters only, 3) both cognitive and learning variables, and 4) the entire set of variables (with additional demographic and clinical data, ‘all’ model), were built to predict immediate and 3-month-follow-up WM. Result: The ‘all’ model predicted verbal WM with the lowest root mean square error (RMSE) compared to the other models, at both immediate (RMSE = 0.184; 95% -CI=[0.184;0.185]) and 3-month follow-up (RMSE = 0.216; 95% -CI=[0.215;0.217]). Cognitive baseline parameters were among the most important predictors in the ‘all’ model. The model combining cognitive and learning parameters significantly outperformed the model solely based on cognitive variables. Conclusion: Commonly assessed demographic, clinical, and cognitive variables provide robust prediction of response to WMT. Nonetheless, inclusion of training-inherent learning parameters further boosts precision of prediction models which in turn may augment training benefits following cognitive interventions in patients with PD. },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35305545,

title = {Parameters from site classification to harmonize MRI clinical studies: Application to a multi-site Parkinson's disease dataset},

author = {Gemma C Monte-Rubio and Barbara Segura and Antonio P Strafella and Thilo van Eimeren and Naroa Ibarretxe-Bilbao and Maria Diez-Cirarda and Carsten Eggers and Olaia Lucas-Jiménez and Natalia Ojeda and Javier Peña and Marina C Ruppert and Roser Sala-Llonch and Hendrik Theis and Carme Uribe and Carme Junque},

doi = {10.1002/hbm.25838},

issn = {1097-0193},

year  = {2022},

date = {2022-07-01},

journal = {Hum Brain Mapp},

volume = {43},

number = {10},

pages = {3130--3142},

abstract = {Multi-site MRI datasets are crucial for big data research. However, neuroimaging studies must face the batch effect. Here, we propose an approach that uses the predictive probabilities provided by Gaussian processes (GPs) to harmonize clinical-based studies. A multi-site dataset of 216 Parkinson's disease (PD) patients and 87 healthy subjects (HS) was used. We performed a site GP classification using MRI data. The outcomes estimated from this classification, redefined like Weighted HARMonization PArameters (WHARMPA), were used as regressors in two different clinical studies: A PD versus HS machine learning classification using GP, and a VBM comparison (FWE-p < .05, k = 100). Same studies were also conducted using conventional Boolean site covariates, and without information about site belonging. The results from site GP classification provided high scores, balanced accuracy (BAC) was 98.39% for grey matter images. PD versus HS classification performed better when the WHARMPA were used to harmonize (BAC = 78.60%; AUC = 0.90) than when using the Boolean site information (BAC = 56.31%; AUC = 0.71) and without it (BAC = 57.22%; AUC = 0.73). The VBM analysis harmonized using WHARMPA provided larger and more statistically robust clusters in regions previously reported in PD than when the Boolean site covariates or no corrections were added to the model. In conclusion, WHARMPA might encode global site-effects quantitatively and allow the harmonization of data. This method is user-friendly and provides a powerful solution, without complex implementations, to clean the analyses by removing variability associated with the differences between sites.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{C.Monte‐Rubio2022,

title = {Parameters from site classification to harmonize MRI clinical studies: Application to a multi‐site Parkinson's disease dataset},

author = {Gemma C. Monte‐Rubio and Barbara Segura and Antonio P. Strafella and Thilo van Eimeren and Naroa Ibarretxe‐Bilbao and Maria Diez‐Cirarda and Carsten Eggers and Olaia Lucas‐Jiménez and Natalia Ojeda and Javier Peña and Marina C. Ruppert and Roser Sala‐Llonch and Hendrik Theis and Carme Uribe and Carme Junque},

doi = {10.1002/hbm.25838},

issn = {1097-0193},

year  = {2022},

date = {2022-07-00},

journal = {Human Brain Mapping},

volume = {43},

number = {10},

pages = {3130--3142},

publisher = {Wiley},

abstract = {AbstractMulti‐site MRI datasets are crucial for big data research. However, neuroimaging studies must face the batch effect. Here, we propose an approach that uses the predictive probabilities provided by Gaussian processes (GPs) to harmonize clinical‐based studies. A multi‐site dataset of 216 Parkinson's disease (PD) patients and 87 healthy subjects (HS) was used. We performed a site GP classification using MRI data. The outcomes estimated from this classification, redefined like Weighted HARMonization PArameters (WHARMPA), were used as regressors in two different clinical studies: A PD versus HS machine learning classification using GP, and a VBM comparison (FWE‐p < .05, k = 100). Same studies were also conducted using conventional Boolean site covariates, and without information about site belonging. The results from site GP classification provided high scores, balanced accuracy (BAC) was 98.39% for grey matter images. PD versus HS classification performed better when the WHARMPA were used to harmonize (BAC = 78.60%; AUC = 0.90) than when using the Boolean site information (BAC = 56.31%; AUC = 0.71) and without it (BAC = 57.22%; AUC = 0.73). The VBM analysis harmonized using WHARMPA provided larger and more statistically robust clusters in regions previously reported in PD than when the Boolean site covariates or no corrections were added to the model. In conclusion, WHARMPA might encode global site‐effects quantitatively and allow the harmonization of data. This method is user‐friendly and provides a powerful solution, without complex implementations, to clean the analyses by removing variability associated with the differences between sites.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Coelho2022,

title = {Moral Agency, Rules, and Temporality in People Who Are Diagnosed With Mild Forms of Autism: In Defense of a Sentimentalist View},

author = {Sara Coelho and Sophia Marlene Bonatti and Elena Doering and Asena Paskaleva-Yankova and Achim Stephan},

doi = {10.3389/fpsyg.2022.875680},

issn = {1664-1078},

year  = {2022},

date = {2022-06-28},

journal = {Front. Psychol.},

volume = {13},

publisher = {Frontiers Media SA},

abstract = {The origin of moral agency is a much-debated issue. While rationalists or Kantians have argued that moral agency is rooted in reason, sentimentalists or Humeans have ascribed its origin to empathic feelings. This debate between rationalists and sentimentalists still stands with respect to persons with mental disorders, such as individuals diagnosed with mild forms of Autism Spectrum Disorder (ASD), without intellectual impairment. Individuals with ASD are typically regarded as moral agents, however their ability for empathy remains debated. The goal of this paper is to investigate the mechanisms of moral actions in people with ASD, by finding arguments for the origin of their moral actions, supporting either the sentimentalist or the rationalist view of the dispute. We propose to revisit the debate using Interpretative Phenomenological Analysis to study the autobiographies of individuals with High-Functioning Autism (HFA) and Asperger Syndrome (AS). While conducting the systematic analysis of 10 autobiographies, we re-examined both the rationalist and the sentimentalist positions, considering the links between empathic feelings and moral agency. The investigation of the temporal dimensions of emotional experiences, an aspect overlooked by previous research, indicated that individuals with ASD empathize with others, but in different ways as compared to neurotypicals. A relationship between emotional experience and the type of moral agency exhibited by individuals with forms of ASD was established. As a consequence, our analyses support the sentimentalist stance on moral action.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ring2021b,

title = {Discounting Behavior in Problem Gambling},

author = {Patrick Ring and Catharina C. Probst and Levent Neyse and Stephan Wolff and Christian Kaernbach and Thilo van Eimeren and Ulrich Schmidt},

doi = {10.1007/s10899-021-10054-x},

issn = {1573-3602},

year  = {2022},

date = {2022-06-00},

journal = {J Gambl Stud},

volume = {38},

number = {2},

pages = {529--543},

publisher = {Springer Science and Business Media LLC},

abstract = {AbstractProblem gamblers discount delayed rewards more rapidly than do non-gambling controls. Understanding this impulsivity is important for developing treatment options. In this article, we seek to make two contributions: First, we ask which of the currently debated economic models of intertemporal choice (exponential versus hyperbolic versus quasi-hyperbolic) provides the best description of gamblers’ discounting behavior. Second, we ask how problem gamblers differ from habitual gamblers and non-gambling controls within the most favored parametrization. Our analysis reveals that the quasi-hyperbolic discounting model is strongly favored over the other two parametrizations. Within the quasi-hyperbolic discounting model, problem gamblers have both a significantly stronger present bias and a smaller long-run discount factor, which suggests that gamblers’ impulsivity has two distinct sources.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Draganova2021,

title = {Motor training‐related brain reorganization in patients with cerebellar degeneration},

author = {Rossitza Draganova and Frank Konietschke and Katharina M. Steiner and Naveen Elangovan and Meltem Gümüs and Sophia M. Göricke and Thomas M. Ernst and Andreas Deistung and Thilo van Eimeren and Jürgen Konczak and Dagmar Timmann},

doi = {10.1002/hbm.25746},

issn = {1097-0193},

year  = {2022},

date = {2022-04-00},

journal = {Human Brain Mapping},

volume = {43},

number = {5},

pages = {1611--1629},

publisher = {Wiley},

abstract = {AbstractCerebellar degeneration progressively impairs motor function. Recent research showed that cerebellar patients can improve motor performance with practice, but the optimal feedback type (visual, proprioceptive, verbal) for such learning and the underlying neuroplastic changes are unknown. Here, patients with cerebellar degeneration (N = 40) and age‐ and sex‐matched healthy controls (N = 40) practiced single‐joint, goal‐directed forearm movements for 5 days. Cerebellar patients improved performance during visuomotor practice, but a training focusing on either proprioceptive feedback, or explicit verbal feedback and instruction did not show additional benefits. Voxel‐based morphometry revealed that after training gray matter volume (GMV) was increased prominently in the visual association cortices of controls, whereas cerebellar patients exhibited GMV increase predominantly in premotor cortex. The premotor cortex as a recipient of cerebellar efferents appears to be an important hub in compensatory remodeling following damage of the cerebro‐cerebellar motor system.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Khodadadifar2021,

title = {In search of convergent regional brain abnormality in cognitive emotion regulation: A transdiagnostic neuroimaging meta‐analysis},

author = {Tina Khodadadifar and Zahra Soltaninejad and Amir Ebneabbasi and Claudia R. Eickhoff and Christian Sorg and Thilo Van Eimeren and Kai Vogeley and Mojtaba Zarei and Simon B. Eickhoff and Masoud Tahmasian},

doi = {10.1002/hbm.25722},

issn = {1097-0193},

year  = {2022},

date = {2022-03-00},

journal = {Human Brain Mapping},

volume = {43},

number = {4},

pages = {1309--1325},

publisher = {Wiley},

abstract = {AbstractIneffective use of adaptive cognitive strategies (e.g., reappraisal) to regulate emotional states is often reported in a wide variety of psychiatric disorders, suggesting a common characteristic across different diagnostic categories. However, the extent of shared neurobiological impairments is incompletely understood. This study, therefore, aimed to identify the transdiagnostic neural signature of disturbed reappraisal using the coordinate‐based meta‐analysis (CBMA) approach. Following the best‐practice guidelines for conducting neuroimaging meta‐analyses, we systematically searched PubMed, ScienceDirect, and Web of Science databases and tracked the references. Out of 1,608 identified publications, 32 whole‐brain neuroimaging studies were retrieved that compared brain activation in patients with psychiatric disorders and healthy controls during a reappraisal task. Then, the reported peak coordinates of group comparisons were extracted and several activation likelihood estimation (ALE) analyses were performed at three hierarchical levels to identify the potential spatial convergence: the global level (i.e., the pooled analysis and the analyses of increased/decreased activations), the experimental‐contrast level (i.e., the analyses of grouped data based on the regulation goal, stimulus valence, and instruction rule) and the disorder‐group level (i.e., the analyses across the experimental‐contrast level focused on increasing homogeneity of disorders). Surprisingly, none of our analyses provided significant convergent findings. This CBMA indicates a lack of transdiagnostic convergent regional abnormality related to reappraisal task, probably due to the complex nature of cognitive emotion regulation, heterogeneity of clinical populations, and/or experimental and statistical flexibility of individual studies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36120792,

title = {Cognitive Performance and Learning Parameters Predict Response to Working Memory Training in Parkinson's Disease},

author = {Anja Ophey and Julian Wenzel and Riya Paul and Kathrin Giehl and Sarah Rehberg and Carsten Eggers and Paul Reker and Thilo van Eimeren and Elke Kalbe and Lana Kambeitz-Ilankovic},

doi = {10.3233/JPD-223448},

issn = {1877-718X},

year  = {2022},

date = {2022-01-01},

journal = {J Parkinsons Dis},

volume = {12},

number = {7},

pages = {2235--2247},

abstract = {BACKGROUND: Working memory (WM) training (WMT) is a popular intervention approach against cognitive decline in patients with Parkinson's disease (PD). However, heterogeneity in WM responsiveness suggests that WMT may not be equally efficient for all patients.nnOBJECTIVE: The present study aims to evaluate a multivariate model to predict post-intervention verbal WM in patients with PD using a supervised machine learning approach. We test the predictive potential of novel learning parameters derived from the WMT and compare their predictiveness to other more commonly used domains including demographic, clinical, and cognitive data.nnMETHODS: 37 patients with PD (age: 64.09±8.56, 48.6% female, 94.7% Hoehn & Yahr stage 2) participated in a 5-week WMT. Four random forest regression models including 1) cognitive variables only, 2) learning parameters only, 3) both cognitive and learning variables, and 4) the entire set of variables (with additional demographic and clinical data, 'all' model), were built to predict immediate and 3-month-follow-up WM.nnRESULT: The 'all' model predicted verbal WM with the lowest root mean square error (RMSE) compared to the other models, at both immediate (RMSE = 0.184; 95% -CI=[0.184;0.185]) and 3-month follow-up (RMSE = 0.216; 95% -CI=[0.215;0.217]). Cognitive baseline parameters were among the most important predictors in the 'all' model. The model combining cognitive and learning parameters significantly outperformed the model solely based on cognitive variables.nnCONCLUSION: Commonly assessed demographic, clinical, and cognitive variables provide robust prediction of response to WMT. Nonetheless, inclusion of training-inherent learning parameters further boosts precision of prediction models which in turn may augment training benefits following cognitive interventions in patients with PD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Peralta2021,

title = {Pragmatic Approach on Neuroimaging Techniques for the Differential Diagnosis of Parkinsonisms},

author = {Cecilia Peralta and Antonio P. Strafella and Thilo van Eimeren and Roberto Ceravolo and Klaus Seppi and Valtteri Kaasinen and Julieta E. Arena and Stephane Lehericy and },

doi = {10.1002/mdc3.13354},

issn = {2330-1619},

year  = {2022},

date = {2022-01-00},

journal = {Movement Disord Clin Pract},

volume = {9},

number = {1},

pages = {6--19},

publisher = {Wiley},

abstract = {ABSTRACTBackgroundRapid advances in neuroimaging technologies in the exploration of the living human brain also apply to movement disorders. However, the accurate diagnosis of Parkinson's disease (PD) and atypical parkinsonian disorders (APDs) still remains a challenge in daily practice.MethodsWe review the literature and our own experience as the Movement Disorder Society–Neuroimaging Study Group in Movement Disorders with the aim of providing a practical approach to the use of imaging technologies in the clinical setting.ResultsThe enormous amount of articles published so far and our increasing recognition of imaging technologies contrast with a lack of imaging protocols and updated algorithms for differential diagnosis. The distinctive pathological involvement in different brain structures and the correlation with imaging findings obtained with magnetic resonance, positron emission tomography, or single‐photon emission computed tomography illustrate what qualitative and quantitative measures may be useful in the clinical setting.ConclusionWe delineate a pragmatic approach to discuss imaging technologies, updated imaging algorithms, and their implications for differential diagnoses in PD and APDs.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34880241,

title = {Unlucky punches: the vulnerability-stress model for the development of impulse control disorders in Parkinson's disease},

author = {Hendrik Theis and Catharina Probst and Pierre-Olivier Fernagut and Thilo van Eimeren},

doi = {10.1038/s41531-021-00253-z},

issn = {2373-8057},

year  = {2021},

date = {2021-12-01},

journal = {NPJ Parkinsons Dis},

volume = {7},

number = {1},

pages = {112},

abstract = {Impulse-control disorders are commonly observed during dopamine-replacement therapy in Parkinson's disease, but the majority of patients seems "immune" to this side effect. Epidemiological evidence suggests that a major risk factor may be a specific difference in the layout of the dopaminergic-reinforcement system, of which the ventral striatum is a central player. A series of imaging studies of the dopaminergic system point toward a presynaptic reduction of dopamine-reuptake transporter density and dopamine synthesis capacity. Here, we review current evidence for a vulnerability-stress model in which a relative reduction of dopaminergic projections to the ventral striatum and concomitant sensitization of postsynaptic neurons represent a predisposing (hypodopaminergic) vulnerability. Stress (hyperdopaminergic) is delivered when dopamine replacement therapy leads to a relative overdosing of the already-sensitized ventral striatum. These alterations are consistent with consecutive changes in reinforcement mechanisms, which stimulate learning from reward and impede learning from punishment, thereby fostering the development of impulse-control disorders. This vulnerability-stress model might also provide important insights into the development of addictions in the non-Parkinsonian population.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Theis2021,

title = {Unlucky punches: the vulnerability-stress model for the development of impulse control disorders in Parkinson’s disease},

author = {Hendrik Theis and Catharina Probst and Pierre-Olivier Fernagut and Thilo van Eimeren},

doi = {10.1038/s41531-021-00253-z},

issn = {2373-8057},

year  = {2021},

date = {2021-12-00},

journal = {npj Parkinsons Dis.},

volume = {7},

number = {1},

publisher = {Springer Science and Business Media LLC},

abstract = {AbstractImpulse-control disorders are commonly observed during dopamine-replacement therapy in Parkinson’s disease, but the majority of patients seems “immune” to this side effect. Epidemiological evidence suggests that a major risk factor may be a specific difference in the layout of the dopaminergic-reinforcement system, of which the ventral striatum is a central player. A series of imaging studies of the dopaminergic system point toward a presynaptic reduction of dopamine-reuptake transporter density and dopamine synthesis capacity. Here, we review current evidence for a vulnerability-stress model in which a relative reduction of dopaminergic projections to the ventral striatum and concomitant sensitization of postsynaptic neurons represent a predisposing (hypodopaminergic) vulnerability. Stress (hyperdopaminergic) is delivered when dopamine replacement therapy leads to a relative overdosing of the already-sensitized ventral striatum. These alterations are consistent with consecutive changes in reinforcement mechanisms, which stimulate learning from reward and impede learning from punishment, thereby fostering the development of impulse-control disorders. This vulnerability-stress model might also provide important insights into the development of addictions in the non-Parkinsonian population.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Tang2021,

title = {Validation of biomarkers in Huntington disease to support the development of disease-modifying therapies: A systematic review and critical appraisal scheme},

author = {Hanna Tang and Thilo van Eimeren and Cristina Sampaio and Tiago A. Mestre},

doi = {10.1016/j.parkreldis.2021.10.013},

issn = {1353-8020},

year  = {2021},

date = {2021-12-00},

journal = {Parkinsonism & Related Disorders},

volume = {93},

pages = {89--96},

publisher = {Elsevier BV},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Zeuner2021,

title = {Never too little: Grip and lift forces following probabilistic weight cues in patients with writer’s cramp},

author = {Kirsten E. Zeuner and Arne Knutzen and Oliver Granert and Leif Trampenau and Alexander Baumann and Stephan Wolff and Olav Jansen and Thilo van Eimeren and Johann P. Kuhtz-Buschbeck},

doi = {10.1016/j.clinph.2021.09.010},

issn = {1388-2457},

year  = {2021},

date = {2021-12-00},

journal = {Clinical Neurophysiology},

volume = {132},

number = {12},

pages = {2937--2947},

publisher = {Elsevier BV},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Song2021,

title = {Binding characteristics of [^{18}F]PI-2620 distinguish the clinically predicted tau isoform in different tauopathies by PET},

author = {Mengmeng Song and Leonie Beyer and Lena Kaiser and Henryk Barthel and Thilo van Eimeren and Ken Marek and Alexander Nitschmann and Maximilian Scheifele and Carla Palleis and Gesine Respondek and Maike Kern and Gloria Biechele and Jochen Hammes and Gèrard Bischof and Michael Barbe and Özgür Onur and Frank Jessen and Dorothee Saur and Matthias L Schroeter and Jost-Julian Rumpf and Michael Rullmann and Andreas Schildan and Marianne Patt and Bernd Neumaier and Olivier Barret and Jennifer Madonia and David S Russell and Andrew W Stephens and Andre Mueller and Sigrun Roeber and Jochen Herms and Kai Bötzel and Adrian Danek and Johannes Levin and Joseph Classen and Günter U Höglinger and Peter Bartenstein and Victor Villemagne and Alexander Drzezga and John Seibyl and Osama Sabri and Guido Boening and Sibylle Ziegler and Matthias Brendel},

doi = {10.1177/0271678x211018904},

issn = {1559-7016},

year  = {2021},

date = {2021-11-00},

journal = {J Cereb Blood Flow Metab},

volume = {41},

number = {11},

pages = {2957--2972},

publisher = {SAGE Publications},

abstract = { The novel tau-PET tracer [18F]PI-2620 detects the 3/4-repeat-(R)-tauopathy Alzheimer’s disease (AD) and the 4R-tauopathies corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP). We determined whether [18F]PI-2620 binding characteristics deriving from non-invasive reference tissue modelling differentiate 3/4R- and 4R-tauopathies. Ten patients with a 3/4R tauopathy (AD continuum) and 29 patients with a 4R tauopathy (CBS, PSP) were evaluated. [18F]PI-2620 PET scans were acquired 0-60 min p.i. and the distribution volume ratio (DVR) was calculated. [18F]PI-2620-positive clusters (DVR ≥ 2.5 SD vs. 11 healthy controls) were evaluated by non-invasive kinetic modelling. R1 (delivery), k2 & k2a (efflux), DVR, 30-60 min standardized-uptake-value-ratios (SUVR30-60) and the linear slope of post-perfusion phase SUVR (9-60 min p.i.) were compared between 3/4R- and 4R-tauopathies. Cortical clusters of 4R-tau cases indicated higher delivery (R1SRTM: 0.92 ± 0.21 vs. 0.83 ± 0.10, p = 0.0007), higher efflux (k2SRTM: 0.17/min ±0.21/min vs. 0.06/min ± 0.07/min, p < 0.0001), lower DVR (1.1 ± 0.1 vs. 1.4 ± 0.2, p < 0.0001), lower SUVR30-60 (1.3 ± 0.2 vs. 1.8 ± 0.3, p < 0.0001) and flatter slopes of the post-perfusion phase (slope9-60: 0.006/min ± 0.007/min vs. 0.016/min ± 0.008/min, p < 0.0001) when compared to 3/4R-tau cases. [18F]PI-2620 binding characteristics in cortical regions differentiate 3/4R- and 4R-tauopathies. Higher tracer clearance indicates less stable binding in 4R tauopathies when compared to 3/4R-tauopathies. },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Song2021b,

title = {Feasibility of short imaging protocols for [18F]PI-2620 tau-PET in progressive supranuclear palsy},

author = {Mengmeng Song and Maximilian Scheifele and Henryk Barthel and Thilo van Eimeren and Leonie Beyer and Ken Marek and Florian Eckenweber and Carla Palleis and Lena Kaiser and Anika Finze and Maike Kern and Alexander Nitschmann and Gloria Biechele and Sabrina Katzdobler and Gèrard Bischof and Jochen Hammes and Frank Jessen and Dorothee Saur and Matthias L. Schroeter and Jost-Julian Rumpf and Michael Rullmann and Andreas Schildan and Marianne Patt and Bernd Neumaier and Andrew W. Stephens and Boris-Stephan Rauchmann and Robert Perneczky and Johannes Levin and Joseph Classen and Günter U. Höglinger and Peter Bartenstein and Guido Boening and Sibylle Ziegler and Victor Villemagne and Alexander Drzezga and John Seibyl and Osama Sabri and Matthias Brendel and },

doi = {10.1007/s00259-021-05391-3},

issn = {1619-7089},

year  = {2021},

date = {2021-11-00},

journal = {Eur J Nucl Med Mol Imaging},

volume = {48},

number = {12},

pages = {3872--3885},

publisher = {Springer Science and Business Media LLC},

abstract = {Abstract

                Purpose

                Dynamic 60-min positron emission tomography (PET) imaging with the novel tau radiotracer [18F]PI-2620 facilitated accurate discrimination between patients with progressive supranuclear palsy (PSP) and healthy controls (HCs). This study investigated if truncated acquisition and static time windows can be used for [18F]PI-2620 tau-PET imaging of PSP.

              

                Methods

                Thirty-seven patients with PSP Richardson syndrome (PSP-RS) were evaluated together with ten HCs. [18F]PI-2620 PET was performed by a dynamic 60-min scan. Distribution volume ratios (DVRs) were calculated using full and truncated scan durations (0–60, 0–50, 0–40, 0–30, and 0–20 min p.i.). Standardized uptake value ratios (SUVrs) were obtained 20–40, 30–50, and 40–60 min p.i.. All DVR and SUVr data were compared with regard to their potential to discriminate patients with PSP-RS from HCs in predefined subcortical and cortical target regions (effect size, area under the curve (AUC), multi-region classifier).

              

                Results

                0–50 and 0–40 DVR showed equivalent effect sizes as 0–60 DVR (averaged Cohen’s d: 1.22 and 1.16 vs. 1.26), whereas the performance dropped for 0–30 or 0–20 DVR. The 20–40 SUVr indicated the best performance of all static acquisition windows (averaged Cohen’s d: 0.99). The globus pallidus internus discriminated patients with PSP-RS and HCs at a similarly high level for 0–60 DVR (AUC: 0.96), 0–40 DVR (AUC: 0.96), and 20–40 SUVr (AUC: 0.94). The multi-region classifier sensitivity of these time windows was consistently 86%.

              

                Conclusion

                Truncated and static imaging windows can be used for [18F]PI-2620 PET imaging of PSP. 0–40 min dynamic scanning offers the best balance between accuracy and economic scanning.

              },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34284259,

title = {Unique regional patterns of amyloid burden predict progression to prodromal and clinical stages of Alzheimer's disease},

author = {Julia Pfeil and Merle C Hoenig and Elena Doering and Thilo van Eimeren and Alexander Drzezga and Gérard N Bischof and },

doi = {10.1016/j.neurobiolaging.2021.06.014},

issn = {1558-1497},

year  = {2021},

date = {2021-10-01},

journal = {Neurobiol Aging},

volume = {106},

pages = {119--129},

abstract = {Although beta-amyloid (Aβ) positivity has shown to be associated with higher risk of progression to Alzheimer's disease (AD) in mild cognitive impairment (MCI), information on the time to conversion to manifest dementia cannot be readily deduced from this binary classification. Here, we assessed if regional patterns of Aβ deposition measured with F-florbetapir may serve as biomarker for progression risk in Aβ-positive cognitively normal (CN) and MCI patients, including clinical follow-up data and cerebrospinal fluid (CSF) biomarkers. Voxel-wise group comparisons between age and sex-matched Aβ-positive groups (i.e., CN-stables [n = 38] vs. CN-to-MCI/AD progressors [n = 38], MCI-stables [n = 104] versus MCI-to-AD progressors [n = 104]) revealed higher Aβ burden in precuneus, subcortical, and parietal regions in CN-to-MCI/AD progressors and cingulate, temporal, and frontal regions in MCI-to-AD progressors. Importantly, these regional patterns predicted progression to advanced stages on the AD spectrum in the short and the long-term beyond global Aβ burden and CSF biomarkers. These results suggest that distinct regional patterns of Aβ burden are a valuable biomarker for risk of disease progression in CN and MCI.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Pfeil2021,

title = {Unique regional patterns of amyloid burden predict progression to prodromal and clinical stages of Alzheimer's disease},

author = {Julia Pfeil and Merle C. Hoenig and Elena Doering and Thilo van Eimeren and Alexander Drzezga and Gérard N. Bischof},

doi = {10.1016/j.neurobiolaging.2021.06.014},

issn = {0197-4580},

year  = {2021},

date = {2021-10-00},

urldate = {2021-10-00},

journal = {Neurobiology of Aging},

volume = {106},

pages = {119--129},

publisher = {Elsevier BV},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ring2021,

title = {Oscillatory brain activity associated with skin conductance responses in the context of risk},

author = {Patrick Ring and Julian Keil and Muthuraman Muthuraman and Stephan Wolff and Til Ole Bergmann and Catharina Probst and Levent Neyse and Ulrich Schmidt and Thilo van Eimeren and Christian Kaernbach},

doi = {10.1152/jn.00014.2021},

issn = {1522-1598},

year  = {2021},

date = {2021-09-01},

journal = {Journal of Neurophysiology},

volume = {126},

number = {3},

pages = {924--933},

publisher = {American Physiological Society},

abstract = { We studied neural oscillations associated with risk-sensitive skin conductance responses. Going beyond previous studies, we applied methods with high-temporal resolution to account for the temporal properties of the sympathetic activity. Preceding skin conductance peaks, we observed decreased occipital cortex oscillatory power and a relationship between the oscillatory power decrease and the skin conductance peak amplitude. Our study suggests an interaction between attention and emotion such as threat perception reflected in skin conductance responses. },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Palleis2021,

title = {Cortical [^{18}F]PI‐2620 Binding Differentiates Corticobasal Syndrome Subtypes},

author = {Carla Palleis and Matthias Brendel and Anika Finze and Endy Weidinger and Kai Bötzel and Adrian Danek and Leonie Beyer and Alexander Nitschmann and Maike Kern and Gloria Biechele and Boris‐Stephan Rauchmann and Jan Häckert and Matthias Höllerhage and Andrew W. Stephens and Alexander Drzezga and Thilo van Eimeren and Victor L. Villemagne and Andreas Schildan and Henryk Barthel and Marianne Patt and Osama Sabri and  and Peter Bartenstein and Robert Perneczky and Christian Haass and Johannes Levin and Günter U. Höglinger},

doi = {10.1002/mds.28624},

issn = {1531-8257},

year  = {2021},

date = {2021-09-00},

journal = {Movement Disorders},

volume = {36},

number = {9},

pages = {2104--2115},

publisher = {Wiley},

abstract = {AbstractBackgroundCorticobasal syndrome is associated with cerebral protein aggregates composed of 4‐repeat (~50% of cases) or mixed 3‐repeat/4‐repeat tau isoforms (~25% of cases) or nontauopathies (~25% of cases).ObjectivesThe aim of this single‐center study was to investigate the diagnostic value of the tau PET‐ligand [18F]PI‐2620 in patients with corticobasal syndrome.MethodsForty‐five patients (71.5 ± 7.6 years) with corticobasal syndrome and 14 age‐matched healthy controls underwent [18F]PI‐2620‐PET. Beta‐amyloid status was determined by cerebral β‐amyloid PET and/or CSF analysis. Subcortical and cortical [18F]PI‐2620 binding was quantitatively and visually compared between β‐amyloid‐positive and ‐negative patients and controls. Regional [18F]PI‐2620 binding was correlated with clinical and demographic data.ResultsTwenty‐four percent (11 of 45) were β‐amyloid‐positive. Significantly elevated [18F]PI‐2620 distribution volume ratios were observed in both β‐amyloid‐positive and β‐amyloid‐negative patients versus controls in the dorsolateral prefrontal cortex and basal ganglia. Cortical [18F]PI‐2620 PET positivity was distinctly higher in β‐amyloid‐positive compared with β‐amyloid‐negative patients with pronounced involvement of the dorsolateral prefrontal cortex. Semiquantitative analysis of [18F]PI‐2620 PET revealed a sensitivity of 91% for β‐amyloid‐positive and of 65% for β‐amyloid‐negative cases, which is in excellent agreement with prior clinicopathological data. Regardless of β‐amyloid status, hemispheric lateralization of [18F]PI‐2620 signal reflected contralateral predominance of clinical disease severity.ConclusionsOur data indicate a value of [18F]PI‐2620 for evaluating corticobasal syndrome, providing quantitatively and regionally distinct signals in β‐amyloid‐positive as well as β‐amyloid‐negative corticobasal syndrome. In corticobasal syndrome, [18F]PI‐2620 may potentially serve for a differential diagnosis and for monitoring disease progression. © 2021 The Authors.Movement Disorderspublished by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Schedlich-Teufer2021,

title = {Assessment of Affective-Behavioral States in Parkinson’s Disease Patients: Towards a New Screening Tool},

author = {Charlotte Schedlich-Teufer and Stefanie Theresa Jost and Paul Krack and Karsten Witt and Daniel Weintraub and Juan Carlos Baldermann and Michael Sommerauer and Deborah Amstutz and Thilo van Eimeren and Haidar Salimi Dafsari and Elke Kalbe and Veerle Visser-Vandewalle and Gereon Rudolf Fink and Josef Kessler and Michael Thomas Barbe},

doi = {10.3233/jpd-202375},

issn = {1877-718X},

year  = {2021},

date = {2021-08-02},

journal = {JPD},

volume = {11},

number = {3},

pages = {1417--1430},

publisher = {SAGE Publications},

abstract = {Background: Assessment of affective-behavioral states in patients with Parkinson’s disease (PD) undergoing deep brain stimulation (DBS) is essential. Objective: To analyze well-established questionnaires as a pilot-study with the long term aim to develop a screening tool evaluating affective-behavioral dysfunction, including depression, anxiety, apathy, mania, and impulse control disorders, in PD patients screened for DBS. Methods: Two hundred ninety-seven inpatients with PD underwent standardized neuropsychiatric testing including German versions of Beck Depression Inventory-II, Hospital Anxiety and Depression Scale, Apathy Evaluation Scale, Self-Report Manic Inventory, and Questionnaire for Impulsive-Compulsive Disorders in PD-Rating Scale, to assess appropriateness for DBS. Statistical item reduction was based on exploratory factor analysis, Cronbach’s alpha, item-total correlations, item difficulty, and inter-item correlations. Confirmatory factor analysis was conducted to assess factorial validity. An expert rating was performed to identify clinically relevant items in the context of PD and DBS, to maintain content validity. We compared the shortened subscales with the original questionnaires using correlations. To determine cutoff points, receiver operating characteristics analysis was performed. Results: The items of the initial questionnaires were reduced from 129 to 38 items. Results of confirmatory factor analyses supported the validity of the shortened pool. It demonstrated high internal consistency (Cronbach’s alpha = 0.72–0.83 across subscales), and the individual subscales were correlated with the corresponding original scales (rs = 0.84–0.95). Sensitivities and specificities exceeded 0.7. Conclusion: The shortened item pool, including 38 items, provides a good basis for the development of a screening tool, capturing affective-behavioral symptoms in PD patients before DBS implantation. Confirmation of the validity of such a screening tool in an independent sample of PD patients is warranted.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Jergas2021,

title = {The impact of subthalamic deep brain stimulation on belief revision and social validation},

author = {Hannah Jergas and Linnéa Grindegård and Thomas Schultze and Sharmili Edwin Thanarajah and Elke Kalbe and Thilo van Eimeren and Haidar S. Dafsari and Till A. Dembek and Veerle Visser-Vandewalle and Gereon R. Fink and Lars Timmermann and Leonhard Schilbach and Michael T. Barbe},

doi = {10.1016/j.parkreldis.2021.06.020},

issn = {1353-8020},

year  = {2021},

date = {2021-08-00},

journal = {Parkinsonism & Related Disorders},

volume = {89},

pages = {84--86},

publisher = {Elsevier BV},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33462630,

title = {Indication of retrograde tau spreading along Braak stages and functional connectivity pathways},

author = {Joseph Seemiller and Gérard N Bischof and Merle C Hoenig and Masoud Tahmasian and Thilo van Eimeren and Alexander Drzezga and },

doi = {10.1007/s00259-020-05183-1},

issn = {1619-7089},

year  = {2021},

date = {2021-07-01},

journal = {Eur J Nucl Med Mol Imaging},

volume = {48},

number = {7},

pages = {2272--2282},

abstract = {PURPOSE: Tau pathology progression in Alzheimer's disease (AD) is explained through the network degeneration hypothesis and the neuropathological Braak stages; however, the compatibility of these models remains unclear.nnMETHODS: We utilized [18F]AV-1451 tau-PET scans of 39 subjects with AD and 39 sex-matched amyloid-negative healthy controls (HC) in the ADNI (Alzheimer's Disease Neuroimaging Initiative) dataset. The peak cluster of tau-tracer uptake was identified in each Braak stage of neuropathological tau deposition and used to create a seed-based functional connectivity network (FCN) using 198 HC subjects, to identify healthy networks unaffected by neurodegeneration.nnRESULTS: Voxel-wise tau deposition was both significantly higher inside relative to outside FCNs and correlated significantly and positively with levels of healthy functional connectivity. Within many isolated Braak stages and regions, the correlation between tau and intrinsic functional connectivity was significantly stronger than it was across the whole brain. In this way, each peak cluster of tau was related to multiple Braak stages traditionally associated with both earlier and later stages of disease.nnCONCLUSION: We show specificity of healthy FCN topography for AD-pathological tau as well as positive voxel-by-voxel correlations between pathological tau and healthy functional connectivity. We propose a model of "up- and downstream" functional tau progression, suggesting that tau pathology evolves along functional connectivity networks not only "downstream" (i.e., along the expected sequence of the established Braak stages) but also in part "upstream" or "retrograde" (i.e., against the expected sequence of the established Braak stages), with pathology in earlier Braak stages intensified by its functional relationship to later disease stages.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33590274,

title = {Clinical validity of second-generation tau PET tracers as biomarkers for Alzheimer's disease in the context of a structured 5-phase development framework},

author = {Gérard N Bischof and Alessandra Dodich and Marina Boccardi and Thilo van Eimeren and Cristina Festari and Henryk Barthel and Oskar Hansson and Agneta Nordberg and Rik Ossenkoppele and Osama Sabri and B Frisoni G Giovanni and Valentina Garibotto and Alexander Drzezga},

doi = {10.1007/s00259-020-05156-4},

issn = {1619-7089},

year  = {2021},

date = {2021-07-01},

journal = {Eur J Nucl Med Mol Imaging},

volume = {48},

number = {7},

pages = {2110--2120},

abstract = {PURPOSE: In 2017, the Geneva Alzheimer's disease (AD) strategic biomarker roadmap initiative proposed a framework of the systematic validation AD biomarkers to harmonize and accelerate their development and implementation in clinical practice. Here, we use this framework to examine the translatability of the second-generation tau PET tracers into the clinical context.nnMETHODS: All available literature was systematically searched based on a set of search terms that related independently to analytic validity (phases 1-2), clinical validity (phase 3-4), and clinical utility (phase 5). The progress on each of the phases was determined based on scientific criteria applied for each phase and coded as fully, partially, preliminary achieved or not achieved at all.nnRESULTS: The validation of the second-generation tau PET tracers has successfully passed the analytical phase 1 of the strategic biomarker roadmap. Assay definition studies showed evidence on the superiority over first-generation tau PET tracers in terms of off-target binding. Studies have partially achieved the primary aim of the analytical validity stage (phase 2), and preliminary evidence has been provided for the assessment of covariates on PET signal retention. Studies investigating of the clinical validity in phases 3, 4, and 5 are still underway.nnCONCLUSION: The current literature provides overall preliminary evidence on the establishment of the second-generation tau PET tracers into the clinical context, thereby successfully addressing some methodological issues from the tau PET tracer of the first generation. Nevertheless, bigger cohort studies, longitudinal follow-up, and examination of diverse disease population are still needed to gauge their clinical validity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33712532,

title = {Toward a Universal Readout for F-Labeled Amyloid Tracers: The CAPTAINs Study},

author = {Gérard N Bischof and Peter Bartenstein and Henryk Barthel and Bart van Berckel and Vincent Doré and Thilo van Eimeren and Norman Foster and Jochen Hammes and Adriaan A Lammertsma and Satoshi Minoshima and Chris Rowe and Osama Sabri and John Seibyl and Koen Van Laere and Rik Vandenberghe and Victor Villemagne and Igor Yakushev and Alexander Drzezga},

doi = {10.2967/jnumed.120.250290},

issn = {1535-5667},

year  = {2021},

date = {2021-07-01},

journal = {J Nucl Med},

volume = {62},

number = {7},

pages = {999--1005},

abstract = {To date, 3 F-labeled PET tracers have been approved for assessing cerebral amyloid plaque pathology in the diagnostic workup of suspected Alzheimer disease (AD). Although scanning protocols are relatively similar across tracers, U.S. Food and Drug Administration- and the European Medicines Agency-approved visual rating protocols differ among the 3 tracers. This proof-of-concept study assessed the comparability of the 3 approved visual rating protocols to classify a scan as amyloid-positive or -negative, when applied by groups of experts and nonexperts to all 3 amyloid tracers.  In an international multicenter approach, both expert ( = 4) and nonexpert raters ( = 3) rated scans acquired with F-florbetaben, F-florbetapir and F-flutemetamol. Scans obtained with each tracer were presented for reading according to all 3 approved visual rating protocols. In a randomized order, every single scan was rated by each reader according to all 3 protocols. Raters were blinded for the amyloid tracer used and asked to rate each scan as positive or negative, giving a confidence judgment after each response. Percentage of visual reader agreement, interrater reliability, and agreement of each visual read with binary quantitative measures (fixed SUV ratio threshold for positive or negative scans) were computed. These metrics were analyzed separately for expert and nonexpert groups.  No significant differences in using the different approved visual rating protocols were observed across the different metrics of agreement in the group of experts. Nominal differences suggested that the F-florbetaben visual rating protocol achieved the highest interrater reliability and accuracy especially under low confidence conditions. For the group of nonexpert raters, significant differences between the different visual rating protocols were observed with overall moderate-to-fair accuracy and with the highest reliability for the F-florbetapir visual rating protocol.  We observed high interrater agreement despite applying different visual rating protocols for all F-labeled amyloid tracers. This implies that the results of the visual interpretation of amyloid imaging can be well standardized and do not depend on the rating protocol in experts. Consequently, the creation of a universal visual assessment protocol for all amyloid imaging tracers appears feasible, which could benefit especially the less-experienced readers.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Bischof2021,

title = {Toward a Universal Readout for^{18}F-Labeled Amyloid Tracers: The CAPTAINs Study},

author = {Gérard N. Bischof and Peter Bartenstein and Henryk Barthel and Bart van Berckel and Vincent Doré and Thilo van Eimeren and Norman Foster and Jochen Hammes and Adriaan A. Lammertsma and Satoshi Minoshima and Chris Rowe and Osama Sabri and John Seibyl and Koen Van Laere and Rik Vandenberghe and Victor Villemagne and Igor Yakushev and Alexander Drzezga},

doi = {10.2967/jnumed.120.250290},

issn = {2159-662X},

year  = {2021},

date = {2021-07-01},

journal = {J Nucl Med},

volume = {62},

number = {7},

pages = {999--1005},

publisher = {Society of Nuclear Medicine},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Bischof2021b,

title = {Clinical validity of second-generation tau PET tracers as biomarkers for Alzheimer’s disease in the context of a structured 5-phase development framework},

author = {Gérard N Bischof and Alessandra Dodich and Marina Boccardi and Thilo van Eimeren and Cristina Festari and Henryk Barthel and Oskar Hansson and Agneta Nordberg and Rik Ossenkoppele and Osama Sabri and B Frisoni G Giovanni and Valentina Garibotto and Alexander Drzezga},

doi = {10.1007/s00259-020-05156-4},

issn = {1619-7089},

year  = {2021},

date = {2021-07-00},

journal = {Eur J Nucl Med Mol Imaging},

volume = {48},

number = {7},

pages = {2110--2120},

publisher = {Springer Science and Business Media LLC},

abstract = {Abstract

                Purpose

                In 2017, the Geneva Alzheimer’s disease (AD) strategic biomarker roadmap initiative proposed a framework of the systematic validation AD biomarkers to harmonize and accelerate their development and implementation in clinical practice. Here, we use this framework to examine the translatability of the second-generation tau PET tracers into the clinical context.

              

                Methods

                All available literature was systematically searched based on a set of search terms that related independently to analytic validity (phases 1–2), clinical validity (phase 3–4), and clinical utility (phase 5). The progress on each of the phases was determined based on scientific criteria applied for each phase and coded as fully, partially, preliminary achieved or not achieved at all.

              

                Results

                The validation of the second-generation tau PET tracers has successfully passed the analytical phase 1 of the strategic biomarker roadmap. Assay definition studies showed evidence on the superiority over first-generation tau PET tracers in terms of off-target binding. Studies have partially achieved the primary aim of the analytical validity stage (phase 2), and preliminary evidence has been provided for the assessment of covariates on PET signal retention. Studies investigating of the clinical validity in phases 3, 4, and 5 are still underway.

              

                Conclusion

                The current literature provides overall preliminary evidence on the establishment of the second-generation tau PET tracers into the clinical context, thereby successfully addressing some methodological issues from the tau PET tracer of the first generation. Nevertheless, bigger cohort studies, longitudinal follow-up, and examination of diverse disease population are still needed to gauge their clinical validity.

              },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Seemiller2021,

title = {Indication of retrograde tau spreading along Braak stages and functional connectivity pathways},

author = {Joseph Seemiller and Gérard N. Bischof and Merle C. Hoenig and Masoud Tahmasian and Thilo van Eimeren and Alexander Drzezga},

doi = {10.1007/s00259-020-05183-1},

issn = {1619-7089},

year  = {2021},

date = {2021-07-00},

urldate = {2021-07-00},

journal = {Eur J Nucl Med Mol Imaging},

volume = {48},

number = {7},

pages = {2272--2282},

publisher = {Springer Science and Business Media LLC},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ruppert2021,

title = {The default mode network and cognition in Parkinson's disease: A multimodal resting‐state network approach},

author = {Marina C. Ruppert and Andrea Greuel and Julia Freigang and Masoud Tahmasian and Franziska Maier and Jochen Hammes and Thilo van Eimeren and Lars Timmermann and Marc Tittgemeyer and Alexander Drzezga and Carsten Eggers},

doi = {10.1002/hbm.25393},

issn = {1097-0193},

year  = {2021},

date = {2021-06-00},

journal = {Human Brain Mapping},

volume = {42},

number = {8},

pages = {2623--2641},

publisher = {Wiley},

abstract = {AbstractInvolvement of the default mode network (DMN) in cognitive symptoms of Parkinson's disease (PD) has been reported by resting‐state functional MRI (rsfMRI) studies. However, the relation to metabolic measures obtained by [18F]‐fluorodeoxyglucose positron emission tomography (FDG‐PET) is largely unknown. We applied multimodal resting‐state network analysis to clarify the association between intrinsic metabolic and functional connectivity abnormalities within the DMN and their significance for cognitive symptoms in PD. PD patients were classified into normal cognition (n = 36) and mild cognitive impairment (MCI; n = 12). The DMN was identified by applying an independent component analysis to FDG‐PET and rsfMRI data of a matched subset (16 controls and 16 PD patients) of the total cohort. Besides metabolic activity, metabolic and functional connectivity within the DMN were compared between the patients' groups and healthy controls (n = 16). Glucose metabolism was significantly reduced in all DMN nodes in both patient groups compared to controls, with the lowest uptake in PD‐MCI (p < .05). Increased metabolic and functional connectivity along fronto‐parietal connections was identified in PD‐MCI patients compared to controls and unimpaired patients. Functional connectivity negatively correlated with cognitive composite z‐scores in patients (r = −.43, p = .005). The current study clarifies the commonalities of metabolic and hemodynamic measures of brain network activity and their individual significance for cognitive symptoms in PD, highlighting the added value of multimodal resting‐state network approaches for identifying prospective biomarkers.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Dembek2020,

title = {Temporal Stability of Lead Orientation in Directional Deep Brain Stimulation},

author = {Till A. Dembek and Adrian L. Asendorf and Jochen Wirths and Michael T. Barbe and Veerle Visser-Vandewalle and Harald Treuer},

doi = {10.1159/000510883},

issn = {1423-0372},

year  = {2021},

date = {2021-04-09},

journal = {Stereotact Funct Neurosurg},

volume = {99},

number = {2},

pages = {167--170},

publisher = {S. Karger AG},

abstract = {\textbf{\textit{Background:}} Directional deep brain stimulation (DBS) enlarges the therapeutic window by increasing side-effect thresholds and improving clinical benefits. To determine the optimal stimulation settings and interpret clinical observations, knowledge of the lead orientation in relation to the patient’s anatomy is required. \textbf{\textit{Objective:}} To determine if directional leads remain in a fixed orientation after implantation or whether orientation changes over time. \textbf{\textit{Method:}} Clinical records of 187 patients with directional DBS electrodes were screened for CT scans in addition to the routine postoperative CT. The orientation angle of each electrode at a specific point in time was reconstructed from CT artifacts using the DiODe algorithm implemented in Lead-DBS. The orientation angles over time were compared with the originally measured orientations from the routine postoperative CT. \textbf{\textit{Results:}} Multiple CT scans were identified in 18 patients and the constancy of the orientation angle was determined for 29 leads at 48 points in time. The median time difference between the observations and the routine postoperative CT scan was 82 (range 1–811) days. The mean difference of the orientation angles compared to the initial measurement was –1.1 ± 3.9° (range –7.6 to 8.7°). Linear regression showed no relevant drift of the absolute value of the orientation angle over time (0.8°/year, adjusted \textit{R}^{2}: 0.040, \textit{p} = 0.093). \textbf{\textit{Conclusion:}} The orientation of directional leads was stable and showed no clinically relevant changes either in the first weeks after implantation or over longer periods of time. },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33356820,

title = {Finding New Communities: A Principle of Neuronal Network Reorganization in Alzheimer's Disease},

author = {Anna Weller and Gérard N Bischof and Philipp Schlüter and Nils Richter and Julian Dronse and Oezguer Onur and Bernd Neumaier and Juraj Kukolja and Karl-Josef Langen and Gereon Fink and Angela Kunoth and Yaping Shao and Thilo van Eimeren and Alexander Drzezga},

doi = {10.1089/brain.2020.0889},

issn = {2158-0022},

year  = {2021},

date = {2021-04-01},

journal = {Brain Connect},

volume = {11},

number = {3},

pages = {225--238},

abstract = { Graph-theoretical analyses have been previously used to investigate changes in the functional connectome in patients with Alzheimer's disease (AD). However, these analyses generally assume static organizational principles, thereby neglecting a fundamental reconfiguration of functional connections in the face of neurodegeneration.  Here, we focus on differences in the community structure of the functional connectome in young and old individuals and patients with AD. Patients with AD, moreover, underwent molecular imaging positron emission tomography by using [18F]AV1451 to measure tau burden, a major hallmark of AD.  Although the overall organizational principles of the community structure of the human functional connectome were preserved even in advanced healthy aging, they were considerably changed in AD. We discovered that the communities in AD are re-organized, with nodes changing their allegiance to communities, thus resulting in an overall less efficient re-organized community structure. We further discovered that nodes with a tendency to leave the communities displayed a relatively higher tau pathology burden.  Together, this study suggests that local tau pathology in AD is associated to fundamental changes in basic organizational principles of the human connectome. Our results shed new light on previous findings obtained by using the graph theory in AD and imply a general principle of the brain in response to neurodegeneration.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Weller2021,

title = {Finding New Communities: A Principle of Neuronal Network Reorganization in Alzheimer's Disease},

author = {Anna Weller and Gérard N. Bischof and Philipp Schlüter and Nils Richter and Julian Dronse and Oezguer Onur and Bernd Neumaier and Juraj Kukolja and Karl-Josef Langen and Gereon Fink and Angela Kunoth and Yaping Shao and Thilo van Eimeren and Alexander Drzezga},

doi = {10.1089/brain.2020.0889},

issn = {2158-0022},

year  = {2021},

date = {2021-04-01},

journal = {Brain Connectivity},

volume = {11},

number = {3},

pages = {225--238},

publisher = {Mary Ann Liebert Inc},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32620704,

title = {One-Stop Shop: F-Flortaucipir PET Differentiates Amyloid-Positive and -Negative Forms of Neurodegenerative Diseases},

author = {Jochen Hammes and Gérard N Bischof and Karl P Bohn and Özgür Onur and Anja Schneider and Klaus Fliessbach and Merle C Hönig and Frank Jessen and Bernd Neumaier and Alexander Drzezga and Thilo van Eimeren},

doi = {10.2967/jnumed.120.244061},

issn = {1535-5667},

year  = {2021},

date = {2021-02-01},

journal = {J Nucl Med},

volume = {62},

number = {2},

pages = {240--246},

abstract = {Tau protein aggregations are a hallmark of amyloid-associated Alzheimer disease and some forms of non-amyloid-associated frontotemporal lobar degeneration. In recent years, several tracers for in vivo tau imaging have been under evaluation. This study investigated the ability of F-flortaucipir PET not only to assess tau positivity but also to differentiate between amyloid-positive and -negative forms of neurodegeneration on the basis of different F-flortaucipir PET signatures.  The F-flortaucipir PET data of 35 patients with amyloid-positive neurodegeneration, 19 patients with amyloid-negative neurodegeneration, and 17 healthy controls were included in a data-driven scaled subprofile model (SSM)/principal-component analysis (PCA) identifying spatial covariance patterns. SSM/PCA pattern expression strengths were tested for their ability to predict amyloid status in a receiver-operating-characteristic analysis and validated with a leave-one-out approach.  Pattern expression strengths predicted amyloid status with a sensitivity of 0.94 and a specificity of 0.83. A support vector machine classification based on pattern expression strengths in 2 different SSM/PCA components yielded a prediction accuracy of 98%. Anatomically, prediction performance was driven by parietooccipital gray matter in amyloid-positive patients versus predominant white matter binding in amyloid-negative patients.  SSM/PCA-derived binding patterns of F-flortaucipir differentiate between amyloid-positive and -negative neurodegenerative diseases with high accuracy. F-flortaucipir PET alone may convey additional information equivalent to that from amyloid PET. Together with a perfusion-weighted early-phase acquisition (F-FDG PET-equivalent), a single scan potentially contains comprehensive information on amyloid (A), tau (T), and neurodegeneration (N) status as required by recent biomarker classification algorithms (A/T/N).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33410387,

title = {Predicting Working Memory Training Responsiveness in Parkinson's Disease: Both "System Hardware" and Room for Improvement Are Needed},

author = {Anja Ophey and Sarah Rehberg and Kathrin Giehl and Carsten Eggers and Paul Reker and Thilo van Eimeren and Elke Kalbe},

doi = {10.1177/1545968320981956},

issn = {1552-6844},

year  = {2021},

date = {2021-02-01},

journal = {Neurorehabil Neural Repair},

volume = {35},

number = {2},

pages = {117--130},

abstract = {. Patients with Parkinson's disease (PD) are highly vulnerable to develop cognitive dysfunctions, and the mitigating potential of early cognitive training (CT) is increasingly recognized. Predictors of CT responsiveness, which could help to tailor interventions individually, have rarely been studied in PD. This study aimed to examine individual characteristics of patients with PD associated with responsiveness to targeted working memory training (WMT). . Data of 75 patients with PD (age: 63.99 ± 9.74 years, 93% Hoehn & Yahr stage 2) without cognitive dysfunctions from a randomized controlled trial were analyzed using structural equation modeling. Latent change score models with and without covariates were estimated and compared between the WMT group ( = 37), who participated in a 5-week adaptive WMT, and a waiting list control group ( = 38). . Latent change score models yielded adequate model fit (χ-test  > .05, SRMR ≤ .08, CFI ≥ .95). For the near-transfer working memory composite, lower baseline performance, younger age, higher education, and higher fluid intelligence were found to significantly predict higher latent change scores in the WMT group, but not in the control group. For the far-transfer executive function composite, higher self-efficacy expectancy tended to significantly predict larger latent change scores. . The identified associations between individual characteristics and WMT responsiveness indicate that there has to be room for improvement (e.g., lower baseline performance) and also sufficient "hardware" (e.g., younger age, higher intelligence) to benefit in training-related cognitive plasticity. Our findings are discussed within the compensation versus magnification account. They need to be replicated by methodological high-quality research applying advanced statistical methods with larger samples.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ophey2021,

title = {Predicting Working Memory Training Responsiveness in Parkinson’s Disease: Both “System Hardware” and Room for Improvement Are Needed},

author = {Anja Ophey and Sarah Rehberg and Kathrin Giehl and Carsten Eggers and Paul Reker and Thilo van Eimeren and Elke Kalbe},

doi = {10.1177/1545968320981956},

issn = {1552-6844},

year  = {2021},

date = {2021-02-00},

journal = {Neurorehabil Neural Repair},

volume = {35},

number = {2},

pages = {117--130},

publisher = {SAGE Publications},

abstract = { Background. Patients with Parkinson’s disease (PD) are highly vulnerable to develop cognitive dysfunctions, and the mitigating potential of early cognitive training (CT) is increasingly recognized. Predictors of CT responsiveness, which could help to tailor interventions individually, have rarely been studied in PD. This study aimed to examine individual characteristics of patients with PD associated with responsiveness to targeted working memory training (WMT). Methods. Data of 75 patients with PD (age: 63.99 ± 9.74 years, 93% Hoehn & Yahr stage 2) without cognitive dysfunctions from a randomized controlled trial were analyzed using structural equation modeling. Latent change score models with and without covariates were estimated and compared between the WMT group ( n = 37), who participated in a 5-week adaptive WMT, and a waiting list control group ( n = 38). Results. Latent change score models yielded adequate model fit (χ2-test p > .05, SRMR ≤ .08, CFI ≥ .95). For the near-transfer working memory composite, lower baseline performance, younger age, higher education, and higher fluid intelligence were found to significantly predict higher latent change scores in the WMT group, but not in the control group. For the far-transfer executive function composite, higher self-efficacy expectancy tended to significantly predict larger latent change scores. Conclusions. The identified associations between individual characteristics and WMT responsiveness indicate that there has to be room for improvement (e.g., lower baseline performance) and also sufficient “hardware” (e.g., younger age, higher intelligence) to benefit in training-related cognitive plasticity. Our findings are discussed within the compensation versus magnification account. They need to be replicated by methodological high-quality research applying advanced statistical methods with larger samples. },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Hammes2020,

title = {One-Stop Shop:^{18}F-Flortaucipir PET Differentiates Amyloid-Positive and -Negative Forms of Neurodegenerative Diseases},

author = {Jochen Hammes and Gérard N. Bischof and Karl P. Bohn and Özgür Onur and Anja Schneider and Klaus Fliessbach and Merle C Hönig and Frank Jessen and Bernd Neumaier and Alexander Drzezga and Thilo van Eimeren},

doi = {10.2967/jnumed.120.244061},

issn = {2159-662X},

year  = {2021},

date = {2021-02-00},

journal = {J Nucl Med},

volume = {62},

number = {2},

pages = {240--246},

publisher = {Society of Nuclear Medicine},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Schaible2021,

title = {Effects of Lee Silverman Voice Treatment BIG and conventional physiotherapy on non-motor and motor symptoms in Parkinson’s disease: a randomized controlled study comparing three exercise models},

author = {Fabian Schaible and Franziska Maier and Timo Marcel Buchwitz and Frank Schwartz and Marius Hoock and Eckhard Schönau and Miriam Libuda and Anke Hordt and Thilo van Eimeren and Lars Timmermann and Carsten Eggers},

doi = {10.1177/1756286420986744},

issn = {1756-2864},

year  = {2021},

date = {2021-01-00},

journal = {Ther Adv Neurol Disord},

volume = {14},

publisher = {SAGE Publications},

abstract = {Background: Parkinson’s disease (PD) patients experience disabling motor dysfunctions as well as non-motor symptoms (NMSs) that can highly impact their perceived quality of life. Besides pharmacological treatment options, active intervention programs have set some attention in managing these symptoms. However, previous studies mainly assessed the effectiveness of active intervention programs on functional mobility and motor symptoms. Objective: This study aimed to investigate the effect of Lee Silverman Voice Treatment (LSVT) BIG, an intensified and personalized physiotherapy (INTENSIVE), and a conventional physiotherapy (NORMAL) on NMSs in PD. Method: Forty-four patients with mild to moderate PD were randomly assigned to one of the three treatment groups. LSVT BIG and INTENSIVE were delivered one-on-one in 16 1-hour sessions within 4 weeks (4×/week). Patients assigned to NORMAL received 16 individual 1-hour sessions within 8 weeks (2×/week). The primary outcome measure was the difference in change from baseline in the non-motor symptom assessment scale for Parkinson’s disease (NMSS) between treatment groups to follow up at week 8. Patients were blinded for the NMSS being the primary outcome, but not the different treatment groups. Results: ANCOVA (Analysis of Covariance) showed reduced NMSS scores for all groups, with INTENSIVE being superior to NORMAL ( p = 0.033). For secondary outcome measures (stride length, gait velocity and chair rising test) LSVT BIG and INTENSIVE were both superior to NORMAL. Conclusions: The study provides evidence that all three exercise programs are effective techniques to improve NMSs as well as motor function in PD. DRKS registration number: DRKS00008732 },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Steidel2021,

title = {Dopaminergic pathways and resting-state functional connectivity in Parkinson’s disease with freezing of gait},

author = {Kenan Steidel and Marina C. Ruppert and Irina Palaghia and Andrea Greuel and Masoud Tahmasian and Franziska Maier and Jochen Hammes and Thilo van Eimeren and Lars Timmermann and Marc Tittgemeyer and Alexander Drzezga and David Pedrosa and Carsten Eggers},

doi = {10.1016/j.nicl.2021.102899},

issn = {2213-1582},

year  = {2021},

date = {2021-00-00},

journal = {NeuroImage: Clinical},

volume = {32},

publisher = {Elsevier BV},

keywords = {},

pubstate = {published},

tppubtype = {article}

}