Publications

@article{Dzialas2025,

title = {Dopamine Transporter Imaging as Objective Monitoring Biomarker in Parkinson's Disease},

author = {Verena Dzialas and Gérard N. Bischof and Kathrin Möllenhoff and Alexander Drzezga and Thilo van Eimeren},

doi = {10.1002/ana.27223},

issn = {1531-8249},

year  = {2025},

date = {2025-03-27},

urldate = {2025-03-27},

journal = {Annals of Neurology},

publisher = {Wiley},

abstract = {<jats:sec><jats:title>Objective</jats:title><jats:p>Although dopamine transporter (DaT) imaging is a valuable diagnostic biomarker, few studies have investigated its utility in objectively monitoring disease progression in patients with Parkinson's disease (PD). To date, no study has established a longitudinal relationship between the DaT signal decline and the motor symptom increase, potentially due to neglected factors such as brain regions, disease laterality, and symptom subtypes, which this study addresses.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>This cohort study included participants who met the Movement Disorder Society (MDS) criteria for PD, with longitudinal imaging and clinical data from the Parkinson's Progression Markers Initiative Database. Linear mixed model analyses were used to investigate the relationship between the DaT signal decline and the motor symptom severity increase over time. We hypothesized that a decline in putaminal DaT availability in the less affected hemisphere would be associated with increasing contralateral motor symptoms, measured by the Unified Parkinson's Disease Rating Scale (UPDRS). Additional models explored the effects of different brain regions (caudate and putamen), symptom categories (MDS UPDRSIII score with and without tremor items), and disease onset laterality (left or right hemisphere).</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>We included 719 participants (443 male patients and 276 female patients; mean age = 62.2 ± 9.5 years) with 1,981 available data points. As hypothesized, we observed a significant association between the decrease in the less affected putaminal DaT signal and motor symptom increase in the contralateral body side, independent of including or excluding tremor scores.</jats:p></jats:sec><jats:sec><jats:title>Interpretation</jats:title><jats:p>Our findings support the use of repetitive DaT imaging for objectively monitoring PD progression. This could facilitate personalized disease tracking, subtyping, and intervention testing in the future. ANN NEUROL 2025</jats:p></jats:sec>},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Kling2025,

title = {Exploring the origins of frequent tau-PET signal in vermal and adjacent regions},

author = {Agnes Kling and Julia Kusche-Palenga and Carla Palleis and Alexander Jäck and Alexander M. Bernhardt and Lukas Frontzkowski and Sebastian N. Roemer and Luna Slemann and Mirlind Zaganjori and Maximilian Scheifele and Lars Paeger and Gérard N. Bischof and Thilo van Eimeren and Alexander Drzezga and Osama Sabri and Michael Rullmann and Henryk Barthel and Johannes Levin and Jochen Herms and Nicolai Franzmeier and Günter Höglinger and Sigrun Roeber and Matthias Brendel and Johannes Gnörich},

doi = {10.1007/s00259-025-07199-x},

issn = {1619-7089},

year  = {2025},

date = {2025-03-18},

urldate = {2025-03-18},

journal = {Eur J Nucl Med Mol Imaging},

publisher = {Springer Science and Business Media LLC},

abstract = {<jats:title>Abstract</jats:title>

          <jats:sec>

            <jats:title>Purpose</jats:title>

            <jats:p>Off-target binding remains a significant challenge in tau-PET neuroimaging. While off-targets including monoamine oxidase enzymes and neuromelanin-containing cells have been identified, recent studies indicated a relevant binding of novel tau tracers to melanin-containing structures. To date, little is known about the effect of melanocytes in the meninges on tracer signals in brain PET data. Thus, we aimed to identify the target structure causal for the frequently observed [<jats:sup>18</jats:sup>F]PI-2620 PET signal in the vermis and adjacent cerebellar regions.</jats:p>

          </jats:sec>

          <jats:sec>

            <jats:title>Methods</jats:title>

            <jats:p>274 participants underwent dynamic [<jats:sup>18</jats:sup>F]PI-2620 tau-PET: 3/4R-tauopathies (n = 85), 4R-tauopathies (n = 147), tau-negative disease controls (n = 24), and healthy controls (n = 18). Standardized uptake value ratio (SUVR) and kinetic parameters including the distribution volume ratio (DVR), tracer clearance (k2) and relative perfusion (R1), were compared among the cohorts and sexes using the Automated Anatomical Labelling (AAL) atlas. Age and p-Tau levels in cerebrospinal fluid (CSF) were assessed for their relationship with vermal tau-PET signal. Furthermore, we combined autoradiographic and histochemical experiments on post-mortem brain tissue of deceased patients (n = 9).</jats:p>

          </jats:sec>

          <jats:sec>

            <jats:title>Results</jats:title>

            <jats:p>Male participants revealed higher mean vermal [<jats:sup>18</jats:sup>F]PI-2620 DVR (0.95 ± 0.13; vs. females 0.88 ± 0.10, p < 0.0001). Sex-related differences were most pronounced in the 3/4R-tauopathy cohort (p < 0.0001). Mean SUVR<jats:sub>Ver/Cbl</jats:sub>, k2 and correlation analyses of kinetic parameters did not differ among groups. Histological assessments revealed co-localization of leptomeningeal pigmented cells with strong autoradiography signal spots within the vermal fissures. Tau-related autoradiography signals, age or p-Tau levels did not correlate significantly with tau-PET signals. Iron deposits did not cause relevant autoradiography signals in the vermis.</jats:p>

          </jats:sec>

          <jats:sec>

            <jats:title>Conclusion</jats:title>

            <jats:p>Leptomeningeal melanocytes are the primary target structure for [<jats:sup>18</jats:sup>F]PI-2620 PET binding in anterior vermis, whereas iron and tau deposits do not contribute significantly.

</jats:p>

          </jats:sec>},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Doering2025,

title = {“Fill States”: PET-derived Markers of the Spatial Extent of Alzheimer Disease Pathology},

author = {Elena Doering and Merle C. Hoenig and Kathrin Giehl and Verena Dzialas and Grégory Andrassy and Abdelmajid Bader and Andreas Bauer and David Elmenhorst and Johannes Ermert and Silke Frensch and Elena Jäger and Frank Jessen and Philipp Krapf and Tina Kroll and Christoph Lerche and Julia Lothmann and Andreas Matusch and Bernd Neumaier and Oezguer A. Onur and Alfredo Ramirez and Nils Richter and Frederik Sand and Lutz Tellmann and Hendrik Theis and Philip Zeyen and Thilo van Eimeren and Alexander Drzezga and Gérard N. Bischof},

doi = {10.1148/radiol.241482},

issn = {1527-1315},

year  = {2025},

date = {2025-03-01},

urldate = {2025-03-01},

journal = {Radiology},

volume = {314},

number = {3},

publisher = {Radiological Society of North America (RSNA)},

abstract = {<jats:p> The spatial extent of amyloid, tau, and neurodegeneration, derived from PET imaging, has higher diagnostic performance for cognitive impairment severity compared with standardized uptake value ratios. </jats:p>},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Bauer2025,

title = {Pragmatic algorithm for visual assessment of 4-Repeat tauopathies in [18F]PI-2620 PET Scans},

author = {Theresa Bauer and Matthias Brendel and Mirlind Zaganjori and Alexander M. Bernhardt and Alexander Jäck and Sophia Stöcklein and Maximilian Scheifele and Johannes Levin and Thilo van Eimeren and Alexander Drzezga and Osama Sabri and Henryk Barthel and Robert Perneczky and Günter Höglinger and Nicolai Franzmeier and Johannes Gnörich},

doi = {10.1016/j.neuroimage.2025.121001},

issn = {1053-8119},

year  = {2025},

date = {2025-02-00},

urldate = {2025-02-00},

journal = {NeuroImage},

volume = {306},

publisher = {Elsevier BV},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Slemann2024,

title = {Neuronal and oligodendroglial, but not astroglial, tau translates to in vivo tau PET signals in individuals with primary tauopathies},

author = {Luna Slemann and Johannes Gnörich and Selina Hummel and Laura M. Bartos and Carolin Klaus and Agnes Kling and Julia Kusche-Palenga and Sebastian T. Kunte and Lea H. Kunze and Amelie L. Englert and Yunlei Li and Letizia Vogler and Sabrina Katzdobler and Carla Palleis and Alexander Bernhardt and Alexander Jäck and Andreas Zwergal and Franziska Hopfner and Sebastian N. Roemer-Cassiano and Gloria Biechele and Sophia Stöcklein and Gerard Bischof and Thilo van Eimeren and Alexander Drzezga and Osama Sabri and Henryk Barthel and Gesine Respondek and Timo Grimmer and Johannes Levin and Jochen Herms and Lars Paeger and Marie Willroider and Leonie Beyer and Günter U. Höglinger and Sigrun Roeber and Nicolai Franzmeier and Matthias Brendel},

doi = {10.1007/s00401-024-02834-7},

issn = {1432-0533},

year  = {2024},

date = {2024-12-00},

urldate = {2024-12-00},

journal = {Acta Neuropathol},

volume = {148},

number = {1},

publisher = {Springer Science and Business Media LLC},

abstract = {<jats:title>Abstract</jats:title><jats:p>Tau PET has attracted increasing interest as an imaging biomarker for 4-repeat (4R)-tauopathy progressive supranuclear palsy (PSP). However, the translation of in vitro 4R-tau binding to in vivo tau PET signals is still unclear. Therefore, we performed a translational study using a broad spectrum of advanced methodologies to investigate the sources of [<jats:sup>18</jats:sup>F]PI-2620 tau PET signals in individuals with 4R-tauopathies, including a pilot PET autopsy study in patients. First, we conducted a longitudinal [<jats:sup>18</jats:sup>F]PI-2620 PET/MRI study in a 4-repeat-tau mouse model (PS19) and detected elevated [<jats:sup>18</jats:sup>F]PI-2620 PET signals in the presence of high levels of neuronal tau. An innovative approach involving cell sorting after radiotracer injection in vivo revealed higher tracer uptake in single neurons than in the astrocytes of PS19 mice. Regional [<jats:sup>18</jats:sup>F]PI-2620 tau PET signals during the lifetime correlated with the abundance of fibrillary tau and with autoradiography signal intensity in PSP patients and disease controls who underwent autopsy 2–63 months after tau PET. In autoradiography, tau-positive neurons and oligodendrocytes with a high AT8 density, but not tau-positive astrocytes, were the drivers of [<jats:sup>18</jats:sup>F]PI-2620 autoradiography signals in individuals with PSP. The high tau abundance in oligodendrocytes at the boundary of gray and white matter facilitated the identification of an optimized frontal lobe target region to detect the tau burden in patients with PSP. In summary, neuronal and oligodendroglial tau constitutes the dominant source of tau PET radiotracer binding in 4-repeat-tauopathies, translating to an in vivo signal.</jats:p>},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Dzialas2024,

title = {Houston, We Have AI Problem! Quality Issues with Neuroimaging‐Based Artificial Intelligence in Parkinson's Disease: A Systematic Review},

author = {Verena Dzialas and Elena Doering and Helena Eich and Antonio P. Strafella and David E. Vaillancourt and Kristina Simonyan and Thilo van Eimeren},

doi = {10.1002/mds.30002},

issn = {1531-8257},

year  = {2024},

date = {2024-12-00},

urldate = {2024-12-00},

journal = {Movement Disorders},

volume = {39},

number = {12},

pages = {2130--2143},

publisher = {Wiley},

abstract = {In recent years, many neuroimaging studies have applied artificial intelligence (AI) to facilitate existing challenges in Parkinson's disease (PD) diagnosis, prognosis, and intervention. The aim of this systematic review was to provide an overview of neuroimaging‐based AI studies and to assess their methodological quality. A PubMed search yielded 810 studies, of which 244 that investigated the utility of neuroimaging‐based AI for PD diagnosis, prognosis, or intervention were included. We systematically categorized studies by outcomes and rated them with respect to five minimal quality criteria (MQC) pertaining to data splitting, data leakage, model complexity, performance reporting, and indication of biological plausibility. We found that the majority of studies aimed to distinguish PD patients from healthy controls (54%) or atypical parkinsonian syndromes (25%), whereas prognostic or interventional studies were sparse. Only 20% of evaluated studies passed all five MQC, with data leakage, non‐minimal model complexity, and reporting of biological plausibility as the primary factors for quality loss. Data leakage was associated with a significant inflation of accuracies. Very few studies employed external test sets (8%), where accuracy was significantly lower, and 19% of studies did not account for data imbalance. Adherence to MQC was low across all observed years and journal impact factors. This review outlines that AI has been applied to a wide variety of research questions pertaining to PD; however, the number of studies failing to pass the MQC is alarming. Therefore, we provide recommendations to enhance the interpretability, generalizability, and clinical utility of future AI applications using neuroimaging in PD. },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Witt2024,

title = {Diagnostics and treatment of impulse control disorders, psychosis and delirium: systemic review-based recommendations - guideline “Parkinson’s disease” of the German Society of Neurology},

author = {Karsten Witt and Johannes Levin and Thilo van Eimeren and Alkomiet Hasan and Georg Ebersbach and and Mathias Bähr and Jos Becktepe and Daniela Berg and Kathrin Brockmann and Carsten Buhmann and Andrés Ceballos-Baumann and Joseph Claßen and Cornelius Deuschl and Günther Deuschl and Richard Dodel and Georg Ebersbach and Carsten Eggers and Thilo van Eimeren and Alessandra Fanciulli and Bruno Fimm and Ann-Kristin Folkerts and Madeleine Gausepohl and Alkomiet Hasan and Wiebke Hermann and Rüdiger Hilker-Roggendorf and Günter Höglinger and Matthias Höllerhage and Franziska Hopfner and Wolfgang Jost and Elke Kalbe and Jan Kassubek and Stephan Klebe and Christine Klein and Martin Klietz and Thomas Köglsperger and Andrea Kühn and Paul Krack and Florian Krismer and Gregor Kuhlenbäumer and Johannes Levin and Inga Liepelt-Scarfone and Paul Lingor and Kai Loewenbrück and Matthias Löhle and Stefan Lorenzl and Sylvia Maaß and Walter Maetzler and Regina Menzel and Philipp T. Meyer and Brit Mollenhauer and Manuela Neumann and Per Odin and Tiago Outeiro and Monika Pötter-Nerger and René Reese and Kathrin Reetz and Olaf Rieß and Viktoria Ruf and Anja Schneider and Christoph Schrader and Alfons Schnitzler and Klaus Seppi and Friederike Sixel-Döring and Alexander Storch and Lars Tönges and Claudia Trenkwalder and Thilo van Eimeren and Uwe Walter and Tobias Wächter and Tobias Warnecke and Florian Wegner and Christian Winkler and Karsten Witt and Dirk Woitalla and Kirsten Zeuner and Martina Bantel and Jonas L. Witt},

doi = {10.1007/s00415-024-12576-x},

issn = {1432-1459},

year  = {2024},

date = {2024-12-00},

urldate = {2024-12-00},

journal = {J Neurol},

volume = {271},

number = {12},

pages = {7402--7421},

publisher = {Springer Science and Business Media LLC},

abstract = {<jats:title>Abstract</jats:title><jats:sec>

                <jats:title>Background and objective</jats:title>

                <jats:p>Impulse control disorders (ICD), psychosis and delirium are part of the spectrum of behavioural changes associated with Parkinson’s disease (PD). The diagnostic and therapeutic management of these rather complex neuropsychiatric conditions has been updated in the clinical guideline by the German Society of Neurology (DGN).</jats:p>

              </jats:sec><jats:sec>

                <jats:title>Methods</jats:title>

                <jats:p>Recommendations are based on a systematic literature reviews, other relevant guidelines and expert opinion.</jats:p>

              </jats:sec><jats:sec>

                <jats:title>Results</jats:title>

                <jats:p>Patients receiving dopamine agonists (DA) therapy should be informed about the symptoms and risks of an ICD and should be routinely screened for ICD symptoms. In the presence of an ICD, DA should be reduced or discontinued and psychotherapeutic treatment may be considered. Non-oral therapies (levodopa/carbidopa intestinal gel infusion or deep brain stimulation) may also be an option for appropriate candidates. Psychosis in PD often has a gradual onset. Cognitive and affective disorders, psychiatric and medical comorbidities as well as polypharmacy are risk factors for a psychosis. Non-pharmacological treatments should be implemented as soon as possible and anti-parkinsonian medications should be adjusted/reduced if feasible. For psychosis associated with PD, quetiapine or clozapine should be used on an as-needed basis and for as short a time as is necessary, with safety monitoring. Delirium in PD may be underdiagnosed due to an overlap with chronic neuropsychiatric features of PD. Although transient by definition, delirium in PD can lead to permanent cognitive decline, motor impairment and increased mortality. Management of delirium includes pharmacological and non-pharmacological interventions.</jats:p>

              </jats:sec><jats:sec>

                <jats:title>Conclusion</jats:title>

                <jats:p>The updated guideline encompasses the evidence-based diagnostic, non-pharmacological and pharmacological management of ICD, psychosis and delirium in PD.</jats:p>

              </jats:sec>},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Dzialas2024b,

title = {Structural underpinnings and long-term effects of resilience in Parkinson’s disease},

author = {Verena Dzialas and Merle C. Hoenig and Stéphane Prange and Gérard N. Bischof and and Alexander Drzezga and Thilo van Eimeren},

doi = {10.1038/s41531-024-00699-x},

issn = {2373-8057},

year  = {2024},

date = {2024-12-00},

urldate = {2024-12-00},

journal = {npj Parkinsons Dis.},

volume = {10},

number = {1},

publisher = {Springer Science and Business Media LLC},

abstract = {<jats:title>Abstract</jats:title><jats:p>Resilience in neuroscience generally refers to an individual’s capacity to counteract the adverse effects of a neuropathological condition. While resilience mechanisms in Alzheimer’s disease are well-investigated, knowledge regarding its quantification, neurobiological underpinnings, network adaptations, and long-term effects in Parkinson’s disease is limited. Our study involved 151 Parkinson’s patients from the Parkinson’s Progression Marker Initiative Database with available Magnetic Resonance Imaging, Dopamine Transporter Single-Photon Emission Computed Tomography scans, and clinical information. We used an improved prediction model linking neuropathology to symptom severity to estimate individual resilience levels. Higher resilience levels were associated with a more active lifestyle, increased grey matter volume in motor-associated regions, a distinct structural connectivity network and maintenance of relative motor functioning for up to a decade. Overall, the results indicate that relative maintenance of motor function in Parkinson’s patients may be associated with greater neuronal substrate, allowing higher tolerance against neurodegenerative processes through dynamic network restructuring.</jats:p>},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Oltra2024,

title = {A multi-site study on sex differences in cortical thickness in non-demented Parkinson’s disease},

author = {Javier Oltra 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 Gemma C. Monté-Rubio and Natalia Ojeda and Javier Peña and Marina C. Ruppert and Roser Sala-Llonch and Hendrik Theis and Carme Uribe and Carme Junque},

doi = {10.1038/s41531-024-00686-2},

issn = {2373-8057},

year  = {2024},

date = {2024-12-00},

urldate = {2024-12-00},

journal = {npj Parkinsons Dis.},

volume = {10},

number = {1},

publisher = {Springer Science and Business Media LLC},

abstract = {<jats:title>Abstract</jats:title><jats:p>Clinical, cognitive, and atrophy characteristics depending on sex have been previously reported in Parkinson’s disease (PD). However, though sex differences in cortical gray matter measures in early drug naïve patients have been described, little is known about differences in cortical thickness (CTh) as the disease advances. Our multi-site sample comprised 211 non-demented PD patients (64.45% males; mean age 65.58 ± 8.44 years old; mean disease duration 6.42 ± 5.11 years) and 86 healthy controls (50% males; mean age 65.49 ± 9.33 years old) with available T1-weighted 3 T MRI data from four international research centers. Sex differences in regional mean CTh estimations were analyzed using generalized linear models. The relation of CTh in regions showing sex differences with age, disease duration, and age of onset was examined through multiple linear regression. PD males showed thinner cortex than PD females in six frontal (bilateral caudal middle frontal, bilateral superior frontal, left precentral and right pars orbitalis), three parietal (bilateral inferior parietal and left supramarginal), and one limbic region (right posterior cingulate). In PD males, lower CTh values in nine out of ten regions were associated with longer disease duration and older age, whereas in PD females, lower CTh was associated with older age but with longer disease duration only in one region. Overall, male patients show a more widespread pattern of reduced CTh compared with female patients. Disease duration seems more relevant to explain reduced CTh in male patients, suggesting worse prognostic over time. Further studies should explore sex-specific cortical atrophy trajectories using large longitudinal multi-site data.</jats:p>},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Passaretti2024,

title = {Neurophysiological markers of motor compensatory mechanisms in early Parkinson’s disease},

author = {Massimiliano Passaretti and Roberto Cilia and Sara Rinaldo and Davide Rossi Sebastiano and Eva Orunesu and Grazia Devigili and Arianna Braccia and Giulia Paparella and Martina De Riggi and Thilo van Eimeren and Antonio Paolo Strafella and Paola Lanteri and Alfredo Berardelli and Matteo Bologna and Roberto Eleopra},

doi = {10.1093/brain/awae210},

issn = {1460-2156},

year  = {2024},

date = {2024-11-04},

volume = {147},

number = {11},

pages = {3714--3726},

publisher = {Oxford University Press (OUP)},

abstract = {Abstract

               Compensatory mechanisms in Parkinson’s disease are defined as the changes that the brain uses to adapt to neurodegeneration and progressive dopamine reduction. Motor compensation in early Parkinson’s disease could, in part, be responsible for a unilateral onset of clinical motor signs despite the presence of bilateral nigrostriatal degeneration. Although several mechanisms have been proposed for compensatory adaptations in Parkinson’s disease, the underlying pathophysiology is unclear.

               Here, we investigate motor compensation in Parkinson’s disease by investigating the relationship between clinical signs, dopamine transporter imaging data and neurophysiological measures of the primary motor cortex (M1), using transcranial magnetic stimulation in presymptomatic and symptomatic hemispheres of patients. In this cross-sectional, multicentre study, we screened 82 individuals with Parkinson’s disease. Patients were evaluated clinically in their medication OFF state using standardized scales. Sixteen Parkinson’s disease patients with bilateral dopamine transporter deficit in the putamina but unilateral symptoms were included. Twenty-eight sex- and age-matched healthy controls were also investigated. In all participants, we tested cortical excitability using single- and paired-pulse techniques, interhemispheric inhibition and cortical plasticity with paired associative stimulation. Data were analysed with ANOVAs, multiple linear regression and logistic regression models. Individual coefficients of motor compensation were defined in patients based on clinical and imaging data, i.e. the motor compensation coefficient. The motor compensation coefficient includes an asymmetry score to balance motor and dopamine transporter data between the two hemispheres, in addition to a hemispheric ratio accounting for the relative mismatch between the magnitude of motor signs and dopaminergic deficit.

               In patients, corticospinal excitability and plasticity were higher in the presymptomatic compared with the symptomatic M1. Also, interhemispheric inhibition from the presymptomatic to the symptomatic M1 was reduced. Lower putamen binding was associated with higher plasticity and reduced interhemispheric inhibition in the presymptomatic hemisphere. The motor compensation coefficient distinguished the presymptomatic from the symptomatic hemisphere. Finally, in the presymptomatic hemisphere, a higher motor compensation coefficient was associated with lower corticospinal excitability and interhemispheric inhibition and with higher plasticity.

               In conclusion, the present study suggests that motor compensation involves M1–striatal networks and intercortical connections becoming more effective with progressive loss of dopaminergic terminals in the putamen. The balance between these motor networks seems to be driven by cortical plasticity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Banwinkler2024,

title = {Putaminal dopamine modulates movement motivation in Parkinson’s disease},

author = {Magdalena Banwinkler and Verena Dzialas and Lionel Rigoux and Adrian L Asendorf and Hendrik Theis and Kathrin Giehl and Marc Tittgemeyer and Merle C Hoenig and Thilo van Eimeren},

doi = {10.1093/brain/awae214},

issn = {1460-2156},

year  = {2024},

date = {2024-10-03},

urldate = {2024-10-03},

journal = {Brain},

volume = {147},

number = {10},

pages = {3352--3357},

publisher = {Oxford University Press (OUP)},

abstract = {<jats:title>Abstract</jats:title>

               <jats:p>The relative inability to produce effortful movements is the most specific motor sign of Parkinson’s disease, which is primarily characterized by loss of dopaminergic terminals in the putamen. The motor motivation hypothesis suggests that this motor deficit may not reflect a deficiency in motor control per se, but a deficiency in cost-benefit considerations for motor effort. For the first time, we investigated the quantitative effect of dopamine depletion on the motivation of motor effort in Parkinson’s disease.</jats:p>

               <jats:p>A total of 21 early-stage, unmedicated patients with Parkinson’s disease and 26 healthy controls were included. An incentivized force task was used to capture the amount of effort participants were willing to invest for different monetary incentive levels and dopamine transporter depletion in the bilateral putamen was assessed.</jats:p>

               <jats:p>Our results demonstrate that patients with Parkinson’s disease applied significantly less grip force than healthy controls, especially for low incentive levels. Congruously, decrease of motor effort with greater loss of putaminal dopaminergic terminals was most pronounced for low incentive levels. This signifies that putaminal dopamine is most critical to motor effort when the trade-off with the benefit is poor.</jats:p>

               <jats:p>Taken together, we provide direct evidence that the reduction of effortful movements in Parkinson’s disease depends on motivation and that this effect is associated with putaminal dopaminergic degeneration.</jats:p>},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Theis2024b,

title = {Imaging Biomarkers in Prodromal and Earliest Phases of Parkinson’s Disease},

author = {Hendrik Theis and Nicola Pavese and Irena Rektorová and Thilo van Eimeren},

doi = {10.3233/jpd-230385},

issn = {1877-718X},

year  = {2024},

date = {2024-10-01},

urldate = {2024-10-01},

journal = {Journal of Parkinson’s Disease},

volume = {14},

number = {s2},

pages = {S353--S365},

publisher = {SAGE Publications},

abstract = {<jats:p> Assessing imaging biomarker in the prodromal and early phases of Parkinson’s disease (PD) is of great importance to ensure an early and safe diagnosis. In the last decades, imaging modalities advanced and are now able to assess many different aspects of neurodegeneration in PD. MRI sequences can measure iron content or neuromelanin. Apart from SPECT imaging with Ioflupane, more specific PET tracers to assess degeneration of the dopaminergic system are available. Furthermore, metabolic PET patterns can be used to anticipate a phenoconversion from prodromal PD to manifest PD. In this regard, it is worth mentioning that PET imaging of inflammation will gain significance. Molecular imaging of neurotransmitters like serotonin, noradrenaline and acetylcholine shed more light on non-motor symptoms. Outside of the brain, molecular imaging of the heart and gut is used to measure PD-related degeneration of the autonomous nervous system. Moreover, optical coherence tomography can noninvasively detect degeneration of retinal fibers as a potential biomarker in PD. In this review, we describe these state-of-the-art imaging modalities in early and prodromal PD and point out in how far these techniques can and will be used in the future to pave the way towards a biomarker-based staging of PD. </jats:p>},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Theis2024,

title = {Progressive Supranuclear Palsy: Subcortical Tau Depositions Are Associated with Cortical Perfusion in Frontal and Limbic Regions},

author = {Hendrik Theis and Michael T. Barbe and Alexander Drzezga and Gereon R. Fink and Bernd Neumaier and Gérard N. Bischof and Thilo van Eimeren},

doi = {10.3233/jpd-240210},

issn = {1877-718X},

year  = {2024},

date = {2024-09-03},

urldate = {2024-09-03},

journal = {Journal of Parkinson’s Disease},

volume = {14},

number = {6},

pages = {1271--1276},

publisher = {SAGE Publications},

abstract = { In progressive supranuclear palsy (PSP), subcortical tau and cortical perfusion can be assessed using the tracer ^{18</jsup>F]PI-2620. We investigated if subcortical tau (globus pallidus internus, dentate nucleus) and frontal/limbic perfusion correlate in a cohort of 32 PSP patients. Tau in subcortical regions showed significant negative correlation with perfusion in limbic cortex. Perfusion in frontal regions was negatively associated with tau in both subcortical regions, but the significance threshold was only passed for the dentate nucleus. A reason could be a diaschisis-like phenomenon; that is, subcortical tau could lead to reduced connectivity to frontal regions and, thereby, to decreased perfusion. },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Asendorf2024,

title = {Dynamic properties in functional connectivity changes and striatal dopamine deficiency in Parkinson's disease},

author = {Adrian L. Asendorf and Hendrik Theis and Marc Tittgemeyer and Lars Timmermann and Gereon R. Fink and Alexander Drzezga and Carsten Eggers and Marina C. Ruppert‐Junck and David J. Pedrosa and Merle C. Hoenig and Thilo van Eimeren},

doi = {10.1002/hbm.26776},

issn = {1097-0193},

year  = {2024},

date = {2024-07-15},

urldate = {2024-07-15},

journal = {Human Brain Mapping},

volume = {45},

number = {10},

publisher = {Wiley},

abstract = {<jats:title>Abstract</jats:title><jats:sec><jats:label/><jats:p>Recent studies in Parkinson's disease (PD) patients reported disruptions in dynamic functional connectivity (dFC, i.e., a characterization of spontaneous fluctuations in functional connectivity over time). Here, we assessed whether the integrity of striatal dopamine terminals directly modulates dFC metrics in two separate PD cohorts, indexing dopamine‐related changes in large‐scale brain network dynamics and its implications in clinical features. We pooled data from two disease‐control cohorts reflecting early PD. From the Parkinson's Progression Marker Initiative (PPMI) cohort, resting‐state functional magnetic resonance imaging (rsfMRI) and dopamine transporter (DaT) single‐photon emission computed tomography (SPECT) were available for 63 PD patients and 16 age‐ and sex‐matched healthy controls. From the clinical research group 219 (KFO) cohort, rsfMRI imaging was available for 52 PD patients and 17 age‐ and sex‐matched healthy controls. A subset of 41 PD patients and 13 healthy control subjects additionally underwent <jats:sup>18</jats:sup>F‐DOPA‐positron emission tomography (PET) imaging. The striatal synthesis capacity of <jats:sup>18</jats:sup>F‐DOPA PET and dopamine terminal quantity of DaT SPECT images were extracted for the putamen and the caudate. After rsfMRI pre‐processing, an independent component analysis was performed on both cohorts simultaneously. Based on the derived components, an individual sliding window approach (44 s window) and a subsequent k‐means clustering were conducted separately for each cohort to derive dFC states (reemerging intra‐ and interindividual connectivity patterns). From these states, we derived temporal metrics, such as average dwell time per state, state attendance, and number of transitions and compared them between groups and cohorts. Further, we correlated these with the respective measures for local dopaminergic impairment and clinical severity. The cohorts did not differ regarding age and sex. Between cohorts, PD groups differed regarding disease duration, education, cognitive scores and L‐dopa equivalent daily dose. In both cohorts, the dFC analysis resulted in three distinct states, varying in connectivity patterns and strength. In the PPMI cohort, PD patients showed a lower state attendance for the globally integrated (GI) state and a lower number of transitions than controls. Significantly, worse motor scores (Unified Parkinson's Disease Rating Scale Part III) and dopaminergic impairment in the putamen and the caudate were associated with low average dwell time in the GI state and a low total number of transitions. These results were not observed in the KFO cohort: No group differences in dFC measures or associations between dFC variables and dopamine synthesis capacity were observed. Notably, worse motor performance was associated with a low number of bidirectional transitions between the GI and the lesser connected (LC) state across the PD groups of both cohorts. Hence, in early PD, relative preservation of motor performance may be linked to a more dynamic engagement of an interconnected brain state. Specifically, those large‐scale network dynamics seem to relate to striatal dopamine availability. Notably, most of these results were obtained only for one cohort, suggesting that dFC is impacted by certain cohort features like educational level, or disease severity. As we could not pinpoint these features with the data at hand, we suspect that other, in our case untracked, demographical features drive connectivity dynamics in PD.</jats:p></jats:sec><jats:sec><jats:title>Practitioner Points</jats:title><jats:p><jats:list list-type="bullet">

<jats:list-item><jats:p>Exploring dopamine's role in brain network dynamics in two Parkinson's disease (PD) cohorts, we unraveled PD‐specific changes in dynamic functional connectivity.</jats:p></jats:list-item>

<jats:list-item><jats:p>Results in the Parkinson's Progression Marker Initiative (PPMI) and the KFO cohort suggest motor performance may be linked to a more dynamic engagement and disengagement of an interconnected brain state.</jats:p></jats:list-item>

<jats:list-item><jats:p>Results only in the PPMI cohort suggest striatal dopamine availability influences large‐scale network dynamics that are relevant in motor control.</jats:p></jats:list-item>

</jats:list></jats:p></jats:sec>},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Smith2024,

title = {Pharmacological Enhancement of Dopamine Neurotransmission Does Not Affect Illusory Pattern Perception},

author = {Elke Smith and Simon Michalski and Kilian Knauth and Deniz Tuzsus and Hendrik Theis and Thilo van Eimeren and Jan Peters},

doi = {10.1523/eneuro.0465-23.2024},

issn = {2373-2822},

year  = {2024},

date = {2024-07-00},

urldate = {2024-07-00},

journal = {eNeuro},

volume = {11},

number = {7},

pages = {ENEURO.0465--23.2024},

publisher = {Society for Neuroscience},

abstract = {<jats:p>Psychotic symptoms and delusional beliefs have been linked to dopamine transmission in both healthy and clinical samples and are assumed to result at least in part from perceiving illusory patterns in noise. However, the existing literature on the role of dopamine in detecting patterns in noise is inconclusive. To address this issue, we assessed the effect of manipulating dopaminergic neurotransmission on illusory pattern perception in healthy individuals (<italic>n </italic>= 48,<italic>n </italic>= 19 female) in a double-blind placebo-controlled within-subjects design. We predicted individuals on versus off ʟ-DOPA to be more likely to perceive illusory patterns, specifically objects in images containing only noise. Using a signal detection model, however, we found no credible evidence that ʟ-DOPA compared with placebo increased false alarm rates. Further, ʟ-DOPA did not reliably modulate measures of accuracy, discrimination sensitivity, and response bias. In all cases, Bayesian statistics revealed strong evidence in favor of the null hypothesis. The task design followed previous work on illusory pattern perception and comprised a limited number of items per condition. The results therefore need to be interpreted with caution, as power was limited. Future studies should address illusory pattern perception using more items and take into account potential dose-dependent effects and differential effects in healthy versus clinical samples.</jats:p>},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Giehl2024,

title = {Sharing brain imaging data in the Open Science era: how and why?},

author = {Kathrin Giehl and Henk-Jan Mutsaerts and Kristien Aarts and Frederik Barkhof and Svenja Caspers and Gaël Chetelat and Marie-Elisabeth Colin and Emrah Düzel and Giovanni B Frisoni and M Arfan Ikram and Jorge Jovicich and Silvia Morbelli and Wolfgang Oertel and Christian Paret and Daniela Perani and Petra Ritter and Bàrbara Segura and Laura E M Wisse and Elke De Witte and Stefano F Cappa and Thilo van Eimeren},

doi = {10.1016/s2589-7500(24)00069-4},

issn = {2589-7500},

year  = {2024},

date = {2024-07-00},

urldate = {2024-07-00},

journal = {The Lancet Digital Health},

volume = {6},

number = {7},

pages = {e526--e535},

publisher = {Elsevier BV},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Bischof2024,

title = {Improved Tau PET SUVR Quantification in 4-Repeat Tau Phenotypes with [^{18}F]PI-2620},

author = {Gérard N. Bischof and Matthias Brendel and Henryk Barthel and Hendrik Theis and Michael Barbe and Peter Bartenstein and Joseph Claasen and Adrian Danek and Günter Höglinger and Johannes Levin and Ken Marek and Bernd Neumaier and Carla Palleis and Marianne Patt and Michael Rullmann and Dorothee Saur and Matthias L. Schroeter and John Seibyl and Mengmeng Song and Andrew Stephens and Osama Sabri and Alexander Drzezga and Thilo van Eimeren},

doi = {10.2967/jnumed.123.265930},

issn = {2159-662X},

year  = {2024},

date = {2024-06-00},

urldate = {2024-06-00},

journal = {J Nucl Med},

volume = {65},

number = {6},

pages = {952--955},

publisher = {Society of Nuclear Medicine},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Langerscheidt2024,

title = {Genetic forms of tauopathies: inherited causes and implications of Alzheimer’s disease-like TAU pathology in primary and secondary tauopathies},

author = {Felix Langerscheidt and Tamara Wied and Mohamed Aghyad Al Kabbani and Thilo van Eimeren and Gilbert Wunderlich and Hans Zempel},

doi = {10.1007/s00415-024-12314-3},

issn = {1432-1459},

year  = {2024},

date = {2024-06-00},

urldate = {2024-06-00},

journal = {J Neurol},

volume = {271},

number = {6},

pages = {2992--3018},

publisher = {Springer Science and Business Media LLC},

abstract = {<jats:title>Abstract</jats:title><jats:p>Tauopathies are a heterogeneous group of neurologic diseases characterized by pathological axodendritic distribution, ectopic expression, and/or phosphorylation and aggregation of the microtubule-associated protein TAU, encoded by the gene <jats:italic>MAPT</jats:italic>. Neuronal dysfunction, dementia, and neurodegeneration are common features of these often detrimental diseases. A neurodegenerative disease is considered a primary tauopathy when <jats:italic>MAPT</jats:italic> mutations/haplotypes are its primary cause and/or TAU is the main pathological feature. In case TAU pathology is observed but superimposed by another pathological hallmark, the condition is classified as a secondary tauopathy. In some tauopathies (e.g. <jats:italic>MAPT</jats:italic>-associated frontotemporal dementia (FTD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and Alzheimer's disease (AD)) TAU is recognized as a significant pathogenic driver of the disease. In many secondary tauopathies, including Parkinson's disease (PD) and Huntington's disease (HD), TAU is suggested to contribute to the development of dementia, but in others (e.g. Niemann-Pick disease (NPC)) TAU may only be a bystander. The genetic and pathological mechanisms underlying TAU pathology are often not fully understood. In this review, the genetic predispositions and variants associated with both primary and secondary tauopathies are examined in detail, assessing evidence for the role of TAU in these conditions. We highlight less common genetic forms of tauopathies to increase awareness for these disorders and the involvement of TAU in their pathology. This approach not only contributes to a deeper understanding of these conditions but may also lay the groundwork for potential TAU-based therapeutic interventions for various tauopathies.</jats:p>},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Giehl2024b,

title = {Working Memory Training Responsiveness in Parkinson’s Disease Is Not Determined by Cortical Thickness or White Matter Lesions},

author = {Kathrin Giehl and Hendrik Theis and Anja Ophey and Jochen Hammes and Paul Reker and Carsten Eggers and Gereon R. Fink and Elke Kalbe and Thilo van Eimeren},

doi = {10.3233/jpd-230367},

issn = {1877-718X},

year  = {2024},

date = {2024-02-03},

urldate = {2024-02-03},

journal = {Journal of Parkinson’s Disease},

volume = {14},

number = {2},

pages = {347--351},

publisher = {SAGE Publications},

abstract = {<jats:p> Patients with Parkinson’s disease are highly vulnerable for cognitive decline. Thus, early intervention by means of working memory training (WMT) may be effective for the preservation of cognition. However, the influence of structural brain properties, i.e., cortical thickness and volume of white matter lesions on training responsiveness have not been studied. Here, behavioral and neuroimaging data of 46 patients with Parkinson’s disease, 21 of whom engaged in home-based, computerized adaptive WMT, was analyzed. While cortical thickness and white matter lesions volume were associated with cognitive performance at baseline, these structural brain properties do not seem to determine WMT responsiveness. </jats:p>},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Doering2023,

title = {MRI or^{18}F-FDG PET for Brain Age Gap Estimation: Links to Cognition, Pathology, and Alzheimer Disease Progression},

author = {Elena Doering and Georgios Antonopoulos and Merle Hoenig and Thilo van Eimeren and Marcel Daamen and Henning Boecker and Frank Jessen and Emrah Düzel and Simon Eickhoff and Kaustubh Patil and Alexander Drzezga},

doi = {10.2967/jnumed.123.265931},

issn = {2159-662X},

year  = {2024},

date = {2024-01-00},

urldate = {2024-01-00},

journal = {J Nucl Med},

volume = {65},

number = {1},

pages = {147--155},

publisher = {Society of Nuclear Medicine},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Theis2023,

title = {Impulsive-compulsive behaviour in early Parkinson’s disease is determined by apathy and dopamine receptor D3 polymorphism},

author = {Hendrik Theis and Stéphane Prange and Gérard N. Bischof and Merle C. Hoenig and Marc Tittgemeyer and Lars Timmermann and Gereon R. Fink and Alexander Drzezga and Carsten Eggers and Thilo van Eimeren},

doi = {10.1038/s41531-023-00596-9},

issn = {2373-8057},

year  = {2023},

date = {2023-12-00},

urldate = {2023-12-00},

journal = {npj Parkinsons Dis.},

volume = {9},

number = {1},

publisher = {Springer Science and Business Media LLC},

abstract = {<jats:title>Abstract</jats:title><jats:p>Impulsive-compulsive behaviour (ICB) is a frequently observed non-motor symptom in early Parkinson’s disease after initiating dopamine replacement therapy. At the opposite end of the motivated behaviour spectrum, apathy occurs in early Parkinson’s disease even before dopamine replacement is started. The co-occurrence of these behavioural conditions in Parkinson’s disease raises questions about their relationship and underlying pathophysiological determinants. In previous imaging or genetic studies, both conditions have been associated with the limbic dopaminergic system. The risk variant of the Ser9Gly polymorphism of the dopamine receptor D3 (DRD3) is linked to increased dopamine affinity in the limbic striatum. With this in mind, we investigated how ICB expression is explained by apathy and DRD3 polymorphisms and their effects on grey matter volume and dopamine synthesis capacity. Fifty-four patients with early Parkinson’s disease took part in anatomical T1-weighted MRI. Forty of them also underwent dynamic PET imaging using [18F]DOPA to measure striatal dopamine synthesis capacity. Further, Ser9Gly (rs6280) gene polymorphism influencing the DRD3 dopamine-binding affinity was determined in all patients. The severity of impulsive-compulsive behaviour and apathy was assessed using the Questionnaire for Impulsive-Compulsive Disorders Rating Scale and the Apathy Evaluation Scale. ICB and the severity of apathy were indeed positively correlated. Apathy and the DRD3 polymorphism were interactive risk factors for ICB severity. Apathy was significantly linked to atrophy of the bilateral putamen. Patients with the DRD3 risk type had reduced dopamine synthesis capacity in the putamen and limbic striatum, apathy was associated with reduced dopamine synthesis capacity in the limbic striatum. The results of [18F]DOPA reached only trend significance. Apathy in drug-naïve PD patients might be a consequence of impaired striatal dopaminergic tone. This may represent a predisposing factor for the development of ICB after the initiation of dopamine replacement therapy. The risk type of DRD3 could further amplify this predisposition due to its higher affinity to dopamine.</jats:p>},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Chakroun2023,

title = {Dopamine regulates decision thresholds in human reinforcement learning in males},

author = {Karima Chakroun and Antonius Wiehler and Ben Wagner and David Mathar and Florian Ganzer and Thilo van Eimeren and Tobias Sommer and Jan Peters},

doi = {10.1038/s41467-023-41130-y},

issn = {2041-1723},

year  = {2023},

date = {2023-12-00},

journal = {Nat Commun},

volume = {14},

number = {1},

publisher = {Springer Science and Business Media LLC},

abstract = {AbstractDopamine fundamentally contributes to reinforcement learning, but recent accounts also suggest a contribution to specific action selection mechanisms and the regulation of response vigour. Here, we examine dopaminergic mechanisms underlying human reinforcement learning and action selection via a combined pharmacological neuroimaging approach in male human volunteers (n = 31, within-subjects; Placebo, 150 mg of the dopamine precursor L-dopa, 2 mg of the D2 receptor antagonist Haloperidol). We found little credible evidence for previously reported beneficial effects of L-dopa vs. Haloperidol on learning from gains and altered neural prediction error signals, which may be partly due to differences experimental design and/or drug dosages. Reinforcement learning drift diffusion models account for learning-related changes in accuracy and response times, and reveal consistent decision threshold reductions under both drugs, in line with the idea that lower dosages of D2 receptor antagonists increase striatal DA release via an autoreceptor-mediated feedback mechanism. These results are in line with the idea that dopamine regulates decision thresholds during reinforcement learning, and may help to bridge action selection and response vigor accounts of dopamine.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Theis2023b,

title = {In Vivo Measurement of Tau Depositions in Anti-IgLON5 Disease Using [18F]PI-2620 PET},

author = {Hendrik Theis and Gérard N. Bischof and Norbert Brüggemann and Justina Dargvainiene and Alexander Drzezga and Thomas Grüter and Jan Lewerenz and Frank Leypoldt and Bernd Neumaier and Klaus-Peter Wandinger and Ilya Ayzenberg and Thilo van Eimeren},

doi = {10.1212/wnl.0000000000207870},

issn = {1526-632X},

year  = {2023},

date = {2023-11-28},

journal = {Neurology},

volume = {101},

number = {22},

publisher = {Ovid Technologies (Wolters Kluwer Health)},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Hoenig2023,

title = {Educational level and its association with dopamine transporter loss in patients with Parkinson's disease},

author = {Merle C. Hoenig and Verena Dzialas and Magdalena Banwinkler and Adrian L. Asendorf and Alexander Drzezga and Thilo van Eimeren},

doi = {10.1016/j.parkreldis.2023.105844},

issn = {1353-8020},

year  = {2023},

date = {2023-10-00},

urldate = {2023-10-00},

journal = {Parkinsonism & Related Disorders},

volume = {115},

publisher = {Elsevier BV},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{vanEimeren2023,

title = {Neuroimaging biomarkers in Huntington's disease: Preparing for a new era of therapeutic development},

author = {Thilo van Eimeren and Kathrin Giehl and Kathrin Reetz and Cristina Sampaio and Tiago A. Mestre},

doi = {10.1016/j.parkreldis.2023.105488},

issn = {1353-8020},

year  = {2023},

date = {2023-09-00},

journal = {Parkinsonism & Related Disorders},

volume = {114},

publisher = {Elsevier BV},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Schröter2023,

title = {Significance of clinical symptoms and red flags in early differential diagnosis of Parkinson’s disease and atypical Parkinsonian syndromes},

author = {Nils Schröter and Thilo van Eimeren and Joseph Classen and Johannes Levin and Christoph Redecker and Martin Wolz and Lars Tönges},

doi = {10.1007/s00702-023-02634-5},

issn = {1435-1463},

year  = {2023},

date = {2023-06-00},

journal = {J Neural Transm},

volume = {130},

number = {6},

pages = {839--846},

publisher = {Springer Science and Business Media LLC},

abstract = {AbstractThe clinical presentation of Parkinson’s disease and atypical Parkinsonian syndromes is often heterogeneous. Additional diagnostic procedures including brain imaging and biomarker analyses can help to appreciate the various syndromes, but a precise clinical evaluation and differentiation is always necessary. To better assess the relevance of distinct clinical symptoms that arose within 1 year of disease manifestation and evaluate their indicative potential for an atypical Parkinsonian syndrome, we conducted a modified Delphi panel with seven movement disorder specialists. Five different topics with several clinical symptom items were discussed and consensus criteria were tested. This resulted in distinct symptom patterns for each atypical Parkinsonian syndrome showing the multitude of clinical involvement in each neurodegenerative disease. Strongly discriminating clinical signs were few and levels of indication were variable. A prospective validation of the assessments made is needed. This demonstrates that both clinical evaluation and elaborate additional diagnostic procedures are needed to achieve a high diagnostic standard.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Madlener2022,

title = {Brain abscess with Ureaplasma parvum in a patient with granulomatosis with polyangiitis},

author = {Marie Madlener and Marianne Breuninger and Arne Meißner and Henning Stetefeld and Sergej Telentschak and Thorsten Wille and Thilo van Eimeren and Norma Jung},

doi = {10.1007/s15010-022-01966-w},

issn = {1439-0973},

year  = {2023},

date = {2023-06-00},

journal = {Infection},

volume = {51},

number = {3},

pages = {779--782},

publisher = {Springer Science and Business Media LLC},

abstract = {Abstract

                Purpose

                Ureaplasma species are associated with urogenital infections, infertility and adverse pregnancy outcomes as well as neonatal infections. Involvement of the central nervous system in adults is extremely rare. We report an unusual case of a brain abscess secondary to otitis media with Ureaplasma parvum in a patient with granulomatosis with polyangiitis (GPA).

              

                Methods

                Imaging and laboratory findings, treatment decisions, and outcome of this case are explicated.

              

                Results

                A young adult with GPA presented with progredient earache after ambulant diagnosis of otitis media. Despite different courses of broad-spectrum antibiotic therapy, she developed meningoencephalitis due to mastoiditis following temporal abscess formation. Mastoidectomy and neurosurgical abscess removal were performed. Standard cultures of cerebrospinal fluid, blood and intracranial abscess material, as well as polymerase chain reaction (PCR) for common bacterial and viral meningitis pathogens remained negative. Only eubacterial PCR of intracranial abscess material returned positive for Ureaplasma parvum. The patient finally improved under antibiotic therapy with moxifloxacin and doxycycline.

              

                Conclusion

                Ureaplasma species are rare causative pathogens in immunocompromised patients. They should be considered in patients with humoral immunodeficiencies with culture-negative infections failing standard therapy. Eubacterial PCR should be performed in early states of infection in these patients for immediate diagnosis and initiation of appropriate treatment to prevent adverse outcomes.

              },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Maier2021,

title = {Impaired self-awareness of cognitive deficits in Parkinson's disease relates to cingulate cortex dysfunction},

author = {Franziska Maier and Andrea Greuel and Marius Hoock and Rajbir Kaur and Masoud Tahmasian and Frank Schwartz and Ilona Csoti and Frank Jessen and Alexander Drzezga and Thilo van Eimeren and Lars Timmermann and Carsten Eggers},

doi = {10.1017/s0033291721002725},

issn = {1469-8978},

year  = {2023},

date = {2023-03-00},

journal = {Psychol. Med.},

volume = {53},

number = {4},

pages = {1244--1253},

publisher = {Cambridge University Press (CUP)},

abstract = {AbstractBackgroundImpaired self-awareness of cognitive deficits (ISAcog) has rarely been investigated in Parkinson's disease (PD). ISAcog is associated with poorer long-term outcome in other diseases. This study examines ISAcog in PD with and without mild cognitive impairment (PD-MCI), compared to healthy controls, and its clinical-behavioral and neuroimaging correlates.MethodsWe examined 63 PD patients and 30 age- and education-matched healthy controls. Cognitive state was examined following the Movement Disorder Society Level II criteria. ISAcog was determined by subtracting z-scores (based on controls' scores) of objective tests and subjective questionnaires. Neural correlates were assessed by structural magnetic resonance imaging (MRI) and 2-[fluorine-18]fluoro-2-deoxy-d-glucose-positron emission tomography (FDG-PET) in 47 patients (43 with MRI) and 11 controls. We analyzed whole-brain glucose metabolism and cortical thickness in regions where FDG-uptake correlated with ISAcog.ResultsPD-MCI patients (N = 23) showed significantly more ISAcog than controls and patients without MCI (N = 40). When all patients who underwent FDG-PET were examined, metabolism in the bilateral superior medial frontal gyrus, anterior and midcingulate cortex negatively correlated with ISAcog (FWE-corrected p < 0.001). In PD-MCI, ISAcog was related to decreased metabolism in the right superior temporal lobe and insula (N = 13; FWE-corrected p = 0.023) as well as the midcingulate cortex (FWE-corrected p = 0.002). Cortical thickness was not associated with ISAcog in these regions. No significant correlations were found between ISAcog and glucose metabolism in controls and patients without MCI.ConclusionsSimilar to Alzheimer's disease, the cingulate cortex seems to be relevant in ISAcog in PD. In PD-MCI patients, ISAcog might result from a disrupted network that regulates awareness of cognition and error processes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@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{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{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{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{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{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{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{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{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}

}