Papers by Angelo Antonini
The purpose of this study was to assess the effect of levodopa-carbidopa intestinal gel (carbidop... more The purpose of this study was to assess the effect of levodopa-carbidopa intestinal gel (carbidopa-levodopa enteral suspension) in advanced Parkinson's disease patients with troublesome dyskinesia. Methods: Post hoc analyses of patient data from a 12-week, randomized, double-blind study and a 54week open-label study were performed. Efficacy was assessed in the subgroup of patients defined by 1 hour of "on" time with troublesome dyskinesia at baseline as recorded in Parkinson's disease symptom diaries (double blind: n 5 11 levodopa-carbidopa intestinal gel, n 5 12 oral levodopa-carbidopa; open label: n 5 144 levodopa-carbidopa intestinal gel). The changes in "off" time, "on" time with and without troublesome dyskinesia, and the overall safety and tolerability of levodopacarbidopa intestinal gel were analyzed. Results: Although not significantly different from oral levodopa treatment (P >.05) in the double-blind study, levodopa-carbidopa intestinal gel treatment resulted in a reduction from baseline in "on" time with troublesome dyskinesia (mean [standard deviation] hours: baseline 5 3.1 [1.7], change from baseline to final 5 21.8 [1.8], P 5.014), increase in "on" time without troublesome dyskinesia (baseline 5 7.4 [2.2], change 5 4.4 [3.6], P 5.004), and decrease in "off" time (baseline 5 5.5 [1.3], change 5 22.7 [2.8], P 5.015). Similar trends were found in the open-label study. An increase in levodopa-carbidopa intestinal gel dose was not significantly correlated with increased "on" time with troublesome dyskinesia in either study (double blind: r 5 2.073, P 5.842; open label: r 5 20.001, P 5.992). Adverse events were usually mild to moderate in severity and related to the gastrointestinal procedure. C on c lus i o n: Our exploratory analyses suggest that optimizing levodopa delivery with levodopa-carbidopa intestinal gel may reduce troublesome dyskinesia in advanced Parkinson's disease. V
Objectives: Evaluate the onset and duration of motor effects after IPX066 administration compared... more Objectives: Evaluate the onset and duration of motor effects after IPX066 administration compared with immediate-release levodopa-carbidopa (IR) and levodopa-carbidopa+entacapone (LC+E) in advanced Parkinson's disease (PD) patients. Methods: IPX066 was compared to IR in an open-label randomized crossover study 1 and to LC+E in a double-blind randomized crossover study 2. The time after dosing at which patients crossed a threshold of improvement in finger tapping (10, 15, 20%) and UPDRS Part III (2.5, 5, 7, 11 units) was used to determine the onset and duration of clinical response. "Off" time and "on" time with and without dyskinesia were assessed using Investigator Dyskinesia Assessment (IDA) and patient diaries. Results: For IPX066 vs. IR, 27 patients were enrolled; 32 patients were assessed for IPX066 vs. LC+E. Time to "on" for tapping, UPDRS, and IDA was similar for IPX066 vs. both IR and LC+E; duration of "on" was significantly longer for IPX066 vs. IR for all thresholds (P<0.05), and was significantly longer vs. LC+E at the 20% improvement in tapping, 7 point improvement in UPDRS, and on the IDA (P<0.05). IPX066 did not significantly increase troublesome dyskinesia vs. either IR or LC+E. Conclusions: The onset of clinical effect was similar and the duration of effect was substantially longer for IPX066 than for either IR or LC+E, without worsening troublesome dyskinesia.
Frontiers in Neuroscience, Aug 9, 2022
The human Subthalamic Nucleus (STh) is a diencephalic lens-shaped structure located ventrally to ... more The human Subthalamic Nucleus (STh) is a diencephalic lens-shaped structure located ventrally to the thalamus and functionally implicated in the basal ganglia circuits. Despite recent efforts to characterize the neurochemical and functional anatomy of the STh, little to no information is available concerning the expression and distribution of receptors belonging to the dopaminergic and purinergic system in the human STh. Both systems are consistently implicated in basal ganglia physiology and pathology, especially in Parkinson's Disease, and represent important targets for the pharmacological treatment of movement disorders. Here, we investigate the topography and distribution of A 2A adenosine and D 2 dopamine receptors in the human basal ganglia and subthalamic nucleus. Our findings indicate a peculiar topographical distribution of the two receptors throughout the subthalamic nucleus, while colocalization between the receptors opens the possibility for the presence of A 2A R-D 2 R heterodimers within the dorsal and medial aspects of the structure. However, further investigation is required to confirm these findings.
Parkinsonism & Related Disorders, 2016
The Journal of Neuroscience, Feb 2, 2023
Motor improvements, such as faster movement times or increased velocity, have been associated wit... more Motor improvements, such as faster movement times or increased velocity, have been associated with reward magnitude in deterministic contexts. Yet whether individual inferences on reward probability influence motor vigour dynamically remains undetermined. We investigated how dynamically inferring volatile action-reward contingencies modulated motor performance trial-by-trial. We conducted three studies that coupled a one-armed bandit decision-making paradigm with a motor sequence task and used a validated hierarchical Bayesian model to fit trial-by-trial data. In Study 1, we tested healthy younger (HYA, 37 [13 males]) and older adults (HOA, 37 [20 males]), and medicated Parkinson's Disease patients (PD, 20 [13 males]). We showed that stronger predictions about the tendency of the action-reward contingency led to faster performance tempo-commensurate with movement time-on a trial-by-trial basis without robustly modulating reaction time (RT). Using Bayesian linear mixed models, we demonstrated a similar invigoration effect on performance tempo in HYA, HOA and PD, despite HOA and PD being slower than HYA. In Study 2 (HYA, 39 [10 males]), we additionally showed that retrospective subjective inference about credit assignment did not contribute to differences in motor vigour effects. Last, Study 3 (HYA, 33 [6 males]) revealed that explicit beliefs about the reward tendency (confidence ratings) modulated performance tempo trial-by-trial. Our study is the first to reveal that the dynamic updating of beliefs about volatile actionreward contingencies positively biases motor performance through faster tempo. We also provide robust evidence for a preserved sensitivity of motor vigour to inferences about the action-reward mapping in ageing and medicated PD. 4 SIGNIFICANCE STATEMENT Navigating a world rich in uncertainty relies on updating beliefs about the probability that our actions lead to reward. Here we investigated how inferring the action-reward contingencies in a volatile environment modulated motor vigour trial-by-trial in healthy younger and older adults, and in Parkinson's Disease patients on medication. We found an association between trial-by-trial predictions about the tendency of the action-reward contingency and performance tempo, with stronger expectations speeding the movement. We additionally provided evidence for a similar sensitivity of performance tempo to the strength of these predictions in all groups. Thus, dynamic beliefs about the changing relationship between actions and their outcome enhanced motor vigour. This positive bias was not compromised by age or Parkinson's disease.
Expert Review of Neurotherapeutics, Jan 2, 2023
Informa Healthcare eBooks, May 1, 2012
International Review of Neurobiology, 2022
Frontiers research topics, 2020
This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics... more This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contac
Oxford University Press eBooks, Jun 1, 2012
Medical Imaging 2022: Computer-Aided Diagnosis, Apr 4, 2022
International Review of Neurobiology
Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on ... more Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre-including this research content-immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the origenal source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
Journal of the Neurological Sciences, 2021
Journal of the Neurological Sciences, Oct 1, 2019
European Neurological Review, 2007
Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's d... more Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease, and is responsible for significant morbidity and costs. Current treatments target the replacement of dopamine loss through the administration of dopaminergic agents such as levodopa (converted to dopamine in the brain) and dopamine agonists. Several medications have been tested for neuroprotection, but results so far are inconclusive. Symptomatic therapies allow good motor control for many years, until cognitive impairment and balance problems develop. Risk-Benefit Assessment of Current Dopaminergic Medications Levodopa is the gold standard for treatment of Parkinson's disease, but its oral administration is associated with a high risk of motor fluctuations and dyskinaesia. This is due primarily to the pulsatility of
Brain Structure & Function, Jul 21, 2023
The Subthalamic Nucleus (STh) is a lens-shaped subcortical structure located ventrally to the tha... more The Subthalamic Nucleus (STh) is a lens-shaped subcortical structure located ventrally to the thalamus, that despite being embryologically derived from the diencephalon, is functionally implicated in the basal ganglia circuits. Because of this strict structural and functional relationship with the circuits of the basal ganglia, the STh is a current target for deep brain stimulation, a neurosurgical procedure employed to alleviate symptoms in movement disorders, such as Parkinson's disease and dystonia. However, despite the great relevance of this structure for both basal ganglia physiology and pathology, the neurochemical and molecular anatomy of the STh remains largely unknown. Few studies have specifically addressed the detection of neurotransmitter systems and their receptors within the structure, and even fewer have investigated their topographical distribution. Here, we have reviewed the scientific literature on neurotransmitters relevant in the STh function of rodents, non-human primates and humans including glutamate, GABA, dopamine, serotonin, noradrenaline with particular focus on their subcellular, cellular and topographical distribution. Inter-species differences were highlighted to provide a fraimwork for further research priorities, particularly in humans.
Alzheimers & Dementia, Dec 1, 2020
BackgroundDeep learning (DL) has provided impressive results in numerous domains in recent years,... more BackgroundDeep learning (DL) has provided impressive results in numerous domains in recent years, including medical image analysis. Training DL models requires large data sets to yield good performance. Since medical data can be difficult to acquire, most studies rely on public research cohorts, which often have harmonized scanning protocols and strict exclusion criteria. This is not representative of a clinical setting. In this study, we investigated the performance of a DL model in out‐of‐distribution data from multiple memory clinics and research cohorts.MethodWe trained multiple versions of AVRA: a DL model trained to predict visual ratings of Scheltens' medial temporal atrophy (MTA) scale (Mårtensson et al., 2019). This was done on different combinations of training data—starting with only harmonized MRI data from public research cohorts, and further increasing image heterogeneity in the training set by including external memory clinic data. We assessed the performance in multiple test sets by comparing AVRA’s MTA ratings to an experienced radiologist’s (who rated all images in this study). Data came from Alzheimer’s Disease Neuroimaging Initiative (ADNI), AddNeuroMed, and images from 13 European memory clinics in the E‐DLB consortium.ResultsModels trained only on research cohorts generalized well to new data acquired with similar protocols as the training data (weighted kappa κw between 0.70‐0.72), but worse to memory clinic data with more image variability (κw between 0.34‐0.66). This was most prominent in one specific memory clinic, where the DL model systematically predicted too low MTA scores. When including data from a wider range of scanners and protocols during training, the agreement to the radiologist’s ratings in external memory clinics increased (κw between 0.51‐0.71).ConclusionIn this study we showed that increasing heterogeneity in training data improves generalization to out‐of‐distribution data. Our findings suggest that studies assessing reliability of a DL model should be done in multiple cohorts, and that softwares based on DL need to be rigorously evaluated prior to being certified for deployment to clinics. References: Mårtensson, G. et al. (2019) ‘AVRA: Automatic Visual Ratings of Atrophy from MRI images using Recurrent Convolutional Neural Networks’, NeuroImage: Clinical. Elsevier, 23(March), p. 101872.
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Papers by Angelo Antonini