scholarly journals Attention and reinforcement learning in Parkinson’s disease

2020 ◽  
Author(s):  
Brónagh McCoy ◽  
Rebecca P. Lawson ◽  
Jan Theeuwes
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Reinforcement Learning ◽  
Interactive Effect ◽  
Learning Task ◽  
Brain Regions ◽  
Learning Performance ◽  
Activation Patterns ◽  
Probabilistic Classification ◽  
Dorsolateral Prefrontal

ABSTRACTDopamine is known to be involved in several important cognitive processes, most notably in learning from rewards and in the ability to attend to task-relevant aspects of the environment. Both of these features of dopaminergic signalling have been studied separately in research involving Parkinson’s disease (PD) patients, who exhibit diminished levels of dopamine. Here, we tie together some of the commonalities in the effects of dopamine on these aspects of cognition by having PD patients (ON and OFF dopaminergic medication) and healthy controls (HCs) perform two tasks that probe these processes. Within-patient behavioural measures of distractibility, from an attentional capture task, and learning performance, from a probabilistic classification reinforcement learning task, were included in one model to assess the role of distractibility during learning. Dopamine medication state and distractibility level were found to have an interactive effect on learning performance; less distractibility in PD ON was associated with higher accuracy during learning, and this was altered in PD OFF. Functional magnetic resonance imaging (fMRI) data acquired during the learning task furthermore allowed us to assess multivariate patterns of positive and negative outcomes in fronto-striatal and visual brain regions involved in both learning processes and the executive control of attention. Here, we demonstrate that while PD ON show a clearer distinction between outcomes than OFF in dorsolateral prefrontal cortex (DLPFC) and putamen, PD OFF show better distinction of activation patterns in visual regions that respond to the stimuli presented during the task. These results demonstrate that dopamine plays a key role in modulating the interaction between attention and learning at the level of both behaviour and activation patterns in the brain.

scholarly journals Effects of levodopa on cognition in healthy volunteers: implications for Parkinson’s disease

2015 ◽  
Vol 42 (S1) ◽  
pp. S17-S17
Author(s):  
A Vo ◽  
KN Seergobin ◽  
S Jiang ◽  
PA MacDonald
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Treatment Strategies ◽  
Critical Factor ◽  
Learning Task ◽  
Brain Regions ◽  
Healthy Adults ◽  
Learning Performance ◽  
Task Completion ◽  
Endogenous Dopamine

Background: Cognitive impairments are now recognized in Parkinson’s disease. Some of these deficits owe to disease pathology itself whereas others are due to paradoxical effects of dopaminergic medications, such as levodopa. The dopamine overdose hypothesis proposes that dissimilar effects of medication on cognition depend on baseline endogenous dopamine levels in underlying brain regions. We sought to directly test this prevalent theory. Methods: We tested healthy adults, who presumably have optimal endogenous dopamine levels, in two sessions. Participants received 100/25 mg of levodopa/carbidopa in one session and an equal volume of placebo in the other. During each session, participants completed a probabilistic reversal learning task. The number of trials to task completion was used as a behavioural proxy of learning performance. Results: A paired t-test covaried with drug-placebo order revealed that healthy adults learned more poorly on levodopa compared to placebo. Conclusions: Our findings suggest that baseline endogenous dopamine levels are a critical factor determining the effects of dopaminergic medications on cognition, independent of Parkinson’s disease pathology. Partitioning which cognitive functions are helped versus hindered by medication and improving our understanding of the underlying psychopharmacology of these effects is important for improving treatment strategies in Parkinson’s disease.

scholarly journals Dopamine and performance in a reinforcement learning task: evidence from Parkinson’s disease

Brain ◽  
2012 ◽  
Vol 135 (6) ◽  
pp. 1871-1883 ◽  
Author(s):  
Tamara Shiner ◽  
Ben Seymour ◽  
Klaus Wunderlich ◽  
Ciaran Hill ◽  
Kailash P. Bhatia ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Reinforcement Learning ◽  
Learning Task ◽  
And Performance

scholarly journals Multisite non-invasive brain stimulation in Parkinson’s disease: A scoping review

2021 ◽  
pp. 1-17
Author(s):  
Camila Beatriz da Silva Machado ◽  
Letícia Maria da Silva ◽  
Alessandra Feitosa Gonçalves ◽  
Palloma Rodrigues de Andrade ◽  
Cristina Katya Torres Teixeira Mendes ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Brain Stimulation ◽  
Primary Motor Cortex ◽  
Neurodegenerative Disorder ◽  
Brain Regions ◽  
Cochrane Library ◽  
Non Invasive ◽  
Dorsolateral Prefrontal ◽  
Motor Component

BACKGROUND: Parkinson’s Disease (PD) is a progressive neurodegenerative disorder, characterized by cardinal motor symptoms in addition to cognitive impairment. New insights concerning multisite non-invasive brain stimulation effects have been gained, which can now be used to develop innovative treatment approaches. OBJECTIVE: Map the researchs involving multisite non-invasive brain stimulation in PD, synthesize the available evidence and discuss future directions. METHODS: The databases PubMed, PsycINFO, CINAHL, LILACS and The Cochrane Library were searched from inception until April 2020, without restrictions on the date of publication or the language in which it was published. The reviewers worked in pairs and sequentially evaluated the titles, abstracts and then the full text of all publications identified as potentially relevant. RESULTS: Twelve articles met the inclusion criteria. The target brain regions included mainly the combination of a motor and a frontal area, such as stimulation of the primary motor córtex associated with the dorsolateral prefrontal cortex. Most of the trials showed that this modality was only more effective for the motor component, or for the cognitive and/or non-motor, separately. CONCLUSIONS: Despite the results being encouraging for the use of the multisite aproach, the indication for PD management should be carried out with caution and deserves scientific deepening.

scholarly journals Effects of dopamine on reinforcement learning in Parkinson’s disease depend on motor phenotype

Brain ◽  
2020 ◽  
Vol 143 (11) ◽  
pp. 3422-3434
Author(s):  
Annelies J van Nuland ◽  
Rick C Helmich ◽  
Michiel F Dirkx ◽  
Heidemarie Zach ◽  
Ivan Toni ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Reinforcement Learning ◽  
Learning Task ◽  
Learning Rate ◽  
Dopamine Depletion ◽  
Large Variability ◽  
Dopaminergic Medication ◽  
Improved Learning ◽  
Motor Phenotype

Abstract Parkinson’s disease is clinically defined by bradykinesia, along with rigidity and tremor. However, the severity of these motor signs is greatly variable between individuals, particularly the presence or absence of tremor. This variability in tremor relates to variation in cognitive/motivational impairment, as well as the spatial distribution of neurodegeneration in the midbrain and dopamine depletion in the striatum. Here we ask whether interindividual heterogeneity in tremor symptoms could account for the puzzlingly large variability in the effects of dopaminergic medication on reinforcement learning, a fundamental cognitive function known to rely on dopamine. Given that tremor-dominant and non-tremor Parkinson’s disease patients have different dopaminergic phenotypes, we hypothesized that effects of dopaminergic medication on reinforcement learning differ between tremor-dominant and non-tremor patients. Forty-three tremor-dominant and 20 non-tremor patients with Parkinson’s disease were recruited to be tested both OFF and ON dopaminergic medication (200/50 mg levodopa-benserazide), while 22 age-matched control subjects were recruited to be tested twice OFF medication. Participants performed a reinforcement learning task designed to dissociate effects on learning rate from effects on motivational choice (i.e. the tendency to ‘Go/NoGo’ in the face of reward/threat of punishment). In non-tremor patients, dopaminergic medication improved reward-based choice, replicating previous studies. In contrast, in tremor-dominant patients, dopaminergic medication improved learning from punishment. Formal modelling showed divergent computational effects of dopaminergic medication as a function of Parkinson’s disease motor phenotype, with a modulation of motivational choice bias and learning rate in non-tremor and tremor patients, respectively. This finding establishes a novel cognitive/motivational difference between tremor and non-tremor Parkinson’s disease patients, and highlights the importance of considering motor phenotype in future work.

scholarly journals Neuroinflammation and protein pathology in Parkinson’s disease dementia

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Antonina Kouli ◽  
Marta Camacho ◽  
Kieren Allinson ◽  
Caroline H. Williams-Gray
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
T Lymphocytes ◽  
Substantia Nigra ◽  
Amyloid Β ◽  
Brain Regions ◽  
Parkinson’S Disease Dementia ◽  
Activated Microglia ◽  
Cell Counts ◽  
The Brain

AbstractParkinson’s disease dementia is neuropathologically characterized by aggregates of α-synuclein (Lewy bodies) in limbic and neocortical areas of the brain with additional involvement of Alzheimer’s disease-type pathology. Whilst immune activation is well-described in Parkinson’s disease (PD), how it links to protein aggregation and its role in PD dementia has not been explored. We hypothesized that neuroinflammatory processes are a critical contributor to the pathology of PDD. To address this hypothesis, we examined 7 brain regions at postmortem from 17 PD patients with no dementia (PDND), 11 patients with PD dementia (PDD), and 14 age and sex-matched neurologically healthy controls. Digital quantification after immunohistochemical staining showed a significant increase in the severity of α-synuclein pathology in the hippocampus, entorhinal and occipitotemporal cortex of PDD compared to PDND cases. In contrast, there was no difference in either tau or amyloid-β pathology between the groups in any of the examined regions. Importantly, we found an increase in activated microglia in the amygdala of demented PD brains compared to controls which correlated significantly with the extent of α-synuclein pathology in this region. Significant infiltration of CD4+ T lymphocytes into the brain parenchyma was commonly observed in PDND and PDD cases compared to controls, in both the substantia nigra and the amygdala. Amongst PDND/PDD cases, CD4+ T cell counts in the amygdala correlated with activated microglia, α-synuclein and tau pathology. Upregulation of the pro-inflammatory cytokine interleukin 1β was also evident in the substantia nigra as well as the frontal cortex in PDND/PDD versus controls with a concomitant upregulation in Toll-like receptor 4 (TLR4) in these regions, as well as the amygdala. The evidence presented in this study show an increased immune response in limbic and cortical brain regions, including increased microglial activation, infiltration of T lymphocytes, upregulation of pro-inflammatory cytokines and TLR gene expression, which has not been previously reported in the postmortem PDD brain.

scholarly journals Growth Factor Therapy for Parkinson’s Disease: Alternative Delivery Systems

2021 ◽  
pp. 1-7
Author(s):  
Sarah Jarrin ◽  
Abrar Hakami ◽  
Ben Newland ◽  
Eilís Dowd
Keyword(s):  
Parkinson’S Disease ◽  
Gene Therapy ◽  
Parkinson's Disease ◽  
Growth Factors ◽  
Growth Factor ◽  
Ex Vivo ◽  
Brain Regions ◽  
Delivery Systems ◽  
Alternative Delivery

Despite decades of research and billions in global investment, there remains no preventative or curative treatment for any neurodegenerative condition, including Parkinson’s disease (PD). Arguably, the most promising approach for neuroprotection and neurorestoration in PD is using growth factors which can promote the growth and survival of degenerating neurons. However, although neurotrophin therapy may seem like the ideal approach for neurodegenerative disease, the use of growth factors as drugs presents major challenges because of their protein structure which creates serious hurdles related to accessing the brain and specific targeting of affected brain regions. To address these challenges, several different delivery systems have been developed, and two major approaches—direct infusion of the growth factor protein into the target brain region and in vivo gene therapy—have progressed to clinical trials in patients with PD. In addition to these clinically evaluated approaches, a range of other delivery methods are in various degrees of development, each with their own unique potential. This review will give a short overview of some of these alternative delivery systems, with a focus on ex vivo gene therapy and biomaterial-aided protein and gene delivery, and will provide some perspectives on their potential for clinical development and translation.

scholarly journals A Guide to the Generation of a 6-Hydroxydopamine Mouse Model of Parkinson’s Disease for the Study of Non-Motor Symptoms

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 598
Author(s):  
Débora Masini ◽  
Carina Plewnia ◽  
Maëlle Bertho ◽  
Nicolas Scalbert ◽  
Vittorio Caggiano ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Survival Rates ◽  
Dorsal Striatum ◽  
Brain Regions ◽  
Motor Symptoms ◽  
Operative Care ◽  
6 Hydroxydopamine ◽  
Non Motor Symptoms

In Parkinson’s disease (PD), a large number of symptoms affecting the peripheral and central nervous system precede, develop in parallel to, the cardinal motor symptoms of the disease. The study of these conditions, which are often refractory to and may even be exacerbated by standard dopamine replacement therapies, relies on the availability of appropriate animal models. Previous work in rodents showed that injection of the neurotoxin 6-hydroxydopamine (6-OHDA) in discrete brain regions reproduces several non-motor comorbidities commonly associated with PD, including cognitive deficits, depression, anxiety, as well as disruption of olfactory discrimination and circadian rhythm. However, the use of 6-OHDA is frequently associated with significant post-surgical mortality. Here, we describe the generation of a mouse model of PD based on bilateral injection of 6-OHDA in the dorsal striatum. We show that the survival rates of males and females subjected to this lesion differ significantly, with a much higher mortality among males, and provide a protocol of enhanced pre- and post-operative care, which nearly eliminates animal loss. We also briefly discuss the utility of this model for the study of non-motor comorbidities of PD.

scholarly journals Intrinsic motivation in patients with Parkinson’s disease: a neuropsychological investigation of curiosity using dopamine transporter imaging

2021 ◽  
Author(s):  
Yayoi Shigemune ◽  
Iori Kawasaki ◽  
Akira Midorikawa ◽  
Toru Baba ◽  
Atsushi Takeda ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Intrinsic Motivation ◽  
Extrinsic Motivation ◽  
Brain Regions ◽  
Word Recall ◽  
Negative Consequences ◽  
Dopamine Transporters ◽  
Trail Making ◽  
Neuropsychological Investigation

AbstractBoth intrinsic and extrinsic motivation are believed to involve brain regions that are innervated by the dopaminergic pathway. Although dopaminergic neurons in the midbrain deteriorate in Parkinson’s disease (PD), it remains unclear whether intrinsic motivation is impaired in PD patients. To address this issue, we investigated intrinsic motivation in PD patients using a task designed to assess the “Pandora effect,” which constitutes a curiosity for resolving uncertainty, even if this curiosity is likely to result in negative consequences. Twenty-seven PD patients and 27 age-matched healthy controls (HCs) completed a curiosity task in which they were required to decide either to view or skip negative pictures (e.g., snakes, spiders) and an examination battery that included the Mini-Mental State Examination, a verbal fluency test, the Trail Making Test, 10-word recall tests, and questionnaires for behavioral inhibition/activation and depression. DaTSCAN images to assess the distribution of dopamine transporters in the striatum were acquired only from PD patients. The results revealed that PD patients, relative to the HCs, viewed the pictures less frequently under both the certain and uncertain conditions. However, both the PD patients and HCs viewed the pictures at a higher frequency under the uncertain condition than under the certain condition. In the PD patients, the proportion of pictures viewed under the certain condition was positively correlated with the distribution of dopamine transporters in the striatum. These results suggest that despite the overall decreasing level of interest in viewing negative pictures, the motivation to resolve uncertainty is relatively intact in PD patients.

Sign in / Sign up

Export Citation Format

Share Document