scholarly journals Prefrontal D1 dopamine-receptor neurons and delta resonance in interval timing

2017 ◽  
Author(s):  
Young-Cho Kim ◽  
Nandakumar S. Narayanan
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Processing ◽  
Cognitive Task ◽  
Interval Timing ◽  
Time Dependent ◽  
Performance Deficits ◽  
Timing Task ◽  
Memory Flexibility ◽  
Receptor Neurons

AbstractConsiderable evidence has shown that prefrontal neurons expressing D1-type dopamine receptors (D1DRs) are critical for working memory, flexibility, and timing. This line of work predicts that frontal neurons expressing D1DRs mediate cognitive processing. During timing tasks, one form this cognitive processing might take is time-dependent ramping activity — monotonic changes in firing rate over time. Thus, we hypothesized the prefrontal D1DR+ neurons would strongly exhibited time-dependent ramping during interval timing. We tested this idea using an interval-timing task in which we used optogenetics to tag D1DR+ neurons in the mouse medial frontal cortex (MFC). While 23% of MFC D1DR+ neurons exhibited ramping, this was significantly less than untagged MFC D1DR+ neurons. By contrast, MFC D1DR+ neurons had strong delta-frequency (1-4 Hz) coherence with other MFC ramping neurons. This coherence was phase-locked to cue onset and was strongest early in the interval. To test the significance of these interactions, we optogenetically stimulated MFC D1DR+ neurons early vs. late in the interval. We found that 2-Hz stimulation early in the interval was particularly effective in rescuing timing-related behavioral performance deficits in dopamine-depleted animals. These findings provide insight into MFC networks and have relevance for disorders such as Parkinson’s disease and schizophrenia.Significance StatementPrefrontal D1DRs are involved in cognitive processing and cognitive dysfunction in human diseases such as Parkinson’s disease and schizophrenia. We use optogenetics to identify these neurons, as well as neurons that are putatively connected to MFC D1DR+ neurons. We study these neurons in detail during an elementary cognitive task. These data could have relevance for cognitive deficits for Parkinson’s disease, schizophrenia, and other diseases involving frontal dopamine.

scholarly journals Relationships between freezing of gait severity and cognitive deficits in Parkinson's disease

2021 ◽  
Author(s):  
Jamie L. Scholl ◽  
Arturo I. Espinoza ◽  
Matt Leedom ◽  
Lee A. Baugh ◽  
Patti Berg-Poppe ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Cognitive Functioning ◽  
Freezing Of Gait ◽  
Interval Timing ◽  
Cognitive Domains ◽  
Timing Task ◽  
The Relationship ◽  
Mediation Models

Introduction: Freezing of gait (FOG) is one of the most debilitating motor symptoms experienced by patients with Parkinson's disease (PD), as it can lead to falls and reduced quality of life. Evidence supports an association between FOG severity and cognitive functioning; however, results are varied. Methods: PD patients with (PDFOG+, n=41) and without FOG (PDFOG-, n=39) and control healthy subjects (n=41) participated in the study. The NIH toolbox cognition battery, Montreal cognitive assessment (MoCA), and interval timing task were used to test cognitive domains. Measurements were compared between groups using multivariable models and adjusting for covariates. Correlation analyses, linear regression, and mediation models were applied to examine relationships among disease duration and severity, FOG severity, and cognitive functioning. Results: Significant differences were observed between controls and PD patients for all cognitive domains. PDFOG+ and PDFOG- exhibited differences in the dimensional change card sort (DCCS) test, interval timing task, and MoCA scores. After adjusting for covariates in two different models, PDFOG+ and PDFOG- differed in both MoCA and DCCS scores. In addition, significant relationships between FOG severity and cognitive function (MoCA, DCCS, and interval timing) were also found. Regression models suggest that FOG severity may be a predictor of cognitive impairment, and mediation models show the effects of cognitive impairment on the relationship between disease severity and FOG severity. Conclusions: Overall, this study provides insight into the relationship between cognitive and gait impairments in patients with PD, which could aid in the development of therapeutic interventions to manage both.

scholarly journals Relationships between Freezing of Gait Severity and Cognitive Deficits in Parkinson’s Disease

2021 ◽  
Vol 11 (11) ◽  
pp. 1496
Author(s):  
Jamie L. Scholl ◽  
Arturo I. Espinoza ◽  
Wijdan Rai ◽  
Matt Leedom ◽  
Lee A. Baugh ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Cognitive Functioning ◽  
Freezing Of Gait ◽  
Interval Timing ◽  
Cognitive Domains ◽  
Timing Task ◽  
The Relationship ◽  
Mediation Models

Freezing of gait (FOG) is one of the most debilitating motor symptoms experienced by patients with Parkinson’s disease (PD), as it can lead to falls and a reduced quality of life. Evidence supports an association between FOG severity and cognitive functioning; however, results remain debatable. PD patients with (PDFOG+, n = 41) and without FOG (PDFOG–, n = 39) and control healthy subjects (n = 41) participated in this study. The NIH toolbox cognition battery, the Montreal Cognitive Assessment (MoCA), and the interval timing task were used to test cognitive domains. Measurements were compared between groups using multivariable models and adjusting for covariates. Correlation analyses, linear regression, and mediation models were applied to examine relationships among disease duration and severity, FOG severity, and cognitive functioning. Significant differences were observed between controls and PD patients for all cognitive domains. PDFOG+ and PDFOG– exhibited differences in Dimensional Change Card Sort (DCCS) test, interval timing task, and MoCA scores. After adjusting for covariates in two different models, PDFOG+ and PDFOG– differed in both MoCA and DCCS scores. In addition, significant relationships between FOG severity and cognitive function (MoCA, DCCS, and interval timing) were also found. Regression models suggest that FOG severity may be a predictor of cognitive impairment, and mediation models show the effects of cognitive impairment on the relationship between disease severity and FOG severity. Overall, this study provides insight into the relationship between cognitive and FOG severity in patients with PD, which could aid in the development of therapeutic interventions to manage both.

Comparison of Cytocidal Activities of L-DOPA and Dopamine in S. cerevisiae and C. glabrata

2020 ◽  
Vol 16 (1) ◽  
pp. 90-93
Author(s):  
Carmen E. Iriarte ◽  
Ian G. Macreadie
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Candida Glabrata ◽  
High Sensitivity ◽  
Time Dependent ◽  
Colony Forming Units ◽  
Dependent Cell ◽  
The Brain

Background: Parkinson's Disease results from a loss of dopaminergic neurons, and reduced levels of the neurotransmitter dopamine. Parkinson's Disease treatments involve increasing dopamine levels through administration of L-DOPA, which can cross the blood brain barrier and be converted to dopamine in the brain. The toxicity of dopamine has previously studied but there has been little study of L-DOPA toxicity. Methods: We have compared the toxicity of dopamine and L-DOPA in the yeasts, Saccharomyces cerevisiae and Candida glabrata by cell viability assays, measuring colony forming units. Results: L-DOPA and dopamine caused time-dependent cell killing in Candida glabrata while only dopamine caused such effects in Saccharomyces cerevisiae. The toxicity of L-DOPA is much lower than dopamine. Conclusion: Candida glabrata exhibits high sensitivity to L-DOPA and may have advantages for studying the cytotoxicity of L-DOPA.

scholarly journals Validation of Cognitive Rehabilitation as a Balance Rehabilitation Strategy in Patients with Parkinson’s Disease: Study Protocol for a Randomized Controlled Trial

Medicina ◽  
2021 ◽  
Vol 57 (4) ◽  
pp. 314
Author(s):  
Aida Arroyo-Ferrer ◽  
Francisco José Sánchez-Cuesta ◽  
Yeray González-Zamorano ◽  
María Dolores del Castillo ◽  
Carolina Sastre-Barrios ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Therapy ◽  
Cognitive Processing ◽  
Processing Speed ◽  
Cognitive Rehabilitation ◽  
Neurodegenerative Disorder ◽  
Control Group ◽  
Motor Symptoms ◽  
The Impact

Background: Parkinson’s disease (PD) is the second most common neurodegenerative disorder. This disease is characterized by motor symptoms, such as bradykinesia, tremor, and rigidity. Although balance impairment is characteristic of advanced stages, it can be present with less intensity since the beginning of the disease. Approximately 60% of PD patients fall once a year and 40% recurrently. On the other hand, cognitive symptoms affect up to 20% of patients with PD in early stages and can even precede the onset of motor symptoms. There are cognitive requirements for balance and can be challenged when attention is diverted or reduced, linking a worse balance and a higher probability of falls with a slower cognitive processing speed and attentional problems. Cognitive rehabilitation of attention and processing speed can lead to an improvement in postural stability in patients with Parkinson’s. Methods: We present a parallel and controlled randomized clinical trial (RCT) to assess the impact on balance of a protocol based on cognitive rehabilitation focused on sustained attention through the NeuronUP platform (Neuronup SI, La Rioja, Spain) in patients with PD. For 4 weeks, patients in the experimental group will receive cognitive therapy three days a week while the control group will not receive any therapy. The protocol has been registered at trials.gov NCT04730466. Conclusions: Cognitive therapy efficacy on balance improvement may open the possibility of new rehabilitation strategies for prevention of falls in PD, reducing morbidity, and saving costs to the health care system.

Pointing to Remembered Targets in 3-D Space in Parkinson's Disease

Motor Control ◽  
1998 ◽  
Vol 2 (3) ◽  
pp. 251-277 ◽  
Author(s):  
Howard Poizner ◽  
Olga I. Fookson ◽  
Michail B. Berkinblit ◽  
Wayne Hening ◽  
Gregory Feldman ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Visual Feedback ◽  
Tracking System ◽  
Three Dimensional ◽  
Performance Deficits ◽  
Normal Speed ◽  
Task Conditions ◽  
Variable Errors ◽  
Target Locations

A three-dimensional tracking system was used to examine whether subjects with Parkinson's disease (PD) would show characteristic performance deficits in an unconstrained pointing task. Five targets were presented in a pyramidal array in space to 11 individuals with mild to moderate PD and 8 age-matched controls. After the target was indicated, subjects closed their eyes and pointed to the remembered target locations without vision. Despite the absence of visual feedback during movement, PD subjects were as accurate overall as controls. However, PD subjects showed greater variable errors, more irregular trajectories, and a vertical endpoint bias in which their endpoints were significantly lower than controls. They also showed deficiencies in the compensatory organization of joint rotations to ensure consistency in azimuthal (horizontal) positioning of the arm endpoint. We concluded that, under appropriate task conditions, PD subjects may not show overall deficits in accuracy even when making targeted movements at normal speed without visual feedback. Nevertheless, our findings indicate that there are certain dimensions of performance which are selectively altered in Parkinson's disease even when overall performance is normal.

Interval timing and Parkinson’s disease: heterogeneity in temporal performance

2007 ◽  
Vol 184 (2) ◽  
pp. 233-248 ◽  
Author(s):  
Hugo Merchant ◽  
Monica Luciana ◽  
Catalina Hooper ◽  
Stacy Majestic ◽  
Paul Tuite
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Interval Timing ◽  
Disease Heterogeneity

scholarly journals Dual task performance: a comparison between healthy elderly individuals and those with Parkinson’s disease

2015 ◽  
Vol 28 (2) ◽  
pp. 251-258 ◽  
Author(s):  
Eduardo Nascimento Floriano ◽  
Jacqueline Frazão Alves ◽  
Isabela Andrelino de Almeida ◽  
Roger Burgo de Souza ◽  
Gustavo Christofoletti ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Functional Performance ◽  
Cognitive Task ◽  
The Elderly ◽  
Berg Balance Scale ◽  
Dual Tasks ◽  
Healthy Elderly ◽  
Significant Difference ◽  
And Performance

Introduction The dual tasks (DT) is learned during the whole life and a prerequisite in functional performance in different activities of daily living. Healthy elderly have reduced ability to perform motor activities and cognitive tasks simultaneously, compared to young adults. Parkinson’s disease (PD) is the second most common neurodegenerative disease in the elderly and classic motor symptoms coexist with prejudice in cognitive domains. Objective To compare balance, gait and performance in dual tasks of individuals with Parkinson’s disease and healthy elderly. Material and method Transversal study consisted of 21 individuals with PD, classified between 1.5 to 3 in Hoehn and Yahr scale and 21 healthy individuals. To evaluate the performance on simple tasks and dual tasks the participants were submitted to five simple tasks (motor) and each was associated with a cognitive task, featuring a DT. To balance and gait evaluation was used the following instruments: Berg Balance Scale, Tinetti Scale and Dynamic Gait Index. Results In respect to gait and performance in dual tasks, there was a statistically significant difference with the worst performance for the group of individuals with PD. Conclusion It was found that the group of elderly people with PD has lower performance in the execution of concurrent tasks when compared with healthy elderly, so the DT can be introduced in rehabilitation programs to improve the performance of these patients.

Time dependent subthalamic local field potential changes after DBS surgery in Parkinson's disease

2010 ◽  
Vol 222 (2) ◽  
pp. 184-190 ◽  
Author(s):  
Manuela Rosa ◽  
Sara Marceglia ◽  
Domenico Servello ◽  
Guglielmo Foffani ◽  
Lorenzo Rossi ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Local Field ◽  
Local Field Potential ◽  
Field Potential ◽  
Time Dependent
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