scholarly journals Disruption of cortical dopaminergic modulation impairs preparatory activity and delays licking initiation

2018 ◽  
Author(s):  
Ke Chen ◽  
Roberto Vincis ◽  
Alfredo Fontanini
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Motor Cortex ◽  
Neural Activity ◽  
Cortical Activity ◽  
Motor Deficits ◽  
Receptor Modulation ◽  
Dopaminergic Modulation ◽  
Preparatory Activity ◽  
Motor Cortical

ABSTRACTDysfunction of motor cortices is thought to contribute to motor disorders such as Parkinson’s disease (PD). However, little is known on the link between cortical dopaminergic loss, abnormalities in motor cortex neural activity and motor deficits. We address the role of dopamine in modulating motor cortical activity by focusing on the anterior lateral motor cortex (ALM) of mice performing a cued-licking task. We first demonstrate licking deficits and concurrent alterations of spiking activity in ALM of mice with unilateral depletion of dopaminergic neurons (i.e., mice injected with 6-OHDA into the medial forebrain bundle). Hemi-lesioned mice displayed delayed licking initiation, shorter duration of licking bouts, and lateral deviation of tongue protrusions. In parallel with these motor deficits, we observed a reduction in the prevalence of cue responsive neurons and altered preparatory activity. Acute and local blockade of D1 receptors in ALM recapitulated some of the key behavioral and neural deficits observed in hemi-lesioned mice. Altogether, our data show a direct relationship between cortical D1 receptor modulation, cue-evoked and preparatory activity in ALM, and licking initiation.SIGNIFICANCE STATEMENTThe link between dopaminergic signaling, motor cortical activity and motor deficits is not fully understood. This manuscript describes alterations in neural activity of the anterior lateral motor cortex (ALM) that correlate with licking deficits in mice with unilateral dopamine depletion or with intra-ALM infusion of dopamine antagonist. The findings emphasize the importance of cortical dopaminergic modulation in motor initiation. These results will appeal not only to researchers interested in cortical control of licking, but also to a broader audience interested in motor control and dopaminergic modulation in physiological and pathological conditions. Specifically, our data suggest that dopamine deficiency in motor cortex could play a role in the pathogenesis of the motor symptoms of Parkinson’s disease.

People With Parkinson’s Disease Exhibit Reduced Cognitive and Motor Cortical Activity When Undertaking Complex Stepping Tasks Requiring Inhibitory Control

2020 ◽  
Vol 34 (12) ◽  
pp. 1088-1098
Author(s):  
Paulo H. S. Pelicioni ◽  
Stephen R. Lord ◽  
Yoshiro Okubo ◽  
Daina L. Sturnieks ◽  
Jasmine C. Menant
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Inhibitory Control ◽  
Near Infrared ◽  
Premotor Cortex ◽  
Cortical Activity ◽  
Cortical Activation ◽  
Functional Near Infrared Spectroscopy ◽  
Dorsolateral Prefrontal ◽  
Motor Cortical

Background People with Parkinson’s disease (PD) have difficulties generating quick and accurate steps in anticipation of and/or in response to environmental hazards. However, neural mechanisms underlying performance in cognitively demanding stepping tasks are unclear. Objective This study compared activation patterns in cognitive and motor cortical regions using functional near-infrared spectroscopy (fNIRS) between people with PD and age-matched healthy older adults (HOA) during stepping tasks. Methods Fifty-two people with PD and 95 HOA performed a simple choice stepping reaction time test (CSRT) and 2 cognitively demanding stepping tests (inhibitory CSRT [iCSRT] and Stroop stepping test [SST]) on a computerized step mat. Cortical activation in the dorsolateral prefrontal cortex (DLPFC), Broca’s area, supplementary motor area (SMA), and premotor cortex (PMC) were recorded using fNIRS. Stepping performance and cortical activity were contrasted between groups and between the CSRT and the iCSRT and SST. Results The PD group performed worse than the HOA in all 3 stepping tests. A consistent pattern of interactions indicated differential hemodynamic responses between the groups. Compared with the CSRT, the PD group exhibited reduced DLPFC activity in the iCSRT and reduced SMA and PMC activity in the SST. The HOA exhibited increased DLPFC, SMA, and PMC activity when performing the SST in comparison with the CSRT task. Conclusions In contrast to the HOA, the PD group demonstrated reduced cortical activity in the DLPFC, SMA, and PMC during the more complex stepping tasks requiring inhibitory control. This may reflect subcortical and/or multiple pathway damage with subsequent deficient use of cognitive and motor resources.

scholarly journals Differences in Dopaminergic Modulation to Motor Cortical Plasticity between Parkinson's Disease and Multiple System Atrophy

PLoS ONE ◽  
2013 ◽  
Vol 8 (5) ◽  
pp. e62515 ◽  
Author(s):  
Shoji Kawashima ◽  
Yoshino Ueki ◽  
Tatsuya Mima ◽  
Hidenao Fukuyama ◽  
Kosei Ojika ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Multiple System Atrophy ◽  
Cortical Plasticity ◽  
Dopaminergic Modulation ◽  
Motor Cortical

scholarly journals Muscarinic receptors mediate motivation via preparatory neural activity in humans

2021 ◽  
Author(s):  
John Patrick Grogan ◽  
Matthias Raemaekers ◽  
Maaike M H van Swieten ◽  
Alexander L. Green ◽  
Martin J. Gillies ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Muscarinic Receptors ◽  
Neural Activity ◽  
Animal Studies ◽  
Reaction Times ◽  
Central Component ◽  
Anticholinergic Drugs ◽  
Motivational Influence ◽  
Preparatory Activity

Motivation depends on dopamine, but might be modulated by acetylcholine which influences dopamine release in the striatum, and amplifies motivation in animal studies. A corresponding effect in humans would be important clinically, since anticholinergic drugs are frequently used in Parkinson's disease, a condition that can also disrupt motivation. Reward and dopamine make us more ready to respond, as indexed by reaction times (RT), and move faster, sometimes termed vigour. These effects may be controlled by preparatory processes that can be tracked using EEG. We measured vigour in a placebo-controlled, double-blinded study of trihexyphenidyl (THP), a muscarinic antagonist, with an incentivised eye movement task and EEG. Participants responded faster and with greater vigour when incentives were high, but THP blunted these motivation effects, suggesting that muscarinic receptors facilitate invigoration by reward. Preparatory EEG build-up (contingent negative variation; CNV) was strengthened by high incentives and by muscarinic blockade. The amplitude of preparatory activity predicted both vigour and RT, although over distinct scalp regions. Frontal activity predicted vigour, whereas a larger, earlier, central component predicted RT. Indeed the incentivisation of RT was partly mediated by the CNV, though vigour was not. Moreover, the CNV mediated the drug's effect on dampening incentives, suggesting that muscarinic receptors underlie the motivational influence on this preparatory activity. Taken together, these findings show that a muscarinic blocker used to treat Parkinson's disease impairs motivated action in healthy people, and that medial frontal preparatory neural activity mediates this for RT.

Role of motor cortex in coordinating multi-joint movements: Is it time for a new paradigm?

2000 ◽  
Vol 78 (11) ◽  
pp. 923-933 ◽  
Author(s):  
Stephen H Scott
Keyword(s):  
Motor Cortex ◽  
Neural Activity ◽  
Cortical Activity ◽  
Reaching Movements ◽  
Cortical Region ◽  
Joint Movement ◽  
Global Features ◽  
Motor Patterns ◽  
New Device ◽  
Motor Cortical

Reaching movements to spatial targets require motor patterns at the shoulder to be coordinated carefully with those at the elbow to smoothly move the hand through space. While the motor cortex is involved in this volitional task, considerable debate remains about how this cortical region participates in planning and controlling movement. This article reviews two opposing interpretations of motor cortical function during multi-joint movements. On the one hand, studies performed predominantly on single-joint movement generally support the notion that motor cortical activity is intimately involved in generating motor patterns at a given joint. In contrast, studies on reaching demonstrate correlations between motor cortical activity and features of movement related to the hand, suggesting that the motor cortex may be involved in more global features of the task. Although this latter paradigm involves a multi-joint motor task in which neural activity is correlated with features of movement related to the hand, this neural activity is also correlated to other movement variables. Therefore it is difficult to assess if and how the motor cortex contributes to the coordination of motor patterns at different joints. In particular, present paradigms cannot assess whether motor cortical activity contributes to the control of one joint or multiple joints during whole-arm tasks. The final point discussed in this article is the development of a new experimental device (KINARM) that can both monitor and manipulate the mechanics of the shoulder and elbow independently during multi-joint motor tasks. It is hoped that this new device will provide a new approach for examining how the motor cortex is involved in motor coordination.Key words: reaching movements, biomechanics, motor coordination, proximal arm.

scholarly journals Impaired auditory-to-motor entrainment in Parkinson’s disease

2017 ◽  
Vol 117 (5) ◽  
pp. 1853-1864 ◽  
Author(s):  
Erik S. te Woerd ◽  
Robert Oostenveld ◽  
Floris P. de Lange ◽  
Peter Praamstra
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neural Activity ◽  
Response Times ◽  
Modulation Depth ◽  
Auditory Target ◽  
Motor Circuits ◽  
Beta Power ◽  
Motor Cortical ◽  
Auditory Cortices

Several electrophysiological studies suggest that Parkinson's disease (PD) patients have a reduced tendency to entrain to regular environmental patterns. Here we investigate whether this reduced entrainment concerns a generalized deficit or is confined to movement-related activity, leaving sensory entrainment intact. Magnetoencephalography was recorded during a rhythmic auditory target detection task in 14 PD patients and 14 control subjects. Participants were instructed to press a button when hearing a target tone amid an isochronous sequence of standard tones. The variable pitch of standard tones indicated the probability of the next tone to be a target. In addition, targets were occasionally omitted to evaluate entrainment uncontaminated by stimulus effects. Response times were not significantly different between groups and both groups benefited equally from the predictive value of standard tones. Analyses of oscillatory beta power over auditory cortices showed equal entrainment to the tones in both groups. By contrast, oscillatory beta power and event-related fields demonstrated a reduced engagement of motor cortical areas in PD patients, expressed in the modulation depth of beta power, in the response to omitted stimuli, and in an absent motor area P300 effect. Together, these results show equally strong entrainment of neural activity over sensory areas in controls and patients, but, in patients, a deficient translation of the adjustment to the task rhythm to motor circuits. We suggest that the reduced activation reflects not merely altered resonance to rhythmic external events, but a compromised recruitment of an endogenous response reflecting internal rhythm generation. NEW & NOTEWORTHY Previous studies suggest that motor cortical activity in PD patients has a reduced tendency to entrain to regular environmental patterns. This study demonstrates that the deficient entrainment in PD concerns the motor system only, by showing equally strong entrainment of neural activity over sensory areas in controls and patients but, in patients, a deficient translation of this adjustment to the task rhythm to motor circuits.

Modulation of motor cortex by subthalamic stimulation in Parkinson's disease

2004 ◽  
Vol 31 (S 1) ◽  
Author(s):  
B Haslinger ◽  
K Kalteis ◽  
F Alesch ◽  
H Boecker ◽  
AO Ceballos-Baumann
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Motor Cortex ◽  
Subthalamic Stimulation

Association of the Non-Motor Burden with Patterns of Striatal Dopamine Loss in de novo Parkinson’s Disease

2020 ◽  
Vol 10 (4) ◽  
pp. 1541-1549
Author(s):  
Seok Jong Chung ◽  
Sangwon Lee ◽  
Han Soo Yoo ◽  
Yang Hyun Lee ◽  
Hye Sun Lee ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
De Novo ◽  
Early Stage ◽  
Striatal Dopamine ◽  
Motor Deficits ◽  
Dopamine Depletion ◽  
Severe Motor ◽  
Severe Group ◽  
Striatal Dopamine Depletion

Background: Striatal dopamine deficits play a key role in the pathogenesis of Parkinson’s disease (PD), and several non-motor symptoms (NMSs) have a dopaminergic component. Objective: To investigate the association between early NMS burden and the patterns of striatal dopamine depletion in patients with de novo PD. Methods: We consecutively recruited 255 patients with drug-naïve early-stage PD who underwent 18F-FP-CIT PET scans. The NMS burden of each patient was assessed using the NMS Questionnaire (NMSQuest), and patients were divided into the mild NMS burden (PDNMS-mild) (NMSQuest score <6; n = 91) and severe NMS burden groups (PDNMS-severe) (NMSQuest score >9; n = 90). We compared the striatal dopamine transporter (DAT) activity between the groups. Results: Patients in the PDNMS-severe group had more severe parkinsonian motor signs than those in the PDNMS-mild group, despite comparable DAT activity in the posterior putamen. DAT activity was more severely depleted in the PDNMS-severe group in the caudate and anterior putamen compared to that in the PDMNS-mild group. The inter-sub-regional ratio of the associative/limbic striatum to the sensorimotor striatum was lower in the PDNMS-severe group, although this value itself lacked fair accuracy for distinguishing between the patients with different NMS burdens. Conclusion: This study demonstrated that PD patients with severe NMS burden exhibited severe motor deficits and relatively diffuse dopamine depletion throughout the striatum. These findings suggest that the level of NMS burden could be associated with distinct patterns of striatal dopamine depletion, which could possibly indicate the overall pathological burden in PD.

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