scholarly journals A neurocomputational model of the basal ganglia for the analysis of motor deficits after dopaminergic loss in Parkinson's disease

2021 ◽  
Author(s):  
Ilaria Gigi ◽  
Rosa Senatore ◽  
Angelo Marcelli
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Basal Ganglia ◽  
Motor Learning ◽  
Early Stage ◽  
Motor Task ◽  
Movement Control ◽  
Neural System ◽  
Motor Deficits ◽  
Cortical Function

The basal ganglia (BG) are part of a basic feedback circuit, regulating cortical function, such as voluntary movement control, via their influence on thalamocortical projections. BG disorders, namely Parkinson's disease (PD), characterized by the loss of neurons in the substantia nigra (SN), involve the progressive loss of motor functions. The process that leads to these neural alterations is still unknown. At the present, PD cannot be cured, but an early diagnosis (ED) could allow to better manage its symptoms and evolution. A branch of neuroscience research is currently investigating the possibility of using motor alterations, e.g. handwriting, caused by the disease as diagnostic signs in the early stage of the disease, expression of small entity of SN lesion. In the present work, we propose a neurocomputational model to investigate the behaviour of the simulated neural system after several degrees of lesion, with the aim of evaluating, if possible, which is the smallest lesion compromising motor learning. The performance of the network in learning a novel motor task has been analyzed, in physiological and pathological conditions. The proposed neural network proves that there may exist abnormalities of motor learning process, due to alterations in the BG, which do not yet involve the presence of symptoms typical of the confirmed diagnosis, since the network shows having some difficulties in motor learning already with 20% DA depletion.

scholarly journals Dopamine and eye movement control in Parkinson’s disease: deficits in corollary discharge signals?

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e6038 ◽  
Author(s):  
Henry Railo ◽  
Henri Olkoniemi ◽  
Enni Eeronheimo ◽  
Oona Pääkkönen ◽  
Juho Joutsa ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Eye Movements ◽  
Eye Movement ◽  
Visual Information ◽  
Early Stage ◽  
Movement Control ◽  
Saccadic Eye Movements ◽  
Corollary Discharge ◽  
Motor Deficits

Movement in Parkinson’s disease (PD) is fragmented, and the patients depend on visual information in their behavior. This suggests that the patients may have deficits in internally monitoring their own movements. Internal monitoring of movements is assumed to rely on corollary discharge signals that enable the brain to predict the sensory consequences of actions. We studied early-stage PD patients (N = 14), and age-matched healthy control participants (N = 14) to examine whether PD patients reveal deficits in updating their sensory representations after eye movements. The participants performed a double-saccade task where, in order to accurately fixate a second target, the participant must correct for the displacement caused by the first saccade. In line with previous reports, the patients had difficulties in fixating the second target when the eye movement was performed without visual guidance. Furthermore, the patients had difficulties in taking into account the error in the first saccade when making a saccade toward the second target, especially when eye movements were made toward the side with dominant motor symptoms. Across PD patients, the impairments in saccadic eye movements correlated with the integrity of the dopaminergic system as measured with [123I]FP-CIT SPECT: Patients with lower striatal (caudate, anterior putamen, and posterior putamen) dopamine transporter binding made larger errors in saccades. This effect was strongest when patients made memory-guided saccades toward the second target. Our results provide tentative evidence that the motor deficits in PD may be partly due to deficits in internal monitoring of movements.

scholarly journals Dopamine and eye movement control in Parkinson’s disease: deficits in corollary discharge signals?

2018 ◽  
Author(s):  
Henry Railo ◽  
Henri Olkoniemi ◽  
Enni Eeronheimo ◽  
Oona Pääkkonen ◽  
Juho Joutsa ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Eye Movements ◽  
Eye Movement ◽  
Visual Information ◽  
Early Stage ◽  
Movement Control ◽  
Saccadic Eye Movements ◽  
Corollary Discharge ◽  
Motor Deficits

Movement in Parkinson’s disease (PD) is fragmented, and the patients depend on visual information in their behavior. This suggests that the patients may have deficits in internally monitoring their own movements. Internal monitoring of movements is assumed to rely on corollary discharge signals that enable the brain to predict the sensory consequences of actions. We studied early-stage PD patients (N=14), and age-matched healthy control participants (N=14) to examine whether PD patients reveal deficits in updating their sensory representations after eye movements. The participants performed a double-saccade task where, in order to accurately fixate a second target, the participant must correct for the displacement caused by the first saccade. In line with previous reports, the patients had difficulties in fixating the second target when the eye movement was performed without visual guidance. Furthermore, the patients had difficulties in taking into account the error in the first saccade when making a saccade towards the second target, especially when eye movements were made towards the side with dominant motor symptoms. Across PD patients, the impairments in saccadic eye movements correlated with the integrity of the dopaminergic system as measured with [123I]FP-CIT SPECT: Patients with lower striatal (caudate, anterior putamen and posterior putamen) dopamine transporter binding made larger errors in saccades. This effect was strongest when patients made memory-guided saccades towards the second target. Our results provide tentative evidence that the motor deficits in PD may be partly accounted by deficits in internal monitoring of movements.

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.

scholarly journals Loss of asymmetric spine synapses in prefrontal cortex of motor-asymptomatic, dopamine-depleted, cognitively impaired MPTP-treated monkeys

2013 ◽  
Vol 16 (4) ◽  
pp. 905-912 ◽  
Author(s):  
John D. Elsworth ◽  
Csaba Leranth ◽  
D. Eugene Redmond ◽  
Robert H. Roth
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Prefrontal Cortex ◽  
Cognitive Deficits ◽  
Cognitive Abilities ◽  
Pyramidal Neurons ◽  
Early Stage ◽  
Motor Deficits ◽  
Dopamine Concentration ◽  
Dorsolateral Prefrontal

Abstract Parkinson's disease is usually characterized as a movement disorder; however, cognitive abilities that are dependent on the prefrontal cortex decline at an early stage of the disease in most patients. The changes that underlie cognitive deficits in Parkinson's disease are not well understood. We hypothesize that reduced dopamine signalling in the prefrontal cortex in Parkinson's disease is a harbinger of detrimental synaptic changes in pyramidal neurons in the prefrontal cortex, whose function is necessary for normal cognition. Our previous data showed that monkeys exposed to the neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), but not exhibiting overt motor deficits (motor-asymptomatic), displayed cognitive deficits in prefrontal cortex-dependent tasks. The present results demonstrate that motor-asymptomatic MPTP-treated monkeys have a reduced dopamine concentration and a substantially lower number (50%) of asymmetric (excitatory) spine synapses in layer II/III, but not layer V, of the dorsolateral prefrontal cortex, compared to controls. In contrast, neither dopamine concentration nor asymmetric synapse number was altered in the entorhinal cortex of MPTP-treated monkeys. Together, these findings suggest that the number of asymmetric spine synapses on dendrites in the prefrontal cortex is dopamine-dependent and that the loss of synapses may be a morphological substrate of the cognitive deficits induced by a reduction in dopamine neurotransmission in this region.

scholarly journals High Cervical Spinal Cord Stimulation: A One Year Follow-Up Study on Motor and Non-Motor Functions in Parkinson’s Disease

2019 ◽  
Vol 9 (4) ◽  
pp. 78 ◽  
Author(s):  
Paolo Mazzone ◽  
Fabio Viselli ◽  
Stefano Ferraina ◽  
Margherita Giamundo ◽  
Massimo Marano ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Spinal Cord ◽  
Parkinson's Disease ◽  
Spinal Cord Stimulation ◽  
Cervical Spinal Cord ◽  
Motor Task ◽  
Motor Deficits ◽  
Failed Back Surgery ◽  
One Year ◽  
High Cervical

Background: The present study investigated the effectiveness of stimulation applied at cervical levels on pain and Parkinson’s disease (PD) symptoms using either tonic or burst stimulation mode. Methods: Tonic high cervical spinal cord stimulation (T-HCSCS) was applied on six PD patients suffering from low back pain and failed back surgery syndrome, while burst HCSCS (B-HCSCS) was applied in twelve PD patients to treat primarily motor deficits. Stimulation was applied percutaneously with quadripolar or octapolar electrodes. Clinical evaluation was assessed by the Unified Parkinson’s Disease Rating Scale (UPDRS) and the Hoehn and Yahr (H&Y) scale. Pain was evaluated by a visual analog scale. Evaluations of gait and of performance in a cognitive motor task were performed in some patients subjected to B-HCSCS. One patient who also suffered from severe autonomic cardiovascular dysfunction was investigated to evaluate the effectiveness of B-HCSCS on autonomic functions. Results: B-HCSCS was more effective and had more consistent effects than T-HCSCS in reducing pain. In addition, B-HCSCS improved UPDRS scores, including motor sub-items and tremor and H&Y score. Motor benefits appeared quickly after the beginning of B-HCSCS, in contrast to long latency improvements induced by T-HCSCS. A slight decrease of effectiveness was observed 12 months after implantation. B-HCSCS also improved gait and ability of patients to correctly perform a cognitive–motor task requiring inhibition of a prepared movement. Finally, B-HCSCS ameliorated autonomic control in the investigated patient. Conclusions: The results support a better usefulness of B-HCSCS compared to T-HCSCS in controlling pain and specific aspects of PD motor and non-motor deficits for at least one year.

Movement without dopamine: striatal dopamine is required to maintain but not to perform learned actions

2007 ◽  
Vol 35 (2) ◽  
pp. 428-432 ◽  
Author(s):  
E. Dowd ◽  
S.B. Dunnett
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Motor Learning ◽  
Motor Performance ◽  
Striatal Dopamine ◽  
Motor Deficits ◽  
Functional Roles ◽  
Gene Therapies ◽  
Different Populations

The different populations of dopaminergic neurons located in the ventral mesencephalon have long been associated with distinct functional roles. The nigrostriatal projection is considered necessary for efficient motor performance, while the mesolimbocortical projection is usually associated with reward signalling. However, a number of recent studies in our laboratory suggest that the divergence between these two functions of dopamine is not as delineated as it may once have seemed. In these experiments, we have been developing improved behavioural methods for assessing the nature of the deficit in rats with unilateral dopamine lesions, as well as the efficacy of various experimental cell and gene therapies for Parkinson's disease. The behavioural task we selected is a lateralized nose-poking task in which rats are trained to respond to stimulus lights on either side of their heads. This task not only allows us to accurately measure aspects of motor performance, but, because it requires extensive training, it also allows us to assess aspects of motor learning. The concurrence of motor performance parameters (which are considered to be dependent on striatal dopamine) and motor learning parameters (which are thought to be dependent on mesolimbocortical reward signalling) within the same task has revealed some surprising consequences of dopamine lesions and neuroprotective/neuroreparative approaches to repair in rat models of Parkinson's disease. The data generated using this task suggest that the motor deficits that occur as a consequence of dopamine lesions may be downstream of a deficit in reward signalling. If so, this could redefine our perception of the role of dopamine in controlling motor function.

scholarly journals Bee Venom Alleviates Motor Deficits and Modulates the Transfer of Cortical Information through the Basal Ganglia in Rat Models of Parkinson’s Disease

PLoS ONE ◽  
2015 ◽  
Vol 10 (11) ◽  
pp. e0142838 ◽  
Author(s):  
Nicolas Maurice ◽  
Thierry Deltheil ◽  
Christophe Melon ◽  
Bertrand Degos ◽  
Christiane Mourre ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Basal Ganglia ◽  
Bee Venom ◽  
Motor Deficits ◽  
Rat Models

scholarly journals Effect of Stimulation of Subthalamic Nucleus onbeta Oscillations and Thalamus Tremor Activity in aComputational Model of Parkinson’s Disease  

2020 ◽  
Author(s):  
Seyed-Mojtaba Alavi ◽  
Amin Mirzaei ◽  
Alireza Valizadeh ◽  
Reza Ebrahimpour
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Basal Ganglia ◽  
Globus Pallidus ◽  
Subthalamic Nucleus ◽  
Experimental Studies ◽  
Underlying Mechanism ◽  
Motor Deficits ◽  
Synaptic Coupling

Abstract Parkinson’s disease (PD) is associated with abnormal b band oscillations (13-30 Hz) in the cortico-basal ganglia circuits.Abnormally increased striato-pallidal inhibition and strengthening the synaptic coupling between subthalamic nucleus (STN)and globus pallidus externa (GPe), due to the loss of dopamine, are accounted as the potential sources of b oscillations in thebasal ganglia. Deep brain stimulation (DBS) of the basal ganglia subregions is known as a way to reduce the pathological boscillations and motor deficits related to PD. Despite the success of the DBS, its underlying mechanism is poorly understoodand, there is controversy about the inhibitory or excitatory role of the DBS in the literature. Here, we utilized a computationalnetwork model of basal ganglia which consists STN, GPe, globus pallidus interna (GPi), and thalamus neuronal population.This model can capture healthy and pathological b oscillations as what has been observed in experimental studies. Using thismodel, we investigated the effect of DBS to understand whether its effect is excitatory or inhibitory. Our results show that theexcitatory DBS (EDBS) is able to quench the pathological synchrony and b oscillations, while, applying inhibitory DBS (IDBS)failed to quench the PD signs. In addition, the EDBS ameliorated the thalamic activity related to tremor in the model, while,the IDBS outperformed. However, with the help of the model results, we conclude that the effect of the DBS on its target isexcitatory

scholarly journals Predictors of Cognitive Decline in the Early Stages of Parkinson's Disease: A Brief Cognitive Assessment Longitudinal Study

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Paulo Bugalho ◽  
Miguel Viana-Baptista
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Decline ◽  
Predictive Factors ◽  
Early Stage ◽  
Cognitive Test ◽  
Motor Deficits ◽  
Longitudinal Assessment ◽  
Early Stages ◽  
Brief Cognitive Assessment

Our objectives were to perform a longitudinal assessment of mental status in early stage Parkinson’s disease (PD) patients, with brief neuropsychological tests, in order to find predictive factors for cognitive decline. Sixty-one, early stage, and nondemented patients were assessed twice, over a 2-year interval, with a global cognitive test (mini-mental state examination (MMSE)) and a frontal function test (frontal assessment battery (FAB)) and motor function scales. Dementia and hallucinations were diagnosed according to the DSM-IV criteria. Cognitive function scores did not decrease significantly, except for FAB lexical fluency score. Four patients presented with dementia at followup. The MMSE score below cut-off, worse gait dysfunction, the nontremor motor subtype, and hallucinations were significantly related to dementia. Rigidity and speech dysfunction were related to dementia and a decrease in FAB scores. We can conclude that decline in the MMSE and FAB scores is small and heterogeneous in the early stages of PD. Scores below cut-off in the MMSE could be helpful to predict dementia. Nontremor motor deficits could be predictive factors for frontal cognitive decline and dementia.

INVESTIGATION OF MOTOR LEARNING IN PARKINSON'S DISEASE USING AN ACTION ACQUISITION TASK

2015 ◽  
Vol 86 (11) ◽  
pp. e4.85-e4
Author(s):  
Conor Fearon ◽  
Louise Newman ◽  
Brendan Quinlivan ◽  
John Butler ◽  
Tim Lynch ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Basal Ganglia ◽  
Motor Learning ◽  
Healthy Controls ◽  
Target Task ◽  
Acquisition Task ◽  
Multiple Structures ◽  
Computer Based ◽  
Dopamine Signaling

Movement learning is complex, involving multiple structures including cortex, cerebellum and the basal ganglia. In idiopathic Parkinson's disease (PD) there is initial loss of dopaminergic innervation to the caudal putamen, which governs habitual movement. With disease progression, however, this spreads to involve more anterior regions of the basal ganglia involved in goal-directed behaviour.Given the loss of phasic dopamine signaling in these areas we expect motor learning to be impaired in PD. The goal of this study is to investigate movement learning in PD and healthy controls using a computer-based action acquisition task.A cohort of PD patients and age-matched healthy controls were asked to repeatedly manipulate a joystick in order to move an unseen cursor on a computer screen, initially to a seen target (task 1) and then to an unseen target (task 2). By examining how these movements are refined in order to locate the target from task 1 to task 2 (which requires action selection by the basal ganglia) we quantify the rate at which movements are learned.The results show differences in parameters associated with the execution of the action acquisition task for the PD cohort when compared to healthy controls, supporting impaired motor learning in PD.

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