A computational basal ganglia model to assess the role of STN-DBS on Impulsivity in Parkinson's disease

Author(s):  
Mandali Alekhya ◽  
V Srinivasa Chakravarthy
2004 ◽  
Vol 18 (2/3) ◽  
pp. 130-139 ◽  
Author(s):  
Guillermo Paradiso ◽  
Danny Cunic ◽  
Robert Chen

Abstract Although it has long been suggested that the basal ganglia and thalamus are involved in movement planning and preparation, there was little direct evidence in humans to support this hypothesis. Deep brain stimulation (DBS) is a well-established treatment for movement disorders such as Parkinson's disease, tremor, and dystonia. In patients undergoing DBS surgery, we recorded simultaneously from scalp contacts and from electrodes surgically implanted in the subthalamic nucleus (STN) of 13 patients with Parkinson's disease and in the “cerebellar” thalamus of 5 patients with tremor. The aim of our studies was to assess the role of the cortico-basal ganglia-thalamocortical loop through the STN and the cerebello-thalamocortical circuit through the “cerebellar” thalamus in movement preparation. The patients were asked to perform self-paced wrist extension movements. All subjects showed a cortical readiness potential (RP) with onset ranging between 1.5 to 2s before the onset of movement. Subcortical RPs were recorded in 11 of 13 with electrodes in the STN and in 4 of 5 patients with electrodes in the thalamus. The onset time of the STN and thalamic RPs were not significantly different from the onset time of the scalp RP. The STN and thalamic RPs were present before both contralateral and ipsilateral hand movements. Postoperative MRI studies showed that contacts with maximum RP amplitude generally were inside the target nucleus. These findings indicate that both the basal ganglia and the cerebellar circuits participate in movement preparation in parallel with the cortex.


2020 ◽  
Author(s):  
Yvan Vachez ◽  
Marie Bahout ◽  
Robin Magnard ◽  
Pierre-Maxime David ◽  
Carole Carcenac ◽  
...  

ABSTRACTApathy is frequently reported in Parkinson’s disease (PD) patients under subthalamic nucleus deep brain stimulation (STN-DBS). The prevailing clinical view for apathy following STN-DBS is the reduction of dopaminergic medication. However, few clinical reports and recent experimental data suggested the pathogenicity of bilateral STN-DBS on motivation, challenging the leading opinion. Here, we investigate whether bilateralism of STN-DBS influences apathy outcome after STN-DBS, combining pre-clinical and clinical approaches. We assess the motivational effects of chronic unilateral STN-DBS in rats in the exact same conditions having highlighted a loss of motivation under bilateral STN-DBS. Clinical data are obtained by the follow-up of a cohort of parkinsonian patients undergoing unilateral STN-DBS and coming from the clinical center that described apathy related to bilateral STN-DBS itself. Despite an acute effect, which fades rapidly, unilateral STN-DBS did not induce a loss of motivation reminiscent to apathy in rats. In patients, apathy did not increase between the preoperative and the post-operative assessment. Together, those data demonstrate that bilateral but not unilateral STN-DBS can induce a loss of motivation in both rats and patients. This constitutes another evidence of the role of STN-DBS itself for apathy in PD.


2009 ◽  
Vol 47 (5) ◽  
pp. 1269-1273 ◽  
Author(s):  
Marieke van Asselen ◽  
Inês Almeida ◽  
Rui Andre ◽  
Cristina Januário ◽  
António Freire Gonçalves ◽  
...  

2012 ◽  
Vol 224 (2) ◽  
pp. 211-220 ◽  
Author(s):  
Carolina Bonivento ◽  
Raffaella I. Rumiati ◽  
Emanuele Biasutti ◽  
Glyn W. Humphreys

Basal Ganglia ◽  
2014 ◽  
Vol 3 (4) ◽  
pp. 203-212 ◽  
Author(s):  
Mariano Andrés Belluscio ◽  
Mariela Verónica Escande ◽  
Ettel Keifman ◽  
Luis Alberto Riquelme ◽  
Mario Gustavo Murer ◽  
...  

2019 ◽  
Author(s):  
Shahab Bakhtiari ◽  
Ayca Altinkaya ◽  
Christopher C. Pack ◽  
Abbas F. Sadikot

AbstractThe ability to inhibit an inappropriate action in a context is an important part of the human cognitive repertoire, and deficiencies in this ability are common in neurological and psychiatric disorders. An anti-saccade is a simple experimental task within the oculomotor repertoire that can be used to test this ability. The task involves an inhibition of a saccade to the peripheral target (pro-saccade) and generation of a voluntary eye movement toward the mirror position (anti-saccade). Previous studies provide evidence for a possible contribution from the basal ganglia in anti-saccade behavior. However, the precise role of different components in generation of anti-saccade behavior is still uncertain. Parkinson’s disease patients with implanted deep brain stimulation (DBS) in subthalamic nucleus (STN) provide us with a unique opportunity to investigate the role of STN in anti-saccade behavior. Previous attempts to show the effect of STN DBS on anti-saccades have produced conflicting observations. For example, the effect of STN DBS on anti-saccade error rate is not yet clear. Part of this inconsistency may be related to differences in dopaminergic states in different studies. Here, we tested Parkinson’s disease patients on anti- and pro-saccade tasks ON and OFF STN DBS and ON and OFF dopaminergic medication. We made three main observations. First, STN DBS increases the anti-saccade error rate while patients are OFF dopamine replacement therapy. Second, there is an interaction between dopamine replacement therapy and STN DBS. More specifically, L-dopa reduces the effect of STN DBS on anti-saccade error rate. Third, STN DBS can induce different effects on pro- and anti-saccades in different patients. These observations provide evidence for an important role for the STN in the circuitry underlying context-dependent modulation of visuomotor action selection.


2019 ◽  
Vol 17 (2) ◽  
pp. 165-175 ◽  
Author(s):  
Sumit Jamwal ◽  
Puneet Kumar

Alteration in neurotransmitters signaling in basal ganglia has been consistently shown to significantly contribute to the pathophysiological basis of Parkinson’s disease and Huntington’s disease. Dopamine is an important neurotransmitter which plays a critical role in coordinated body movements. Alteration in the level of brain dopamine and receptor radically contributes to irregular movements, glutamate mediated excitotoxic neuronal death and further leads to imbalance in the levels of other neurotransmitters viz. GABA, adenosine, acetylcholine and endocannabinoids. This review is based upon the data from clinical and preclinical studies to characterize the role of various striatal neurotransmitters in the pathogenesis of Parkinson’s disease and Huntington’s disease. Further, we have collected data of altered level of various neurotransmitters and their metabolites and receptor density in basal ganglia region. Although the exact mechanisms underlying neuropathology of movement disorders are not fully understood, but several mechanisms related to neurotransmitters alteration, excitotoxic neuronal death, oxidative stress, mitochondrial dysfunction, neuroinflammation are being put forward. Restoring neurotransmitters level and downstream signaling has been considered to be beneficial in the treatment of Parkinson’s disease and Huntington’s disease. Therefore, there is an urgent need to identify more specific drugs and drug targets that can restore the altered neurotransmitters level in brain and prevent/delay neurodegeneration.


Sign in / Sign up

Export Citation Format

Share Document