scholarly journals The motor inhibitory network in patients with asymmetrical Parkinson’s disease: An fMRI study

Author(s):  
Francis R. Loayza ◽  
Ignacio Obeso ◽  
Rafael González Redondo ◽  
Federico Villagra ◽  
Elkin Luis ◽  
...  

AbstractRecent imaging studies with the stop-signal task in healthy individuals indicate that the subthalamic nucleus, the pre-supplementary motor area and the inferior frontal gyrus are key components of the right hemisphere “inhibitory network”. Limited information is available regarding neural substrates of inhibitory processing in patients with asymmetric Parkinson’s disease. The aim of the current fMRI study was to identify the neural changes underlying deficient inhibitory processing on the stop-signal task in patients with predominantly left-sided Parkinson’s disease. Fourteen patients and 23 healthy controls performed a stop-signal task with the left and right hands. Behaviorally, patients showed delayed response inhibition with either hand compared to controls. We found small imaging differences for the right hand, however for the more affected left hand when behavior was successfully inhibited we found reduced activation of the inferior frontal gyrus bilaterally and the insula. Using the stop-signal delay as regressor, contralateral underactivation in the right dorsolateral prefrontal cortex, inferior frontal and anterior putamen were found in patients. This finding indicates dysfunction of the right inhibitory network in left-sided Parkinson’s disease. Functional connectivity analysis of the left subthalamic nucleus showed a significant increase of connectivity with bilateral insula. In contrast, the right subthalamic nucleus showed increased connectivity with visuomotor and sensorimotor regions of the cerebellum. We conclude that altered inhibitory control in left-sided Parkinson’s disease is associated with reduced activation in regions dedicated to inhibition in healthy controls, which requires engagement of additional regions, not observed in controls, to successfully stop ongoing actions.

2013 ◽  
Vol 239 ◽  
pp. 1-12 ◽  
Author(s):  
Manuel Alegre ◽  
Jon Lopez-Azcarate ◽  
Ignacio Obeso ◽  
Leonora Wilkinson ◽  
Maria C. Rodriguez-Oroz ◽  
...  

2021 ◽  
Vol 13 ◽  
Author(s):  
Song’an Shang ◽  
Hongying Zhang ◽  
Yuan Feng ◽  
Jingtao Wu ◽  
Weiqiang Dou ◽  
...  

Background: Cognitive deficits are prominent non-motor symptoms in Parkinson’s disease (PD) and have been shown to involve the neurovascular unit (NVU). However, there is a lack of sufficient neuroimaging research on the associated modulating mechanisms. The objective of this study was to identify the contribution of neurovascular decoupling to the pathogenesis of cognitive decline in PD.Methods: Regional homogeneity (ReHo), a measure of neuronal activity, and cerebral blood flow (CBF), a measure of vascular responses, were obtained from patients with PD with mild cognitive impairment (MCI) and normal cognition (NC) as well as matched healthy controls (HCs). Imaging metrics of neurovascular coupling (global and regional CBF-ReHo correlation coefficients and CBF-ReHo ratios) were compared among the groups.Results: Neurovascular coupling was impaired in patients with PD-MCI with a decreased global CBF-ReHo correlation coefficient relative to HC subjects (P < 0.05). Regional dysregulation was specific to the PD-MCI group and localized to the right middle frontal gyrus, right middle cingulate cortex, right middle occipital gyrus, right inferior parietal gyrus, right supramarginal gyrus, and right angular gyrus (P < 0.05). Compared with HC subjects, patients with PD-MCI showed higher CBF-ReHo ratios in the bilateral lingual gyri (LG), bilateral putamen, and left postcentral gyrus and lower CBF-ReHo ratios in the right superior temporal gyrus, bilateral middle temporal gyri, bilateral parahippocampal gyri, and right inferior frontal gyrus. Relative to the HC and PD-NC groups, the PD-MCI group showed an increased CBF-ReHo ratio in the left LG, which was correlated with poor visual–spatial performance (r = −0.36 and P = 0.014).Conclusion: The involvement of neurovascular decoupling in cognitive impairment in PD is regionally specific and most prominent in the visual–spatial cortices, which could potentially provide a complementary understanding of the pathophysiological mechanisms underlying cognitive deficits in PD.


2020 ◽  
Author(s):  
Claire O'Callaghan ◽  
Frank Hubert Hezemans ◽  
Rong Ye ◽  
Catarina Rua ◽  
P Simon Jones ◽  
...  

Cognitive decline is a common feature of Parkinson's disease, and many of these cognitive deficits fail to respond to dopaminergic therapy. Therefore, targeting other neuromodulatory systems represents an important therapeutic strategy. Among these, the locus coeruleus-noradrenaline system has been extensively implicated in response inhibition deficits. Restoring noradrenaline levels using the noradrenergic reuptake inhibitor atomoxetine can improve response inhibition in some patients with Parkinson's disease, but there is considerable heterogeneity in treatment response. Accurately predicting the patients who would benefit from therapies targeting this neurotransmitter system remains a critical goal, in order to design the necessary clinical trials with stratified patient selection to establish the therapeutic potential of atomoxetine. Here, we test the hypothesis that integrity of the noradrenergic locus coeruleus explains the variation in improvement of response inhibition following atomoxetine. In a double-blind placebo-controlled randomised crossover design, 19 people with Parkinson's disease completed an acute psychopharmacological challenge with 40 mg of oral atomoxetine or placebo. A stop-signal task was used to measure response inhibition, with stop-signal reaction times obtained through hierarchical Bayesian estimation of an ex-Gaussian race model. Twenty-six control subjects completed the same task without undergoing the drug manipulation. In a separate session, patients and controls underwent ultra-high field 7T imaging of the locus coeruleus using a neuromelanin-sensitive magnetisation transfer sequence. The principal result was that atomoxetine improved stop-signal reaction times in those patients with lower locus coeruleus integrity. This was in the context of a general impairment in response inhibition, as patients on placebo had longer stop-signal reaction times compared to controls. We also found that the caudal portion of the locus coeruleus showed the largest neuromelanin signal decrease in the patients compared to controls. Our results highlight a link between the integrity of the noradrenergic locus coeruleus and response inhibition in Parkinson's disease patients. Furthermore, they demonstrate the importance of baseline noradrenergic state in determining the response to atomoxetine. We suggest that locus coeruleus neuromelanin imaging offers a marker of noradrenergic capacity that could be used to stratify patients in trials of noradrenergic therapy and to ultimately inform personalised treatment approaches.


2020 ◽  
pp. 1-7
Author(s):  
Weiyuan Huang ◽  
Richard Ogbuji ◽  
Liangdong Zhou ◽  
Lingfei Guo ◽  
Yi Wang ◽  
...  

OBJECTIVEThe objective of this study was to investigate the correlation between the quantitative susceptibility mapping (QSM) signal gradient of the subthalamic nucleus (STN) and motor impairment in patients with Parkinson’s disease (PD).METHODSAll PD patients who had undergone QSM MRI for presurgical deep brain stimulation (DBS) planning were eligible for inclusion in this study. The entire STN and its three functional subdivisions, as well as the adjacent white matter (WM), were segmented and measured. The QSM value difference between the entire STN and adjacent WM (STN-WM), between the limbic and associative regions of the STN (L-A), and between the associative and motor regions of the STN (A-M) were obtained as measures of gradient and were input into an unsupervised k-means clustering algorithm to automatically categorize the overall boundary distinctness between the STN and adjacent WM and between STN subdivisions (gradient blur [GB] and gradient sharp [GS] groups). Statistical tests were performed to compare clinical and image measurements for discrimination between GB and GS groups.RESULTSOf the 39 study patients, 19 were categorized into the GB group and 20 into the GS group, based on quantitative cluster analysis. The GB group had a significantly higher presurgical off-medication Unified Parkinson’s Disease Rating Scale Part III score (51.289 ± 20.741) than the GS group (38.5 ± 16.028; p = 0.037). The GB group had significantly higher QSM values for the STN and its three subdivisions and adjacent WM than those for the GS group (p < 0.01). The GB group also demonstrated a significantly higher STN-WM gradient in the right STN (p = 0.01). The GB group demonstrated a significantly lower L-A gradient in both the left and the right STN (p < 0.02).CONCLUSIONSAdvancing PD with more severe motor impairment leads to more iron deposition in the STN and adjacent WM, as shown in the QSM signal. Loss of the STN inner QSM signal gradient should be considered as an image marker for more severe motor impairment in PD patients.


2012 ◽  
Vol 108 (2) ◽  
pp. 380-389 ◽  
Author(s):  
Weidong Cai ◽  
Jobi S. George ◽  
Frederick Verbruggen ◽  
Christopher D. Chambers ◽  
Adam R. Aron

Rapidly stopping action engages a network in the brain including the right presupplementary motor area (preSMA), the right inferior frontal gyrus, and the basal ganglia. Yet the functional role of these different regions within the overall network still remains unclear. Here we focused on the role of the right preSMA in behavioral stopping. We hypothesized that the underlying neurocognitive function of this region is one or more of setting up a stopping rule in advance, modulating response tendencies (e.g., slowing down in anticipation of stopping), and implementing stopping when the stop signal occurs. We performed two experiments with magnetic resonance imaging (MRI)–guided, event-related, transcranial magnetic stimulation(TMS), during the performance of variants of the stop signal task. In experiment 1 we show that stimulation of the right preSMA versus vertex (control site) slowed the implementation of stopping (measured via stop signal reaction time) but had no influence on modulation of response tendencies. In experiment 2, we showed that stimulation of the right preSMA slowed implementation of stopping in a mechanistically selective form of stopping but had no influence on setting up stopping rules. The results go beyond the replication of prior findings by showing that TMS of the right preSMA impairs stopping behavior (including a behaviorally selective form of stopping) through a specific disruption of the implementation of stopping. Future studies are required to establish whether this was due to stimulation of the right preSMA itself or because of remote effects on the wider stopping network.


2013 ◽  
Vol 2013 ◽  
pp. 1-2
Author(s):  
Dursun Aygun ◽  
Ersoy Kocabicak ◽  
Onur Yildiz ◽  
Musa Kazim Onar ◽  
Hatice Guz ◽  
...  

In advanced Parkinson's disease (PD), deep brain stimulation (DBS) may be an alternative option for the treatment of motor symptoms. Side effects associated with subthalamic nucleus (STN) DBS in patients with PD are emerging as the most frequent sensory and motor symptoms. DBS-related syncope is reported as extremely rare. We wanted to discuss the mechanisms of syncope associated with STN DBS in a patient with Parkinson's disease.Case report.Sixty-three-year-old female patient is followed up with diagnosis of idiopathic Parkinson's disease for 6 years in our clinic. The patient has undergone STN DBS due to painful dystonia and drug resistant tremor. During the operation, when the left STN was stimulated at 5 milliampere (mAmp), the patient developed presyncopal symptoms. However, when the stimulation was stopped symptoms improved. During the early period after the operation, when the right STN was stimulated at 1.3 millivolts (mV), she developed the pre-yncopal symptoms and then syncope. Our case shows that STN DBS may lead to directly autonomic symptoms resulting in syncope during stimulation-on (stim-on).


2007 ◽  
Vol 98 (6) ◽  
pp. 3638-3647 ◽  
Author(s):  
Christopher D. Chambers ◽  
Mark A. Bellgrove ◽  
Ian C. Gould ◽  
Therese English ◽  
Hugh Garavan ◽  
...  

Intelligent behavior depends on the ability to suppress inappropriate actions and resolve interference between competing responses. Recent clinical and neuroimaging evidence has demonstrated the involvement of prefrontal, parietal, and premotor areas during behaviors that emphasize conflict and inhibition. It remains unclear, however, whether discrete subregions within this network are crucial for overseeing more specific inhibitory demands. Here we probed the functional specialization of human prefrontal cortex by combining repetitive transcranial magnetic stimulation (rTMS) with integrated behavioral measures of response inhibition (stop-signal task) and response competition (flanker task). Participants undertook a combined stop-signal/flanker task after rTMS of the inferior frontal gyrus (IFG) or dorsal premotor cortex (dPM) in each hemisphere. Stimulation of the right IFG impaired stop-signal inhibition under conditions of heightened response competition but did not influence the ability to suppress a competing response. In contrast, stimulation of the right dPM facilitated execution but had no effect on inhibition. Neither of these results was observed during rTMS of corresponding left-hemisphere regions. Overall, our findings are consistent with existing evidence that the right IFG is crucial for inhibitory control. The observed double dissociation of neurodisruptive effects between the right IFG and right dPM further implies that response inhibition and execution rely on distinct neural processes despite activating a common cortical network.


Author(s):  
F. A. Zeiler ◽  
M. Wilkinson ◽  
J. P. Krcek

Abstract:Introduction:Subthalamic nucleus (STN) deep brain stimulation (DBS) is currently the main surgical procedure for medically refractory Parkinson's disease. The benefit of intra-operative microelectrode recording (MER) for the purpose of neurophysiological localization and mapping of the STN continues to be debated.Methods:A retrospective review of the charts and operative reports of all patients receiving STN DBS implantation for Parkinson's disease at our institution from January 2004 to March 2011 was done.Results:Data from 43 of 44 patients with Parkinson's disease treated with STN DBS were reviewed. The average number of tracts on the left was 2.4, versus 2.3 on the right. The average dorsal and ventral anatomical boundaries of the STN based on Schaltenbrand's Stereotactic Atlas were estimated to be at -5.0 mm above and +1.4 mm below target respectively. The average dorsal and ventral boundaries of the STN using MER were -2.6 mm above and +2.0 mm below target respectively. The average dorsal-ventral distance of the STN as predicted by Stereotactic Atlas was 6.4 mm, compared to 4.6 mm as determined by MER. MER demonstrated the average dorsal and ventral boundaries on the left side were -2.6 mm and +2.2 mm from target respectively, while the average dorsal and ventral boundaries on the right side were -2.5 mm and +1.8 mm from target respectively with MER.Conclusions:MER in STN DBS surgery demonstrated measurable difference between stereotactic atlas/MRI STN target and neurophysiologic STN localization.


2020 ◽  
Author(s):  
Lina Cheng ◽  
Xiaoyan Wu ◽  
Ruomi Guo ◽  
Yuzhou Wang ◽  
Wensheng Wang ◽  
...  

Abstract Background: Accurate identification of Parkinson's disease (PD) and Parkinsonism-Plus syndrome (PPS), especially in the early stage of the disease, is very important. The purpose of this study was to investigate the discriminative spatial pattern of cerebral blood flow (CBF) between patients with PD and PPS.Methods: Arterial spin labeling (ASL) perfusion-weighted imaging was performed in 20 patients with PD (mean age 56.35±7.56 years), 16 patients with PPS (mean age 59.62±6.89 years), and 17 healthy controls (HCs, mean age 54.17±6.58 years). Voxel-wise comparison of the CBF was performed among PD, PPS and HC groups. The receiver operating characteristic (ROC) curve was used to evaluate the performance of CBF in discriminating between PD and PPS.Results: PD group showed a significantly decreased CBF in the right cerebelum_crus2, the left middle frontal gyrus (MFG), the triangle inferior frontal gyrus (IFG_Tri), the left frontal medial orbital gyrus (FG_Med_Orb) and the left caudate nucleus (CN) compared with the HC group (P < 0.05). Besides the above regions, the left supplementary motor area (SMA), the right thalamus had decreased CBF in the PPS group compared with the HC group (P < 0.05). PPS group had lower CBF value in the left MFG, the left IFG_Tri, the left CN, the left SMA, and the right thalamus compared with the PD group (P < 0.05). CBFs in left IFG_Tri, the left CN, the left SMA, and the right thalamus had moderate to high capacity in discriminating between PD and PPS patients (AUC 0.719-0.831).Conclusion: PD and PPS patients have certain discriminative patterns of reduced CBFs, which can be used as a surrogate marker for differential diagnosis.


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