Differential dopaminergic modulation of spontaneous cortico-subthalamic activity in Parkinson's disease.
Ontology highlight
ABSTRACT:
SUBMITTER: Sharma A
PROVIDER: S-EPMC8177893 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundTransient improvement in motor symptoms are immediately observed in patients with Parkinson's disease (PD) after an electrode has been implanted into the subthalamic nucleus (STN) for deep brain stimulation (DBS). This phenomenon is known as the microlesion effect (MLE). However, the underlying mechanisms of MLE is poorly understood.PurposeWe utilized resting state functional MRI (rs-fMRI) to evaluate changes in spontaneous brain activity and networks in PD patients during the microlesion period after DBS.MethodOverall, 37 PD patients and 13 gender- and age-matched healthy controls (HCs) were recruited for this study. Rs-MRI information was collected from PD patients three days before DBS and one day after DBS, whereas the HCs group was scanned once. We utilized the amplitude of low-frequency fluctuation (ALFF) method in order to analyze differences in spontaneous whole-brain activity among all subjects. Furthermore, functional connectivity (FC) was applied to investigate connections between other brain regions and brain areas with significantly different ALFF before and after surgery in PD patients.ResultRelative to the PD-Pre-DBS group, the PD-Post-DBS group had higher ALFF in the right putamen, right inferior frontal gyrus, right precentral gyrus and lower ALFF in right angular gyrus, right precuneus, right posterior cingulate gyrus (PCC), left insula, left middle temporal gyrus (MTG), bilateral middle frontal gyrus and bilateral superior frontal gyrus (dorsolateral). Functional connectivity analysis revealed that these brain regions with significantly different ALFF scores demonstrated abnormal FC, largely in the temporal, prefrontal cortices and default mode network (DMN).ConclusionThe subthalamic microlesion caused by DBS in PD was found to not only improve the activity of the basal ganglia-thalamocortical circuit, but also reduce the activity of the DMN and executive control network (ECN) related brain regions. Results from this study provide new insights into the mechanism of MLE.
| S-EPMC8329380 | biostudies-literature
Project description:Excessive beta oscillatory activity in the subthalamic nucleus (STN) is linked to Parkinson's Disease (PD) motor symptoms. However, previous works have been inconsistent regarding the functional role of beta activity in untreated Parkinsonian states, questioning such role. We hypothesized that this inconsistency is due to the influence of electrophysiological broadband activity -a neurophysiological indicator of synaptic excitation/inhibition ratio- that could confound measurements of beta activity in STN recordings. Here we propose a data-driven, automatic and individualized mathematical model that disentangles beta activity and 1/f broadband activity in the STN power spectrum, and investigate the link between these individual components and motor symptoms in thirteen Parkinsonian patients. We show, using both modeled and actual data, how beta oscillatory activity significantly correlates with motor symptoms (bradykinesia and rigidity) only when broadband activity is not considered in the biomarker estimations, providing solid evidence that oscillatory beta activity does correlate with motor symptoms in untreated PD states as well as the significant impact of broadband activity. These findings emphasize the importance of data-driven models and the identification of better biomarkers for characterizing symptom severity and closed-loop applications.
| S-EPMC6218479 | biostudies-literature
Project description:The dopaminergic system has a unique gating function in the initiation and execution of movements. When the interhemispheric imbalance of dopamine inherent to the healthy brain is disrupted, as in Parkinson's disease (PD), compensatory mechanisms act to stave off behavioral changes. It has been proposed that two such compensatory mechanisms may be (a) a decrease in motor lateralization, observed in drug-naïve PD patients and (b) reduced inhibition - increased facilitation. Seeking to investigate the differential effect of dopamine depletion and subsequent substitution on compensatory mechanisms in non-drug-naïve PD, we studied 10 PD patients and 16 healthy controls, with patients undergoing two test sessions - "ON" and "OFF" medication. Using a simple visually-cued motor response task and fMRI, we investigated cortical motor activation - in terms of laterality, contra- and ipsilateral percent BOLD signal change and effective connectivity in the parametric empirical Bayes framework. We found that decreased motor lateralization persists in non-drug-naïve PD and is concurrent with decreased contralateral activation in the cortical motor network. Normal lateralization is not reinstated by dopamine substitution. In terms of effective connectivity, disease-related changes primarily affect ipsilaterally-lateralized homotopic cortical motor connections, while medication-related changes affect contralaterally-lateralized homotopic connections. Our findings suggest that, in non-drug-naïve PD, decreased lateralization is no longer an adaptive cortical mechanism, but rather the result of maladaptive changes, related to disease progression and long-term dopamine replacement. These findings highlight the need for the development of noninvasive therapies, which would promote the adaptive mechanisms of the PD brain.
| S-EPMC6865418 | biostudies-literature
Project description:Local field potentials (LFP) of the subthalamic nucleus (STN) recorded during walking may provide clues for determining the function of the STN during gait and also, may be used as biomarker to steer adaptive brain stimulation devices. Here, we present LFP recordings from an implanted sensing neurostimulator (Medtronic Activa PC?+?S) during walking and rest with and without stimulation in 10 patients with Parkinson's disease and electrodes placed bilaterally in the STN. We also present recordings from two of these patients recorded with externalized leads. We analyzed changes in overall frequency power, bilateral connectivity, high beta frequency oscillatory characteristics and gait-cycle related oscillatory activity. We report that deep brain stimulation improves gait parameters. High beta frequency power (20-30?Hz) and bilateral oscillatory connectivity are reduced during gait, while the attenuation of high beta power is absent during stimulation. Oscillatory characteristics are affected in a similar way. We describe a reduction in overall high beta burst amplitude and burst lifetimes during gait as compared to rest off stimulation. Investigating gait cycle related oscillatory dynamics, we found that alpha, beta and gamma frequency power is modulated in time during gait, locked to the gait cycle. We argue that these changes are related to movement induced artifacts and that these issues have important implications for similar research.
| S-EPMC6051498 | biostudies-literature
Project description:Electrode implantation into the subthalamic nucleus for deep brain stimulation in Parkinson's disease (PD) is associated with a temporary motor improvement occurring prior to neurostimulation. We studied this phenomenon by functional magnetic resonance imaging (fMRI) when considering the Unified Parkinson's Disease Rating Scale (UPDRS-III) and collateral oedema. Twelve patients with PD (age 55.9± (SD)6.8 years, PD duration 9-15 years) underwent bilateral electrode implantation into the subthalamic nucleus. The fMRI was carried out after an overnight withdrawal of levodopa (OFF condition): (i) before and (ii) within three days after surgery in absence of neurostimulation. The motor task involved visually triggered finger tapping. The OFF/UPDRS-III score dropped from 33.8±8.7 before to 23.3±4.8 after the surgery (p<0.001), correlating with the postoperative oedema score (p<0.05). During the motor task, bilateral activation of the thalamus and basal ganglia, motor cortex and insula were preoperatively higher than after surgery (p<0.001). The results became more enhanced after compensation for the oedema and UPDRS-III scores. In addition, the rigidity and axial symptoms score correlated inversely with activation of the putamen and globus pallidus (p<0.0001). One month later, the OFF/UPDRS-III score had returned to the preoperative level (35.8±7.0, p = 0.4).In conclusion, motor improvement induced by insertion of an inactive electrode into the subthalamic nucleus caused an acute microlesion which was at least partially related to the collateral oedema and associated with extensive impact on the motor network. This was postoperatively manifested as lowered movement-related activation at the cortical and subcortical levels and differed from the known effects of neurostimulation or levodopa. The motor system finally adapted to the microlesion within one month as suggested by loss of motor improvement and good efficacy of deep brain stimulation.
| S-EPMC3492182 | biostudies-literature
Project description:Dopaminergic medication for Parkinson's disease (PD) modulates neuronal oscillations and functional connectivity (FC) across the basal ganglia-thalamic-cortical circuit. However, the non-oscillatory component of the neuronal activity, potentially indicating a state of excitation/inhibition balance, has not yet been investigated and previous studies have shown inconsistent changes of cortico-cortical connectivity as a response to dopaminergic medication. To further elucidate changes of regional non-oscillatory component of the neuronal power spectra, FC, and to determine which aspects of network organization obtained with graph theory respond to dopaminergic medication, we analyzed a resting-state electroencephalography (EEG) dataset including 15 PD patients during OFF and ON medication conditions. We found that the spectral slope, typically used to quantify the broadband non-oscillatory component of power spectra, steepened particularly in the left central region in the ON compared to OFF condition. In addition, using lagged coherence as a FC measure, we found that the FC in the beta frequency range between centro-parietal and frontal regions was enhanced in the ON compared to the OFF condition. After applying graph theory analysis, we observed that at the lower level of topology the node degree was increased, particularly in the centro-parietal area. Yet, results showed no significant difference in global topological organization between the two conditions: either in global efficiency or clustering coefficient for measuring global and local integration, respectively. Interestingly, we found a close association between local/global spectral slope and functional network global efficiency in the OFF condition, suggesting a crucial role of local non-oscillatory dynamics in forming the functional global integration which characterizes PD. These results provide further evidence and a more complete picture for the engagement of multiple cortical regions at various levels in response to dopaminergic medication in PD.
| S-EPMC9106139 | biostudies-literature
Project description:The neural substrates that enable individuals to achieve their fastest and strongest motor responses have long been enigmatic. Importantly, characterization of such activities may inform novel therapeutic strategies for patients with hypokinetic disorders, such as Parkinson's disease. Here, we ask whether the basal ganglia may play an important role, not only in the attainment of maximal motor responses under standard conditions but also in the setting of the performance enhancements known to be engendered by delivery of intense stimuli. To this end, we recorded local field potentials from deep brain stimulation electrodes implanted bilaterally in the subthalamic nuclei of 10 patients with Parkinson's disease, as they executed their fastest and strongest handgrips in response to a visual cue, which was accompanied by a brief 96-dB auditory tone on random trials. We identified a striking correlation between both theta/alpha (5-12?Hz) and high-gamma/high-frequency (55-375 Hz) subthalamic nucleus activity and force measures, which explained close to 70% of interindividual variance in maximal motor responses to the visual cue alone, when patients were ON their usual dopaminergic medication. Loud auditory stimuli were found to enhance reaction time and peak rate of development of force still further, independent of whether patients were ON or OFF l-DOPA, and were associated with increases in subthalamic nucleus power over a broad gamma range. However, the contribution of this broad gamma activity to the performance enhancements observed was only modest (?13%). The results implicate frequency-specific subthalamic nucleus activities as substantial factors in optimizing an individual's peak motor responses at maximal effort of will, but much less so in the performance increments engendered by intense auditory stimuli.
| S-EPMC3437023 | biostudies-literature
Project description:Whilst exaggerated bursts of beta frequency band oscillatory synchronization in the subthalamic nucleus have been associated with motor impairment in Parkinson's disease, a plausible mechanism linking the two phenomena has been lacking. Here we test the hypothesis that increased synchronization denoted by beta bursting might compromise information coding capacity in basal ganglia networks. To this end we recorded local field potential activity in the subthalamic nucleus of 18 patients with Parkinson's disease as they executed cued upper and lower limb movements. We used the accuracy of local field potential-based classification of the limb to be moved on each trial as an index of the information held by the system with respect to intended action. Machine learning using the naïve Bayes conditional probability model was used for classification. Local field potential dynamics allowed accurate prediction of intended movements well ahead of their execution, with an area under the receiver operator characteristic curve of 0.80 ± 0.04 before imperative cues when the demanded action was known ahead of time. The presence of bursts of local field potential activity in the alpha, and even more so, in the beta frequency band significantly compromised the prediction of the limb to be moved. We conclude that low frequency bursts, particularly those in the beta band, restrict the capacity of the basal ganglia system to encode physiologically relevant information about intended actions. The current findings are also important as they suggest that local subthalamic activity may potentially be decoded to enable effector selection, in addition to force control in restorative brain-machine interface applications.
| S-EPMC7009471 | biostudies-literature
Project description:Parkinson's disease (PD) is associated with distinct metabolic covariance patterns that relate to the motor and cognitive manifestations of the disorder. It is not known, however, how the expression of these patterns relates to measurements of nigrostriatal dopaminergic activity from the same individuals. To explore these associations, we studied 106 PD subjects who underwent cerebral PET with both (18) F-fluorodeoxyglucose (FDG) and (18) F-fluoro-L-dopa (FDOPA). Expression values for the PD motor- and cognition-related metabolic patterns (PDRP and PDCP, respectively) were computed for each subject; these measures were correlated with FDOPA uptake on a voxel-by-voxel basis. To explore the relationship between dopaminergic function and local metabolic activity, caudate and putamen FDOPA PET signal was correlated voxel-wise with FDG uptake over the entire brain. PDRP expression correlated with FDOPA uptake in caudate and putamen (P?<?0.001), while PDCP expression correlated with uptake in the anterior striatum (P?<?0.001). While statistically significant, the correlations were only of modest size, accounting for less than 20% of the overall variation in these measures. After controlling for PDCP expression, PDRP correlations were significant only in the posterior putamen. Of note, voxel-wise correlations between caudate/putamen FDOPA uptake and whole-brain FDG uptake were significant almost exclusively in PDRP regions. Overall, the data indicate that PDRP and PDCP expression correlates significantly with PET indices of presynaptic dopaminergic functioning obtained in the same individuals. Even so, the modest size of these correlations suggests that in PD patients, individual differences in network activity cannot be explained solely by nigrostriatal dopamine loss.
| S-EPMC6869564 | biostudies-literature
Project description:Motivational influence on bradykinesia in Parkinson's disease may be observed in situations of emotional and physical stress, a phenomenon known as paradoxical kinesis. However, little is known about motivational modulation of movement speed beyond these extreme circumstances. In particular, it is not known if motivational factors affect movement speed by improving movement preparation/initiation or execution (or both) and how this effect relates to the patients' medication state. In the present study, we tested if provision of motivational incentive through monetary reward would speed-up movement initiation and/or execution in Parkinson's disease patients and if this effect depended on dopaminergic medication. We studied the effect of monetary incentive on simple reaction time in 11 Parkinson's disease patients both "off" and "on" dopaminergic medication and in 11 healthy participants. The simple reaction time task was performed across unrewarded and rewarded blocks. The initiation time and movement time were quantified separately. Anticipation errors and long responses were also recorded. The prospect of reward improved initiation times in Parkinson's disease patients both "off" and "on" dopaminergic medication, to a similar extent as in healthy participants. However, for "off" medication, this improvement was associated with increased frequency of anticipation errors, which were eliminated by dopamine replacement. Dopamine replacement had an additional, albeit small effect, on reward-related improvement of movement execution. Motivational strategies are helpful in overcoming bradykinesia in Parkinson's disease. Motivational factors may have a greater effect on bradykinesia when patients are "on" medication, as dopamine appears to be required for overcoming speed-accuracy trade-off and for improvement of movement execution. Thus, medication status should be an important consideration in movement rehabilitation programmes for patients with Parkinson's disease.
| S-EPMC4057625 | biostudies-literature