Dataset Information

Altered Interhemispheric Functional Connectivity Associated With Early Verbal Fluency Decline After Deep Brain Stimulation in Parkinson's Disease.

ABSTRACT:

Background

Patients with Parkinson's disease (PD) experience a decline in verbal fluency (VF) immediately after undergoing deep brain stimulation (DBS) of the subthalamic nucleus (STN). This phenomenon is thought to be related to surgical microlesions.

Purpose

We investigated the alterations in interhemispheric functional connectivity after STN-DBS in PD patients. We also evaluated the correlation between these changes and decreased VF scores.

Method

Overall, 30 patients with PD were enrolled in the study. Resting-state functional magnetic resonance imaging scans were performed twice, once before and once after DBS, in PD patients. Voxel-mirrored homotopic connectivity (VMHC) was applied in order to evaluate the synchronicity of functional connectivity between the hemispheres.

Result

After undergoing STN-DBS, PD patients demonstrated reduced VMHC value in the posterior cerebellum lobe, angular gyrus, precuneus/posterior cingulate gyrus (PCC), supramarginal gyrus, superior frontal gyrus (SFG) (medial and dorsolateral) and middle frontal gyrus (MFG). In addition, we observed a significant positive correlation between the altered VMHC value in the SFG and MFG and the change of phonemic VF scores.

Conclusion

PD patients demonstrated an interhemispheric coordination disorder in the prefrontal cortex, cerebellum, supramarginal gyrus and DMN after undergoing STN-DBS. The positive correlation between reduced VMHC value in the SFG and MFG and the changes of VF scores provides a novel understanding with regard to the decline of VF after DBS.

SUBMITTER: Luo B

PROVIDER: S-EPMC9011328 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Altered Interhemispheric Functional Connectivity Associated With Early Verbal Fluency Decline After Deep Brain Stimulation in Parkinson's Disease.

Luo Bei B Dong Wenwen W Chang Lei L Qiu Chang C Lu Yue Y Liu Dongming D Xue Chen C Zhang Li L Liu Weiguo W Zhang Wenbin W Yan Jun J

Frontiers in aging neuroscience 20220401

<h4>Background</h4>Patients with Parkinson's disease (PD) experience a decline in verbal fluency (VF) immediately after undergoing deep brain stimulation (DBS) of the subthalamic nucleus (STN). This phenomenon is thought to be related to surgical microlesions.<h4>Purpose</h4>We investigated the alterations in interhemispheric functional connectivity after STN-DBS in PD patients. We also evaluated the correlation between these changes and decreased VF scores.<h4>Method</h4>Overall, 30 patients wi ...[more]

PMID: 35431904

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Project description:Deep brain stimulation is an effective treatment for Parkinson's disease but can be complicated by side-effects such as cognitive decline. There is often a delay before this side-effect is apparent and the mechanism is unknown, making it difficult to identify patients at risk or select appropriate deep brain stimulation settings. Here, we test whether connectivity between the stimulation site and other brain regions is associated with cognitive decline following deep brain stimulation. First, we studied a unique patient cohort with cognitive decline following subthalamic deep brain stimulation for Parkinson's disease (n = 10) where reprogramming relieved the side-effect without loss of motor benefit. Using resting state functional connectivity data from a large normative cohort (n = 1000), we computed connectivity between each stimulation site and the subiculum, an a priori brain region functionally connected to brain lesions causing memory impairment. Connectivity between deep brain stimulation sites and this same subiculum region was significantly associated with deep brain stimulation induced cognitive decline (P < 0.02). We next performed a data-driven analysis to identify connections most associated with deep brain stimulation induced cognitive decline. Deep brain stimulation sites causing cognitive decline (versus those that did not) were more connected to the anterior cingulate, caudate nucleus, hippocampus, and cognitive regions of the cerebellum (PFWE < 0.05). The spatial topography of this deep brain stimulation-based circuit for cognitive decline aligned with an a priori lesion-based circuit for memory impairment (P = 0.017). To begin translating these results into a clinical tool that might be used for deep brain stimulation programming, we generated a 'heat map' in which the intensity of each voxel reflects the connectivity to our cognitive decline circuit. We then validated this heat map using an independent dataset of Parkinson's disease patients in which cognitive performance was measured following subthalamic deep brain stimulation (n = 33). Intersection of deep brain stimulation sites with our heat map was correlated with changes in the Mattis dementia rating scale 1 year after lead implantation (r = 0.39; P = 0.028). Finally, to illustrate how this heat map might be used in clinical practice, we present a case that was flagged as 'high risk' for cognitive decline based on intersection of the patient's deep brain stimulation site with our heat map. This patient had indeed experienced cognitive decline and our heat map was used to select alternative deep brain stimulation parameters. At 14 days follow-up the patient's cognition improved without loss of motor benefit. These results lend insight into the mechanism of deep brain stimulation induced cognitive decline and suggest that connectivity-based heat maps may help identify patients at risk and who might benefit from deep brain stimulation reprogramming.

Project description:Subthalamic nucleus deep brain stimulation is an effective treatment for advanced Parkinson's disease; however, its therapeutic mechanism is unclear. Previous modelling of functional MRI data has suggested that deep brain stimulation has modulatory effects on a number of basal ganglia pathways. This work uses an enhanced data collection protocol to collect rare functional MRI data in patients with subthalamic nucleus deep brain stimulation. Eleven patients with Parkinson's disease and subthalamic nucleus deep brain stimulation underwent functional MRI at rest and during a movement task; once with active deep brain stimulation, and once with deep brain stimulation switched off. Dynamic causal modelling and Bayesian model selection were first used to compare a series of plausible biophysical models of the cortico-basal ganglia circuit that could explain the functional MRI activity at rest in an attempt to reproduce and extend the findings from our previous work. General linear modelling of the movement task functional MRI data revealed deep brain stimulation-associated signal increases in the primary motor and cerebellar cortices. Given the significance of the cerebellum in voluntary movement, we then built a more complete model of the motor system by including cerebellar-basal ganglia interactions, and compared the modulatory effects deep brain stimulation had on different circuit components during the movement task and again using the resting state data. Consistent with previous results from our independent cohort, model comparison found that the rest data were best explained by deep brain stimulation-induced increased (effective) connectivity of the cortico-striatal, thalamo-cortical and direct pathway and reduced coupling of subthalamic nucleus afferent and efferent connections. No changes in cerebellar connectivity were identified at rest. In contrast, during the movement task, there was functional recruitment of subcortical-cerebellar pathways, which were additionally modulated by deep brain stimulation, as well as modulation of local (intrinsic) cortical and cerebellar circuits. This work provides in vivo evidence for the modulatory effects of subthalamic nucleus deep brain stimulation on effective connectivity within the cortico-basal ganglia loops at rest, as well as further modulations in the cortico-cerebellar motor system during voluntary movement. We propose that deep brain stimulation has both behaviour-independent effects on basal ganglia connectivity, as well as behaviour-dependent modulatory effects.

Project description:ObjectivesFirstly, to identify subthalamic region stimulation clusters that predict maximum improvement in rigidity, bradykinesia and tremor, or emergence of side-effects; and secondly, to map-out the cortical fingerprint, mediated by the hyperdirect pathways which predict maximum efficacy.MethodsHigh angular resolution diffusion imaging in twenty patients with advanced Parkinson's disease was acquired prior to bilateral subthalamic nucleus deep brain stimulation. All contacts were screened one-year from surgery for efficacy and side-effects at different amplitudes. Voxel-based statistical analysis of volumes of tissue activated models was used to identify significant treatment clusters. Probabilistic tractography was employed to identify cortical connectivity patterns associated with treatment efficacy.ResultsAll patients responded well to treatment (46% mean improvement off medication UPDRS-III [p < 0.0001]) without significant adverse events. Cluster corresponding to maximum improvement in tremor was in the posterior, superior and lateral portion of the nucleus. Clusters corresponding to improvement in bradykinesia and rigidity were nearer the superior border in a further medial and posterior location. The rigidity cluster extended beyond the superior border to the area of the zona incerta and Forel-H2 field. When the clusters where averaged, the coordinates of the area with maximum overall efficacy was X = -10(-9.5), Y = -13(-1) and Z = -7(-3) in MNI(AC-PC) space. Cortical connectivity to primary motor area was predictive of higher improvement in tremor; whilst that to supplementary motor area was predictive of improvement in bradykinesia and rigidity; and connectivity to prefrontal cortex was predictive of improvement in rigidity.InterpretationThese findings support the presence of overlapping stimulation sites within the subthalamic nucleus and its superior border, with different cortical connectivity patterns, associated with maximum improvement in tremor, rigidity and bradykinesia.

Dataset Information

Altered Interhemispheric Functional Connectivity Associated With Early Verbal Fluency Decline After Deep Brain Stimulation in Parkinson's Disease.

Background

Purpose

Method

Result

Conclusion

Publications

Altered Interhemispheric Functional Connectivity Associated With Early Verbal Fluency Decline After Deep Brain Stimulation in Parkinson's Disease.

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