Subthalamic nucleus--sensorimotor cortex functional connectivity in de novo and moderate Parkinson's disease.
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ABSTRACT:
SUBMITTER: Kurani AS
PROVIDER: S-EPMC4268125 | biostudies-literature | 2015 Jan
REPOSITORIES: biostudies-literature
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Project description:A typical feature of Parkinson's disease (PD) is pathological activity in the subthalamic nucleus (STN). Here, we tested whether in patients with PD under dopaminergic treatment functional connectivity of the STN differs from healthy controls (HC) and whether some brain regions show (anti-) correlations between functional connectivity with STN and motor symptoms. We used functional magnetic resonance imaging to investigate whole-brain resting-state functional connectivity with STN in 54 patients with PD and 55 HC matched for age, gender, and within-scanner motion. Compared to HC, we found attenuated negative STN-coupling with Crus I of the right cerebellum and with right ventromedial prefrontal regions in patients with PD. Furthermore, we observed enhanced negative STN-coupling with bilateral intraparietal sulcus/superior parietal cortex, right sensorimotor, right premotor, and left visual cortex compared to HC. Finally, we found a decline in positive STN-coupling with the left insula related to severity of motor symptoms and a decline of inter-hemispheric functional connectivity between left and right STN with progression of PD-related motor symptoms. Motor symptom related uncoupling of the insula, a key region in the saliency network and for executive function, from the STN might be associated with well-known executive dysfunction in PD. Moreover, uncoupling between insula and STN might also induce an insufficient setting of thresholds for the discrimination between relevant and irrelevant salient environmental stimuli, explaining observations of disturbed response control in PD. In sum, motor symptoms in PD are associated with a reduced coupling between STN and a key region for executive function.
| S-EPMC6867311 | biostudies-literature
Project description:Neurophysiological changes within the cortico-basal ganglia-thalamocortical circuits appear to be a characteristic of Parkinson's disease (PD) pathophysiology. The subthalamic nucleus (STN) is one of the basal ganglia components showing pathological neural activity patterns in PD. In this study, perfusion imaging data, acquired noninvasively using arterial spin-labeled (ASL) perfusion MRI, were used to assess the resting state functional connectivity (FC) of the STN in 24 early-to-moderate PD patients and 34 age-matched healthy controls, to determine whether altered FC in the very low frequency range of the perfusion time signal occurs as a result of the disease. Our results showed that the healthy STN was functionally connected with other nuclei of the basal ganglia and the thalamus, as well as with discrete cortical areas including the insular cortex and the hippocampus. In PD patients, connectivity of the STN was increased with two cortical areas involved in motor and cognitive processes. These findings suggest that hyperconnectivity of the STN could underlie some of the motor and cognitive deficits often present even at early stages of the disease. The FC measures provided good discrimination between controls and patients, suggesting that ASL-derived FC metrics could be a putative PD biomarker.
| S-EPMC6869392 | biostudies-literature
Project description:Parkinson's disease (PD) is characterized by degenerative changes of nigral dopamine neurons, resulting in the dopaminergic denervation of the striatum. Resting state networks studies have demonstrated that dopamine modulates distinct network connectivity patterns in both a linear and a nonlinear fashion, but quantitative analyses of dopamine-dependent functional connectivity secondary to PD pathology were less informative. In the present study, we performed a correlation analysis between striatal dopamine levels assessed quantitatively by FP-CIT positron emission tomography imaging and resting-state functional connectivity in 23 drug naïve de novo patients with PD to elucidate dopamine-dependent functional networks. The major finding is that the patterns of dopamine-dependent positive functional connectivity varied depending on the location of striatal seeds. Dopamine-dependent functional connectivity with the caudate predominantly overlay pericentral cortical areas, whereas dopamine-dependent structures functionally connected with the posterior putamen predominantly involved cerebellar areas. The dorsolateral frontal area overlapped as a dopamine-dependent cortical region that was positively connected with the anterior and posterior putamen. On the other hand, cortical areas where functional connectivity from the posterior cingulate was negatively correlated with dopaminergic status in the posterior putamen were localized in the left anterior prefrontal area and the parietal area. Additionally, functional connectivity between the anterior putamen and mesiofrontal areas was negatively coupled with striatal dopamine levels. The present study demonstrated that dopamine-dependent functional network connectivity secondary to PD pathology mainly exhibits a consistent pattern, albeit with some variation. These patterns may reflect the diverse effects of dopaminergic medication on parkinsonian-related motor and cognitive performance.
| S-EPMC6869560 | biostudies-literature
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:The salience network is responsive during a range of conditions requiring immediate behavioral responses, including pain processing. Resting-state functional connectivity of the salience network to the sensorimotor cortex is altered in chronic pain. However, little is understood about their fundamental communication in the absence of pain. In this study, we mapped salience network resting-state functional connectivity across sensorimotor cortex in healthy individuals. Using electromyography and task-based functional magnetic resonance imaging (fMRI), we first localized distinct regions-of-interest across sensorimotor cortex in medial (gluteal), intermediate (shoulder), and lateral (hand) areas. We then used resting-state fMRI for two cohorts (primary and replication) of healthy individuals from public repositories to map salience network resting-state functional connectivity across sensorimotor cortex. Both the primary and replication cohorts exhibited significant heterogeneity in salience network resting-state functional connectivity across the sensorimotor regions-of-interest. Using a cortical flatmap to visualize the entire sensorimotor surface, we observed similar heterogeneity in both cohorts. In general, the somatotopic representation of proximal body regions (trunk/face) had higher salience network resting-state functional connectivity compared to distal body regions (upper/lower limbs). We conclude that sensorimotor cortex is spatially heterogeneous in its interaction with the salience network in healthy individuals.
| S-EPMC8462097 | biostudies-literature
Project description:BackgroundParkinson's disease (PD) manifests with the appearance of non-motor symptoms before motor symptoms onset. Among these, dysfunctioning visual structures have recently been reported to occur at early disease stages.ObjectiveThis study addresses effective connectivity in the visual network of PD patients.MethodsUsing functional MRI and dynamic causal modeling analysis, we evaluated the connectivity between the superior colliculus, the lateral geniculate nucleus and the primary visual area V1 in de novo untreated PD patients (n = 22). A subset of the PD patients (n = 8) was longitudinally assessed two times at two months and at six months after starting dopaminergic treatment. Results were compared to those of age-matched healthy controls (n = 22).ResultsOur results indicate that the superior colliculus drives cerebral activity for luminance contrast processing both in healthy controls and untreated PD patients. The same effective connectivity was observed with neuromodulatory differences in terms of neuronal dynamic interactions. Our main findings were that the modulation induced by luminance contrast changes of the superior colliculus connectivity (self-connectivity and connectivity to the lateral geniculate nucleus) was inhibited in PD patients (effect of contrast: p = 0.79 and p = 0.77 respectively). The introduction of dopaminergic medication in a subset (n = 8) of the PD patients failed to restore the effective connectivity modulation observed in the healthy controls.InterpretationThe deficits in luminance contrast processing in PD was associated with a deficiency in connectivity adjustment from the superior colliculus to the lateral geniculate nucleus and to V1. No differences in cerebral blood flow were observed between controls and PD patients suggesting that the deficiency was at the neuronal level. Administration of a dopaminergic treatment over six months was not able to normalize the observed alterations in inter-regional coupling. These findings highlight the presence of early dysfunctions in primary visual areas, which might be used as early markers of the disease.
| S-EPMC8670854 | biostudies-literature
Project description:Recent evidence has suggested that prefrontal cortical structures may inhibit impulsive actions during conflict through activation of the subthalamic nucleus (STN). Consistent with this hypothesis, deep brain stimulation to the STN has been associated with altered prefrontal cortical activity and impaired response inhibition. The interactions between oscillatory activity in the STN and its presumably antikinetic neuronal spiking, however, remain poorly understood. Here, we simultaneously recorded intraoperative local field potential and spiking activity from the human STN as participants performed a sensorimotor action selection task involving conflict. We identified several STN neuronal response types that exhibited different temporal dynamics during the task. Some neurons showed early, cue-related firing rate increases that remained elevated longer during high conflict trials, whereas other neurons showed late, movement-related firing rate increases. Notably, the high conflict trials were associated with an entrainment of individual neurons by theta- and beta-band oscillations, both of which have been observed in cortical structures involved in response inhibition. Our data suggest that frequency-specific activity in the beta and theta bands influence STN firing to inhibit impulsivity during conflict.
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Project description:How the basal ganglia participate in the uniquely human behavior of speech is poorly understood, despite their known role in modulating critical aspects of cognitive and motor behavior. The subthalamic nucleus (STN) is well positioned to facilitate basal ganglia functions critical for speech. Using electrocorticography in patients undergoing awake deep brain stimulation (DBS) surgery, evidence is reported for a left opercular hyperdirect pathway in humans via stimulating the STN and examining antidromic-evoked activity in the left temporal, parietal, and frontal opercular cortex. These high-resolution cortical and subcortical mapping data provide evidence for hyperdirect connectivity between the inferior frontal gyrus and the STN. In addition, evoked potential data are consistent with the presence of monosynaptic projections from areas of the opercular speech cortex that are primarily sensory, including the auditory cortex, to the STN. These connections may be unique to humans, evolving alongside the ability for speech.
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Project description:Mature cortical pyramidal neurons receive excitatory inputs onto small protrusions emanating from their dendrites called spines. Spines undergo activity-dependent remodelling, stabilization and pruning during development, and similar structural changes can be triggered by learning and changes in sensory experiences. However, the biochemical triggers and mechanisms of de novo spine formation in the developing brain and the functional significance of new spines to neuronal connectivity are largely unknown. Here we develop an approach to induce and monitor de novo spine formation in real time using combined two-photon laser-scanning microscopy and two-photon laser uncaging of glutamate. Our data demonstrate that, in mouse cortical layer 2/3 pyramidal neurons, glutamate is sufficient to trigger de novo spine growth from the dendrite shaft in a location-specific manner. We find that glutamate-induced spinogenesis requires opening of NMDARs (N-methyl-D-aspartate-type glutamate receptors) and activation of protein kinase A (PKA) but is independent of calcium-calmodulin-dependent kinase II (CaMKII) and tyrosine kinase receptor B (TrkB) receptors. Furthermore, newly formed spines express glutamate receptors and are rapidly functional such that they transduce presynaptic activity into postsynaptic signals. Together, our data demonstrate that early neural connectivity is shaped by activity in a spatially precise manner and that nascent dendrite spines are rapidly functionally incorporated into cortical circuits.
| S-EPMC3107907 | biostudies-literature
Project description:BackgroundDeep brain stimulation (DBS) is an effective and approved therapy for advanced Parkinson's disease (PD), and a recent study suggests efficacy in mid-stage disease. This manuscript reports the results of a pilot trial investigating preliminary safety and tolerability of DBS in early PD.MethodsThirty subjects with idiopathic PD (Hoehn & Yahr Stage II off medication), age 50-75, on medication ≥6 months but ≤4 years, and without motor fluctuations or dyskinesias were randomized to optimal drug therapy (ODT) (n = 15) or DBS + ODT (n = 15). Co-primary endpoints were the time to reach a 4-point worsening from baseline in the UPDRS-III off therapy and the change in levodopa equivalent daily dose from baseline to 24 months.ResultsAs hypothesized, the mean UPDRS total and part III scores were not significantly different on or off therapy at 24 months. Medication requirements in the DBS + ODT group were lower at all time points with a maximal difference at 18 months. With a few exceptions, differences in neuropsychological functioning were not significant. Two subjects in the DBS + ODT group suffered serious adverse events; remaining adverse events were mild or transient.ConclusionsThis study demonstrates that subjects with early stage PD will enroll in and complete trials testing invasive therapies and provides preliminary evidence that DBS is well tolerated in early PD. The results of this trial provide the data necessary to design a large, phase III, double-blind, multicenter trial investigating the safety and efficacy of DBS in early PD.
| S-EPMC4103427 | biostudies-literature