Studying the functional connectivity of the primary motor cortex with the binarized cross recurrence plot: The influence of Parkinson's disease.
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ABSTRACT:
SUBMITTER: Rodriguez-Sabate C
PROVIDER: S-EPMC8183987 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe primary motor cortex (M1) is a critical node in Parkinson's disease (PD)-related motor circuitry; however, the functional roles of its subregions are poorly understood. In this study, we investigated changes in the functional connectivity patterns of M1 subregions and their relationships to improved clinical symptoms following levodopa administration.MethodsThirty-six PD patients and 37 healthy controls (HCs) were enrolled. A formal levodopa challenge test was conducted in the PD group, and the Unified Parkinson's Disease Rating Scale motor section (UPDRS-III) was assessed before (off state) and 1 h after administration of levodopa (on state). The PD group underwent resting-state functional magnetic resonance imaging in both off and on states, whereas the HC group was scanned once. We used the Human Brainnetome Atlas template to subdivide M1 into twelve regions of interest (ROIs). Functional connectivity (FC) was compared between PD on and off states [paired t-test, voxel-level p < 0.001, cluster-level p < 0.05, Gaussian random field (GRF) correction] and between patients and HC (two-sample t-test voxel-level p < 0.001, cluster-level p < 0.05). Correlations between ΔFC (differences in FC between PD off and on states) and clinical symptom improvements were examined.ResultsThere was decreased FC between the right caudal dorsolateral area 6 and the anterior cingulate gyrus (ACC), the right upper limb region and the left medial dorsal thalamus (mdTHA), as well as increased FC between the left tongue and larynx region and the left medial frontal gyrus. ΔFC between the right caudal dorsolateral area 6 and ACC was positively correlated with improvements in UPDRS-III total scores as well as the rigidity (item 22) and bradykinesia (items 23-26 and 31) subscores. ΔFC between the right upper limb region and left thalamus was positively correlated with improvements in the left upper limb tremor (items 20c and 21b) and postural tremor (item 21b) subscores.ConclusionsOur results reveal novel information regarding the underlying mechanisms in the motor circuits in the M1 and a promising way to explore the internal function of the M1 in PD patients. Notably, M1 is a potential therapeutic target in PD, and the exploration of its subregions provides a basis and a source of new insights for clinical intervention and precise drug treatment.
| S-EPMC7360730 | biostudies-literature
Project description:ObjectiveGrowing evidence indicates that autism spectrum disorder (ASD) stems from abnormal structural and functional connectivity of neural networks. Although diagnostic symptoms are sociocommunicative, motor-related functions (beyond repetitive mannerisms) are also impaired. However, evidence on connectivity at the level of basic motor execution is limited, which we address here.MethodWe compared right-handed children and adolescents (aged 7-18 years) with ASD (n = 44) to matched typically developing participants (TD, n = 36) using magnetic resonance imaging (MRI). Diffusion-weighted imaging and probabilistic tractography measured microstructure of the corticospinal tract (CST). Intrinsic functional connectivity MRI examined whole-brain voxelwise correlations, both with identical precentral gyrus (PCG) seeds.ResultsIn the group with ASD, radial and mean diffusivity were increased bilaterally in the CST, particularly in superior segments, and a leftward asymmetry of CST volume detected in the TD group was reversed. Functionally, overconnectivity was found for both left and right PCG with prefrontal, parietal, medial occipital, and cingulate cortices. The group with ASD also showed significantly reduced asymmetry of functional connectivity for both left and right PCG seeds. Finally, in the group with ASD, significant correlations were found for functional overconnectivity of the right PCG seed with anisotropy and mean diffusivity in the right CST.ConclusionThe findings, implicating both functional and anatomical connectivity of the primary motor cortex, suggest that network anomalies in ASD go well beyond sociocommunicative domains, affecting basic motor execution. They also suggest that even in right-handed adolescents with ASD, typical left hemisphere dominance is reduced, both anatomically and functionally, with an unusual degree of right hemisphere motor participation.
| S-EPMC4697829 | biostudies-literature
Project description:Parkinson's disease (PD) is a progressive neurologic disorder primarily characterized by an altered motor function. Lower extremity forced exercise (FE) has been shown to reduce motor symptoms in patients with PD. Recent functional magnetic resonance imaging (fMRI) studies have shown that FE and medication produce similar changes in brain activation patterns. Functional connectivity MRI (fcMRI) affords the ability to look at how strongly nodes of the motor circuit communicate with each other and can provide insight into the complementary effects of various therapies. Past work has demonstrated an abnormal motor connectivity in patients with PD compared to controls and subsequent normalization after treatment. Here we compare the effects of FE and medication using both resting and continuous visuomotor task fcMRI. Ten patients with mild to moderate PD completed three fMRI and fcMRI scanning sessions randomized under the following conditions: on PD medication, off PD medication, and FE+off medication. Blinded clinical ratings of motor function (a Unified Parkinson's Disease Rating Motor Scale-III exam) indicated that FE and medication resulted in 51% and 33% improvement in clinical ratings, respectively. In most nodes of the motor circuit, the observed changes in the functional connectivity produced by FE and medication were strongly positively correlated. These findings suggest that medication and FE likely use the same pathways to produce symptomatic relief in patients with PD. However, the connectivity changes, while consistent across therapy, were inconsistent in polarity for each patient. This finding may explain some past inconsistencies in connectivity changes after medication therapy.
| S-EPMC3634143 | biostudies-literature
Project description:Background:Motor information in the brain is transmitted from the dorsal premotor cortex (PMd) to the primary motor cortex (M1), where it is further processed and relayed to the spinal cord to eventually generate muscle movement. However, how information from the PMd affects M1 processing and the final output is unclear. Here, we applied intermittent theta burst stimulation (iTBS) to the PMd to alter cortical excitability not only at the application site but also at the PMd projection site of M1. We aimed to determine how PMd iTBS-altered information changed M1 processing and the corticospinal output. Methods:In total, 16 young, healthy participants underwent PMd iTBS with 600 pulses (iTBS600) or sham-iTBS600. Corticospinal excitability, short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF) were measured using transcranial magnetic stimulation before and up to 60 min after stimulation. Results:Corticospinal excitability in M1 was significantly greater 15 min after PMd iTBS600 than that after sham-iTBS600 (p = 0.012). Compared with that after sham-iTBS600, at 0 (p = 0.014) and 15 (p = 0.037) min after iTBS600, SICI in M1 was significantly decreased, whereas 15 min after iTBS600, ICF in M1 was significantly increased (p = 0.033). Conclusion:Our results suggested that projections from the PMd to M1 facilitated M1 corticospinal output and that this facilitation may be attributable in part to decreased intracortical inhibition and increased intracortical facilitation in M1. Such a facilitatory network may inform future understanding of the allocation of resources to achieve optimal motion output.
| S-EPMC7346859 | biostudies-literature
Project description:Lateralization of function is an important organizational feature of the motor system. Each effector is predominantly controlled by the contralateral cerebral cortex and the ipsilateral cerebellum. Transcranial magnetic stimulation studies have revealed hemispheric differences in the stimulation strength required to evoke a muscle response from the primary motor cortex (M1), with the dominant hemisphere typically requiring less stimulation than the nondominant. The current study assessed whether the strength of the connection between the cerebellum and M1 (CB-M1), known to change in association with motor learning, have hemispheric differences and whether these differences have any behavioral correlate. We observed, in right-handed individuals, that the connection between the right cerebellum and left M1 is typically stronger than the contralateral network. Behaviorally, we detected no lateralized learning processes, though we did find a significant effect on the amplitude of reaching movements across hands. Furthermore, we observed that the strength of the CB-M1 connection is correlated with the amplitude variability of reaching movements, a measure of movement precision, where stronger connectivity was associated with better precision. These findings indicate that lateralization in the motor system is present beyond the primary motor cortex, and points to an association between cerebellar M1 connectivity and movement execution.
| S-EPMC4459286 | biostudies-literature
Project description:Freezing of gait (FoG) is a brief, episodic absence or marked reduction of forward progression of the feet, despite the intention to walk, that is common in people with Parkinson's disease (PD). We hypothesized that not only motor, but higher level cognitive and attention areas may be impaired in freezers. In this study, we aimed to characterize differences in cortical and subcortical functional connectivity specific to FoG. We examined resting state neuroimaging and objective measures of FoG severity and gait from 103 individuals (28 PD + FoG, 36 PD - FoG and 39 healthy controls). Inertial sensors were used to quantify freezing severity and gait. Groups with and without FoG were matched on age, disease severity, cognitive status, and levodopa medication. MRI data was processed using surface-based registration. High-quality imaging data were used to characterize differences in connectivity specific to FoG using a pre-defined set of Regions of Interest (ROIs) and validated using whole-brain connectivity analysis. Associations between functional connectivity and objective measures of FoG were determined via predictive modeling using hold-out cross validation. We found that connectivity between the left globus pallidus (GP) and left somatosensory cortex and between two brain areas in the default and insular/vestibular networks exhibited significant differences specific to FoG and were also strong and significant predictors of FoG severity. Our findings suggest that the interplay among motor, default and vestibular areas of the left cortex are critical in the pathology of FoG.
| S-EPMC7503210 | biostudies-literature
Project description:There is abundant evidence that the pathophysiology of Parkinson's disease (PD) is not confined to the nigrostriatal dopaminergic pathway but propagates along the cortico-basal ganglia-thalamo-cortical neural network. A critical node in this functional circuit impacted by PD is the primary motor cortex (M1), which plays a key role in generating neural impulses that regulate movements. The past several decades have lay witness to numerous in vivo neuroimaging techniques that provide a window into the function and structure of M1. A consistent observation from numerous studies is that during voluntary movement, but also at rest, the functional activity of M1 is altered in PD relative to healthy individuals, and it relates to many of the motor signs. Although this abnormal functional activity can be partially restored with acute dopaminergic medication, it continues to deteriorate with disease progression and may predate structural degeneration of M1. The current review discusses the evidence that M1 is fundamental to the pathophysiology of PD, as measured by neuroimaging techniques such as positron emission tomography, single-photon emission computed tomography, electroencephalography, magnetoencephalography, and functional and structural MRI. Although novel treatments that target the cortex will not cure PD, they could significantly slow down and alter the progressive course of the disease and thus improve clinical care for this degenerative disease. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
| S-EPMC6261674 | biostudies-literature
Project description:BACKGROUND:Inhibitory deficits in motor cortex in schizophrenia have been well demonstrated using short-interval intracortical inhibition (SICI) by transcranial magnetic stimulation. However, it remains unknown whether these deficits originate from dysfunction of motor cortex itself or reflect abnormal modulations of motor cortex by other schizophrenia-related brain areas. METHODS:The study was completed by 24 patients with schizophrenia spectrum disorders and 30 healthy control subjects. SICI was obtained by delivering transcranial magnetic stimulation over the left motor cortex. Resting-state functional magnetic resonance imaging and diffusion tensor imaging fractional anisotropy were used to measure functional connectivity (FC) and white matter microstructures, respectively. Stimulation sites for SICI at motor cortex were used as the seeds to obtain whole-brain FC maps. Clinical symptoms were assessed with the Brief Psychiatric Rating Scale. RESULTS:In schizophrenia, left prefrontal cortex-motor cortex FC was inversely associated with SICI but positively associated with the underlying white matter microstructure at the left corona radiata and also associated with overall symptoms (all corrected p < .05). Mediation analysis showed that the prefrontal-motor cortex FC significantly mediated the corona radiata white matter effects on SICI (p = .007). CONCLUSIONS:Higher resting-state left prefrontal-motor cortex FC, accompanied by a higher fractional anisotropy of left corona radiata, predicted fewer inhibitory deficits, suggesting that the inhibitory deficits in motor cortex in schizophrenia may in part be mediated by a top-down prefrontal influence. SICI may serve as a robust biomarker indexing inhibitory dysfunction at anatomic as well as circuitry levels in schizophrenia.
| S-EPMC6289820 | biostudies-literature
Project description:The dorsal premotor cortex (dPMC) is a key region for motor learning and sensorimotor integration, yet we have limited understanding of its functional interactions with other regions. Previous work has started to examine functional connectivity in several brain areas using resting state functional connectivity (RSFC) and meta-analytical connectivity modelling (MACM). More recently, structural covariance (SC) has been proposed as a technique that may also allow delineation of functional connectivity. Here, we applied these three approaches to provide a comprehensive characterization of functional connectivity with a seed in the left dPMC that a previous meta-analysis of functional neuroimaging studies has identified as playing a key role in motor learning. Using data from two sources (the Rockland sample, containing resting state data and anatomical scans from 132 participants, and the BrainMap database, which contains peak activation foci from over 10,000 experiments), we conducted independent whole-brain functional connectivity mapping analyses of a dPMC seed. RSFC and MACM revealed similar connectivity maps spanning prefrontal, premotor, and parietal regions, while the SC map identified more widespread frontal regions. Analyses indicated a relatively consistent pattern of functional connectivity between RSFC and MACM that was distinct from that identified by SC. Notably, results indicate that the seed is functionally connected to areas involved in visuomotor control and executive functions, suggesting that the dPMC acts as an interface between motor control and cognition.
| S-EPMC4780681 | biostudies-literature
Project description:The presence of mutations in glucocerebrosidase (GBA) gene is a known factor increasing the risk of developing Parkinson's disease (PD). Mutations carriers have earlier disease onset and are more likely to develop neuropsychiatric symptoms than other sporadic PD cases. These symptoms have primarily been observed in Parkinson's patients carrying the most common pathogenic mutations L444P and N370S. However, recent findings suggest that other variants across the gene may have a different impact on the phenotype as well as on the disease progression. We aimed to explore the influence of variants across GBA gene on the clinical features and treatment related complications in PD. In this study, we screened the GBA gene in a cohort of 532 well-characterised PD patients and 542 controls from southern Spain. The potential pathogeniticy of the identified variants was assessed using in-silico analysis and subsequently classified as benign or deleterious. As a result, we observed a higher frequency of GBA variants in PD patients (12.2% vs. 7.9% in controls, p = 0.021), earlier mean age at disease onset in GBA variant carriers (50.6 vs. 56.6 years; p = 0.013), as well as more prevalent motor and non-motor symptoms in patients carrying deleterious variants. In addition, we found that dopaminergic motor complications are influenced by both benign and deleterious variants. Our results highlight the fact that the impact on the phenotype highly depends on the potential pathogenicity of the carried variants. Therefore, the course of motor and non-motor symptoms as well as treatment-related motor complications could be influenced by GBA variants.
| S-EPMC5193380 | biostudies-literature