Cerebello-Cortical Control of Tremor Rhythm and Amplitude in Parkinson's Disease.
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ABSTRACT:
SUBMITTER: Helmich RC
PROVIDER: S-EPMC8359958 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Purpose: Recently, the cerebellum's role in Parkinson's disease (PD) has been highlighted. Therefore, this study sought to test the hypothesis that functional connectivity (FC) between cerebellar and cortical nodes of the resting-state networks differentiates PD patients from controls by scanning participants at rest using functional magnetic resonance imaging (fMRI) and investigating connectivity of the cerebellar nodes of the resting-state networks. Materials and Methods: Sixty-two PD participants off medication for at least 12 h and 33 normal controls (NCs) were scanned at rest using blood oxygenation level-dependent fMRI scans. Motor and cognitive functions were assessed with the Movement Disorder Society's Revision of the Unified Parkinson's Disease Rating Scale III and Montreal Cognitive Assessment, respectively. Connectivity was investigated with cerebellar seeds defined by Buckner's 7-network atlas. Results: PD participants had significant differences in FC when compared to NC participants. Most notably, PD patients had higher FC between cerebellar nodes of the somatomotor network (SMN) and the corresponding cortical nodes. Cognitive functioning was differentially associated with connectivity of the cerebellar SMN and dorsal attention network. Further, cerebellar connectivity of frontoparietal and default mode networks correlated with the severity of motor function. Conclusion: Our study demonstrates altered cerebello-cortical FC in PD, as well as an association of this FC with PD-related motor and cognitive disruptions, thus providing additional evidence for the cerebellum's role in PD.
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Project description:Essential Tremor (ET) is a common movement disorder, characterised by a posture or movement-related tremor of the upper limbs. Abnormalities within cerebellar circuits are thought to underlie the pathogenesis of ET, resulting in aberrant synchronous oscillatory activity within the thalamo-cortical network leading to tremors. Harmaline produces pathological oscillations within the cerebellum, and a tremor that phenotypically resembles ET. However, the neural network dynamics in cerebellar-thalamo-cortical circuits in harmaline-induced tremor remains unclear, including the way circuit interactions may be influenced by behavioural state. Here, we examined the effect of harmaline on cerebello-thalamo-cortical oscillations during rest and movement. EEG recordings from the sensorimotor cortex and local field potentials (LFP) from thalamic and medial cerebellar nuclei were simultaneously recorded in awake behaving rats, alongside measures of tremor using EMG and accelerometery. Analyses compared neural oscillations before and after systemic administration of harmaline (10 mg/kg, I.P), and coherence across periods when rats were resting vs. moving. During movement, harmaline increased the 9-15 Hz behavioural tremor amplitude and increased thalamic LFP coherence with tremor. Medial cerebellar nuclei and cerebellar vermis LFP coherence with tremor however remained unchanged from rest. These findings suggest harmaline-induced cerebellar oscillations are independent of behavioural state and associated changes in tremor amplitude. By contrast, thalamic oscillations are dependent on behavioural state and related changes in tremor amplitude. This study provides new insights into the role of cerebello-thalamo-cortical network interactions in tremor, whereby neural oscillations in thalamocortical, but not cerebellar circuits can be influenced by movement and/or behavioural tremor amplitude in the harmaline model.
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Project description:Deep brain stimulation (DBS) is increasingly applied for the treatment of brain disorders, but its mechanism of action remains unknown. Here we evaluate the effect of basal ganglia DBS on cortical function using invasive cortical recordings in Parkinson's disease (PD) patients undergoing DBS implantation surgery. In the primary motor cortex of PD patients, neuronal population spiking is excessively synchronized to the phase of network oscillations. This manifests in brain surface recordings as exaggerated coupling between the phase of the beta rhythm and the amplitude of broadband activity. We show that acute therapeutic DBS reversibly reduces phase-amplitude interactions over a similar time course as that of the reduction in parkinsonian motor signs. We propose that DBS of the basal ganglia improves cortical function by alleviating excessive beta phase locking of motor cortex neurons.
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Project description:Recent electrocorticography data have demonstrated excessive coupling of beta-phase to gamma-amplitude in primary motor cortex and that deep brain stimulation facilitates motor improvement by decreasing baseline phase-amplitude coupling. However, both the dynamic modulation of phase-amplitude coupling during movement and the general cortical neurophysiology of other movement disorders, such as essential tremor, are relatively unexplored. To clarify the relationship of these interactions in cortical oscillatory activity to movement and disease state, we recorded local field potentials from hand sensorimotor cortex using subdural electrocorticography during a visually cued, incentivized handgrip task in subjects with Parkinson's disease (n = 11), with essential tremor (n = 9) and without a movement disorder (n = 6). We demonstrate that abnormal coupling of the phase of low frequency oscillations to the amplitude of gamma oscillations is not specific to Parkinson's disease, but also occurs in essential tremor, most prominently for the coupling of alpha to gamma oscillations. Movement kinematics were not significantly different between these groups, allowing us to show for the first time that robust alpha and beta desynchronization is a shared feature of sensorimotor cortical activity in Parkinson's disease and essential tremor, with the greatest high-beta desynchronization occurring in Parkinson's disease and the greatest alpha desynchronization occurring in essential tremor. We also show that the spatial extent of cortical phase-amplitude decoupling during movement is much greater in subjects with Parkinson's disease and essential tremor than in subjects without a movement disorder. These findings suggest that subjects with Parkinson's disease and essential tremor can produce movements that are kinematically similar to those of subjects without a movement disorder by reducing excess sensorimotor cortical phase-amplitude coupling that is characteristic of these diseases.
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| S-EPMC6353404 | biostudies-literature
Project description:Cerebello-thalamo-cortical network is suggested to be involved in the pathophysiology of Essential Tremor (ET). 23 patients with ET and 23 matched HC underwent a 3T-MRI with acquisition of a resting state sequence. Connectivity was investigated using a seed-based regression analyses approach. In ET patients were observed: Reduced connectivity between left primary motor cortex (M1) seed and right premotor cortex and cerebellum and bilateral premotor, parietal areas, supplementary motor area (SMA); Increased connectivity between left somatosensory cortex (S1) seed and parietal areas, M1, premotor cortex, SMA; reduced connectivity of this seed with cerebellum. Increased connectivity of SMA seed with premotor cortex and decreased with parietal and precentral areas; Increased connectivity between left thalamus seed and cerebellum; Reduced connectivity between right cerebellum seeds and other cerebellar areas, precentral and premotor areas. ET showed altered connectivity within the cortical sensory-motor network and between cerebral cortex and cerebellum. The increased connectivity between cerebellum and thalamus is consistent with their crucial role in tremor generation. These findings support the dynamical entrainment of multiple central oscillators throughout the cerebello-thalamo-cortical network in ET. This evidence is strengthened by the finding that this network is altered also when the core symptom is absent.
| S-EPMC7541442 | biostudies-literature
Project description:Essential tremor is a movement disorder characterized by tremor during voluntary movements, mainly affecting the upper limbs. The cerebellum and its connections to the cortex are known to be involved in essential tremor, but no task-free intrinsic signatures of tremor related to structural cerebellar defects have so far been found in the cortical motor network. Here we used voxel-based morphometry, tractography and resting-state functional MRI at 3 T to compare structural and functional features in 19 patients with essential tremor and homogeneous symptoms in the upper limbs, and 19 age- and gender-matched healthy volunteers. Both structural and functional abnormalities were found in the patients' cerebellum and supplementary motor area. Relative to the healthy controls, the essential tremor patients' cerebellum exhibited less grey matter in lobule VIII and less effective connectivity between each cerebellar cortex and the ipsilateral dentate nucleus. The patient's supplementary motor area exhibited (i) more grey matter; (ii) a lower amplitude of low-frequency fluctuation of the blood oxygenation level-dependent signal; (iii) less effective connectivity between each supplementary motor area and the ipsilateral primary motor hand area, and (iv) a higher probability of connection between supplementary motor area fibres and the spinal cord. Structural and functional changes in the supplementary motor area, but not in the cerebellum, correlated with clinical severity. In addition, changes in the cerebellum and supplementary motor area were interrelated, as shown by a correlation between the lower amplitude of low-frequency fluctuation in the supplementary motor area and grey matter loss in the cerebellum. The structural and functional changes observed in the supplementary motor area might thus be a direct consequence of cerebellar defects: the supplementary motor area would attempt to reduce tremor in the motor output by reducing its communication with M1 hand areas and by directly modulating motor output via its corticospinal projections.See Raethjen and Muthuraman (doi:10.1093/brain/awv238) for a scientific commentary on this article.
| S-EPMC4747645 | biostudies-literature
Project description:Background:This is a case of re-emergent kinetic tremor in Parkinson's Disease (PD). Phenomenology shown:The video shows re-emergent kinetic tremor while drawing a spiral and with repeated attempts to drink water from a cup. Educational value:The kinetic tremor described by patients with PD can be a re-emergent tremor which occurs after a few repetitive movements.
| S-EPMC6691624 | biostudies-literature
Project description:Surprisingly little has been written about the combined clinical entity, essential tremor-Parkinson's disease (ET-PD), which is the result of a double disease hit. We carefully quantified tremor burden using a wide range of measures (tremor severity, tremor-related disability, tremor-related quality of life) and furthermore, studied additional motor and non-motor features in ET-PD.In this prospective, clinical-epidemiological study, we performed a standardized, structured clinical evaluation of 27 ET-PD patients, comparing them to age-matched samples of 35 PD and 109 ET patients.The number of hours/day shaking was lowest in PD (median=3.0), intermediate in ET (median=10.0) and highest in ET-PD (median=14.0) (p<0.001). All measures of mobility and balance (Berg Balance test, Activities-specific Balance Confidence Scale, Timed Up and Go test) worsened across groups in a stepwise manner from ET to PD to ET-PD (p<0.05). Mini-mental state test scores worsened (p=0.002) and daytime sleepiness increased (p=0.002) across groups from ET to PD to ET-PD.The ET-PD patient seems to be more than just a PD patient with a little more kinetic tremor. Aside from a significantly greater tremor burden, ET-PD patients exhibited more cognitive and sleep problems and more mobility and balance problems than patients with isolated PD.
| S-EPMC5300045 | biostudies-literature
Project description:BackgroundDespite the significance of tremor in Parkinson's disease (PD) diagnosis, classification, and patient's quality of life, there is a relative lack of data on prevalence and relationship of different tremor types in PD.MethodsThe presence of rest tremor (RT) and action tremor (AT; defined as combination of both postural and kinetic tremor) was determined and RT severity was defined using the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) at baseline in the Progression Marker Initiative (PPMI, n = 423), the Fox Investigation for New Discovery of Biomarkers (BioFIND, n = 118) and the Parkinson's Disease Biomarkers Program (PDBP, n = 873) cohorts.ResultsAcross baseline data of all three cohorts, RT prevalence (58.2%) was higher than AT prevalence (39.0%). Patients with RT had significantly higher (Chi-square test, p < 0.05) prevalence of AT compared to patients without RT in the PPMI (40.0% versus 30.1%), BioFIND (48.0% versus 40.0%) and PDBP (49.9% versus 21.0%) cohorts. Furthermore, patients with AT had significantly (Student t-test, p < 0.05) higher RT severity that those without AT in PPMI (5.7 ± 5.4 versus 3.9 ± 3.3), BioFIND, 6.4 ± 6.3 versus 3.8 ± 4.4) and PDBP (6.4 ± 6.6 versus 3.7 ± 4.4) cohorts. In the BioFIND cohort, the prevalence of all types of tremor and their combinations significantly decreased from the off-state to on-state.DiscussionThe RT is the most frequent tremor type and present in more than half of the PD patients. However, AT is also present in nearly one-third of the PD patients. Our results also indicate that RT and AT may have cross-interactions in PD, and that dopaminergic treatment influences both RT and AT.
| S-EPMC7757606 | biostudies-literature