Facilitatory rTMS over the Supplementary Motor Cortex Impedes Gait Performance in Parkinson Patients with Freezing of Gait.
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ABSTRACT:
SUBMITTER: Brugger F
PROVIDER: S-EPMC7999694 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND AND PURPOSE:Freezing of gait (FOG) is a frustrating problem in Parkinson's disease (PD) for which there is no effective treatment. Our aim was to find brain stimulation areas showing greater responses for reducing FOG. METHODS:Twelve PD patients with FOG were selected for inclusion. We explored the therapeutic effect of repetitive transcranial magnetic stimulation (rTMS) in the supplementary motor area (SMA) and the motor cortex (MC). We measured the number of steps, completion time, and freezing episodes during the stand-walk-sit test before and after rTMS treatment. We also tested freezing episodes in two FOG-provoking tasks. RESULTS:There was a trend for a greater reduction in freezing episodes with SMA stimulation than MC stimulation (p=0.071). FOG was significantly improved after SMA stimulation (p<0.05) but not after MC stimulation. CONCLUSIONS:Our study suggests that the SMA is a more-appropriate target for brain stimulation when treating PD patients with FOG. This study provides evidence that stimulating the SMA using rTMS is beneficial to FOG, which might be useful for future developments of therapeutic strategies.
| S-EPMC6032003 | biostudies-literature
Project description:ObjectiveWe investigated if anodal transcranial direct current stimulation (A-tDCS), applied over the supplementary motor areas (SMAs), could improve gait initiation in Parkinson's disease (PD) with freezing of gait (FOG).MethodsIn this double-blinded cross-over pilot study, ten PD with FOG underwent two stimulation sessions: A-tDCS (1 mA, 10 min) and sham stimulation. Eight blocks of gait initiation were collected per session: (1) pre-tDCS, with acoustic cueing; (2) pre-tDCS, self-initiated (no cue); and (3-8) post-tDCS, self-initiated. Gait initiation kinetics were analyzed with two-way repeated measures ANOVAs for the effects of A-tDCS.ResultsA-tDCS did not significantly improve the magnitude or timing of anticipatory postural adjustments or the execution of the first step during self-initiated gait compared with baseline measures (p > .13). The lack of significant change was not due to an inability to generate functional APAs since external cueing markedly improved gait initiation (p < .01).ConclusionsA single dose of A-tDCS over the SMAs did not improve self-initiated gait in PD and FOG. Alternative approaches using a different dose or cortical target are worthy of exploration since individuals demonstrated the capacity to improve.SignificanceNeuromodulation strategies tailored to facilitate SMA activity may be ineffective for the treatment of gait initiation impairment in people with PD and FOG.
| S-EPMC7089588 | biostudies-literature
Project description:INTRODUCTION:Exercise improves gait in Parkinson disease (PD), but whether exercise differentially affects people with PD with (freezers) and without freezing of gait (non-freezers) remains unclear. This study examines exercise's effects on gait performance, neural correlates related to these effects, and potential neural activation differences between freezers and non-freezers during motor imagery (MI) of gait. METHODS:Thirty-seven participants from a larger exercise intervention completed behavioral assessments and functional magnetic resonance imaging (fMRI) scans before and after a 12-week exercise intervention. Gait performance was characterized using gait velocity and stride length, and a region of interest (ROI) fMRI analysis examined task-based blood oxygen-level dependent (BOLD) signal changes of the somatomotor network (SMN) during MI of forward (IMG-FWD) and backward (IMG-BWD) gait. RESULTS:Velocity (F(1,34)?=?55.04, p?<?0.001) and stride length (F(1,34)?=?77.58, p?<?0.001) were significantly lower for backward versus forward walking in all participants. The ROI analysis showed freezers had lower BOLD signal compared to non-freezers in the cerebellum (F(1,32)?=?7.01, p?=?0.01), primary motor (left: F(1,32)?=?7.09, p?=?0.01; right: F(1,32)?=?7.45, p?=?0.01), and primary sensory (left: F(1,32)?=?9.59, p?=?0.004; right: F(1,32)?=?8.18, p?=?0.007) cortices during IMG-BWD only. The evidence suggests the exercise intervention did not affect gait or BOLD signal during MI. CONCLUSION:While all participants had significantly slower and shorter backward velocity and stride length, respectively, the exercise intervention had no effect. Similarly, BOLD signal during MI did not change with exercise; however, freezers had significantly lower BOLD signal during IMG-BWD compared to non-freezers. This suggests potential decreased recruitment of the SMN during MI of gait in freezers.
| S-EPMC6120800 | biostudies-literature
Project description:The study aimed to investigate the neural changes that differentiate Parkinson's disease patients with freezing of gait and age-matched controls, using ambulatory electroencephalography event-related features. Compared to controls, definite freezers exhibited significantly less alpha desynchronization at the motor cortex about 300 ms before and after the start of overground walking and decreased low-beta desynchronization about 300 ms before and about 300 and 700 ms after walking onset. The late slope of motor potentials also differed in the sensory and motor areas between groups of controls, definite, and probable freezers. This difference was found both in preparation and during the execution of normal walking. The average frontal peak of motor potential was also found to be largely reduced in the definite freezers compared with the probable freezers and controls. These findings provide valuable insights into the underlying structures that are affected in patients with freezing of gait, which could be used to tailor drug development and personalize drug care for disease subtypes. In addition, the study's findings can help in the evaluation and validation of nonpharmacological therapies for patients with Parkinson's disease.
| S-EPMC10495228 | biostudies-literature
Project description:Ventral premotor cortex (PMv) is widely accepted to exert an important influence over primary motor cortex (M1) when hand movements are made. Although study of these interactions has typically focused on their excitatory nature, given its strong connections with both ventral and opercular frontal regions, one feature of the influence of PMv over M1 may be inhibitory. Paired-pulse transcranial magnetic stimulation (ppTMS) was used to examine functional interactions between human PMv and M1 during the selection and reprogramming of a naturalistic goal-directed action. One of two cylinders was illuminated on each trial. It was then grasped and picked up. On some trials, however, subjects had to reprogram the action as the illuminated cylinder was switched off and the other illuminated simultaneously with reach initiation. At a neurophysiological level, the PMv paired-pulse effect (PPE) on M1 corticospinal activity was facilitatory after the initial target presentation and during movement initiation. When reprogramming was required, however, the PPE became strongly inhibitory. This context-dependent change from facilitation to inhibition occurred within 75 ms of the change of target. Behaviorally, PMv-M1 ppTMS disrupted reprogramming. Diffusion-weighted magnetic resonance image scans were taken of each subject. Intersubject differences in the facilitation-inhibition contrast of PMv-M1 interactions were correlated with fractional anisotropy of white-matter in ventral prefrontal, premotor, and intraparietal brain areas. These results suggest that a network of brain areas centered on PMv inhibits M1 corticospinal activity associated with undesired movements when action plans change.
| S-EPMC2880444 | biostudies-other
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:ObjectiveThe objective of this cross-sectional study was to test the hypothesis that patients with Parkinson disease (PD) and freezing of gait (PD+FOG) would demonstrate sleep disturbances comparable to those seen in patients with REM sleep behavior disorder (RBD) and these changes would be significantly different from those in PD patients without FOG (PD-FOG) and age-matched controls.MethodsWe conducted overnight polysomnography studies in 4 groups of subjects: RBD, PD-FOG, PD+FOG, and controls. Tonic and phasic muscle activity during REM sleep were quantified using EMG recordings from the chin, compared among study groups, and correlated with disease metrics.ResultsThere were no significant differences in measures of disease severity, duration, or dopaminergic medications between the PD+FOG and PD-FOG groups. Tonic muscle activity was increased significantly (p < 0.007) in the RBD and PD+FOG groups compared to the PD-FOG and control groups. There was no significant difference in tonic EMG between the PD+FOG and RBD group (p = 0.364), or in tonic or phasic EMG between the PD-FOG and control group (p = 0.107). Phasic muscle activity was significantly increased in the RBD group compared to all other groups (p = 0.029) and between the PD+FOG and control group (p = 0.001), but not between the PD+FOG and PD-FOG groups (p = 0.059).ConclusionsThese findings provide evidence that increased muscle activity during REM sleep is a comorbid feature of patients with PD who exhibit FOG as a motor manifestation of their disease.
| S-EPMC3795590 | biostudies-literature
Project description:BackgroundFreezing in the levodopa-medicated-state (ON-state) is a debilitating feature of Parkinson's disease without treatment options. Studies detailing the distinguishing features between people with freezing of gait that improves with levodopa and those whose freezing continues even on levodopa are lacking.ObjectiveTo characterize the gross motor, gait, and non-motor features of this phenotype.MethodsInstrumented continuous gait was collected in the levodopa-medicated-state in 105 patients: 43 non-freezers (no-FOG), 36 with freezing only OFF-levodopa (OFF-FOG) and 26 with freezing both ON- and OFF-levodopa (ONOFF-FOG). Evaluation of motor and non-motor disease features was undertaken using validated scales. A linear mixed model with age, sex, disease duration, and motor UPDRS scores as covariates was used to determine differences in spatiotemporal gait and non-motor disease features among the groups.ResultsCompared to OFF-FOG, the ONOFF-FOG group had greater disease severity (on the Unified Parkinson's disease Rating Scale) and worse cognition (on the Montreal Cognitive Assessment, Frontal Assessment Battery and Scales for Outcome in Parkinson's disease-Cognition scales) and quality of life (on the PDQ-39), but similar mood (on the Hamilton depression and anxiety scales) and sleep quality (on Epworth sleepiness scale and RBD questionnaire). For several gait features, differences between the ONOFF-OFF groups were at least as large and in the opposite direction as differences between OFF-no groups, controlling for disease severity. Variability in ONOFF-FOG was greater than in other groups. Using results from our study and others, a power analysis for a potential future study reveals sample sizes of at least 80 ONOFF and 80 OFF-FOG patients would be needed to detect clinically meaningful differences.ConclusionsIntra-patient variability in spatiotemporal gait features was much greater in ONOFF-FOG than in the other two groups. Our results suggest that multifactorial deficits may lead to ONOFF-FOG development.
| S-EPMC9162361 | biostudies-literature
Project description:Freezing of gait (FoG) is a transient inability to initiate or maintain stepping that often accompanies advanced Parkinson's disease (PD) and significantly impairs mobility. The current study uses a multimodal neuroimaging approach to assess differences in the functional and structural locomotor neural network in PD patients with and without FoG and relates these findings to measures of FoG severity. Twenty-six PD patients and fifteen age-matched controls underwent resting-state functional magnetic resonance imaging and diffusion tensor imaging along with self-reported and clinical assessments of FoG. After stringent movement correction, fifteen PD patients and fourteen control participants were available for analysis. We assessed functional connectivity strength between the supplementary motor area (SMA) and the following locomotor hubs: 1) subthalamic nucleus (STN), 2) mesencephalic and 3) cerebellar locomotor region (MLR and CLR, respectively) within each hemisphere. Additionally, we quantified structural connectivity strength between locomotor hubs and assessed relationships with metrics of FoG. FoG+ patients showed greater functional connectivity between the SMA and bilateral MLR and between the SMA and left CLR compared to both FoG- and controls. Importantly, greater functional connectivity between the SMA and MLR was positively correlated with i) clinical, ii) self-reported and iii) objective ratings of freezing severity in FoG+, potentially reflecting a maladaptive neural compensation. The current findings demonstrate a re-organization of functional communication within the locomotor network in FoG+ patients whereby the higher-order motor cortex (SMA) responsible for gait initiation communicates with the MLR and CLR to a greater extent than in FoG- patients and controls. The observed pattern of altered connectivity in FoG+ may indicate a failed attempt by the CNS to compensate for the loss of connectivity between the STN and SMA and may reflect a loss of lower-order, automatic control of gait by the basal ganglia.
| S-EPMC4061081 | biostudies-literature
Project description:Background and purposeFOG is a troublesome symptom of PD. Despite growing evidence suggesting that FOG in PD may be associated with cognitive dysfunction, the relationship between regional brain atrophy and FOG has been poorly investigated.Materials and methodsOptimized VBM was applied to 3T brain MR images of 24 patients with PD and 12 HC. Patients were classified as either FOG- or FOG+ (n = 12) based on their responses to a validated FOG Questionnaire and clinical observation. All patients with PD also underwent a detailed neuropsychological evaluation.ResultsThe VBM analysis in patients with FOG+ showed a reduced GM volume in the left cuneus, precuneus, lingual gyrus, and posterior cingulate cortex compared with both patients with FOG- and HC. We did not detect any significant change of GM volume when comparing HC versus all patients with PD (FOG- and FOG+). FOG clinical severity was significantly correlated with GM loss in posterior cortical regions. Finally, patients with FOG+ scored lower on tests of frontal lobe function.ConclusionsOur findings provide the first evidence that the development of FOG in patients with PD is associated with posterior GM atrophy, which may play a role in the complex pathophysiology of this disabling symptom.
| S-EPMC7964749 | biostudies-literature