Amgad Droby, PhD, Inbal Maidan, Yael Jacob,
Nir Giladi, Jeffrey M. Hausdorff, PhD, and Anat Mirelman, PhD
Overview
In this study, we sought to extend earlier fMRI findings, and investigate patterns of functional connectivity (FC) in large-scale, task-negative functional networks in the PD patients trained for 6 weeks in either TT or TT + VR motor training as part of the V-TIME study.
Methods:
In this sub-study of the V-TIME project,16 N = 42 PD patients were enrolled if they met the following inclusion criteria: (1) idiopathic PD patients aged 60 to 85 years diagnosed according to the UK Brain Bank criteria, (2) Hoehn and Yahr (H&R) stages I – III, (3) treatment with anti-Parkinsonian medication, (4) stable medication for the past 1 month, (5) ability to walk unassisted for 5 minutes, (6) adequate hearing and vision, and (7) at least 2 fall episodes in the previous 6 months prior to enrollment. Exclusion criteria were (1) MRI contraindications, (2) psychiatric comorbidity, (3) clinically significant cognitive impairment (Mini Mental State Examination [MMSE] <24), (4) a history of a neurological disorder aside from PD, (5) orthopedic problems, (6) unstable other medical condition, or (7) excessive head motion during MRI scan (>3 mm average frame-wise displacement). The study was approved by the institutional review board (IRB) at Tel Aviv Sourasky Medical Center. All included participants gave their informed written consent.
Results:
In this sub-study of the V-TIME project,16 N = 42 PD patients were enrolled if they met the following inclusion criteria: (1) idiopathic PD patients aged 60 to 85 years diagnosed according to the UK Brain Bank criteria, (2) Hoehn and Yahr (H&R) stages I – III, (3) treatment with anti-Parkinsonian medication, (4) stable medication for the past 1 month, (5) ability to walk unassisted for 5 minutes, (6) adequate hearing and vision, and (7) at least 2 fall episodes in the previous 6 months prior to enrollment. Exclusion criteria were (1) MRI contraindications, (2) psychiatric comorbidity, (3) clinically significant cognitive impairment (Mini Mental State Examination [MMSE] <24), (4) a history of a neurological disorder aside from PD, (5) orthopedic problems, (6) unstable other medical condition, or (7) excessive head motion during MRI scan (>3 mm average frame-wise displacement). All testing was done “ON” medication, approximately 1 hour after taking medication. The cognitive assessment included the Montreal Cognitive Assessment (MoCA)17 and Color Trails Test (CTT) to evaluate executive function.
Conclusions:
The results indicate that while both training programs resulted in similar patterns of FC decrease in brain regions within the BGN, FSN, and ECN networks, as well as FC increase in regions within the SMN; FC increase in the SMA and R PCG within the SMN, and R MFG within the CBL network were observed in the TT + VR training group only. Decreased FC levels in dopaminergic mesocorticolimbic regions involved in multisensory executive and direction of motor functions including the thalamus, pMCC, and cuneus within multiple brain functional networks were observed as a result of both training programs. These patterns of FC decrease were found to be correlated with improvement in gait speed in both usual and dual-task walking, as well as dual task stride time. Additionally, both groups demonstrated post treatment FC increase in the angular gyrus, caudate, and the aMCC within the SMN, and this observed increase was associated with improved gait performance. These findings further emphasize the involvement of brain regions implicated in visuospatial processing, information integration and attention during walking and coordination of gait. Recent studies have highlighted the role of higher cortical brain regions during walking.
The fact that in both training groups similar patterns of post treatment FC decrease in BGN, FSN, and ECN networks were observed can be attributed to the use of the treadmill component, reflecting successful compensatory mechanisms involved in externally-guided rhythmic movements provided by the treadmill rhythm. The treadmill can act as an external cue by setting the walking pattern, surpassing the depleted striatal networks via the facilitation of higher motor and cognitive pathways that contribute to gait pacing, leading to improvements in gait in PD. Moreover, the post treatment FC increase observed in both groups in the caudate, MCC, and R angular gyrus regions within the SMN is indicative that TT also affects the higher order aspects of gait. In line with this, a previous study in PD patients demonstrated both cognitive and motor improvements following one month of treadmill training, arguing that this can effectively improve both cognitive and motor features in patients with PD. This assertion can be further emphasized by the fact that the overtime FC change in these regions was found to correlate with both usual walking and dual task stride length in TT + VR group, where the addition of the VR component might have further augmented the modulation of FC within regions involved in the higher-order aspects of gait. Most interestingly, a significant interaction was observed in both the SMN and CBL networks. In which, TT + VR demonstrated post training FC increases in the R PCG and SMA within the SMN network as well as in the R MFG within the CBL network were detected. The FC levels in the R MFG at follow-up were found to be associated with the change (over time) in DT stride time. Recently, the role of the fronto-cerebellar connections in gait have been implicated, highlighting its involvement in the allocation of attentional resources for maintaining automated motor sequences. In the TT group, FC levels in the aforementioned regions within the SMN and CBL were reduced post training. The amount of change in FC from pre- to- post training correlated with DT stride length increase, as well as poorer balance performance. The role of SMA and prefrontal cortical regions has been implicated in high-order multisensory integration and postural stabilization during the execution of every-day routine motor tasks. For example, a positron emission tomography study including healthy participants, activation of SMA and bilateral motor cortices was observed when the participants simulated bicycling movements compared with rest condition. Moreover, transcranial magnetic stimulation to SMA was found to be effective for motor signs improvements in PD.
The V-TIME academic research project that has led to many of these papers is implemented commercially by GaitBetter.
GaitBetter has implemented commercially the V-TIME academic research project, that has led to many of these papers.