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Brief Summary
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INTRODUCTION Freezing of gait (FOG) is a highly disabling motor symptom that is commonly experienced by individuals with Parkinson’s disease (PD). However, despite its negative consequences and prevalence, there is currently no effective treatment for FOG and it does not respond well to the treatments currently used for PD, such as dopamine replacement or deep brain stimulation. The cognitive contribution to freezing is hypothesized to be due to an over-demand of cognitive resources that are being used to control walking and complete a secondary task, thus leading to a freezing episode. To improve the cognitive mechanisms of FOG, cognitive training may be utilized as a therapy. Several studies involving individuals with PD have investigated this type of treatment, and have demonstrated improvements in general cognitive function,14-19 as well as in the specific executive function domains, which may be responsible for FOG (ie, set-shifting ability and inhibitory control).Interestingly, a study conducted by Paris et al,16 which utilized a computerized cognitive training program (Smart Brain) for 45-minute sessions, 3 times weekly over 4 weeks, demonstrated significant improvements in the greatest number of cognitive outcomes, including set-shifting ability and inhibitory control. These findings demonstrated the efficacy of the cognitive training programs on individuals with PD. However, the functional benefits to motor performance or severity of FOG have yet to be investigated, up until the current study. FoG is defined as a “brief, episodic absence or marked reduction of forward progression of the feet despite the intention to walkâ€.. Up to 63% of patients with idiopathic Parkinson’s disease (PD) Risk factors for FoG include male sex, left-sided disease onset, early gait abnormalities, more axial symptoms, higher daily dose of levodopa, and other nonmotor symptoms such as hallucinations, depression, and anxiety. Episodes can be brief or exceed 30 sec Specifically, three patterns of FoG have been distinguished including: 1) trembling in place, shuffling forward, and 3) complete akinesia. These episodes are more likely to occur when initiating walking, turning, and passing through narrow passages or certain circumstances such as approaching a destination (8). FoG causes falls, reduces quality of life, and likelihood of independent living (13). Furthermore, the functional impact of FoG is independently linked to reduced health-related quality of life (HRQoL), irrespective of other general disease severity measures Standard medical treatment for PD, dopamine replacement therapy, have shown limited benefit. While research into this debilitating symptom is of growing interest, effective therapies remain elusive. This is because normal gait is a complex process that involves concomitant balance and locomotion processes. A hierarchy of supraspinal regions send signals to the central pattern generators (CPG) of the spinal cord to modify stereotyped locomotion in certain situations such as initiating gait, turning, stopping, and avoiding obstacles. The locomotor network involves spinal CPGs, mesencephalic and cerebellar locomotor areas (MLR, CLR), subthalami locomotor region (SLR) and various cortical areas including frontal–parietal, supplementary motor, and motor areas. PATHOPHYSIOLOGY OF FREEZING OF GAIT
While poorly understood, there are hypotheses on the pathogenesis of FoG based on clinical–anatomical correlations, functional imaging, and neurophysiology studies . Hypotheses for the origin of FoG have ranged from failure of distal sources (central pattern generators of the spinal cord) to more proximal dysfunction (the frontal lobe) along the locomotion axis. In PD, GABA-ergic output levels are abnormally increased. Takakusaki et al. proposed that gait disturbances are produced by abnormal increases in SNr-induced inhibition of the MLR . Furthermore, features of PD-induced gait deficiencies resemble SNr-stimulated movement . Non-human primate studies also confirm the importance of cholinergic neurons in the PPN in the control of gait . Damage to these neurons is associated with frequent falling in PD . However, there is no consensus regarding a common anatomical location that accounts for FoG. It is likely the case that FoG is a manifestation of an imbalance or dysregulation of one or several key nodes along the locomotor network manifesting in the same clinical phenotype . Advances in imaging and neurophysiology have supported this interpretation: many neurological conditions are disorders of network perturbations, the so-called circuitopathies . Extending this concept to FoG, in a lesion-network mapping investigation Fasano et al. reviewed 14 cases oflesion inducedFoG . While lesion locations were heterogeneous (parasagittal frontal areas, left postcentral gyrus, cerebellum, midbrain tegmentum, brainstem, and basal ganglia), >90% of lesions were functionally connected to a focal area in the dorsal medial cerebellum. Diffusion tensor imaging in patients with PD and FoG has also demonstrated decreased connectivity between the PPN and the cerebellum . While the lesion-network mapping findings may not share the same neuroanatomical substrate with PD associated FoG, they highlight the involvement of the cerebellum as an important node and possible target for future therapies . Studies have also examined FoG neural circuitry using resting-state fMRI (rs-fMRI) with a virtual reality (VR) gait paradigm. Gilat et al. used a VR turning condition to trigger freezing in 17 patients with FoG. Findings in this study demonstrated increased activation in inferior frontal regions, which have been implicated in the recruitment of a putative stopping network . The hypothesis generated from these studies suggest frontal activation of an aberrant stopping signal via hyperdirect connections to the STN resulting in the arrest of locomotion. FoG has been associated with reduced functional connectivity within visual, sensorimotor, attentional fronto-parietal areas, and default mode networks . Reduced functional connectivity of the MLR and CLR with the SMA has also been observed and thought to reflect a decreased automatic control of movement, as well as reduced functional connectivity between the STN and SMA proposed to reflect reduced capacity to inhibit competing motor programs . Interestingly, a recent rs-fMRI study by Potvin-Desrochers et al. demonstrated increased thalamic/GPi connectivity with visual areas as well as between the left putamen and cerebellum in patients with FoG compared to those without. In contrast to prior studies, this increased connectivity in cortical and subcortical regions involved in sensory and visuospatial processing may serve as a compensatory pathway for sensorimotor deficits in FoG . A limitation of functional imaging studies is that they do not capture Rahimpour et al. Page 5 Neuromodulation. Author manuscript; available in PMC 2021 July 22. Author Manuscript Author Manuscript Author Manuscript Author Manuscript the brain network activities during gait freezing episodes. Therefore, while they inform us about the overall network activity patterns in patients with FoG tendencies, they do not represent actual brain dynamics during FoG. Outside of neuroimaging studies, electrophysiological data obtained from DBS have also revealed important information on the pathophysiology of FoG. The decoupling model, as proposed by Jacobs et al., describes FoG events as a decoupling between preplanned motor programs and the motor output response . In a recent study, Pozzi et al. investigated the communication between the cortex and subthalamic nucleus in patients who underwent STN-DBS .During effective walking, the cortex and STN were synchronized in the lowfrequency band (4–13 Hz). In contrast, freezing episodes were characterized by cortical– subcortical decoupling. These findings were specific to locomotor cortical areas (i.e., SMA, primary motor and parietal cortex). A recent fMRI study evaluated door-way provoked FoG using virtual reality and found selective hypoactivation in the preSMAbilaterally . These studies suggest that FoG reflects a degree of impaired and disrupted signaling between certain locomotor cortical areas and the STN .
3}freezing of gait (FOG) affects more than one-third of individuals with Parkinson’s disease (PD), and it is a common causes of falls, dependency, and poor quality of life. FOG is a complex phenomenon and its pathophysiology remains unknown. FOG typically occurs during step initiation and turns,4 likely due to abnormal postural preparation for step initiation.4, 5 Individuals with FOG (freezers) show delayed step initiation associated with repetitive anticipatory postural adjustments (APAs) as if they cannot inhibit their postural preparation and release their stepping motor program.6 In fact, FOG has been associated with small and prolonged APAs during step initiation7 and deficits in cognitive inhibition To improve the cognitive mechanisms of FOG, cognitive training may be utilized as a therapy. Several studies involving individuals with PD have investigated this type of treatment, and have demonstrated improvements in general cognitive function,14-19 as well as in the specific executive function domains, which may be responsible for FOG (i.e., set-shifting ability and inhibitory control).
Thus the aim of the present study was to investigate cognition training on individuals with FOG, to determine which has the greatest therapeutic benefits and greatest improvements in FOG functional outcomes. NEED FOR STUDY: Ø As previous articles have found prevalence of freezing of gait episodes in Parkinson’s patient and there is very few interventional literature available for its treatment also the conventional therapies are also less in number for treatment of this episodes. Hence this study will be focusing on the freezing gait episodes in Parkinson’s by cognitive training to reduce FOG episode. Research helps identify new treatment targets, enhances existing interventions, and contributes to the overall advancement of rehabilitation. Refining personalized treatment approaches, ultimately improving the quality of life for individuals affected by the condition. Research can help identify novel treatment options, improve existing interventions, and enhance patients’ gait and quality of life This study will act as a base for base for further treatment protocol will contribute to decrease freezing of gait severity. |