On-Demand Cueing for Freezing of Gait in Parkinson's Disease: A Randomized Controlled Trial.

BACKGROUND: Cueing can alleviate freezing of gait (FOG) in people with Parkinson's disease (PD), but using the same cues continuously in daily life may compromise effectiveness. Therefore, we developed the DeFOG-system to deliver personalized auditory cues on detection of a FOG episode. OBJECTIVES: We aimed to evaluate the effects of DeFOG during a FOG-provoking protocol: (1) after 4 weeks of DeFOG-use in daily life against an active control group; (2) after immediate DeFOG-use (within-group) in different medication states. METHOD: In this randomized controlled trial, 63 people with PD and daily FOG were allocated to the DeFOG or active control group. Both groups received feedback on their daily living step counts using the device, but the DeFOG group also received on-demand cueing. Video-rated FOG severity was compared pre- and post-intervention through a FOG-provoking protocol administered at home off and on-medication, but without using DeFOG. Within-group effects were tested by comparing FOG during the protocol with and without DeFOG. RESULTS: DeFOG-use during the 4 weeks was similar between groups, but we found no between-group differences in FOG-severity. However, the within-group analysis showed that FOG was alleviated by DeFOG (effect size d = 0.57), regardless of medication state. Combining DeFOG and medication yielded an effect size of d = 0.67. CONCLUSIONS: DeFOG reduced FOG considerably in a population of severe freezers both off and on medication. Nonetheless, 4 weeks of DeFOG-use in daily life did not ameliorate FOG during the protocol unless DeFOG was worn. These findings suggest that on-demand cueing is only effective when used, similar to other walking aids. © 2024 International Parkinson and Movement Disorder Society.

Multitarget Transcranial Electrical Stimulation for Freezing of Gait: A Randomized Controlled Trial.

BACKGROUND: Treatments of freezing of gait (FOG) in Parkinson's disease are suboptimal. OBJECTIVE: The aim of this study was to evaluate the effects of multiple sessions of transcranial direct current stimulation (tDCS) targeting the left dorsolateral prefrontal cortex and primary motor cortex (M1) on FOG. METHODS: Seventy-seven individuals with Parkinson's disease and FOG were enrolled in a double-blinded randomized trial. tDCS and sham interventions comprised 10 sessions over 2 weeks followed by five once-weekly sessions. FOG-provoking test performance (primary outcome), functional outcomes, and self-reported FOG severity were assessed. RESULTS: Primary analyses demonstrated no advantage for tDCS in the FOG-provoking test. In secondary analyses, tDCS, compared with sham, decreased self-reported FOG severity and increased daily living step counts. Among individuals with mild-to-moderate FOG severity, tDCS improved FOG-provoking test time and self-report of FOG. CONCLUSIONS: Multisession tDCS targeting the left dorsolateral prefrontal cortex and M1 did not improve laboratory-based FOG-provoking test performance. Improvements observed in participants with mild-to-moderate FOG severity warrant further investigation. © 2021 International Parkinson and Movement Disorder Society.

Tossing and Turning in Bed: Nocturnal Movements in Parkinson's Disease.

BACKGROUND: Sleep disturbances and nocturnal hypokinesia are common in Parkinson's disease (PD). Recent work using wearable technologies showed fewer nocturnal movements in PD when compared with controls. However, it is unclear how these manifest across the disease spectrum. OBJECTIVES: We assessed the prevalence of sleep disturbances and nocturnal hypokinesia in early and advanced PD and their relation to nonmotor symptoms and dopaminergic medication. METHODS: A total of 305 patients with PD with diverse disease severity (Hoehn and Yahr [H&Y] stage 1 = 47, H&Y stage 2 = 181, H&Y stage 3 = 77) and 205 healthy controls continuously wore a tri-axial accelerometer on the lower back for at least 2 days. Lying, turning, and upright -time at night were extracted from the acceleration signals. Percent upright time and nighttime walking were classified as sleep interruptions. The number, velocity, time, side, and degree of rotations in bed were used to evaluate nocturnal movements. RESULTS: Nocturnal lying time was similar among all groups (healthy controls, 7.5 ± 1.2 hours; H&Y stage 1, 7.3 ± 0.9 hours; H&Y stage 2, 7.2 ± 1.3 hours; H&Y stage 3, 7.4 ± 1.6 hours; P = 0.501). However, patients with advanced PD had more upright periods, whereas the number and velocity of their turns were reduced (P ≤ 0.021). Recently diagnosed patients (<1 year from diagnosis) were similar to controls in the number of nocturnal turns (P = 0.148), but showed longer turning time (P = 0.001) and reduced turn magnitude (P = 0.002). Reduced nocturnal movements were associated with increased PD motor severity and worse dysautonomia and cognition and with dopaminergic medication. CONCLUSIONS: Using wearable sensors for continuous monitoring of movement at night may offer an unbiased measure of disease severity that could enhance optimal nighttime dopaminergic treatment and utilization of turning strategies. © 2020 International Parkinson and Movement Disorder Society.

Validation of the Hebrew Version of the Unified Dyskinesia Rating Scale.

BACKGROUND: The Unified Dyskinesia Rating Scale (UDysRS) is a well-established tool for producing comprehensive assessments of severity and disability associated with dyskinesia in patients with Parkinson's disease (PD). The scale was originally developed in English, and a broad international effort has been undertaken to develop and validate versions in additional languages. Our aim was to validate the Hebrew version of the UDysRS. METHODS: We translated the UDysRS into Hebrew, back-translated it into English, and carried out cognitive pretesting. We then administered the scale to non-demented native Hebrew-speaking patients who fulfilled the Brain Bank diagnostic criteria for probable PD (n = 250). Data were compared to the Reference Standard data used for validating UDysRS translations. RESULTS: The different portions of the Hebrew UDysRS showed high internal consistency (α ≥ 0.92). A confirmatory factor analysis in which we compared the Hebrew UDysRS to the Reference Standard version produced a comparative fit index (CFI) of 0.98, exceeding the threshold criterion of CFI > 0.9 indicating factor validity. A secondary exploratory factor analysis provided further support to the consistency between the factor structures of the Hebrew and Reference Standard versions of the UDysRS. CONCLUSION: The UDysRS Hebrew version shows strong clinimetric properties and fulfills the criteria for designation as an official International Parkinson and Movement Disorder Society-approved translation for use in clinical and research settings.

Sensor-Based and Patient-Based Assessment of Daily-Living Physical Activity in People with Parkinson's Disease: Do Motor Subtypes Play a Role?

The benefits of daily-living physical activity are clear. Nonetheless, the relationship between physical activity levels and motor subtypes of Parkinson's disease (PD), i.e., tremor dominant (TD) and postural instability gait difficulty (PIGD), have not been well-studied. It is also unclear if patient perspectives and motor symptom severity are related to objective, sensor-based assessment of daily-living activity in those subtypes. To address these questions, total daily-living physical activity was quantified in 73 patients with PD and 29 healthy controls using a 3D-accelerometer worn on the lower back for at least three days. We found that individuals with the PIGD subtype were significantly less active than healthy older adults (p = 0.007), unlike individuals with the TD subtype. Among the PIGD subtype, higher daily physical activity was negatively associated with more severe ON bradykinesia (rS = -0.499, p = 0.002), motor symptoms (higher ON MDS-UPDRS (Unified Parkinson's Disease Rating Scale motor examination)-III scores), gait difficulties (rS = -0.502, p = 0.002), motor complications (rS = 0.466, p = 0.004), and balance (rS = 0.519, p = 0.001). In contrast, among the TD subtype, disease-related characteristics were not related to daily-living physical activity. Intriguingly, physical activity was not related to self-report of ADL difficulties (scores of the MDS-UPDRS Parts I or II) in both motor subtypes. These findings highlight the importance of objective daily-living physical activity monitoring and suggest that self-report does not necessarily reflect objective physical activity levels. Furthermore, the results point to important differences in factors related to physical activity in PD motor subtypes, setting the stage for personalized treatment programs.

Using Wearable Sensors and Machine Learning to Automatically Detect Freezing of Gait during a FOG-Provoking Test.

Freezing of gait (FOG) is a debilitating motor phenomenon that is common among individuals with advanced Parkinson's disease. Objective and sensitive measures are needed to better quantify FOG. The present work addresses this need by leveraging wearable devices and machine-learning methods to develop and evaluate automated detection of FOG and quantification of its severity. Seventy-one subjects with FOG completed a FOG-provoking test while wearing three wearable sensors (lower back and each ankle). Subjects were videotaped before (OFF state) and after (ON state) they took their antiparkinsonian medications. Annotations of the videos provided the "ground-truth" for FOG detection. A leave-one-patient-out validation process with a training set of 57 subjects resulted in 84.1% sensitivity, 83.4% specificity, and 85.0% accuracy for FOG detection. Similar results were seen in an independent test set (data from 14 other subjects). Two derived outcomes, percent time frozen and number of FOG episodes, were associated with self-report of FOG. Bother derived-metrics were higher in the OFF state than in the ON state and in the most challenging level of the FOG-provoking test, compared to the least challenging level. These results suggest that this automated machine-learning approach can objectively assess FOG and that its outcomes are responsive to therapeutic interventions.

Multitarget transcranial direct current stimulation for freezing of gait in Parkinson's disease.

BACKGROUND: Recent findings suggest that transcranial direct current stimulation of the primary motor cortex may ameliorate freezing of gait. However, the effects of multitarget simultaneous stimulation of motor and cognitive networks are mostly unknown. The objective of this study was to evaluate the effects of multitarget transcranial direct current stimulation of the primary motor cortex and left dorsolateral prefrontal cortex on freezing of gait and related outcomes. METHODS: Twenty patients with Parkinson's disease and freezing of gait received 20 minutes of transcranial direct current stimulation on 3 separate visits. Transcranial direct current stimulation targeted the primary motor cortex and left dorsolateral prefrontal cortex simultaneously, primary motor cortex only, or sham stimulation (order randomized and double-blinded assessments). Participants completed a freezing of gait-provoking test, the Timed Up and Go, and the Stroop test before and after each transcranial direct current stimulation session. RESULTS: Performance on the freezing of gait-provoking test (P = 0.010), Timed Up and Go (P = 0.006), and the Stroop test (P = 0.016) improved after simultaneous stimulation of the primary motor cortex and left dorsolateral prefrontal cortex, but not after primary motor cortex only or sham stimulation. CONCLUSIONS: Transcranial direct current stimulation designed to simultaneously target motor and cognitive regions apparently induces immediate aftereffects in the brain that translate into reduced freezing of gait and improvements in executive function and mobility. © 2018 International Parkinson and Movement Disorder Society.

Who will remain tremor dominant? The possible role of cognitive reserve in the time course of two common Parkinson's disease motor subtypes.

In a prospective 5-year study among Parkinson's disease (PD) tremor-dominant (TD) patients, we investigated who will remain TD and who will later convert into the postural instability gait difficulty (PIGD) phenotype. At follow-up, 38% were still considered TD. At baseline the TD non-convertors had more years of education and better cognitive function than the convertors and significantly smaller deterioration in gait, balance, cognitive function and other non-motor symptoms. These results highlight the potential role of cognition in protecting against the development of PIGD symptoms.

Cerebral Imaging Markers of GBA and LRRK2 Related Parkinson's Disease and Their First-Degree Unaffected Relatives.

Cerebral atrophy has been detected in patients with Parkinson's disease (PD) both with and without dementia, however differentiation based on genetic status has thus far not yielded robust findings. We assessed cortical thickness and subcortical volumes in a cohort of PD patients and healthy controls carriers of the G2019S mutation in the LRRK2 gene and the common GBA mutations, in an attempt to determine whether genetic status influences structural indexes. Cortical thickness and subcortical volumes were computed and compared between six groups of participants; idiopathic PD, GBA-PD, LRRK2-PD, non-manifesting non-carriers (NMNC), GBA-non-manifesting carriers (NMC) and LRRK2-NMC utilizing the FreeSurfer software program. All participants were cognitively intact based on a computerized cognitive assessment battery. Fifty-seven idiopathic PD patients, 9 LRRK2-PD, 12 GBA-PD, 49 NMNC, 41 LRRK2-NMC and 14 GBA-NMC participated in this study. Lower volumes among patients with PD compared to unaffected participants were detected in bilateral hippocampus, nucleus accumbens, caudate, thalamus, putamen and amygdala and the right pallidum (p = 0.016). PD patients demonstrated lower cortical thickness indexes in a majority of regions assessed compared with non-manifesting participants. No differences in cortical thickness and subcortical volumes were detected within each of the groups of participants based on genetic status. Mutations in the GBA and LRRK2 genes are not important determinants of cortical thickness and subcortical volumes in both patients with PD and non-manifesting participants. PD is associated with a general reduction in cortical thickness and sub-cortical atrophy even in cognitively intact patients.

SPARC: a new approach to quantifying gait smoothness in patients with Parkinson's disease.

BACKGROUND: Impairments in biomechanics and neural control can disrupt the timing and muscle pattern activation necessary for smooth gait. Gait is one of the most affected motor characteristics in Parkinson's disease (PD), but its smoothness has not been well-studied. This work applies the recently proposed spectral arc length measure (SPARC) to study, for the first time, gait in patients with PD. We hypothesized that the gait of patients with PD would be less smooth than that of healthy controls, as reflected in the SPARC measures. METHODS: The gait of 101 PD patients and 39 healthy controls was assessed using an inertial sensor. Smoothness of gait was estimated with SPARC (respectively from acceleration and angular velocity signals, SPARC-Acc and SPARC-Gyro) and harmonic ratios. Correlations between SPARC, traditional gait measures and the motor part of the Unified Parkinson's Disease Rating Scale (UPDRS) were evaluated. Measurements and analysis were conducted with and without anti-PD medication. RESULTS: SPARC measures were lower (less smooth) in PD than in controls (SPARC-Acc: PD: - 6.11 ± 0.74; CO: -5.17 ± 0.79; p <  0.001). When comparing PD to controls, SPARC-Acc differed more than other measures of gait (i.e., largest effect size, which was > 1). SPARC measures were correlated with UPDRS motor score (r = - 0.65), while they were independent of other measures of gait smoothness. PD gait in the on state was smoother than in the off state (p <  0.001). CONCLUSIONS: SPARC calculated from trunk acceleration and angular velocity signals provide valid measures of walking smoothness in PD. SPARC is sensitive to Parkinson's disease and PD medications and can be used of as another, complementary measure of the motor control of walking in PD.

The role of the prefrontal cortex in freezing of gait in Parkinson's disease: insights from a deep repetitive transcranial magnetic stimulation exploratory study.

Freezing of Gait (FOG) is one of the most debilitating gait impairments in Parkinson's disease (PD), leading to increased fall risk and reduced health-related quality of life. The utility of parkinsonian medications is often limited in the case of FOG and it frequently becomes dopamine resistant. Recent studies have suggested that pre-frontal cortex (PFC) dysfunction contributes to FOG; however, most previous findings provide only indirect evidence. To better understand the role of the PFC, we aimed to investigate the impact of high frequency, deep, repetitive transcranial magnetic stimulation (drTMS) of the medial PFC on FOG and its mediators. Nine patients with advanced PD participated in a randomized, cross-over exploratory study. We applied drTMS over the medial PFC for 16 weeks, with real and sham conditions; each condition included an intensive (i.e., 3 times a week) phase and a maintenance (once a week) phase. Scores on a FOG-provoking test, the motor part of the Unified Parkinson's Disease Rating Scale, and gait variability significantly improved after real drTMS, but not after the sham condition. Self-report of FOG severity and cognitive scores did not improve. Due to discomfort and pain during treatment, two patients dropped out and the study was halted. These initial findings support the cause-and-effect role of the pre-frontal cortex in FOG among patients with PD. Due to the small sample size, findings should be interpreted cautiously. Further studies are needed to more fully assess the role of the medial PFC in the underlying mechanism of FOG and the possibility of using non-invasive brain stimulation to modify FOG.

New evidence for gait abnormalities among Parkinson's disease patients who suffer from freezing of gait: insights using a body-fixed sensor worn for 3 days.

Previous studies conducted in laboratory settings suggest that the gait pattern in between freezing of gait (FOG) episodes is abnormal among patients with Parkinson's disease (PD) who suffer from FOG (i.e., "freezers"), compared to those who do not (i.e., "non-freezers"). We evaluated whether long-term recordings also reveal gait alterations in freezers and if these features were related to freezing severity and its impact on daily function. 72 patients with PD wore a 3-D accelerometer for 3 days. Acceleration-derived gait features included quantity (e.g., the amount of walking) and quality measures (e.g., gait variability). The New FOG-Questionnaire evaluated the subject's perceptions of FOG severity and its impact. Age, gender, and disease duration were similar (p > 0.19) in the 28 freezers and 44 non-freezers. Walking quantity was similar in the two groups, while freezers walked with higher gait variability (i.e., larger anterior-posterior power spectral density width; p = 0.003) and lower gait consistency (i.e., lower vertical stride regularity; p = 0.007). Group differences were observed when comparing the typical (i.e., median), best, and worst performance among the multiple walking bouts measured. Vertical and medio-lateral gait consistency were associated with the impact of FOG on daily living (r < -0.39, p < 0.044). The present findings demonstrate that freezers have altered gait variability and consistency during spontaneous community ambulation, even during optimal performance, and that these measures are associated with the impact of FOG on daily function. Long-term recordings may provide new insights into PD and augment the monitoring of FOG and its response to therapy.

Cognitive function and other non-motor features in non-demented Parkinson's disease motor subtypes.

Among patients with Parkinson's disease (PD), a wide range of non-motor symptoms (NMS) are evident. We assessed markers of NMS and explored their behavioral correlates with the tremor-dominant (TD) and postural instability gait difficulty (PIGD) subtypes. 110 non-demented patients with PD were evaluated and stratified into the PIGD and TD subtypes and, using stricter criteria, into predominant subgroups: p-PIGD (n = 31) and p-TD (n = 32). Non-motor signs that were assessed included cognitive function (pen and paper and a computerized battery), autonomic function (NMSQest and SCOPA-AUT), mood, and sleep. Health-related quality of life was evaluated using the PDQ-39. The p-PIGD subgroup had a higher score on the NMSQest (p = 0.033) and a higher score (i.e., worse) on the PDQ-39 (p-PIGD: 26.28 ± 12.47; p-TD: 16.93 ± 12.22; p = 0.004), compared to the p-TD subgroup, while these measures did not differ in the larger PIGD and TD group. The p-PIGD subgroup used more sleep medications compared to the p-TD subgroup (1.0 ± 1.39 vs. 0.41 ± 0.94, p = 0.05, respectively). Most cognitive scores were similar in both subgroups; however, the visuospatial components of the Montreal Cognitive Assessment and the computerized catch game were significantly worse among the p-PIGD subgroup. Mild associations were found between certain non-motor symptoms, but not cognitive function, and the PIGD score. Non-demented patients from the PIGD subtype experience more non-motor symptoms and poorer quality of life compared to the TD subtype. These findings suggest that the clinical management of non-motor and motor symptoms in patients with PD may be enhanced by a personalized approach.

Gray matter atrophy and freezing of gait in Parkinson's disease: Is the evidence black-on-white?

OBJECTIVES: The pathophysiology underlying freezing of gait (FOG) in Parkinson's disease (PD) is poorly understood. We tested whether gray matter (GM) atrophy contributes to FOG in PD. METHODS: Voxel-based morphometry quantified GM atrophy in 106 patients who were classified as freezers (n = 30) or nonfreezers (n = 76). Well-matched smaller subgroups were also studied. Balance, gait, and cognitive function were assessed, and we evaluated the relationship between GM, FOG severity, and symptoms associated with FOG. RESULTS: GM was significantly reduced in the inferior parietal lobe and angular gyrus in the matched freezers (n = 22), compared to nonfreezers (n = 22; P < 0.015, cluster-level corrected). In the entire cohort, FOG severity was related to bilateral caudate volumes. CONCLUSIONS: GM atrophy in cortical (i.e., parietal lobe and angular gyrus) and subcortical areas (i.e., caudate) are related to FOG. Disparities among the existing findings suggest that inferences regarding specific brain regions should be made with caution.

Identifying axial and cognitive correlates in patients with Parkinson's disease motor subtype using the instrumented Timed Up and Go.

Parkinson's disease (PD) is clinically highly heterogeneous, often divided into tremor dominant (TD) and postural instability gait difficulty (PIGD). To better understand these subtypes and to help stratify patients, we applied an objective marker, i.e., an instrumented version of the traditional "Timed Up and Go" test (iTUG). It is not known whether the iTUG is sensitive to PD motor phenotypes or what are its behavioral and cognitive correlates. Subjects performed the iTUG wearing a body-fixed sensor. Subcomponents were studied including walking, transitions and turning. Gait, balance and cognitive function and the associations between iTUG, behavioral and cognitive domains were assessed. We also compared two representative subtypes, with minimal symptom overlap, referred to here as predominant PIGD (p-PIGD) and predominant TD (p-TD). One hundred and six patients with PD performed the iTUG. Significant correlations were found between iTUG measures and the PIGD score, but not with TD score. Thirty p-PIGD and 31 p-TD patients were identified. Both groups were similar with respect to age and disease duration (p > 0.75). The p-PIGD patients took significantly longer to complete the iTUG (p = 0.026), used more steps (p = 0.031), albeit with similar step duration (p = 0.936). In the sit-to-stand transition, the p-PIGD patients exhibited lower anterior-posterior jerk (p = 0.04) and lower pitch range (p = 0.012). During the turn, the p-PIGD patients had a lower yaw amplitude (p < 0.038). Cognitive domains were correlated with iTUG measures in the p-PIGD patients, but not in the p-TD. These findings demonstrate that a single sensor can identify axial and cognitive correlates using subcomponents of the iTUG and reveals subtle alterations between the PD motor subtypes.

Dual-task training on a treadmill to improve gait and cognitive function in elderly idiopathic fallers.

BACKGROUND AND PURPOSE: Daily activities require the ability to dual task (DT), utilizing cognitive resources while walking to negotiate complex environmental conditions. For older adults, these additional cognitive demands often lead to reduced gait quality that increases the risk of falls. The aim of this study was to assess whether a combined intervention, consisting of treadmill training (TT) while performing DT, improves cognitive and motor performance in older adults with a history of multiple falls. METHODS: A repeated measures design was used to evaluate the effects of training in 10 elderly fallers (mean age, 78.1 ± 5.81 y, 7 women). The progressive intensive training sessions included walking on a treadmill while practicing a variety of dual tasks 3 times a week for more than 6 weeks. Cognitive and motor measures were used to assess the effects of the intervention immediately after training and 1 month posttraining. RESULTS: Improvements were observed in Berg Balance Scale (P = 0.02), Dynamic Gait Index (P = 0.03), gait speed during usual walking and while DT (P < 0.05), and cognitive performance as measured by the Trails Making Test B (P = 0.02). Furthermore, quality of life improved (SF-36: P = 0.01) as did physical activity (Physical Activity Scale for Elderly: P = 0.02). At 1 month postintervention, changes were not significant. DISCUSSION AND CONCLUSIONS: After 6 weeks of TT + DT program, elderly fallers demonstrated improved scores on tests of mobility, functional performance tasks, and cognition.Dual task training can be readily implemented by therapists as a component of a fall-risk reduction training program.Video Abstract available. See Video (Supplemental Digital Content 1, http://links.lww.com/JNPT/A81) for more insights from the authors.

Automated detection of missteps during community ambulation in patients with Parkinson's disease: a new approach for quantifying fall risk in the community setting.

BACKGROUND: Falls are a leading cause of morbidity and mortality among older adults and patients with neurological disease like Parkinson's disease (PD). Self-report of missteps, also referred to as near falls, has been related to fall risk in patients with PD. We developed an objective tool for detecting missteps under real-world, daily life conditions to enhance the evaluation of fall risk and applied this new method to 3 day continuous recordings. METHODS: 40 patients with PD (mean age ± SD: 62.2 ± 10.0 yrs, disease duration: 5.3 ± 3.5 yrs) wore a small device that contained accelerometers and gyroscopes on the lower back while participating in a protocol designed to provoke missteps in the laboratory. Afterwards, the subjects wore the sensor for 3 days as they carried out their routine activities of daily living. An algorithm designed to automatically identify missteps was developed based on the laboratory data and was validated on the 3 days recordings. RESULTS: In the laboratory, we recorded 29 missteps and more than 60 hours of data. When applied to this dataset, the algorithm achieved a 93.1% hit ratio and 98.6% specificity. When we applied this algorithm to the 3 days recordings, patients who reported two falls or more in the 6 months prior to the study (i.e., fallers) were significantly more likely to have a detected misstep during the 3 day recordings (p = 0.010) compared to the non-fallers. CONCLUSIONS: These findings suggest that this novel approach can be applied to detect missteps during daily life among patients with PD and will likely help in the longitudinal assessment of disease progression and fall risk.

Neuroimaging as a window into gait disturbances and freezing of gait in patients with Parkinson's disease.

Neuroimaging has been applied to better understand the neural mechanisms underlying gait disturbances in Parkinson's disease (PD). In the present paper, we review studies that used neuroimaging methods to investigate mobility, walking and freezing of gait (FOG) in PD, focusing on the recent literature. Examination of these studies suggests that gait changes in PD are due to widespread alterations in the structure and function of the brain that go beyond the basal ganglia. For example, cortical structures including the frontal and parietal lobes, the mesencephalic locomotor region and specifically, the pedunculopontine nucleus, all apparently play important roles in the control of gait in PD. Nonetheless, there are some significant inconsistencies across the different studies and many questions remain regarding the precise pathological processes that contribute to gait disturbances, in general, and to FOG, more specifically. A discussion of new insights into the neural mechanisms underlying gait disturbances are presented along with a summary of the disadvantages and limitations of the existing techniques and suggestions for future directions.