Stride width and postural stability in frontal gait disorders and Parkinson's disease.

Older adults, as well as those with certain neurological disorders, may compensate for poor neural control of postural stability by widening their base of foot support while walking. However, the extent to which this wide-based gait improves postural stability or affects postural control strategies has not been explored. People with idiopathic Parkinson's disease (iPD, n = 72), frontal gait disorders (FGD, n = 16), and healthy older adults (n = 32) performed walking trials at their preferred speed over an 8-m-long, instrumented walkway. People with iPD were tested in their OFF medication state. Analyses of covariance were performed to determine the associations between stride width and measures of lateral stability control. People with FGD exhibited a wide-based gait compared to both healthy older adults and iPD. An increased stride width was associated with an increase in lateral margin of stability in FGD. Unlike healthy older adults or iPD, people with FGD did not externally rotate their feet (toe-out angle) or shift their center of pressure laterally to aid lateral dynamic stability during walking but slowed their gait instead to increase stability. By adopting a slow, wide-based gait, people with FGD take advantage of the passive, pendular mechanics of walking.

Motor networks, but also non-motor networks predict motor signs in Parkinson's disease.

OBJECTIVE: Investigate the brain functional networks associated with motor impairment in people with Parkinson's disease (PD). BACKGROUND: PD is primarily characterized by motor dysfunction. Resting-state functional connectivity (RsFC) offers a unique opportunity to non-invasively characterize brain function. In this study, we hypothesized that the motor dysfunction observed in people with PD involves atypical connectivity not only in motor but also in higher-level attention networks. Understanding the interaction between motor and non-motor RsFC that are related to the motor signs could provide insights into PD pathophysiology. METHODS: We used data from 88 people with PD (mean age: 68.2(SD:10), 55 M/33F) coming from 2 cohorts. Motor severity was assessed in practical OFF-medication state, using MDS-UPDRS Part-III motor scores (mean: 49 (SD:10)). RsFC was characterized using an atlas of 384 regions that were grouped into 13 functional networks. Associations between RsFC and motor severity were assessed independently for each RsFC using predictive modeling. RESULTS: The top 5 % models that predicted the MDS-UPDRS-III motor scores with effect size >0.5 were the connectivity between (1) the somatomotor and Subcortical-Basal-ganglia, (2) somatomotor and Visual and (3) CinguloOpercular (CiO) and language/Ventral attention (Lan/VeA) network pairs. DISCUSSION: Our findings suggest that, along with motor networks, visual- and attention-related cortical networks are also associated with the motor symptoms of PD. Non-motor networks may be involved indirectly in motor-coordination. When people with PD have deficits in motor networks, more attention may be needed to carry out formerly automatic motor functions, consistent with compensatory mechanisms in parkinsonian movement disorders.

Digital measures of freezing of gait across the spectrum of normal, non-freezers, possible freezers and definite freezers.

Over the course of the disease, freezing of gait (FoG) will gradually impact over 80% of people with Parkinson's disease (PD). Clinical decision-making and research design are often based on classification of patients as 'freezers' or 'non-freezers'. We derived an objective measure of FoG severity from inertial sensors on the legs to examine the continuum of FoG from absent to possible and severe in people with PD and in healthy controls. One hundred and forty-seven people with PD (Off-medication) and 83 healthy control subjects turned 360° in-place for 1 minute while wearing three wearable sensors used to calculate a novel Freezing Index. People with PD were classified as: 'definite freezers', new FoG questionnaire (NFOGQ) score > 0 and clinically observed FoG; 'non-freezers', NFOGQ = 0 and no clinically observed FoG; and 'possible freezers', either NFOGQ > 0 but no FoG observed or NFOGQ = 0 but FoG observed. Linear mixed models were used to investigate differences in participant characteristics among groups. The Freezing Index significantly increased from healthy controls to non-freezers to possible freezers and to definite freezers and showed, in average, excellent test-retest reliability (ICC = 0.89). Unlike the Freezing Index, sway, gait and turning impairments were similar across non-freezers, possible and definite freezers. The Freezing Index was significantly related to NFOG-Q, disease duration, severity, balance confidence, and the SCOPA-Cog (p < 0.01). An increase in the Freezing Index, objectively assessed with wearable sensors during a turning- in-place test, may help identify prodromal FoG in people with PD prior to clinically-observable or patient-perceived freezing. Future work should follow objective measures of FoG longitudinally.

Gait and turning characteristics from daily life increase ability to predict future falls in people with Parkinson's disease.

Objectives: To investigate if digital measures of gait (walking and turning) collected passively over a week of daily activities in people with Parkinson's disease (PD) increases the discriminative ability to predict future falls compared to fall history alone. Methods: We recruited 34 individuals with PD (17 with history of falls and 17 non-fallers), age: 68 ± 6 years, MDS-UPDRS III ON: 31 ± 9. Participants were classified as fallers (at least one fall) or non-fallers based on self-reported falls in past 6 months. Eighty digital measures of gait were derived from 3 inertial sensors (Opal® V2 System) placed on the feet and lower back for a week of passive gait monitoring. Logistic regression employing a "best subsets selection strategy" was used to find combinations of measures that discriminated future fallers from non-fallers, and the Area Under Curve (AUC). Participants were followed via email every 2 weeks over the year after the study for self-reported falls. Results: Twenty-five subjects reported falls in the follow-up year. Quantity of gait and turning measures (e.g., number of gait bouts and turns per hour) were similar in future fallers and non-fallers. The AUC to discriminate future fallers from non-fallers using fall history alone was 0.77 (95% CI: [0.50-1.00]). In contrast, the highest AUC for gait and turning digital measures with 4 combinations was 0.94 [0.84-1.00]. From the top 10 models (all AUCs>0.90) via the best subsets strategy, the most consistently selected measures were variability of toe-out angle of the foot (9 out of 10), pitch angle of the foot during mid-swing (8 out of 10), and peak turn velocity (7 out of 10). Conclusions: These findings highlight the importance of considering precise digital measures, captured via sensors strategically placed on the feet and low back, to quantify several different aspects of gait (walking and turning) during daily life to improve the classification of future fallers in PD.

Effect of Levodopa and Environmental Setting on Gait and Turning Digital Markers Related to Falls in People with Parkinson's Disease.

Background: It is unknown whether medication status (off and on levodopa) or laboratory versus home settings plays a role in discriminating fallers and non-fallers in people with Parkinson's disease (PD). Objectives: To investigate which specific digital gait and turning measures, obtained with body-worn sensors, best discriminated fallers from non-fallers with PD in the clinic and during daily life. Methods: We recruited 34 subjects with PD (17 fallers and 17 non-fallers based on the past 6 month's falls). Subjects wore three inertial sensors attached to both feet and the lumbar region in the laboratory for a 3-minute walking task (both off and on levodopa) and during daily life activities for a week. We derived 24 digital (18 gait and 6 turn) measures from the 3-minute walk and from daily life. Results: In clinic, none of the gait and turning measures collected during on levodopa state were significantly different between fallers and non-fallers. In contrast, digital measures collected in the off levodopa state were significantly different between groups, (average turn velocity, average number of steps to complete a turn, and variability of gait speed, P < 0.03). During daily life, the variability of average turn velocity (P = 0.023) was significantly different in fallers than non-fallers. Last, the average number of steps to complete a turn was significantly correlated with the patient-reported outcomes. Conclusions: Digital measures of turning, but not gait, were different in fallers compared to non-fallers with PD, in the laboratory when off medication and during a daily life.

Exploring the effects of dopamine on sensorimotor inhibition and mobility in older adults.

Dopaminergic activity decreases in older adults (OAs) with normal aging and is further reduced in Parkinson's disease (PD), affecting cortical motor and sensorimotor pathways. Levodopa is the prevailing therapy to counter dopamine loss in PD, though not all PD motor signs improve with levodopa. The purpose of this preliminary study was to explore the effects of levodopa on sensorimotor inhibition, gait and quiet standing in OAs and to investigate the relationships between sensorimotor inhibition and both gait and standing balance both OFF- and ON-levodopa. Fifteen OA males completed a gait, balance and sensorimotor assessments before and 1 h after they were given a 100 mg dose of levodopa. Short-latency afferent inhibition quantified sensorimotor inhibition. Wearable sensors characterized gait (two-minute walk) and standing balance (1-min stance). No sensorimotor inhibition, gait, or standing balance measures changed from OFF- to ON-levodopa. When OFF-levodopa, worse inhibition significantly related to increased double stance (r = 0.62; p = 0.01), increased jerkiness of sway (r = 0.57; p = 0.03) and sway area (r = 0.58; p = 0.02). While ON-levodopa, worse inhibition related to increased arm swing range of motion (r = 0.63; p = 0.01) and jerkiness of sway (r = 0.53; p = 0.04). The relationship between SAI and arm swing excursion significantly changed from OFF- to ON-levodopa (z = - 3.05; p = 0.002; 95% confidence interval = - 0.95, - 0.21). Sensorimotor inhibition relationships to both gait and balance may be affected by dopamine in OAs. Cortical restructuring due to the loss of dopamine may be responsible for the heterogeneity of levodopa effect in people with PD and OAs.

Does Cueing Need Attention? A Pilot Study in People with Parkinson's Disease.

We previously showed that both open-loop (beat of a metronome) and closed-loop (phase-dependent tactile feedback) cueing may be similarly effective in reducing Freezing of Gait (FoG), assessed with a quantitative FoG Index, while turning in place in the laboratory in a group of people with Parkinson's disease (PD). Despite the similar changes on the FoG Index, it is not known whether both cueing responses require attentional control, which would explain FoG Index improvement. The mechanisms underlying cueing responses are poorly understood. Here, we tested the hypothesis that the salience network would predict responsiveness (i.e., FoG Index improvement) to open-loop and closed-loop cueing in people with and without FoG of PD, as salience network contributes to tasks requiring attention to external stimuli in healthy adults. Thirteen people with PD with high-quality imaging data were analyzed to characterize relationships between resting-state MRI functional connectivity and responses to cues. The interaction of the salience network and retrosplenial-temporal networks was the best predictor of responsiveness to open-loop cueing, presenting the largest effect size (d = 1.16). The interaction between the salience network and subcortical as well as cingulo-parietal and subcortical networks were the strongest predictors of responsiveness to closed-loop cueing, presenting the largest effect sizes (d = 1.06 and d = 0.84, respectively). Salience network activity was a common predictor of responsiveness to both cueing, which suggests that auditory and proprioceptive stimuli during turning may require some level of cognitive and insular activity, anchored within the salience network, which explain FoG Index improvements in people with PD.

Resting state functional networks predict different aspects of postural control in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder causing postural control impairments. Postural control involves multiple domains, such as control of postural sway in stance, automatic postural responses (APRs) and anticipatory postural adjustments (APAs). We hypothesize that impairments in each postural domain is associated with resting-state functional connectivity (rsFC), accounted by predictive modeling and that cortical and cerebellar networks would predict postural control in people with PD (PwPD). OBJECTIVE: To determine whether rsFC can predict three domains of postural control independently in PwPD and older adults (OA) based on predictive accuracy of models. METHODS: The cohort consisted of 65 PwPD (67.7 +8.1 age) tested in their OFF-state and 42 OA (69.7 +8.2 age). Six body-worn, inertial sensors measured postural sway area while standing on foam, step length of APRs to a backward push-and-release perturbation, and magnitude of lateral APAs prior to voluntary gait initiation. Resting state-fMRI data was reported on 384 regions of interest that were grouped into 13 functional brain networks. Associations between rsFC and postural metrics were characterized using predictive modeling, with an independent training (n = 67) and validation (n = 40) dataset. Models were trained in the training sample and performance of the best model was validated in the independent test dataset. RESULTS: rsFC of different brain networks predicted each domain of postural control in PD: Frontoparietal and Ventral Attention rsFC for APAs; Cerebellar-Subcortical and Visual rsFC and Auditory and Cerebellar-Subcortical rsFC for APRs; Ventral Attention and Ventral Multimodal rsFC for postural sway. In OA, CinguloOpercular and Somatomotor rsFC predicted APAs. CONCLUSIONS: Our findings suggest that cortical networks predict postural control in PD and there is little overlap in brain network connectivities that predict different domains of postural control, given the rsFC methodology used. PwPD use different cortical networks for APAs compared to OA.

Effects of a Cognitively Challenging Agility Boot Camp Program on Balance and Gait in People With Parkinson's Disease: Does Freezing of Gait Status Matter?

BACKGROUND AND AIM: Individuals with Parkinson's disease (PD) with and without freezing of Gait (FoG) may respond differently to exercise interventions for several reasons, including disease duration. This study aimed to determine whether both people with and without FoG benefit from the Agility Boot Camp with Cognitive Challenges (ABC-C) program. METHODS: This secondary analysis of our ABC-C trial included 86 PD subjects: 44 without FoG (PD-FoG) and 42 with FoG (PD + FoG). We collected measures of standing sway balance, anticipatory postural adjustments, postural responses, and a 2-minute walk with and without a cognitive task. Two-way repeated analysis of variance, with disease duration as covariate, was used to investigate the effects of ABC-C program. Effect sizes were calculated using standardized response mean (SRM) for PD-FoG and PD + FoG, separately. RESULTS: The ABC-C program was effective in improving gait performance in both PD-FoG and PD + FoG, even after controlling for disease duration. Specifically, dual-task gait speed (P < .0001), dual-cost stride length (P = .012), and these single-task measures: arm range of motion (P < .0001), toe-off angle (P = .005), gait cycle duration variability (P = .019), trunk coronal range of motion (P = .042), and stance time (P = .046) improved in both PD-FoG and PD + FoG. There was no interaction effect between time (before and after exercise) and group (PD-FoG/PD + FoG) in all 24 objective measures of balance and gait. Dual-task gait speed improved the most in PD + FoG (SRM = 1.01), whereas single-task arm range of motion improved the most in PD-FoG (SRM = 1.01). CONCLUSION: The ABC-C program was similarly effective in improving gait (and not balance) performance in both PD-FoG and PD + FoG.

Relationship Between Brain Volumes and Objective Balance and Gait Measures in Parkinson's Disease.

BACKGROUND: Instrumented measures of balance and gait measure more specific balance and gait impairments than clinical rating scales. No prior studies have used objective balance/gait measures to examine associations with ventricular and brain volumes in people with Parkinson's disease (PD). OBJECTIVE: To test the hypothesis that larger ventricular and smaller cortical and subcortical volumes are associated with impaired balance and gait in people with PD. METHODS: Regional volumes from structural brain images were included from 96 PD and 50 control subjects. Wearable inertial sensors quantified gait, anticipatory postural adjustments prior to step initiation (APAs), postural responses to a manual push, and standing postural sway on a foam surface. Multiple linear regression models assessed the relationship between brain volumes and balance/gait and their interactions in PD and controls, controlling for sex, age and corrected for multiple comparisons. RESULTS: Smaller brainstem and subcortical gray matter volumes were associated with larger sway area in people with PD, but not healthy controls. In contrast, larger ventricle volume was associated with smaller APAs in healthy controls, but not in people with PD. A sub-analysis in PD showed significant interactions between freezers and non-freezers, in several subcortical areas with stride time variability, gait speed and step initiation. CONCLUSION: Our models indicate that smaller subcortical and brainstem volumes may be indicators of standing balance dysfunction in people with PD whereas enlarged ventricles may be related to step initiation difficulties in healthy aging. Also, multiple subcortical region atrophy may be associated with freezing of gait in PD.

Discussion of Research Priorities for Gait Disorders in Parkinson's Disease.

Gait and balance abnormalities develop commonly in Parkinson's disease and are among the motor symptoms most disabling and refractory to dopaminergic or other treatments, including deep brain stimulation. Efforts to develop effective therapies are challenged by limited understanding of these complex disorders. There is a major need for novel and appropriately targeted research to expedite progress in this area. The Scientific Issues Committee of the International Parkinson and Movement Disorder Society has charged a panel of experts in the field to consider the current knowledge gaps and determine the research routes with highest potential to generate groundbreaking data. © 2021 International Parkinson and Movement Disorder Society.

Functional limits of stability and standing balance in people with Parkinson's disease with and without freezing of gait using wearable sensors.

BACKGROUND: People with from Parkinson's disease (PD) and freezing of gait (FoG) have more frequent falls compared to those who do not freeze but there is no consensus on which, specific objective measures of postural instability are worse in freezers (PD + FoG) than non-freezers (PD-FoG). RESEARCH QUESTION: Are functional limits of stability (fLoS) or postural sway during stance measured with wearable inertial sensors different between PD + FoG versus PD-FoG, as well as between PD versus healthy control subjects (HC)? METHODS: Sixty-four PD subjects with FoG (MDS-UPDRS Part III: 45.9 ±â€¯12.5) and 80 PD subjects without FoG (MDS-UPDRS Part III: 36.2 ±â€¯10.9) were tested Off medication and compared with 79 HC. Balance was quantified with inertial sensors worn on the lumbar spine while performing the following balance tasks: 1) fLoS as defined by the maximum displacement in the forward and backward directions and 2) postural sway area while standing with eyes open on a firm and foam surface. An ANOVA, controlling for disease duration, compared postural control between groups. RESULTS: PD + FoG had significantly smaller fLoS compared to PD-FoG (p =  0.004) and to healthy controls (p <  0.001). However, PD-FoG showed similar fLoS compared to healthy controls (p =  0.48). Both PD+FoG and PD-FoG showed larger postural sway on a foam surface compared to healthy controls (p =  0.001) but there was no significant difference in postural sway between PD+FoG and PD-FoG. SIGNIFICANCE: People with PD and FoG showed task-specific, postural impairments with smaller fLoS compared to non-freezers, even when controlling for disease duration. However, individuals with PD with or without FoG had similar difficulties standing quietly on an unreliable surface compared to healthy controls. Wearable inertial sensors can reveal worse fLoS in freezers than non-freezers that may contribute to FoG and help explain their more frequent falls.

Changes in prefrontal cortical activity and turning in response to dopaminergic and cholinergic therapy in Parkinson's disease: A randomized cross-over trial.

INTRODUCTION: Cholinergic dysfunction contributes to mobility deficits in Parkinson's disease (PD). People with PD rely on limited prefrontal executive-attentional resources for the control of locomotion, including turning. Cortical and behavioral responses to cholinergic augmentation during turning remains unclear. We examined prefrontal cortex (PFC) activity while turning-in-place and spatiotemporal measures of turns in response to usual dopaminergic medication and adjunct cholinergic augmentation. METHODS: This study consisted of a single-site, randomized, double-blind crossover trial. Twenty PD participants were assessed in the levodopa-off state and then randomized to either levodopa + donepezil (5 mg) or levodopa + placebo treatments for two weeks followed by a 2-week washout before crossover. The primary outcome was change from off state in PFC activity while turning-in-place (assessed with functional near-infrared spectroscopy). Secondary outcomes were changes in spatiotemporal turning measures (assessed with body-worn inertial measurement units) and accuracy in the secondary task. RESULTS: Nineteen participants completed the trial. While levodopa + placebo had no effect on PFC activity when turning-in-place with a dual-task, levodopa + donepezil led to a large reduction in PFC activity (effect size, -0.82). Spatiotemporal measures of turning improved with both treatments, with slightly greater effect sizes observed for levodopa + donepezil. Additionally, the accuracy in the concurrent cognitive task improved only with levodopa + donepezil (effect size, 0.63). CONCLUSION: The addition of cholinergic therapy with donepezil (5 mg/day for 2 weeks) to standard dopaminergic therapy reduced the burden on prefrontal executive-attentional resources while turning with a dual-task and improved secondary task accuracy and turning.

Measuring freezing of gait during daily-life: an open-source, wearable sensors approach.

BACKGROUND: Although a growing number of studies focus on the measurement and detection of freezing of gait (FoG) in laboratory settings, only a few studies have attempted to measure FoG during daily life with body-worn sensors. Here, we presented a novel algorithm to detect FoG in a group of people with Parkinson's disease (PD) in the laboratory (Study I) and extended the algorithm in a second cohort of people with PD at home during daily life (Study II). METHODS: In Study I, we described of our novel FoG detection algorithm based on five inertial sensors attached to the feet, shins and lumbar region while walking in 40 participants with PD. We compared the performance of the algorithm with two expert clinical raters who scored the number of FoG episodes from video recordings of walking and turning based on duration of the episodes: very short (< 1 s), short (2-5 s), and long (> 5 s). In Study II, a different cohort of 48 people with PD (with and without FoG) wore 3 wearable sensors on their feet and lumbar region for 7 days. Our primary outcome measures for freezing were the % time spent freezing and its variability. RESULTS: We showed moderate to good agreement in the number of FoG episodes detected in the laboratory (Study I) between clinical raters and the algorithm (if wearable sensors were placed on the feet) for short and long FoG episodes, but not for very short FoG episodes. When extending this methodology to unsupervised home monitoring (Study II), we found that percent time spent freezing and the variability of time spent freezing differentiated between people with and without FoG (p < 0.05), and that short FoG episodes account for 69% of the total FoG episodes. CONCLUSION: Our findings showed that objective measures of freezing in PD using inertial sensors on the feet in the laboratory are matching well with clinical scores. Although results found during daily life are promising, they need to be validated. Objective measures of FoG with wearable technology during community-living would be useful for managing this distressing feature of mobility disability in PD.

Dual-Task Costs of Quantitative Gait Parameters While Walking and Turning in People with Parkinson's Disease: Beyond Gait Speed.

BACKGROUND: There is a lack of recommendations for selecting the most appropriate gait measures of Parkinson's disease (PD)-specific dual-task costs to use in clinical practice and research. OBJECTIVE: We aimed to identify measures of dual-task costs of gait and turning that best discriminate performance in people with PD from healthy individuals. We also investigated the relationship between the most discriminative measures of dual-task costs of gait and turning with disease severity and disease duration. METHODS: People with mild-to-moderate PD (n = 144) and age-matched healthy individuals (n = 79) wore 8 inertial sensors while walking under single and dual-task (reciting every other letter of the alphabet) conditions. Outcome measures included 26 objective measures within four gait domains (upper/lower body, turning and variability). The area under the curve (AUC) from the receiver-operator characteristic plot was calculated to compare discriminative ability of dual-task costs on gait across outcome measures. RESULTS: PD-specific, dual-task interference was identified for arm range of motion, foot strike angle, turn velocity and turn duration. Arm range of motion (AUC = 0.73) and foot strike angle (AUC = 0.68) had the largest AUCs across dual-task costs measures and they were associated with disease severity and/or disease duration. In contrast, the most commonly used dual-task gait measure, gait speed, showed an AUC of only 0.54. CONCLUSION: Findings suggest that people with PD rely more than healthy individuals on executive-attentional resources to control arm swing, foot strike, and turning, but not gait speed. The dual-task costs of arm range of motion best discriminated people with PD from healthy individuals.

Relating Response Inhibition, Brain Connectivity, and Freezing of Gait in People with Parkinson's Disease.

OBJECTIVE: Freezing of gait (FoG) in Parkinson's disease (PD) has been associated with response inhibition. However, the relationship between response inhibition, neural dysfunction, and PD remains unclear. We assessed response inhibition and microstructural integrity of brain regions involved in response inhibition [right hemisphere inferior frontal cortex (IFC), bilateral pre-supplementary motor areas (preSMA), and subthalamic nuclei (STN)] in PD subjects with and without FoG and elderly controls. METHOD: Twenty-one people with PD and FoG (PD-FoG), 18 without FoG (PD-noFoG), and 19 age-matched controls (HC) completed a Stop-Signal Task (SST) and MRI scan. Probabilistic fiber tractography assessed structural integrity (fractional anisotropy, FA) among IFC, preSMA, and STN regions. RESULTS: Stop-signal performance did not differ between PD and HC, nor between PD-FoG and PD-noFoG. Differences in white matter integrity were observed across groups (.001 < p < .064), but were restricted to PD versus HC groups; no differences in FA were observed between PD-FoG and PD-noFoG (p > .096). Interestingly, worse FoG was associated with higher (better) mean FA in the r-preSMA, (ß = .547, p = .015). Microstructural integrity of the r-IFC, r-preSMA, and r-STN tracts correlated with stop-signal performance in HC (p ≤ .019), but not people with PD. CONCLUSION: These results do not support inefficient response inhibition in PD-FoG. Those with PD exhibited white matter loss in the response inhibition network, but this was not associated with FoG, nor with response inhibition deficits, suggesting FoG-specific neural changes may occur outside the response inhibition network. As shown previously, white matter loss was associated with response inhibition in elderly controls, suggesting PD may disturb this relationship.

Cortical thickness as predictor of response to exercise in people with Parkinson's disease.

We previously showed that dual-task cost (DTC) on gait speed in people with Parkinson's disease (PD) improved after 6 weeks of the Agility Boot Camp with Cognitive Challenge (ABC-C) exercise program. Since deficits in dual-task gait speed are associated with freezing of gait and gray matter atrophy, here we performed preplanned secondary analyses to answer two questions: (a) Do people with PD who are freezers present similar improvements compared to nonfreezers in DTC on gait speed with ABC-C? (b) Can cortical thickness at baseline predict responsiveness to the ABC-C? The DTC from 39 freezers and 43 nonfreezers who completed 6 weeks of ABC-C were analyzed. A subset of 51 participants (21 freezers and 30 nonfreezers) with high quality imaging data were used to characterize relationships between baseline cortical thickness and delta (Δ) DTC on gait speed following ABC-C. Freezers showed larger ΔDTC on gait speed than nonfreezers with ABC-C program (p < .05). Cortical thickness in visual and fronto-parietal areas predicted ΔDTC on gait speed in freezers, whereas sensorimotor-lateral thickness predicted ΔDTC on gait speed in nonfreezers (p < .05). When matched for motor severity, visual cortical thickness was a common predictor of response to exercise in all individuals, presenting the largest effect size. In conclusion, freezers improved gait automaticity even more than nonfreezers from cognitively challenging exercise. DTC on gait speed improvement was associated with larger baseline cortical thickness from different brain areas, depending on freezing status, but visual cortex thickness showed the most robust relationship with exercise-induced improvements in DTC.