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Objective: Aside from the cognitive impairment, patients with dementia with Lewy bodies (DLB) have a high frequency of visual hallucinations and a number of other vision-related symptoms, whereas auditory hallucinations are less frequent. To better understand the differential dysfunction of the visual network in DLB, we compared auditory and visual event-related potentials and oscillations in patients with DLB., Methods: Event-related potentials elicited by visual and auditory oddball tasks were recorded in 23 patients with DLB and 22 healthy controls and analyzed in time and time-frequency domain., Results: DLB patients had decreased theta band activity related to both early sensory and later cognitive processing in the visual, but not in the auditory task. Patients had lower delta and higher alpha and beta bands power related to later cognitive processing in both auditory and visual tasks., Conclusions: In DLB visual event-related oscillations are characterized by a decrease in theta and lack of inhibition in alpha bands., Significance: Decreased theta and a lack of inhibition in alpha band power might be an oscillatory underpinning of some classical DLB symptoms such as fluctuations in attention and high-level visual disturbances and a potential marker of dysfunction of the visual system in DLB., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background . Nigrostriatal dopaminergic loss is a hallmark of Parkinson's disease (PD) pathophysiology, leading to motor Parkinsonism. Different intervention protocols have shown that motor and cognitive functions improvement in PD occur via the modulation of distinct motor and cognitive pathways. Objective . To investigate the effects of two motor training programs on the brains' functional networks in PD patients. Methods . Thirty-seven PD patients were prospectively studied. All enrolled patients underwent either treadmill training (TT) (n = 19) or treadmill with virtual reality (TT + VR) (n = 18) for 6 weeks. Magnetic resonance imaging (MRI) scans (3 T) acquiring 3-dimensional T1-weighted and resting-state functional MRI (rs-fMRI) data sets were performed at baseline and after 6 weeks. Independent component analysis (ICA) was conducted, and functional connectivity (FC) changes within large-scale functional brain networks were examined. Results . In both groups, significant post-training FC decrease in striatal, limbic, and parietal regions within the basal ganglia network, executive control network, and frontal-striatal network, and significant FC increase in the caudate, and cingulate within the sensorimotor network (SMN) were observed. Moreover, a significant time × group interaction was detected where TT + VR training had greater effects on FC levels in the supplementary motor area (SMA) and right precentral gyrus within the SMN, and in the right middle frontal gyrus (MFG) within the cerebellar network. These FC alterations were associated with improved usual and dual-task walking performance. Conclusions . These results suggest that TT with-and-without the addition of a VR component affects distinct neural pathways, highlighting the potential for beneficial neural plasticity in PD. Such distinctive task-specific pathways may foster the facilitation of interventions tailored to the individual needs of PD patients. Registered at Clinicaltrials.gov number: NCT01732653.

Introduction: Falls are associated with numerous risk factors, such as motor and cognitive impairments. However, the neural correlates of falls are poorly understood., Objectives: Here, we aimed to assess patterns of structural, and resting-state functional connectivity (FC) alterations related to falls in a group of older adults with a history of falls compared to non-fallers., Methods: Fourteen elderly fallers (mean age = 78.1 ± 1.5 yrs, >2 falls previous six months), and 20 healthy controls (mean age = 69.6 ± 1.3 yrs) were examined. All participants underwent a 3T MRI scan obtaining 3D T1-weighted images, and eyes-open resting-state (rs)-fMRI. Voxel-based morphometry was conducted to detect grey matter differences between the groups. Independent component analysis was conducted based on rs-fMRI and number of attention-and-motor related functional networks was identified and compared between groups using an independent-sample T-test., Results: No differences were observed in grey matter between the groups after correcting for age and gender (p > 0.01, FWEc). Compared with non-fallers, the fallers had lower FC in cerebellar, frontal and parietal cortical nodes within the sensorimotor network (SMN), lateral motor network (M1), Cerebellar network (CBL), frontal-striatal network (FSN), executive control network (ECN), and dorsal attention network (DAN). Moreover, fallers had increased FC in the basal ganglia network (BGN), Left paracentral in M1 and SMN, and right hippocampus in DAN (p < 0.01, FWEc)., Conclusions: Among fallers, reduced connectivity was observed in areas that relate to integration of information, while increased connectivity was found in areas associated with motor and sensory information processing. Together, these results provide evidence to the complex multidimensionality of the neural underpinnings of falls. Furthermore, these findings may help emphasize the importance of interventions that target both motor and cognitive aspects., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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., (© 2020 International Parkinson and Movement Disorder Society.)

In this study, we present algorithms developed for gait analysis, but suitable for many other signal processing tasks. A novel general-purpose algorithm for extremum estimation of quasi-periodic noisy signals is proposed. This algorithm is both flexible and robust, and allows custom adjustments to detect a predetermined wave pattern while being immune to signal noise and variability. A method for signal segmentation was also developed for analyzing kinematic data recorded while performing on obstacle avoidance task. The segmentation allows detecting preparation and recovery phases related to obstacle avoidance. A simple kernel-based clustering method was used for classification of unsupervised data containing features of steps within the walking trial and discriminating abnormal from regular steps. Moreover, a novel algorithm for missing data approximation and adaptive signal filtering is also presented. This algorithm allows restoring faulty data with high accuracy based on the surrounding information. In addition, a predictive machine learning technique is proposed for supervised multiclass labeling with non-standard label structure.

Background: Tripping over an obstacle is one of the most common causes of falls among older adults; however, the impact of obstacle parameters and subject characteristics are not well described., Objectives: To evaluate age-associated changes in the ability to negotiate obstacles and the role of obstacle parameters (e.g., anticipated vs. unanticipated, height, and available response time [ART]), and subject characteristics., Methods: Twenty healthy older adults (77.7 ± 3.4 years; 50% women) and 20 healthy young adults (29.3 ± 3.8 years; 50% women) underwent cognitive, gait, and balance testing before negotiating a computer-controlled obstacle course. The primary outcome measure was the ability to successfully negotiate the obstacles (without touching them)., Results: The success rate for all subjects was higher when the obstacle was anticipated (99.0 ± 2.8%) than when unanticipated (66.0 ± 20.2%; p < 0.001). The obstacle height had a significant effect on the success rate (p = 0.022); the success rate was lower when the obstacle height was lower. No significant interaction between group and obstacle height was observed (p = 0.096). ART had no significant effect on the success rate (p = 0.294) in both of the groups (ART × group, p = 0.136). However, a significant interaction between group, obstacle height, and ART was found (p = 0.013), reflecting a lower success rate in the older adults when the obstacles were low and unanticipated. In general, older adults demonstrated a trend towards a lower success rate in all types of obstacles compared to the young adults (p = 0.057). Among the older adults, the success rate in the anticipated obstacle condition was correlated with stride length (ρ = 0.600, p = 0.005), step time coefficient of variation (ρ = -0.635, p = 0.003), and gait speed (rho = 0.530, p = 0.016). Montreal Cognitive Assessment scores tended to be related to the difference in the success rate between the anticipated and unanticipated conditions., Conclusions: These findings support the idea that motor and, to some degree, cognitive functions are needed to successfully negotiate obstacles, and provide new insights into the ability of older adults to successfully negotiate obstacles. Furthermore, the present results suggest that when it comes to the physical properties of obstacles, not all is as expected, and low obstacles may impose a greater danger to tripping than obstacles that have a higher height., (© 2019 S. Karger AG, Basel.)

Objective: Cognition and mobility are interrelated. However, this association can be impacted by the specific facets of cognition and mobility that are measured, and further by the different task conditions, e.g., single- versus dual-task walking, under which these associations are evaluated. Systematically studying the multiple facets of cognitive-mobility associations under both the task conditions is critical because both cognition and mobility change with age and pose significant risks associated with falls, morbidity, and disability., Methods: Using a cross-sectional, prospective study design, data from 124 healthy adults [mean age (SD) = 61.51 (11.90); mean education (SD) = 15.94 (2.18)] were collected. A comprehensive battery of cognitive tests was administered, and gait was assessed using a small, lightweight, three-axis accelerometer with a gyroscope., Analytical Plan: Data were transformed, and only relatively strong relationships survived after strict statistical criteria adjusting for multiple comparisons were applied. Spearman rho correlation coefficients were used to examine the matrix of correlations between the cognitive-motor variables while adjusting for age and gender., Results: Executive functions, processing speed, and language were associated with distinct facets of variability, pace, and asymmetry, especially under the dual-task walking condition. Both turns and transitions were also associated with cognition during the Timed Up and Go Task., Conclusion: Our results extend converging evidence of the involvement of executive functions and processing speed in specific aspects of mobility, along with the role of language. The study has important implications for aging in terms of both assessment and rehabilitation of cognition and gait as well as for the emerging dual-tasking theories and the role of the neural pathways involved in mobility.

Introduction: Deficits in executive function and attention have been associated with freezing of gait (FOG) in patients with Parkinson's disease (PD). However, the exact changes in the ventral and dorsal attentional networks that may contribute to FOG are unknown. Our aim was to examine the changes in connectivity of the attentional networks in patients with PD and their role in FOG., Methods: Resting-state fMRI was obtained in 20 healthy controls (age: 69.7 ± 1.3yrs), 11 patients without FOG (age: 74.1 ± 1.2yrs), and 26 patients with FOG (age: 72.3 ± 1.3yrs). Graph theory analysis was used to examine differences in previously defined attention networks between groups., Results: We found differences between the groups in the dorsal attentional network (Global Efficiency: p = 0.007, Local Efficiency: p = 0.017, Between Centrality: p = 0.010). Global efficiency was lower in patients with FOG compared to healthy controls (p = 0.003) and patients without FOG (p = 0.025). Local efficiency was higher in patients with FOG compared to healthy controls (p = 0.014) but not compared to patients without FOG (p = 0.109). In contrast, no differences were found in the ventral attentional network between the groups (Global Efficiency: p = 0.258, Local Efficiency: p = 0.114, Between Centrality: p = 0.130)., Conclusions: Altered organization of the dorsal attention network in patients with FOG may explain the higher risk for FOG during complex walking situations. In contrast, the lack of changes in the ventral attention network may partially explain the effectiveness of external cues on gait in patients with PD. Our findings support the idea that attentional networks play an important role in FOG., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: To investigate EEG changes during an auditory odd-ball task while walking (dual-task) in young adults, older adults, and patients with Parkinson's disease., Methods: 11 young adults, 10 older adults, and 10 patients with Parkinson's disease (PD) performed an auditory oddball task during standing and walking on a treadmill, while wearing a wireless EEG cap. The amplitude and latency of P300 were compared between groups and within conditions using linear mix model analysis. Gait was evaluated using wearable sensors and cognition was assessed using the Color Trail Test., Results: P300 latency became longer during walking in all groups (p = 0.005). During walking, older adults (p = 0.005) and patients with PD (p = 0.001) showed prolonged P300 latency compared to young adults. Significant task by group interaction was found in P300 amplitude (p = 0.008). Patients with PD demonstrated reduced P300 amplitude during walking compared to standing (p = 0.023). Among all subjects, better motor and cognitive performance correlated with shorter P300 latency (r = 0.457, p = 0.014 and r = 0.431, p = 0.040, respectively)., Conclusions: These findings provide direct evidence of the physiological recruitment of attentional networks during walking and their impact by ageing and disease., Significance: This study is the first to report on changes in P300 latency and amplitude during dual-task oddball walking in older adults and patients with PD., (Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

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.

A substantial corpus of evidence suggests that the cognitive involvement in postural control and gait increases with aging. A large portion of such studies were based on dual-task experimental designs, which typically use the simultaneous performance of a motor task (e.g., static or dynamic balancing, walking) and a continuous cognitive task (e.g., mental arithmetic, tone detection). This focused review takes a cognitive neuroscience of aging perspective in interpreting cognitive motor dual-task findings. Specifically, we consider the importance of identifying the neural circuits that are engaged by the cognitive task in relation to those that are engaged during motor task performance. Following the principle of neural overlap, dual-task interference should be greatest when the cognitive and motor tasks engage the same neural circuits. Moreover, the literature on brain aging in general, and models of dedifferentiation and compensation, in particular, suggest that in cognitive motor dual-task performance, the cognitive task engages different neural substrates in young as compared to older adults. Also considered is the concept of multisensory aging, and the degree to which the age-related decline of other systems (e.g., vision, hearing) contribute to cognitive load. Finally, we discuss recent work on focused cognitive training, exercise and multimodal training of older adults and their effects on postural and gait outcomes. In keeping with the principle of neural overlap, the available cognitive training research suggests that targeting processes such as dividing attention and inhibition lead to improved balance and gait in older adults. However, more studies are needed that include functional neuroimaging during actual, upright performance of gait and balance tasks, in order to directly test the principle of neural overlap, and to better optimize the design of intervention studies to improve gait and posture.

Background: Among patients with Parkinson's disease (PD), gait is typically disturbed and less automatic. These gait changes are associated with impaired rhythmicity and increased prefrontal activation, presumably in an attempt to compensate for reduced automaticity., Research Question: We investigated whether during treadmill walking, when the pace is determined and fixed, prefrontal activation in patients with PD is lower, as compared to over-ground walking., Methods: Twenty patients with PD (age: 69.8 ± 6.5 yrs.; MoCA: 26.9 ± 2.4; disease duration: 7.9 ± 4.2 yrs) walked at a self-selected walking speed over-ground and on a treadmill. A wireless functional near infrared spectroscopy (fNIRS) system measured prefrontal lobe activation, i.e., oxygenated hemoglobin (Hb02) in the pre-frontal area. Gait was evaluated using 3D-accelerometers attached to the lower back and ankles (Opal™, APDM). Dynamic gait stability was assessed using the maximum Lyapunov exponent to investigate automaticity of the walking pattern., Results: Hb02 was lower during treadmill walking than during over-ground walking (p = 0.001). Gait stability was greater on the treadmill, compared to over-ground walking, in both the anteroposterior and medio-lateral axes (p < 0.001)., Significance: These findings support the notion that when gait is externally paced, prefrontal lobe activation is reduced in patients with PD, perhaps reflecting a reduced need for compensatory cognitive mechanisms., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Obstacle negotiation is a daily activity that requires the integration of sensorimotor and cognitive information. Recent studies provide evidence for the important role of prefrontal cortex during obstacle negotiation. We aimed to explore the effects of obstacle height and available response time on prefrontal activation., Methods: Twenty healthy young adults (age: 30.1 ± 1.0 years; 50% women) walked in an obstacle course while negotiating anticipated and unanticipated obstacles at heights of 50 mm and 100 mm. Prefrontal activation was measured using a functional near-infrared spectroscopy system. Kinect cameras measured the obstacle negotiation strategy. Prefrontal activation was defined based on mean level of HbO 2 before, during and after obstacle negotiation and the HbO 2 slope from gait initiation and throughout the task. Changes between types of obstacles were assessed using linear-mix models and partial correlation analyses evaluated the relationship between prefrontal activation and the distance between the feet as the subjects traversed the obstacles., Results: Different obstacle heights showed similar changes in prefrontal activation measures (p > 0.210). However, during unanticipated obstacles, the slope of the HbO 2 response was steeper (p = 0.048), as compared to anticipated obstacles. These changes in prefrontal activation during negotiation of unanticipated obstacles were correlated with greater distance of the leading foot after the obstacles (r = 0.831, p = 0.041)., Conclusions: These findings are the first to show that the pattern of prefrontal activation depends on the nature of the obstacle. More specifically, during unanticipated obstacles the recruitment of the prefrontal cortex is faster and greater than during negotiating anticipated obstacles. These results provide evidence of the important role of the prefrontal cortex and the ability of healthy young adults to tailor the activation pattern to different types of obstacles., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: In a randomized control trial conducted in patients with Parkinson's disease, a treadmill training program combined with virtual reality that targeted motor and cognitive aspects of safe ambulation led to fewer falls, compared with treadmill training alone., Objective: To investigate if the 2 types of training differentially affected prefrontal activation and if this might explain differences in fall rates after the intervention., Methods: Sixty-four patients with Parkinson's disease were randomized into the treadmill training arm (n = 34, mean age 73.1 ± 1.1 years, 64% men, disease duration 9.7 ± 1.0 years) or treadmill training with virtual reality arm (n = 30, mean age 70.1 ± 1.3 years, 71% men, disease duration 8.9 ± 1.1 years). Prefrontal activation during usual, dual-task, and obstacle negotiation walking was assessed before and after 6 weeks of training, using a functional near-infrared spectroscopy system., Results: Treadmill training with and without virtual reality reduced prefrontal activation during walking ( P < .001), with specific interactions related to training arm ( P = .01), lateralization ( P = .05), and walking condition ( P = .001). For example, among the subjects who trained with treadmill training alone, prefrontal activation during dual-task walking and obstacle negotiation increased after training, while in the combined training arm, activation decreased., Conclusions: Prefrontal activation during usual and during more challenging walking conditions can be altered in response to 2 different types of training. The addition of a cognitive training component to a treadmill exercise program apparently modifies the effects of the training on the magnitude and lateralization of prefrontal activation and on falls, extending the understanding of the plasticity of the brain in PD.

Gait is one of the keys to functional independence. For a long-time, walking was considered an automatic process involving minimal higher-level cognitive input. Indeed, walking does not take place without muscles that move the limbs and the "lower-level" control that regulates the timely activation of the muscles. However, a growing body of literature suggests that walking can be viewed as a cognitive process that requires "higher-level" cognitive control, especially during challenging walking conditions that require executive function and attention. Two main locomotor pathways have been identified involving multiple brain areas for the control of posture and gait: the dorsal pathway of cognitive locomotor control and the ventral pathway for emotional locomotor control. These pathways may be distinctly affected in different pathologies that have important implications for rehabilitation and therapy. The clinical assessment of gait should be a focused, simple, and cost-effective process that provides both quantifiable and qualitative information on performance. In the last two decades, gait analysis has gradually shifted from analysis of a few steps in a restricted space to long-term monitoring of gait using body fixed sensors, capturing real-life and routine behavior in the home and community environment. The chapter also describes this evolution and its implications., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: To compare the effects of 2 forms of exercise, i.e., a 6-week trial of treadmill training with virtual reality (TT + VR) that targets motor and cognitive aspects of safe ambulation and a 6-week trial of treadmill training alone (TT), on brain activation in patients with Parkinson disease (PD)., Methods: As part of a randomized controlled trial, patients were randomly assigned to 6 weeks of TT (n = 17, mean age 71.5 ± 1.5 years, disease duration 11.6 ± 1.6 years; 70% men) or TT + VR (n = 17, mean age 71.2 ± 1.7 years, disease duration 7.9 ± 1.4 years; 65% men). A previously validated fMRI imagery paradigm assessed changes in neural activation pretraining and post-training. Participants imagined themselves walking in 2 virtual scenes projected in the fMRI: (1) a clear path and (2) a path with virtual obstacles. Whole brain and region of interest analyses were performed., Results: Brain activation patterns were similar between training arms before the interventions. After training, participants in the TT + VR arm had lower activation than the TT arm in Brodmann area 10 and the inferior frontal gyrus (cluster level familywise error-corrected [FWEcorr] p < 0.012), while the TT arm had lower activation than TT + VR in the cerebellum and middle temporal gyrus (cluster level FWEcorr p < 0.001). Changes in fall frequency and brain activation were correlated in the TT + VR arm., Conclusions: Exercise modifies brain activation patterns in patients with PD in a mode-specific manner. Motor-cognitive training decreased the reliance on frontal regions, which apparently resulted in improved function, perhaps reflecting increased brain efficiency., (© 2017 American Academy of Neurology.)

Turning has been implicated as a complex task that requires both motor and cognitive resources. Accumulating evidence shows that patients with Parkinson's disease (PD) require more steps and more time to complete a turn, however, the role of the prefrontal cortex during turning is not clear. Forty nine patients with PD without freezing of gait (mean age 71.7 ± 1.0 years; 67% men, disease duration 9.7 ± 1.3 years) performed motor and cognitive tests. Prefrontal activation, specifically in Brodmann area 10 (BA10), during turning and usual walking was measured using functional near infrared spectroscopy (fNIRS). The patients with PD were further divided into two subgroups with high and low functional status based on limitations in community ambulation. General Linear Model analysis adjusted for age, gender, disease duration and turn duration was used to assess differences between tasks and subgroups of patients with PD. In addition, Pearson's correlation was performed to assess association between BA10 activation and motor and cognitive scores. Activation in BA10 increased during walking (p < 0.001), while it decreased during turning (p = 0.006). A comparison between the two subgroups of patients with PD revealed that patients with relatively better ambulation decreased prefrontal activation during turning, as compared to patients with relatively worse ambulation (p < 0.001). These findings are the first to show that BA10 plays a different role during turning and walking and that ambulation status may alter BA10 activation during turning. Higher prefrontal activation during turning in the subgroup of patients with relatively worse ambulation may reflect a compensatory attempt at improving performance.

Background: Deficits in cognitive domains, in particular, those related to the prefrontal cortex, contribute to diminished walking performance in complex conditions in older age. Studies using functional near infra-red spectroscopy (fNIRS) reported inconsistent findings of brain activation age-related changes in response to increased task demands. We aimed to study the effects of aging on gait and prefrontal activation in complex walking tasks with internal and external task demands., Methods: Twenty-three healthy young adults (30.9±3.7yrs) and 20 healthy older adults (69.7±5.8yrs) participated in this study. Gait and prefrontal activation were assessed during three walking conditions: (1) usual walking, (2) dual tasking (internal task demands) and, (3) obstacle negotiation (external task demands). fNIRS measured changes in oxygenated hemoglobin concentrations in the prefrontal cortex., Results: Several gait measures were worse in older compared to younger adults under all walking conditions (p<0.005). Even at the lowest level of challenge, older adults had significant increases in HbO2 levels during usual walking, relative to standing (p=0.006). Both groups showed increased activation during dual-task (p<0.002) and during obstacle negotiation (p<0.003)., Conclusions: Prefrontal activation during walking is dependent on age and task properties and that older adults apparently rely more on cognitive resources even during usual walking task., (Copyright © 2017 Elsevier Inc. All rights reserved.)

See Bell et al. (doi:10.1093/awx063) for a scientific commentary on this article. Impaired dual tasking, namely the inability to concurrently perform a cognitive and a motor task (e.g. 'stops walking while talking'), is a largely unexplained and frequent symptom of Parkinson's disease. Here we consider two circuit-level accounts of how striatal dopamine depletion might lead to impaired dual tasking in patients with Parkinson's disease. First, the loss of segregation between striatal territories induced by dopamine depletion may lead to dysfunctional overlaps between the motor and cognitive processes usually implemented in parallel cortico-striatal circuits. Second, the known dorso-posterior to ventro-anterior gradient of dopamine depletion in patients with Parkinson's disease may cause a funnelling of motor and cognitive processes into the relatively spared ventro-anterior putamen, causing a neural bottleneck. Using functional magnetic resonance imaging, we measured brain activity in 19 patients with Parkinson's disease and 26 control subjects during performance of a motor task (auditory-cued ankle movements), a cognitive task (implementing a switch-stay rule), and both tasks simultaneously (dual task). The distribution of task-related activity respected the known segregation between motor and cognitive territories of the putamen in both groups, with motor-related responses in the dorso-posterior putamen and task switch-related responses in the ventro-anterior putamen. During dual task performance, patients made more motor and cognitive errors than control subjects. They recruited a striatal territory (ventro-posterior putamen) not engaged during either the cognitive or the motor task, nor used by controls. Relatively higher ventro-posterior putamen activity in controls was associated with worse dual task performance. These observations suggest that dual task impairments in Parkinson's disease are related to reduced spatial focusing of striatal activity. This pattern of striatal activity may be explained by a loss of functional segregation between neighbouring striatal territories that occurs specifically in a dual task context., (© The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Gait is influenced by higher order cognitive and cortical control mechanisms. Functional near infrared spectroscopy (fNIRS) has been used to examine frontal activation during walking in healthy older adults, reporting increased oxygenated hemoglobin (HbO2) levels during dual task walking (DT), compared with usual walking., Objective: To investigate the role of the frontal lobe during DT and obstacle negotiation, in healthy older adults and patients with Parkinson's disease (PD)., Methods: Thirty-eight healthy older adults (mean age 70.4 ± 0.9 years) and 68 patients with PD (mean age 71.7 ± 1.1 years,) performed 3 walking tasks: (a) usual walking, (b) DT walking, and (c) obstacles negotiation, with fNIRS and accelerometers. Linear-mix models were used to detect changes between groups and within tasks., Results: Patients with PD had higher activation during usual walking (P < .030). During DT, HbO2 increased only in healthy older adults (P < .001). During obstacle negotiation, HbO2 increased in patients with PD (P = .001) and tended to increase in healthy older adults (P = .053). Higher DT and obstacle cost (P < .003) and worse cognitive performance were observed in patients with PD (P = .001)., Conclusions: A different pattern of frontal activation during walking was observed between groups. The higher activation during usual walking in patients with PD suggests that the prefrontal cortex plays an important role already during simple walking. However, higher activation relative to baseline during obstacle negotiation and not during DT in the patients with PD demonstrates that prefrontal activation depends on the nature of the task. These findings may have important implications for rehabilitation of gait in patients with PD., (© The Author(s) 2016.)

Background: Many patients with Parkinson's disease (PD) have difficulties in performing a second task during walking (i.e., dual task walking). Functional near-infrared spectroscopy (fNIRS) is a promising approach to study the presumed contribution of dysfunction within the prefrontal cortex (PFC) to such difficulties. In this pilot study, we examined the feasibility of using a new portable and wireless fNIRS device to measure PFC activity during different dual task walking protocols in PD. Specifically, we tested whether PD patients were able to perform the protocol and whether we were able to measure the typical fNIRS signal of neuronal activity., Methods: We included 14 PD patients (age 71.2 ± 5.4 years, Hoehn and Yahr stage II/III). The protocol consisted of five repetitions of three conditions: walking while (i) counting forwards, (ii) serially subtracting, and (iii) reciting digit spans. Ability to complete this protocol, perceived exertion, burden of the fNIRS devices, and concentrations of oxygenated (O 2 Hb) and deoxygenated (HHb) hemoglobin from the left and right PFC were measured., Results: Two participants were unable to complete the protocol due to fatigue and mobility safety concerns. The remaining 12 participants experienced no burden from the two fNIRS devices and completed the protocol with ease. Bilateral PFC O 2 Hb concentrations increased during walking while serially subtracting (left PFC 0.46 μmol/L, 95 % confidence interval (CI) 0.12-0.81, right PFC 0.49 μmol/L, 95 % CI 0.14-0.84) and reciting digit spans (left PFC 0.36 μmol/L, 95 % CI 0.03-0.70, right PFC 0.44 μmol/L, 95 % CI 0.09-0.78) when compared to rest. HHb concentrations did not differ between the walking tasks and rest., Conclusions: These findings suggest that a new wireless fNIRS device is a feasible measure of PFC activity in PD during dual task walking. Future studies should reduce the level of noise and inter-individual variability to enable measuring differences in PFC activity between different dual walking conditions and across health states.

Background: Age-associated motor and cognitive deficits increase the risk of falls, a major cause of morbidity and mortality. Because of the significant ramifications of falls, many interventions have been proposed, but few have aimed to prevent falls via an integrated approach targeting both motor and cognitive function. We aimed to test the hypothesis that an intervention combining treadmill training with non-immersive virtual reality (VR) to target both cognitive aspects of safe ambulation and mobility would lead to fewer falls than would treadmill training alone., Methods: We carried out this randomised controlled trial at five clinical centres across five countries (Belgium, Israel, Italy, the Netherlands, and the UK). Adults aged 60-90 years with a high risk of falls based on a history of two or more falls in the 6 months before the study and with varied motor and cognitive deficits were randomly assigned by use of computer-based allocation to receive 6 weeks of either treadmill training plus VR or treadmill training alone. Randomisation was stratified by subgroups of patients (those with a history of idiopathic falls, those with mild cognitive impairment, and those with Parkinson's disease) and sex, with stratification per clinical site. Group allocation was done by a third party not involved in onsite study procedures. Both groups aimed to train three times per week for 6 weeks, with each session lasting about 45 min and structured training progression individualised to the participant's level of performance. The VR system consisted of a motion-capture camera and a computer-generated simulation projected on to a large screen, which was specifically designed to reduce fall risk in older adults by including real-life challenges such as obstacles, multiple pathways, and distracters that required continual adjustment of steps. The primary outcome was the incident rate of falls during the 6 months after the end of training, which was assessed in a modified intention-to-treat population. Safety was assessed in all patients who were assigned a treatment. This study is registered with ClinicalTrials.gov, NCT01732653., Findings: Between Jan 6, 2013, and April 3, 2015, 302 adults were randomly assigned to either the treadmill training plus VR group (n=154) or treadmill training alone group (n=148). Data from 282 (93%) participants were included in the prespecified, modified intention-to-treat analysis. Before training, the incident rate of falls was similar in both groups (10·7 [SD 35·6] falls per 6 months for treadmill training alone vs 11·9 [39·5] falls per 6 months for treadmill training plus VR). In the 6 months after training, the incident rate was significantly lower in the treadmill training plus VR group than it had been before training (6·00 [95% CI 4·36-8·25] falls per 6 months; p<0·0001 vs before training), whereas the incident rate did not decrease significantly in the treadmill training alone group (8·27 [5·55-12·31] falls per 6 months; p=0·49). 6 months after the end of training, the incident rate of falls was also significantly lower in the treadmill training plus VR group than in the treadmill training group (incident rate ratio 0·58, 95% CI 0·36-0·96; p=0·033). No serious training-related adverse events occurred., Interpretation: In a diverse group of older adults at high risk for falls, treadmill training plus VR led to reduced fall rates compared with treadmill training alone., Funding: European Commission., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Patients with Parkinson's disease (PD) have difficulties in executive functions including conflict monitoring. The neural mechanisms underlying these difficulties are not yet fully understood. In order to examine the neural mechanisms related to conflict monitoring in PD, we evaluated 35 patients with PD and 20 healthy older adults while they performed a word-color Stroop paradigm in the MRI. Specifically, we focused on changes between the groups in task-related functional connectivity using psycho-physiological interaction (PPI) analysis. The anterior cingulate cortex (ACC), which is a brain node previously associated with the Stroop paradigm, was selected as the seed region for this analysis. Patients with PD, as compared to healthy controls, had reduced task-related functional connectivity between the ACC and parietal regions including the precuneus and inferior parietal lobe. This was seen only in the incongruent Stroop condition. A higher level of connectivity between the ACC and precuneus was correlated with a lower error rate in the conflicting, incongruent Stroop condition in the healthy controls, but not in the patients with PD. Furthermore, the patients also had reduced functional connectivity between the ACC and the superior frontal gyrus which was present in both the incongruent and congruent task condition. The present findings shed light on brain mechanisms that are apparently associated with specific cognitive difficulties in patients with PD. Among patients with PD, impaired conflict monitoring processing within the ACC-based fronto-parietal network may contribute to difficulties under increased executive demands., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Recent studies have suggested that deficits in executive function contribute to freezing of gait (FOG), an episodic disturbance common among patients with Parkinson's disease (PD). To date, most findings provide only indirect evidence of this relationship. Here, we evaluated a more direct link between FOG and frontal lobe dysfunction. Functional, near infrared spectroscopy measured frontal activation, i.e., oxygenated hemoglobin (HbO2) levels in Brodmann area 10 before and during FOG. Eleven patients with PD and eleven healthy older adults were studied. Changes in frontal lobe activation before and during FOG that occurred during turns were determined. Altogether, 49 FOG episodes were observed-28 occurred during turns that were anticipated (i.e., the patient knew in advance that the turn was coming), 21 during unanticipated turns that were performed "abruptly", according to the examiner's request. During anticipated turns, HbO2 increased by 0.22 ± 0.08 µM (p = 0.004) before FOG and by an additional 0.19 ± 0.13 µM (p = 0.072) during FOG. In contrast, during unanticipated turns, HbO2 did not increase before or during FOG. HbO2 decreased by 0.32 ± 0.08 µM (p = 0.004) during turns without FOG; in healthy controls HbO2 did not change during turns. These findings support the existence of an association between FOG episodes and changes in frontal lobe HbO2. Increased activation in Brodmann area 10 before FOG, specifically during anticipated turns, highlights the connections between motor planning, information processing, and FOG. These results support the idea that alterations in executive control play a role in this debilitating motor disturbance.

Background: Current literature views safe gait as a complex task, relying on motor and cognitive resources. The use of virtual reality (VR) in gait training offers a multifactorial approach, showing positive effects on mobility, balance, and fall risk in elderly people and individuals with neurological disorders. This form of training has been described as a viable research tool; however, it has not been applied routinely in clinical practice. Recently, VR was used to develop an adjunct training method for use by physical therapists in an ambulatory clinical setting., Objective: The aim of this article is to describe the initial clinical experience of applying a 5-week VR clinical service to improve gait and mobility in people with a history of falls, poor mobility, or postural instability., Design: A retrospective data analysis was conducted., Methods: The clinical records of the first 60 patients who completed the VR gait training program were examined. Training was provided 3 times per week for 5 weeks, with each session lasting approximately 1 hour and consisting of walking on a treadmill while negotiating virtual obstacles. Main outcome measures were compared across time and included the Timed "Up & Go" Test (TUG), the Two-Minute Walk Test (2MWT), and the Four Square Step Test (FSST)., Results: After 5 weeks of training, time to complete the TUG decreased by 10.3%, the distance walked during the 2MWT increased by 9.5%, and performance on the FSST improved by 13%., Limitations: Limitations of the study include the use of a retrospective analysis with no control group and the lack of objective cognitive assessment., Conclusions: Treadmill training with VR appears to be an effective and practical tool that can be applied in an outpatient physical therapy clinic. This training apparently leads to improvements in gait, mobility, and postural control. It, perhaps, also may augment cognitive and functional aspects., (© 2014 American Physical Therapy Association.)

Background: Accumulating evidence suggests that gait is influenced by higher order cognitive and cortical control mechanisms. Recently, several studies used functional near infrared spectroscopy (fNIRS) to examine brain activity during walking, demonstrating increased oxygenated hemoglobin (HbO2) levels in the frontal cortex during walking while subjects completed a verbal cognitive task. It is, however, still unclear whether this increase in activation was related to verbalization, if the response was specific to gait, or if it would also be observed during standing, a different motor control task. The aim of this study was to investigate whether an increase in frontal activation is specific to dual tasking during walking., Methods: Twenty-three healthy young adults (mean 30.9 ± 3.7 yrs, 13 females) were assessed using an electronic walkway. Frontal brain activation was assessed using an fNIRS system consisting of two probes placed on the forehead of the subjects. Assessments included: walking in a self-selected speed; walking while counting forward; walking while serially subtracting 7s (Walking+S7); and standing while serially subtracting 7s (Standing+S7). Data was collected from 5 walks of 30 meters in each condition. Twenty seconds of quiet standing before each walk served as baseline frontal lobe activity. Repeated Measures Analysis of Variance (RM ANOVA) tested for differences between the conditions., Results: Significant differences were observed in HbO2 levels between all conditions (p = 0.007). HbO2 levels appeared to be graded; walking alone demonstrated the lowest levels of HbO2 followed by walking+counting condition (p = 0.03) followed by Walking+S7 condition significantly increased compared to the two other walking conditions (p < 0.01). No significant differences in HbO2 levels were observed between usual walking and the standing condition (p = 0.38) or between standing with or without serial subtraction (p = 0.76)., Conclusions: This study provides direct evidence that dual tasking during walking is associated with frontal brain activation in healthy young adults. The observed changes are apparently not a response to the verbalization of words and are related to the cognitive load during gait.

Motor imagery (MI) and virtual reality (VR) are two evolving therapeutic approaches that make use of cognitive function to study and enhance movement, in particular, balance and mobility of people with Parkinson's disease (PD). This review examines the literature on the use of VR and MI in the assessment of mobility and as a therapeutic intervention to improve balance and gait in patients with PD. A study was eligible for inclusion if MI or VR were used to assess motor or cognitive function to improve gait, balance, or mobility in patients with PD. Data were extracted on the following categories: participants; study design; intervention (type, duration, and frequency); and outcomes. Intervention studies were evaluated for quality using the Physiotherapy Evidence Database scale. Sixteen studies were identified; 4 articles used MI and 12 used VR for assessment and treatment of gait impairments in PD. The studies included small samples and were diverse in terms of methodology. Quality of the intervention trials varied from fair for VR to good for MI. The benefits of using MI and VR for assessment and treatment were noted. Encouraging findings on the potential benefits of using MI and VR in PD were found, although further good-quality research is still needed. Questions remain on the optimal use, content of interventions, and generalizability of findings across the different stages of the disease. The possible mechanisms underlying MI and VR and recommendations for future research and therapy are also presented., (© 2013 Movement Disorder Society.)

Background and Purpose: This case report describes the clinical reasoning process used to examine a person after stroke and intervene with a novel integrated motor imagery treatment designed for the rehabilitation of walking and delivered in the home through telerehabilitation. The integrated motor imagery treatment consisted of patient-centered goal setting and physical practice combined with motor and motivational imagery., Case Description: The patient was a 38-year-old woman who had had a diffuse left subarachnoid hemorrhagic stroke 10 years earlier. She lived independently in an assisted living complex and carried a straight cane during long walks or in unfamiliar environments. Examination revealed a slow gait speed, reduced walking endurance, and decreased balance confidence. Although she was in the chronic phase, patient-centered integrated motor imagery was predicted to improve her community mobility. Treatment sessions of 45 to 60 minutes were held 3 times per week for 4 weeks. The practiced tasks included transitioning from sitting to standing, obstacle clearance, and navigation in interior and exterior environments; these tasks were first executed and then imagined at ratios of 1:5. Task execution allowed the creation of a scene based on movement observation. Imagery scenarios were customized to address the patient's goals and observed movement problems. Motivational elements of arousal, problem solving, and reward were embedded in the imagery scenarios. Half of the sessions were provided on site, and the remaining sessions were delivered remotely. Seven sessions were delivered by the clinician in the home, and 5 sessions were delivered using telerehabilitation., Outcomes: Improvements in motor imagery ability, gait parameters, and balance were observed after training. Most gains were retained at the 3-month follow-up. Compared with on-site delivery, the telerehabilitation sessions resulted in less therapist travel time and cost, as well as shorter therapy sessions., Discussion: The delivery of integrated motor imagery practice for walking recovery was feasible both on site and remotely.

Background: Gait and cognitive disturbances are common in Parkinson's disease (PD). These deficits exacerbate fall risk and difficulties with mobility, especially during complex or dual-task walking. Traditional gait training generally fails to fully address these complex gait activities. Virtual reality (VR) incorporates principles of motor learning while delivering engaging and challenging training in complex environments. We hypothesized that VR may be applied to address the multifaceted deficits associated with fall risk in PD., Methods: Twenty patients received 18 sessions (3 per week) of progressive intensive treadmill training with virtual obstacles (TT + VR). Outcome measures included gait under usual-walking and dual-task conditions and while negotiating physical obstacles. Cognitive function and functional performance were also assessed., Results: Patients were 67.1 ± 6.5 years and had a mean disease duration of 9.8 ± 5.6 years. Posttraining, gait speed significantly improved during usual walking, during dual task, and while negotiating overground obstacles. Dual-task gait variability decreased (ie, improved) and Trail Making Test times (parts A and B) improved. Gains in functional performance measures and retention effects, 1 month later, were also observed., Conclusions: To our knowledge, this is the first time that TT + VR has been used for gait training in PD. The results indicate that TT + VR is viable in PD and may significantly improve physical performance, gait during complex challenging conditions, and even certain aspects of cognitive function. These findings have important implications for understanding motor learning in the presence of PD and for treating fall risk in PD, aging, and others who share a heightened risk of falls.

Freezing of gait (FOG) is one of the most disabling symptoms that affect patients with Parkinson's disease (PD). Although the pathophysiology underlying FOG largely remains an enigma, several lines of evidence suggest that the autonomic nervous system might be involved. To this end, we tested the hypothesis that heart rate (HR) increases during FOG and, further, that HR increases just before FOG. To evaluate these hypotheses, 15 healthy older adults, 10 patients with PD who experienced FOG, and 10 patients who did not were studied. Patients with PD were tested during their "off" medication state. HR and HR variability were measured as subjects carried out tasks that frequently provoke FOG; 120 FOG episodes were evaluated. During FOG, HR increased (P = 0.001) by an average of 1.8 bpm, compared with HR measured before the beginning of FOG. HR also increased just before FOG, by 1 bpm (P < 0.0001). In contrast, during sudden stops and 180° turns, HR decreased by almost 2 bpm (P < 0.0001). HR variability was not associated with FOG. To our knowledge, these findings are the first to document the association of FOG to autonomic system activation, as manifested by HR dynamics. One explanation is that the changes in HR before and during FOG may be a sympathetic response that, secondary to limbic activation, contributes to the development of freezing. Although further studies are needed to evaluate these associations, the current results provide experimental evidence linking impaired motor blockades to autonomic nervous system function among patients with PD.

Introduction: The Timed Up and Go (TUG) test is a widely used measure of mobility and fall risk in older adults and in Parkinson's disease (PD). We tested the hypothesis that body-fixed accelerometers can provide insight into TUG performance in PD patients., Methods: We examined 17 patients with PD (Hoehn and Yahr score: 2.7+/-0.7; ON state) and 15 age-matched healthy controls; mean ages were 66.8+/-5.9 years, 67.6+/-9.6 years, respectively. Subjects wore a 3D-accelerometer (ADXL330, Analog Devices) on the lower back while performing the TUG test. Sit-to-Stand and Stand-to-Sit times were extracted from the anterior-posterior (AP) signal. Parameters included Sit-to-Stand, Stand-to-Sit durations, amplitude range (Range) and slopes (Jerk). Acceleration median and standard deviation (SD) were also calculated., Results: Stopwatch-based TUG duration tended to be higher for the PD patients compared to the control group, although not significantly (p=0.08). In contrast, the TUG duration that was extracted from the acceleration signal was significantly (p<0.02) higher in the PD group compared to the control group. Many acceleration-parameters were also significantly different (p<0.05) between groups; most were not correlated with TUG duration., Conclusions: Accelerometer-derived parameters are sensitive to group differences, indicating that PD patients have poorer mobility during specific aspects of the TUG. In addition to test duration, these measures may serve as complementary and objective bio-markers of PD to augment the evaluation of disease progression and the response to therapeutic interventions., ((c) 2009 IPEM. Published by Elsevier Ltd. All rights reserved.)