Prefrontal cortex activation during obstacle negotiation: What's the effect size and timing?

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 ±â€¯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 HbO2 before, during and after obstacle negotiation and the HbO2 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 HbO2 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.

When is Higher Level Cognitive Control Needed for Locomotor Tasks Among Patients with Parkinson's Disease?

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.

Effects of aging on prefrontal brain activation during challenging walking conditions.

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.

Arm swing as a potential new prodromal marker of Parkinson's disease.

BACKGROUND: Reduced arm swing is a well-known clinical feature of Parkinson's disease (PD), often observed early in the course of the disease. We hypothesized that subtle changes in arm swing and axial rotation may also be detectable in the prodromal phase. OBJECTIVE: The purpose of this study was to evaluate the relationship between the LRRK2-G2019S mutation, arm swing, and axial rotation in healthy nonmanifesting carriers and noncarriers of the G2019S mutation and in patients with PD. METHODS: A total of 380 participants (186 healthy nonmanifesting controls and 194 PD patients) from 6 clinical sites underwent gait analysis while wearing synchronized 3-axis body-fixed sensors on the lower back and bilateral wrists. Participants walked for 1 minute under the following 2 conditions: (1) usual walking and (2) dual-task walking. Arm swing amplitudes, asymmetry, variability, and smoothness were calculated for both arms along with measures of axial rotation. RESULTS: A total of 122 nonmanifesting participants and 67 PD patients were carriers of the G2019S mutation. Nonmanifesting mutation carriers walked with greater arm swing asymmetry and variability and lower axial rotation smoothness under the dual task condition when compared with noncarriers (P < .04). In the nonmanifesting mutation carriers, arm swing asymmetry was associated with gait variability under dual task (P = .003). PD carriers showed greater asymmetry and variability of movement than PD noncarriers, even after controlling for disease severity (P < .009). CONCLUSIONS: The G2019S mutation is associated with increased asymmetry and variability among nonmanifesting participants and patients with PD. Prospective studies should determine if arm swing asymmetry and axial rotation smoothness may be used as motor markers of prodromal PD. © 2016 International Parkinson and Movement Disorder Society.

Increased frontal brain activation during walking while dual tasking: an fNIRS study in healthy young adults.

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.

Transcranial Direct Current Stimulation May Reduce Prefrontal Recruitment During Dual Task Walking in Functionally Limited Older Adults - A Pilot Study.

Introduction: Transcranial direct current stimulation (tDCS) targeting the left dorsolateral prefrontal cortex (dlPFC) improves dual task walking in older adults, when tested just after stimulation. The acute effects of tDCS on the cortical physiology of walking, however, remains unknown. Methods: In a previous study, older adults with slow gait and executive dysfunction completed a dual task walking assessment before and after 20 min of tDCS targeting the left dlPFC or sham stimulation. In a subset of seven participants per group, functional near-infrared spectroscopy (fNIRS) was used to quantify left and right prefrontal recruitment defined as the oxygenated hemoglobin response to usual and dual task walking (ΔHbO2), as well as the absolute change in this metric from usual to dual task conditions (i.e., ΔHbO2 cost ). Paired t-tests examined pre- to post-stimulation differences in each fNIRS metric within each group. Results: The tDCS group exhibited pre- to post-stimulation reduction in left prefrontal ΔHbO2 cost (p = 0.03). This mitigation of dual task "cost" to prefrontal recruitment was induced primarily by a reduction in left prefrontal ΔHbO2 specifically within the dual task condition (p = 0.001), an effect that was observed in all seven participants within this group. Sham stimulation did not influence ΔHbO2 cost or ΔHbO2 in either walking condition (p > 0.35), and neither tDCS nor sham substantially influenced right prefrontal recruitment (p > 0.16). Discussion: This preliminary fNIRS data suggests that tDCS over the left dlPFC may modulate prefrontal recruitment, as reflected by a relative reduction in the oxygen consumption of this brain region in response to dual task walking.

Dopaminergic therapy and prefrontal activation during walking in individuals with Parkinson's disease: does the levodopa overdose hypothesis extend to gait?

The "levodopa-overdose hypothesis" posits that dopaminergic replacement therapy (1) increases performance on tasks that depend on the nigrostriatal-pathway (e.g., motor-control circuits), yet (2) decreases performance on tasks that depend upon the mesocorticolimbic-pathway (e.g., prefrontal cortex, PFC). Previous work in Parkinson's disease (PD) investigated this model while focusing on cognitive function. Here, we evaluated whether this model applies to gait in patients with PD and freezing of gait (FOG). Forty participants were examined in both the OFF anti-Parkinsonian medication state (hypo-dopaminergic) and ON state (hyper-dopaminergic) while walking with and without the concurrent performance of a serial subtraction task. Wireless functional near-infrared spectroscopy measured PFC activation during walking. Consistent with the "overdose-hypothesis", performance on the subtraction task decreased (p = 0.027) after dopamine intake. Moreover, the effect of walking condition on PFC activation depended on the dopaminergic state (i.e., interaction effect p = 0.001). Gait significantly improved after levodopa administration (p < 0.001). Nonetheless, PFC activation was higher (p = 0.013) in this state than in the OFF state during usual-walking. This increase in PFC activation in the ON state suggests that dopamine treatment interfered with PFC functioning. Otherwise, PFC activation, putatively a reflection of cognitive compensation, should have decreased. Moreover, in contrast to the OFF state, in the ON state, PFC activation failed to increase (p = 0.313) during dual-tasking, perhaps due to a "ceiling effect". These findings extend the "levodopa-overdose hypothesis" and suggest that it also applies to gait in PD patients. While dopaminergic therapy improves certain aspects of motor performance, optimal treatment should consider the "double-edged sword" of levodopa.

The effects of dual tasking on gait synchronization during over-ground side-by-side walking.

Recent studies have shown that gait synchronization during natural walking is not merely anecdotal, but it is a repeatable phenomenon that is quantifiable and is apparently related to available sensory feedback modalities. However, the mechanisms underlying this phase-locking of gait have only recently begun to be investigated. For example, it is not known what role, if any, attention plays. We employed a dual tasking paradigm in order to investigate the role attention plays in gait synchronization. Sixteen pairs of subjects walked under six conditions that manipulated the available sensory feedback and the degree of difficulty of the dual task, i.e., the attention. Movement was quantified using a trunk-mounted tri-axial accelerometer. A gait synchronization index (GSI) was calculated in order to quantify the degree of synchronization of the gait pattern. A simple dual task resulted in an increased level of synchronization, whereas a more complex dual task lead to a reduction in synchronization. Handholding increased synchronization, compared to the same attention condition without handholding. These results indicate that in order for two walkers to synchronize, some level of attention is apparently required, such that a relatively complex dual task utilizes enough attentional resources to reduce the occurrence of synchronization.

Evidence for Differential Effects of 2 Forms of Exercise on Prefrontal Plasticity During Walking in Parkinson's Disease.

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.

Treadmill walking reduces pre-frontal activation in patients with Parkinson's disease.

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 ±â€¯6.5 yrs.; MoCA: 26.9 ±â€¯2.4; disease duration: 7.9 ±â€¯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.

Objective characterization of daily living transitions in patients with Parkinson's disease using a single body-fixed sensor.

Body-fixed sensors (BFS), e.g., accelerometers worn for several days, can be used to augment the traditional clinical assessment. Long-term recordings obtained with BFS have been applied to study tremor, postural control, freezing of gait, turning abilities, motor response fluctuations and fall risk among older adults and patients with Parkinson's disease (PD). We aimed to test whether BFS-derived measures of transitions differ between patients with PD and healthy controls, and to evaluate whether there are differences among patients with mild PD, compared to more severe patients, and to controls. We also explored the added value of the metrics extracted from the sensor as compared to traditional testing in the lab. Ninety-nine patients with PD and 38 healthy older adults (HOA) participated in this study and wore a body-fixed sensor for 3 days. Walk-to-sit (n = 3286) and Sit-to-walk (n = 2858) transitions were analyzed and a machine learning algorithm was applied to distinguish between the groups. Significant differences in transitions were observed between PD patients and HOA, between mild and severe PD, and between mild PD and HOA, both in temporal and distribution features. The machine learning algorithm discriminated patients from HOA (accuracy = 92.3 %), mild from severe patients (accuracy = 89.8 %), and mild patients from HOA (accuracy = 85.9 %). These initial results suggest that body-fixed sensor-derived metrics of everyday transitions can characterize disease severity and differentiate mild PD patients from healthy older adults. Perhaps this approach can help with the integration of BFS into clinical care and the tracking of disease progression and the response to therapy.

The Role of the Frontal Lobe in Complex Walking Among Patients With Parkinson's Disease and Healthy Older Adults: An fNIRS Study.

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.

Changes in oxygenated hemoglobin link freezing of gait to frontal activation in patients with Parkinson disease: an fNIRS study of transient motor-cognitive failures.

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.

Effects of Aging on Arm Swing during Gait: The Role of Gait Speed and Dual Tasking.

Healthy walking is characterized by pronounced arm swing and axial rotation. Aging effects on gait speed, stride length and stride time variability have been previously reported, however, less is known about aging effects on arm swing and axial rotation and their relationship to age-associated gait changes during usual walking and during more challenging conditions like dual tasking. Sixty healthy adults between the ages of 30-77 were included in this study designed to address this gap. Lightweight body fixed sensors were placed on each wrist and lower back. Participants walked under 3 walking conditions each of 1 minute: 1) comfortable speed, 2) walking while serially subtracting 3's (Dual Task), 3) walking at fast speed. Aging effects on arm swing amplitude, range, symmetry, jerk and axial rotation amplitude and jerk were compared between decades of age (30-40; 41-50; 51-60; 61-77 years). As expected, older adults walked slower (p = 0.03) and with increased stride variability (p = 0.02). Arm swing amplitude decreased with age under all conditions (p = 0.04). In the oldest group, arm swing decreased during dual task and increased during the fast walking condition (p<0.0001). Similarly, arm swing asymmetry increased during the dual task in the older groups (p<0.004), but not in the younger groups (p = 0.67). Significant differences between groups and within conditions were observed in arm swing jerk (p<0.02), axial rotation amplitude (p<0.02) and axial jerk (p<0.001). Gait speed, arm swing amplitude of the dominant arm, arm swing asymmetry and axial rotation jerk were all independent predictors of age in a multivariate model. These findings suggest that the effects of gait speed and dual tasking on arm swing and axial rotation during walking are altered among healthy older adults. Follow-up work is needed to examine if these effects contribute to reduced stability in aging.