Resting state brain network segregation is associated with walking speed and working memory in older adults.

Older adults exhibit larger individual differences in walking ability and cognitive function than young adults. Characterizing intrinsic brain connectivity differences in older adults across a wide walking performance spectrum may provide insight into the mechanisms of functional decline in some older adults and resilience in others. Thus, the objectives of this study were to: (1) determine whether young adults and high- and low-functioning older adults show group differences in brain network segregation, and (2) determine whether network segregation is associated with working memory and walking function in these groups. The analysis included 21 young adults and 81 older adults. Older adults were further categorized according to their physical function using a standardized assessment; 54 older adults had low physical function while 27 were considered high functioning. Structural and functional resting state magnetic resonance images were collected using a Siemens Prisma 3T scanner. Working memory was assessed with the NIH Toolbox list sorting test. Walking speed was assessed with a 400 m-walk test at participants' self-selected speed. We found that network segregation in mobility-related networks (sensorimotor, vestibular, and visual networks) was higher in younger adults compared to older adults. There were no group differences in laterality effects on network segregation. We found multivariate associations between working memory and walking speed with network segregation scores. Higher right anterior cingulate cortex network segregation was associated with higher working memory function. Higher right sensorimotor, right vestibular, right anterior cingulate cortex, and lower left anterior cingulate cortex network segregation was associated with faster walking speed. These results are unique and significant because they demonstrate higher network segregation is largely related to higher physical function and not age alone.

Neural correlates of gait adaptation in younger and older adults.

Mobility decline is a major concern for older adults. A key component of maintaining mobility with advancing age is the ability to learn and adapt to the environment. The split-belt treadmill paradigm is an experimental protocol that tests the ability to adapt to a dynamic environment. Here we examined the magnetic resonance imaging (MRI) derived structural neural correlates of individual differences in adaptation to split-belt walking for younger and older adults. We have previously shown that younger adults adopt an asymmetric walking pattern during split-belt walking, particularly in the medial-lateral (ML) direction, but older adults do not. We collected T[Formula: see text]-weighted and diffusion-weighted MRI scans to quantify brain morphological characteristics (i.e. in the gray matter and white matter) on these same participants. We investigated two distinct questions: (1) Are there structural brain metrics that are associated with the ability to adopt asymmetry during split-belt walking; and (2) Are there different brain-behavior relationships for younger and older adults? Given the growing evidence that indicates the brain has a critical role in the maintenance of gait and balance, we hypothesized that brain areas commonly associated with locomotion (i.e. basal ganglia, sensorimotor cortex, cerebellum) would be associated with ML asymmetry and that older adults would show more associations between split-belt walking and prefrontal brain areas. We identified multiple brain-behavior associations. More gray matter volume in the superior frontal gyrus and cerebellar lobules VIIB and VIII, more sulcal depth in the insula, more gyrification in the pre/post central gyri, and more fractional anisotropy in the corticospinal tract and inferior longitudinal fasciculus corresponded to more gait asymmetry. These associations did not differ between younger and older adults. This work progresses our understanding of how brain structure is associated with balance during walking, particularly during adaptation.

Age differences in adaptation of medial-lateral gait parameters during split-belt treadmill walking.

The split-belt treadmill has been used to examine the adaptation of spatial and temporal gait parameters. Historically, similar studies have focused on anterior-posterior (AP) spatiotemporal gait parameters because this paradigm is primarily a perturbation in the AP direction, but it is important to understand whether and how medial-lateral (ML) control adapts in this scenario. The ML control of balance must be actively controlled and adapted in different walking environments. Furthermore, it is well established that older adults have balance difficulties. Therefore, we seek to determine whether ML balance adaptation differs in older age. We analyzed split belt induced changes in gait parameters including variables which inform us about ML balance control in younger and older adults. Our primary finding is that younger adults showed sustained asymmetric changes in these ML balance parameters during the split condition. Specifically, younger adults sustained a greater displacement between their fast stance foot and their upper body, relative to the slow stance foot, in the ML direction. This finding suggests that younger adults may be exploiting passive dynamics in the ML direction, which may be more metabolically efficient. Older adults did not display the same degree of asymmetry, suggesting older adults may be more concerned about maintaining a stable gait.

Brain activity during walking in older adults: Implications for compensatory versus dysfunctional accounts.

A prominent trend in the functional brain imaging literature is that older adults exhibit increased brain activity compared to young adults to perform a given task. This phenomenon has been extensively studied for cognitive tasks, with the field converging on interpretations described in two alternative accounts. One account interprets over-activation in older adults as reflecting neural dysfunction (increased brain activity - indicates poorer performance), whereas another interprets it as neural compensation (increased brain activity - supports better performance). Here we review studies that have recorded brain activity and walking measurements in older adults, and we categorize their findings as reflecting either neural dysfunction or neural compensation. Based on this synthesis, we recommend including multiple task difficulty levels in future work to help differentiate if and when compensation fails as the locomotion task becomes more difficult. Using multiple task difficulty levels with neuroimaging will lead to a more advanced understanding of how age-related changes in locomotor brain activity fit with existing accounts of brain aging and support the development of targeted neural rehabilitation techniques.

Interactions Between Different Age-Related Factors Affecting Balance Control in Walking.

Maintaining balance during walking is a continuous sensorimotor control problem. Throughout the movement, the central nervous system has to collect sensory data about the current state of the body in space, use this information to detect possible threats to balance and adapt the movement pattern to ensure stability. Failure of this sensorimotor loop can lead to dire consequences in the form of falls, injury and death. Such failures tend to become more prevalent as people get older. While research has established a number of factors associated with higher risk of falls, we know relatively little about age-related changes of the underlying sensorimotor control loop and how such changes are related to empirically established risk factors. This paper approaches the problem of age-related fall risk from a neural control perspective. We begin by summarizing recent empirical findings about the neural control laws mapping sensory input to motor output for balance control during walking. These findings were established in young, neurotypical study populations and establish a baseline of sensorimotor control of balance. We then review correlates for deteriorating balance control in older adults, of muscle weakness, slow walking, cognitive decline, and increased visual dependency. While empirical associations between these factors and fall risk have been established reasonably well, we know relatively little about the underlying causal relationships. Establishing such causal relationships is hard, because the different factors all co-vary with age and are difficult to isolate empirically. One option to analyze the role of an individual factor for balance control is to use computational models of walking comprising all levels of the sensorimotor control loop. We introduce one such model that generates walking movement patterns from a short list of spinal reflex modules with limited supraspinal modulation for balance. We show how this model can be used to simulate empirical studies, and how comparison between the model and empirical results can indicate gaps in our current understanding of balance control. We also show how different aspects of aging can be added to this model to study their effect on balance control in isolation.

Interdependence of balance mechanisms during bipedal locomotion.

Our main interest is to identify how humans maintain upright while walking. Balance during standing and walking is different, primarily due to a gait cycle which the nervous system must contend with a variety of body configurations and frequent perturbations (i.e., heel-strike). We have identified three mechanisms that healthy young adults use to respond to a visually perceived fall to the side. The lateral ankle mechanism and the foot placement mechanism are used to shift the center of pressure in the direction of the perceived fall, and the center of mass away from the perceived fall. The push-off mechanism, a systematic change in ankle plantarflexion angle in the trailing leg, results in fine adjustments to medial-lateral balance near the end of double stance. The focus here is to understand how the three basic balance mechanisms are coordinated to produce an overall balance response. The results indicate that lateral ankle and foot placement mechanisms are inversely related. Larger lateral ankle responses lead to smaller foot placement changes. Correlations involving the push-off mechanism, while significant, were weak. However, the consistency of the correlations across stimulus conditions suggest the push-off mechanism has the role of small adjustments to medial-lateral movement near the end of the balance response. This verifies that a fundamental feature of human bipedal gait is a highly flexible balance system that recruits and coordinates multiple mechanisms to maintain upright balance during walking to accommodate extreme changes in body configuration and frequent perturbations.

Phase-Dependency of Medial-Lateral Balance Responses to Sensory Perturbations During Walking.

The human body is mechanically unstable during walking. Maintaining upright stability requires constant regulation of muscle force by the central nervous system to push against the ground and move the body mass in the desired way. Activation of muscles in the lower body in response to sensory or mechanical perturbations during walking is usually highly phase-dependent, because the effect any specific muscle force has on the body movement depends upon the body configuration. Yet the resulting movement patterns of the upper body after the same perturbations are largely phase-independent. This is puzzling, because any change of upper-body movement must be generated by parts of the lower body pushing against the ground. How do phase-dependent muscle activation patterns along the lower body generate phase-independent movement patterns of the upper body? We hypothesize that when a sensory system detects a deviation of the body in space from a desired state that indicates the onset of a fall, the nervous system generates a functional response by pushing against the ground in any way possible with the current body configuration. This predicts that the changes in the ground reaction force patterns following a balance perturbation should be phase-independent. Here we test this hypothesis by disturbing upright balance in the frontal plane using Galvanic vestibular stimulation at three different points in the gait cycle. We measure the resulting changes in whole-body center of mass movement and the location of the center of pressure of the ground reaction force. We find that the magnitude of the initial center of pressure shift in the direction of the perceived fall is larger for perturbations late in the gait cycle, while there is no statistically significant difference in onset time. These results contradict our hypothesis by showing that even the initial CoP shift in response to a balance perturbation depends upon the phase of the gait cycle. Contrary to expectation, we also find that the whole-body balance response is not phase-independent. Both the onset time and the magnitude of the whole-body center of mass shift depend on the phase of the perturbation. We conclude that the central nervous system recruits any available mechanism to generate a functional balance response by pushing against the ground as fast as possible in response to a perturbation, but that the different mechanisms available at different phases in the gait cycle are not equally strong, leading to phase-dependent differences in the overall response.

Walking Cadence Affects the Recruitment of the Medial-Lateral Balance Mechanisms.

We have previously identified three balance mechanisms that young healthy adults use to maintain balance while walking. The three mechanisms are: (1) The lateral ankle mechanism, an active modulation of ankle inversion/eversion in stance; (2) The foot placement mechanism, an active shift of the swing foot placement; and (3) The push-off mechanism, an active modulation of the ankle plantarflexion angle during double stance. Here we seek to determine whether there are changes in neural control of balance when walking at different cadences and speeds. Twenty-one healthy young adults walked on a self-paced treadmill while immersed in a 3D virtual reality cave, and periodically received balance perturbations (bipolar galvanic vestibular stimulation) eliciting a perceived fall to the side. Subjects were instructed to match two cadences specified by a metronome, 110 bpm (High) and 80 bpm (Low), which in this experiment, led to faster and slower gait speeds, respectively. The results indicate that subjects altered the use of the balance mechanisms at different cadences. The lateral ankle mechanism was used more in the Low condition, while the foot placement mechanism was used more in the High condition. There was no difference in the use of the push-off mechanism between cadence conditions. These results suggest that neural control of balance is altered when gait characteristics, such as cadence change, suggesting a flexible balance response that is sensitive to the constraints of the gait cycle. We speculate that the use of the balance mechanisms may be a factor resulting in well-known characteristics of gait in populations with compromised balance control, such as slower gait speed in older adults or higher cadence in people with Parkinson's disease.

Neural Control of Balance During Walking.

Neural control of standing balance has been extensively studied. However, most falls occur during walking rather than standing, and findings from standing balance research do not necessarily carry over to walking. This is primarily due to the constraints of the gait cycle: Body configuration changes dramatically over the gait cycle, necessitating different responses as this configuration changes. Notably, certain responses can only be initiated at specific points in the gait cycle, leading to onset times ranging from 350 to 600 ms, much longer than what is observed during standing (50-200 ms). Here, we investigated the neural control of upright balance during walking. Specifically, how the brain transforms sensory information related to upright balance into corrective motor responses. We used visual disturbances of 20 healthy young subjects walking in a virtual reality cave to induce the perception of a fall to the side and analyzed the muscular responses, changes in ground reaction forces and body kinematics. Our results showed changes in swing leg foot placement and stance leg ankle roll that accelerate the body in the direction opposite of the visually induced fall stimulus, consistent with previous results. Surprisingly, ankle musculature activity changed rapidly in response to the stimulus, suggesting the presence of a direct reflexive pathway from the visual system to the spinal cord, similar to the vestibulospinal pathway. We also observed systematic modulation of the ankle push-off, indicating the discovery of a previously unobserved balance mechanism. Such modulation has implications not only for balance but plays a role in modulation of step width and length as well as cadence. These results indicated a temporally-coordinated series of balance responses over the gait cycle that insures flexible control of upright balance during walking.

Complementary mechanisms for upright balance during walking.

Lateral balance is a critical factor in keeping the human body upright during walking. Two important mechanisms for balance control are the stepping strategy, in which the foot placement is changed in the direction of a sensed fall to modulate how the gravitational force acts on the body, and the lateral ankle strategy, in which the body mass is actively accelerated by an ankle torque. Currently, there is minimal evidence about how these two strategies complement one another to achieve upright balance during locomotion. We use Galvanic vestibular stimulation (GVS) to induce the sensation of a fall at heel-off during gait initiation. We found that young healthy adults respond to the illusory fall using both the lateral ankle strategy and the stepping strategy. The stance foot center of pressure (CoP) is shifted in the direction of the perceived fall by ≈2.5 mm, starting ≈247 ms after stimulus onset. The foot placement of the following step is shifted by ≈15 mm in the same direction. The temporal delay between these two mechanisms suggests that they independently contribute to upright balance during locomotion, potentially in a serially coordinated manner. Modeling results indicate that without the lateral ankle strategy, a much larger step width is required to maintain upright balance, suggesting that the small but early CoP shift induced by the lateral ankle strategy is critical for upright stability during locomotion. The relative importance of each mechanism and how neurological disorders may affect their implementation remain an open question.