Cerebellar contributions to locomotor adaptations during splitbelt treadmill walking

Abstract

Locomotor adaptability ranges from the simple and fast-acting to the complex and long-lasting and is a requirement for successful mobility in an unpredictable environment. Several neural structures, including the spinal cord, brainstem, cerebellum, and motor cortex, have been implicated in the control of various types of locomotor adaptation. However, it is not known which structures control which types of adaptation and the specific mechanisms by which the appropriate adjustments are made. Here, we used a splitbelt treadmill to test cerebellar contributions to two different forms of locomotor adaptation in humans. We found that cerebellar damage does not impair the ability to make reactive feedback-driven motor adaptations, but significantly disrupts predictive feedforward motor adaptations during splitbelt treadmill locomotion. Our results speak to two important aspects of locomotor control. First, we have demonstrated that different levels of locomotor adaptability are clearly dissociable. Second, the cerebellum seems to play an essential role in predictive but not reactive locomotor adjustments. We postulate that reactive adjustments may instead be predominantly controlled by lower neural centers, such as the spinal cord or brainstem.

Figure 1.

A, Time course for the experimental paradigm showing baseline, adaptation, and postadaptation periods and tied and splitbelt conditions. B, Illustration of the method to calculate step and stride lengths. IC, Initial contact. The schematic depicts overground walking with a forward progression, but recall that during treadmill locomotion there is no real forward progression. Therefore, stride length could not be calculated as the distance the ankle traveled between subsequent initial contacts on a limb. Rather, we measured stride length as the distance the ankle traveled between initial contact and lift-off on a limb (for details, see Materials and Methods). C, Illustration of the method to calculate limb angles.

Figure 2.

Reactive feedback adaptations. A, B, Stride length (A) and stance time (B) values for the slow and fast legs for sequential strides on the treadmill from a typical control (top row) and cerebellar (bottom row) subject across all testing periods. The first 50 strides are plotted for each component of the baseline period and for the postadaptation period; the first 75 strides are plotted for the adaptation period. C, D, Average stride length (C) and stance time (D) values on the slow and fast legs for control and cerebellar groups. Each data point represents values averaged over the early or late portions of each testing period. Error bars indicate ±1 SE. Asterisks indicate a significance level of p < 0.05 for the post hoc analysis; ns, not significant.

Figure 3.

Predictive feedforward adaptations. A, B, Step length (A) and double support time (B) values for sequential strides on the treadmill from a typical control (top row) and cerebellar (bottom row) subject across all testing periods. The control and cerebellar subjects in A are the same subjects as shown in Figure 2A; the control and cerebellar subjects in B are the same subjects as shown in Figure 2B. The first 50 strides are plotted for each component of the baseline period and for the postadaptation period; the first 75 strides are plotted for the adaptation period. Circles indicate the difference between the legs (fast leg minus slow leg) in step length and double support time values. C, D, Average step length (C) and double support time (D) differences for control and cerebellar groups. Each data point represents values averaged over the early or late portions of each testing period. Error bars indicate ±1 SE. Asterisks indicate a significance level of p < 0.05 for the post hoc analysis; ns, not significant.

Figure 4.

Limb angle interlimb phase. A, Limb angles on the slow (dashed line) and fast (solid line) legs plotted over two successive strides from a typical control (top three pairs of traces) and cerebellar (bottom three pairs of traces) subject. Pairs of strides are from the early adaptation period (top), the late adaptation period (middle), and the early postadaptation period (bottom). Stride times are normalized to percentage of stride for ease of viewing. All strides are aligned on the first initial contact (IC) on the slow leg (arrows indicate the times of slow leg contact). Light gray bars show the duration from peak limb flexion on the fast leg to peak limb extension on the slow leg; dark gray bars show the duration from peak limb flexion on the slow leg to peak limb extension on the fast leg. During symmetric walking, these two durations are equal; we show them here to illustrate the clear temporal shift in limb angles that occurs during the early adaptation and early postadaptation periods. These phase shifts are quantified over the duration of the limb angle cycle in the cross-correlation measures. B, Limb angle interlimb phasing values for sequential strides on the treadmill from the same control (top) and cerebellar (bottom) subject shown in A. The first 50 strides are plotted for each component of the baseline period and for the postadaptation period; the first 75 strides are plotted for the adaptation period. Circles indicate the lag time at the peak in the cross-correlation function between the two limb angles; a lag time of 0.50 indicates the ideal interlimb phase relationship of 180° out of phase. C, Average limb angle interlimb phasing values for the control and cerebellar groups. Each data point represents the lag time at the peak in the cross-correlation function between the two limb angles, averaged over the early or late portions of each testing period. Error bars indicate ±1 SE. Asterisks indicate a significance level of p < 0.05 for the post hoc analysis; ns, not significant.

Figure 5.

A, Scatter plot showing the relationship between the posture and gait ICARS subscore and the capability for predictive adaptability (as measured by the magnitude of the negative aftereffect in the step length difference measure) for all subjects in the cerebellar group plus the five additional cerebellar subjects recruited for this analysis. The diagonal line indicates the fit derived from the correlation equation. B, Posture and gait (left bar in each of the three pairs) and limb kinetics (right bar) ICARS subscores for three subgroups of cerebellar subjects. Subscore values are expressed in percentages, or the raw score for each category divided by the maximum possible score for that category, multiplied by 100. Light gray bars indicate average data from cerebellar subgroup 1 (subjects CB-1, -2, and -3), who had evidence of ataxia of both gait and posture and voluntary limb movements. Open bars depict average data from cerebellar subgroup 2, two new cerebellar subjects who were not part of the main study because their total ICARS scores were not high (severe) enough to meet the inclusion criteria. These subjects had clinical evidence of gait ataxia with only minimal evidence of limb ataxia. Dark gray bars show average data from cerebellar subgroup 3, three other new cerebellar subjects who were also not part of the main study because they did not meet inclusion criteria for total ICARS scores. They had clinical evidence of limb ataxia with only minimal gait and posture deficits. C, D, Average predictive adaptation performance for the same three subgroups of cerebellar subjects. Large circles represent average performance by each subgroup (light gray, subgroup 1; open, subgroup 2; dark gray, subgroup 3). Individual subjects are indicated with the smaller symbols: triangle, CB-3; circle, CB-1; square, CB-2; hexagon, a 62-year-old male with a total ICARS score of 12; x, a 70-year-old male with a total ICARS score of 22; diamond, a 20-year-old male with a total ICARS score of 24; inverted triangle, a 40-year-old female with a total ICARS score of 17; cross, a 30-year-old female with a total ICARS score of 23. C, Average step length residual errors for the cerebellar subgroups. Residual errors were calculated as the difference in step-length difference values from the late baseline to the late adaptation periods. A score of zero indicates full predictive adaptability (a return to baseline levels); positive values indicate a failure to return to baseline, or poor predictive adaptability; negative values indicate late adaptation values that exceeded baseline levels. D, Average step length negative aftereffects for the cerebellar subgroups. Negative aftereffects were taken from the early postadaptation period. Error bars indicate ±1 SE.