Discussion

The cortico-cerebellar network plays a crucial role in motor control. Controlling the timing and predictive sequencing ensures performing any movement with precision and accuracy.^{Reference Lawrenson, Bares and Kamondi7} Any dysfunction in this network results in inadequacy of force generation, dysregulated agonist–antagonist muscle activity and impaired acquisition of sensory feedback, impacting multiple motor domains.^{Reference Manto8,Reference Bodranghien, Bastian and Casali9} In this study, the spatiotemporal impact of this dysfunctional network was assessed on speech, arm movements and gait from a kinematic perspective.

Clinical assessment of ataxia was done using the SARA scale. However, there are several limitations of this rating scale including high inter-rater reliability and test-retest variability.^{Reference Weyer, Abele and Schmitz-Hübsch10} Furthermore, SARA is inadequate for assessing individual complexities of ataxic movements like difficulties in initiation and termination or altered trajectories of the movements. Additional objective tools are thus necessary to precisely detect these changes while performing complicated multi-joint movements. Similarly, the speech sub-score of SARA is suboptimal to analyze ataxic speech in time and spectral domains. Assessment of variability of the individual components of ataxic speech necessitates more sophisticated acoustic software analysis.

In speech analysis, it was found that the participants with ataxia had “tuh” SR performance that was approximately two times slower and three times more variable than the healthy controls. The finding is consistent with previous studies on ataxic dysarthria. Slow rate and irregularity in timing across the syllable chain in ataxic patients were classified as “atypical diadochokinesis (DDK)” by Kent et al.^{Reference Kent, Kim and Chen4,Reference Kent, Kent, Duffy, Thomas, Weismer and Stuntebeck11} Our study provides additional support for the hypothesis that excessive SR variability is a distinctive and diagnostically important characteristic of ataxic dysarthria.^{Reference Spencer, Amaral and Lansford5} The additional finding that the participants with ataxia were perceived as having a speech severity score that was six times greater than the healthy controls is also consistent with previous studies of ataxic dysarthria.^{Reference Spencer and France12,Reference Darley, Aronson and Brown13} Two of the most prominent perceptual features reported in ataxic dysarthria are imprecise consonants and irregular articulatory breakdowns during connected speech tasks.

Compared to controls, ataxia patients could reach fewer targets in KINARM reaching tasks and displayed less accuracy and efficacy as measured by EE and MPE. Additionally, patients with a larger deviation from the ideal trajectory (more MPE) finally missed the target with a bigger margin (more EE), illustrating the clinical correlation of dysmetria. Dysmetria has been hypothesized to occur as a result of impaired prediction of movement due to misrepresentation of limb dynamics and abnormal sequencing of motor actions, highlighting a critical role of the cerebellum in maintaining and updating accurate internal models of dynamics and sequencing elementary commands.^{Reference Bodranghien, Bastian and Casali9} Trajectories of limb movement in dysmetria are characterized by increased curvature, reinforcing the finding of more deviation (more curvature) from the ideal trajectory (more MPE or less efficacy) resulting in more dysmetria (more EE, less accuracy).^{Reference Manto14} Any goal-directed action requires planning, monitoring and error detection while performing the task. Impairment in these steps in cerebellar degeneration can lead to a deviation from the right trajectory (MPE) and inaccuracy in reaching the target (EE). It was also noted that the mean and peak velocity of arm movements were slower, and the time required to reach the targets was higher, compared to controls. It has been proposed that a decrease in speed is possibly an adaptive mechanism for dysmetria as dysmetria worsens at higher velocities, supporting the findings of higher EE (lower accuracy) with higher velocity.^{Reference Manto, Bower and Conforto1,Reference Manto14} Moreover, ataxia patients demonstrated prolonged RT as suggested previously by different studies.^{Reference Manto8,Reference Bodranghien, Bastian and Casali9,Reference Manto, Serrao and Filippo Castiglia15} Prolonged RT or impaired initiation likely results from cerebellar involvement in executive control of voluntary actions through cognitive load-dependent influence on the cortico-striatal network. Increased inter-trial variability in ataxia, as shown in previous studies, has been hypothesized to result from impaired “timing” function of the cerebellum in “sculpting” the motor sequence through precisely timed “inhibitory volleys,” while performing a multi-joint movement.^{Reference Lawrenson, Bares and Kamondi7,Reference Bodranghien, Bastian and Casali9,Reference Timmann, Watts and Hore16,Reference Topka, Konczak and Dichgans17} Lastly, there was more EE (less accuracy) observed while applying load (inertia) during arm movement. Interestingly, the error was larger when applying a discontinuous load than a continuous one. Inertia sensitivity has been proposed as a hallmark of cerebellar dysmetria.^{Reference Manto, Godaux and Jacquy18} The cerebellum tunes the timing, duration and amplitude of antagonist and synergist muscle activity during an ongoing movement based on the starting position of the limb, target location and inertia to overcome.^{Reference Manto14,Reference Cabaraux, Gandini, Kakei, Manto, Mitoma and Tanaka19} When a load is applied to the ongoing movement, normal subjects can adapt to this scenario by accelerating agonist muscle activity or “launching force” and still reach the target with accuracy by the acceleration of antagonist muscle activity or “braking force.” In contrast, patients with impaired cerebellar servo mechanisms failed to accelerate the antagonist activity (more of this “brake” is required with discontinuous load) despite being able to increase the agonist activity, resulting in more EE.^{Reference Manto, Godaux and Jacquy18}

Compared to healthy controls, ataxia patients demonstrated reduced cadence (steps/minute), reduced stride velocity and reduced step length during gait analysis, as demonstrated in previous studies.^{Reference Serrao, Pierelli and Ranavolo20,Reference Buckley, Mazzà and McNeill21} Slowing the pace along with shorter step length are likely compensatory mechanisms to avoid falls due to truncal instability and dynamic imbalance, like speed-dependency of dysmetria, as observed in KINARM tasks.^{Reference Palliyath, Hallett, Thomas and Lebiedowska22,Reference McAndrew Young and Dingwell23} Similarly, in gait cycle analysis, ataxia patients took a longer time to complete the gait cycle and also spent a longer time in the double support phase, as a consequence of slowness in walking.^{Reference Palliyath, Hallett, Thomas and Lebiedowska22} Increasing double support time, along with reduced step length, is likely a strategy to reduce the sway in a less stable monopedal stance.^{Reference Bodranghien, Bastian and Casali9} Notably, while correlating upper limb movement velocity recorded in KINARM with gait velocity recorded in Zeno Walkway, there was a correlation in patients with less severe ataxia (SARA < 15), while no such correlation was noted in the more severe group (SARA >15). This may indicate parallel deterioration of the upper and lower limb movements up to a point of ataxia severity, beyond which they progress independently with varying intensity. Moreover, increased variability of step length, stride velocity, double support percentage and gait cycle time in ataxia patients, consistent with the previous studies.^{Reference Serrao, Pierelli and Ranavolo20,Reference Ilg, Golla, Thier and Giese24,Reference Stolze, Klebe, Petersen, Raethjen, Wenzelburger and Witt25} Though not measured in our study, lateral step deviation (another measure of gait variability) has been noted to be a sensitive marker for ataxia severity in recent studies.^{Reference Seemann, Daghsen and Cazier26} Such variability results from a complex interplay between the primary deficit and the compensatory mechanisms. Primary deficit includes deficit in the sensory feedback and integration of sensory cues, imprecise execution of a movement due to irregular timing, amplitude and force generation while performing a multi-joint movement and inability to maintain “stability” of locomotion due to dynamic imbalance.^{Reference Manto, Serrao and Filippo Castiglia15,Reference McAndrew Young and Dingwell23,Reference Hausdorff27} As a result, the adopted compensatory mechanism facilitates a continuous “step-by-step adjustment” of the gait strategy.^{Reference Bodranghien, Bastian and Casali9}