Anti-Saccades in Cerebellar Ataxias Reveal a Contribution of the Cerebellum in Executive Functions

Abstract

ObjectiveIncreasing evidence suggests a cerebellar contribution to modulate cognitive aspects of motor behavior and executive functions. Supporting findings come from studies on patients with neurodegenerative diseases, in which however, given the extent of the disease, the specific role of the cerebellum, could not be clearly isolated. Anti-saccades are considered a sensitive tool to test executive functions. The anti-saccade underlying neural network, consisting of different cortical areas and their downstream connections including the lateral cerebellum, has been largely clarified. To separate the role of the cerebellum with respect to other cortical structures in executive control, we compared the anti-saccade performances in two distinct cohorts of patients with cerebellar disorders (with and without cerebral cortical involvement).MethodsEye movements during the execution of anti-saccades were recorded in 12 patients with spinocerebellar ataxia type 2 (a cortical-subcortical neurodegenerative disease), 10 patients with late onset cerebellar ataxia (an isolated cerebellar atrophy), and 34 matched controls.ResultsIn the anti-saccade task, besides dynamic changes already demonstrated in the pro-saccades of these patients, we found in both groups of cerebellar patients prolonged latency with larger variability than normal and increased directional error rate. Errors, however, were corrected by cerebellar patients as frequently as normal. No significant differences were found in patients with and without cortical involvement.ConclusionOur results indicate, in a large cohort of cerebellar patients, that the cerebellum plays a critical role in the regulation of executive motor control not only, as well known, by controlling the end of a movement, but also modulating its initiation and reducing reflexive responses that would perturb voluntary actions.

Purkinje Cell Activity in the Medial and Lateral Cerebellum During Suppression of Voluntary Eye Movements in Rhesus Macaques

“…This suggests that the observed activity was not merely an efference copy of the motor command but reflects the preparatory or planning phase of the voluntary movement in which the PC firing is determined by the cue. This is in line with the recent findings in patients with spinocerebellar ataxia type 2 and the late onset of cerebellar ataxia, who are presented with deficits in executive functions during an antisaccade test ( Pretegiani et al, 2018 ) and in patients with cerebellar atrophy who show impairments when making goal-oriented movements ( Piu et al, 2019 ). To what extent the SS responses in our study also correlate with the presence or absence of reward at the end of the trials remains to be seen.…”

“…We hypothesize that through the pre-learned associations of parallel fiber and climbing fiber signals, relevant evidence from the stimulus (i.e., dot color in instruction) for the selection of the required action (i.e., pro- or anti-saccade) can be rapidly relayed from the lateral cerebellum to the frontal saccade areas. In cerebellar patients, latencies for antisaccades are prolonged, indicating a less efficient decision-making process in the absence of cerebellar input ( Pretegiani et al, 2018 ; Piu et al, 2019 ).…”

Eye-tracking-aided characterization of saccades and antisaccades in SYNE1 ataxia patients: a pilot study

“…A similar relationship was not detected in the FA group. Previously published studies indicated higher antisaccadic error rates in other hereditary and idiopathic cerebellar disorders, including ataxia with oculomotor apraxia type 1, 2, ataxia telangiectasia, SCA1, 2, 3 and late onset cerebellar ataxia (LOCA) [ 28 , 33 – 35 ]. Additionally, Pretegiani et al revealed that SCA2 and LOCA patients showed equally poor antisaccade performance irrespective of cortical involvement [ 33 ].…”

“…Previously published studies indicated higher antisaccadic error rates in other hereditary and idiopathic cerebellar disorders, including ataxia with oculomotor apraxia type 1, 2, ataxia telangiectasia, SCA1, 2, 3 and late onset cerebellar ataxia (LOCA) [28,[33][34][35]. Additionally, Pretegiani et al revealed that SCA2 and LOCA patients showed equally poor antisaccade performance irrespective of cortical involvement [33]. Additionally, a thorough investigation of a SCA2 patient cohort confirmed that impaired antisaccade efficacy was associated with executive test deficits, including Stroop interference task and verbal fluency test [34].…”

Ophthalmic Manifestations and Genetics of the Polyglutamine Autosomal Dominant Spinocerebellar Ataxias: A Review

“…Saccadic slowing was present even in the early stage of SCA2, can insidiously progress, eventually leading to ophthalmoplegia in late stage (Velázquez-Pérez et al, 2009;Stephen and Schmahmann, 2019). It has been reported a saccadic pursuits, nystagmus, saccadic hypometria, prolonged latency and increased rate of directional errors of anti-saccades in SCA2 (Rodríguez-Labrada et al, 2011;Pretegiani et al, 2018). SCA2 patients may not have typical gaze-evoked nystagmus of cerebellar disease in relation to impaired ability to produce saccadic corrective phases (Geiner et al, 2008).…”