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Cerebellar reserve compensates for and restores functions lost through cerebellar damage. This is a fundamental property of cerebellar circuitry. Clinical studies suggest (1) the involvement of synaptic plasticity in the cerebellar cortex for functional compensation and restoration, and (2) that the integrity of the cerebellar reserve requires the survival and functioning of cerebellar nuclei. On the other hand, recent physiological studies have shown that the internal forward model, embedded within the cerebellum, controls motor accuracy in a predictive fashion, and that maintaining predictive control to achieve accurate motion ultimately promotes learning and compensatory processes. Furthermore, within the proposed framework of the Kalman filter, the current status is transformed into a predictive state in the cerebellar cortex (prediction step), whereas the predictive state and sensory feedback from the periphery are integrated into a filtered state at the cerebellar nuclei (filtering step). Based on the abovementioned clinical and physiological studies, we propose that the cerebellar reserve consists of two elementary mechanisms which are critical for cerebellar functions: the first is involved in updating predictions in the residual or affected cerebellar cortex, while the second acts by adjusting its updated forecasts with the current status in the cerebellar nuclei. Cerebellar cortical lesions would impair predictive behavior, whereas cerebellar nuclear lesions would impact on adjustments of neuronal commands. We postulate that the multiple forms of distributed plasticity at the cerebellar cortex and cerebellar nuclei are the neuronal events which allow the cerebellar reserve to operate in vivo. This cortico-deep cerebellar nuclei loop model attributes two complementary functions as the underpinnings behind cerebellar reserve.

The cerebellar reserve is defined as the capacity of the cerebellum for compensation and restoration following injury. This unique cerebellar ability is attributed to various forms of synaptic plasticity that incorporate multimodal and redundant cerebellar inputs, two major features of the cerebellar circuitry. It is assumed that the cerebellar reserve is acquired from the age of 12 years after the maturation of both the cerebellar adaptative behaviors and cerebellar functional connectivity. However, acquiring the cerebellar reserve is also affected by two other factors: vulnerability and growth potential in the developing cerebellum. First, cerebellar injury during the critical period of neural circuit formation (especially during fetal and neonatal life and infancy) leads to persistent dysfunction of the cerebellum and its targets, resulting in the limitation of the cerebellar reserve. Secondly, growth potential appears to facilitate cerebellar reserve during the stage when the cerebellar reserve is still immature. Based on these findings, the present mini-review proposes a possible developmental trajectory underlying the acquisition of cerebellar reserve. We highlight the importance of studies dedicated to the understanding of the cerebellar resilience to injuries.

The cerebellum is endowed with the capacity for compensation and restoration after pathological injury, a property known as cerebellar reserve. Such capacity is attributed to two unique morphological and physiological features of the cerebellum. First, mossy fibers that convey peripheral and central information run mediolaterally over a wide area of the cerebellum, resulting in the innervation of multiple microzones, commonly known as cerebellar functional units. Thus, a single microzone receives redundant information that can be used in pathological conditions. Secondly, the circuitry is characterized by a co-operative interplay among various forms of synaptic plasticity. Recent progress in understanding the mechanisms of redundant information and synaptic plasticity has allowed outlining therapeutic strategies potentiating these neural substrates to enhance the cerebellar reserve, taking advantage of the unique physiological properties of the cerebellum which appears as a modular and potentially reconfiguring brain structure.

The terminology of cerebellar dysmetria embraces a ubiquitous symptom in motor deficits, oculomotor symptoms, and cognitive/emotional symptoms occurring in cerebellar ataxias. Patients with episodic ataxia exhibit recurrent episodes of ataxia, including motor dysmetria. Despite the consensus that cerebellar dysmetria is a cardinal symptom, there is still no agreement on its pathophysiological mechanisms to date since its first clinical description by Babinski. We argue that impairment in the predictive computation for voluntary movements explains a range of characteristics accompanied by dysmetria. Within this framework, the cerebellum acquires and maintains an internal forward model, which predicts current and future states of the body by integrating an estimate of the previous state and a given efference copy of motor commands. Two of our recent studies experimentally support the internal-forward-model hypothesis of the cerebellar circuitry. First, the cerebellar outputs (firing rates of dentate nucleus cells) contain predictive information for the future cerebellar inputs (firing rates of mossy fibers). Second, a component of movement kinematics is predictive for target motions in control subjects. In cerebellar patients, the predictive component lags behind a target motion and is compensated with a feedback component. Furthermore, a clinical analysis has examined kinematic and electromyography (EMG) features using a task of elbow flexion goal-directed movements, which mimics the finger-to-nose test. Consistent with the hypothesis of the internal forward model, the predictive activations in the triceps muscles are impaired, and the impaired predictive activations result in hypermetria (overshoot). Dysmetria stems from deficits in the predictive computation of the internal forward model in the cerebellum. Errors in this fundamental mechanism result in undershoot (hypometria) and overshoot during voluntary motor actions. The predictive computation of the forward model affords error-based motor learning, coordination of multiple degrees of freedom, and adequate timing of muscle activities. Both the timing and synergy theory fit with the internal forward model, microzones being the elemental computational unit, and the anatomical organization of converging inputs to the Purkinje neurons providing them the unique property of a perceptron in the brain. We propose that motor dysmetria observed in attacks of ataxia occurs as a result of impaired predictive computation of the internal forward model in the cerebellum.