Dysmetria and Errors in Predictions: The Role of Internal Forward Model

Abstract

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.

The Forward Model: A Unifying Theory for the Role of the Cerebellum in Motor Control and Sense of Agency

“…The cerebellum is a complex structure that is connected with the entire central nervous system (Stoodley and Schmahmann, 2018). The connectivity of the cerebellum is organized in a series of parallel loops with the cerebral cortex, the striatum, and the spinal cord, which makes the cerebellum a key sensorimotor interface: each region of the cerebellum receives inputs from a specific region of the central nervous system, and sends back projections to these same regions (Sokolov et al, 2017;Diedrichsen et al, 2019;Cabaraux et al, 2020;Tanaka et al, 2020; Figure 2). Via the afferent connections, it receives information from the cerebral cortex and processes sensory feedback from the peripheral system (muscles, joint position, auditory, visual, vestibular, and proprioceptive information; Baumann et al, 2015).…”

“…The unique architecture of the cerebellum could explain its involvement in such a diverse range of functions. The connectivity between the cerebellum and the cerebral cortex is organized in parallel loops: different regions of the cerebellum receive inputs from a large set of cerebral regions (not only from motor regions, but also from associative areas) through the pontine nuclei (PN), and in return, the deep cerebellar nuclei send projections back to the same cerebral regions through the thalamus, thus forming a Cerebro-Pontocerebello-dentato-thalamocortical pathway (Ito, 2006;Sokolov et al, 2017;Diedrichsen et al, 2019;Cabaraux et al, 2020;Tanaka et al, 2020). Contrary to the neocortex, the local circuitry of the cerebellum is highly uniform across its different regions, suggesting that the diversity of cerebellar functions could rely on a single cerebellar computation that would be embedded in parallel cerebro-cerebellar loops (Diedrichsen et al, 2019).…”

Shared internal models for feedforward and feedback control of arm dynamics in non‐human primates

“…For example, M1 is highly connected with the cerebellum (Allen & Tsukahara, 1974; Holdefer et al., 2000; Hoover & Strick, 1999; Wagner et al., 2019), which is also a site that has been long proposed to contain the computations for internal models that underlie feedforward motor control (Wolpert & Kawato, 1998; Wolpert et al., 1998). The cerebellum is also critical for feedforward and feedback control of the intersegmental arm dynamics, as a deficit in this region in patients has been reported to substantially impact the ability to coordinate across joints (Bastian et al., 1996, 2000; Goodkin et al., 1993; Holmes, 1939; Kurtzer et al., 2013) and to generate motor predictions (Cabaraux et al., 2020; Kakei et al., 2019; Tanaka et al., 2019, 2020). Demonstrating learning and transfer in monkeys, as we do here, sets the stage for further neurophysiology experiments for hunting these potential neural mechanisms of feedforward and feedback control of the arm dynamics.…”

Cerebellar long-term depression and auto-immune target of auto-antibodies: the concept of LTDpathies

“…Evidence suggests that online predictive computations that employ the internal forward model coordinate limb voluntary movements [46][47][48][49][50]. The predictive computation of the forward model affords coordination of multiple degrees of freedom and appropriate timing of muscle activities [39]. Since the deficits in predictive activation of the triceps muscles results in dysmetria, it is assumed that dysmetria occurs as a result of impaired predictive computation of the internal forward model in the cerebellum [39].…”