A compelling example of auditory-visual multisensory integration is the McGurk effect, in which an auditory syllable is perceived very differently depending on whether it is accompanied by a visual movie of a speaker pronouncing the same syllable or a different, incongruent syllable. Anatomical and physiological studies in human and nonhuman primates have suggested that the superior temporal sulcus (STS) is involved in auditory-visual integration for both speech and nonspeech stimuli. We hypothesized that the STS plays a critical role in the creation of the McGurk percept. Because the location of multisensory integration in the STS varies from subject to subject, the location of auditory-visual speech processing in the STS was first identified in each subject with fMRI. Then, activity in this region of the STS was disrupted with single-pulse transcranial magnetic stimulation (

The cerebellum has been hypothesized to provide internal models for limb movement control. If the cerebellum is the site of an inverse dynamics model, then cerebellar neural activity should signal limb dynamics and be coupled to arm muscle activity. To address this, we recorded from 166 task-related Purkinje cells in two monkeys performing circular manual tracking under varying viscous and elastic loads. Hand forces and arm muscle activity increased with the load, and their spatial tuning differed markedly between the viscous and elastic fields. In contrast, the simple spike firing of 91.0% of the Purkinje cells was not significantly modulated by the force nor was their spatial tuning affected. For the 15 cells with a significant force effect, changes were small and isolated. These results do not support the hypothesis that Purkinje cells represent the output of an inverse dynamics model of the arm. Instead these neurons provide a kinematic representation of arm movements.

The cerebellum plays an essential role in pursuit tracking with the eye and with the hand. During smooth pursuit eye movements, both tracking position and velocity are signaled by Purkinje cells. Purkinje cell simple spike discharge is also modulated by direction and speed during linear manual tracking. This study evaluated how all three parameters, position, movement direction, and speed, are signaled in the simple spike discharge of Purkinje cells during circular manual tracking. Three rhesus monkeys intercepted and then tracked a target moving in a circle in both counterclockwise and clockwise directions across a range of constant target speeds. Two sets of analyses of the simple spike firing of 97 Purkinje cells examined the effects of position, movement direction, and speed. The first approach was the incremental improvement of regression models, initially modeling a pure position dependence, then incorporating movement direction, and finally incorporating speed dependence. The second was a modelindependent approach, without any explicit assumptions about the character of the directional tuning or speed effects. Both analyses revealed the same three results: (1) Purkinje cell discharge is spatially tuned, to both the position and direction of movement, and (2) this spatial tuning is not altered by the speed, except (3) the speed scales the average firing and/or depth of modulation.The results suggest that the population of Purkinje cells forms a representation of the entire position-direction space of arm movements, and that the speed modulates the scale of that representation. This speed scaling provides insights into the cerebellar processing of movement-related timing.

Encoding of movement kinematics in Purkinje cell simple spike discharge has important implications for hypotheses of cerebellar cortical function. Several outstanding questions remain regarding representation of these kinematic signals. It is uncertain whether kinematic encoding occurs in unpredictable, feedback-dependent tasks or kinematic signals are conserved across tasks. Additionally, there is a need to understand the signals encoded in the instantaneous discharge of single cells without averaging across trials or time. To address these questions, this study recorded Purkinje cell firing in monkeys trained to perform a manual random tracking task in addition to circular tracking and center-out reach. Random tracking provides for extensive coverage of kinematic workspaces. Direction and speed errors are significantly greater during random than circular tracking. Cross-correlation analyses comparing hand and target velocity profiles show that hand velocity lags target velocity during random tracking. Correlations between simple spike firing from 120 Purkinje cells and hand position, velocity, and speed were evaluated with linear regression models including a time constant, τ, as a measure of the firing lead/lag relative to the kinematic parameters. Across the population, velocity accounts for the majority of simple spike firing variability (63 ± 30% of R(adj)(2)), followed by position (28 ± 24% of R(adj)(2)) and speed (11 ± 19% of R(adj)(2)). Simple spike firing often leads hand kinematics. Comparison of regression models based on averaged vs. nonaveraged firing and kinematics reveals lower R(adj)(2) values for nonaveraged data; however, regression coefficients and τ values are highly similar. Finally, for most cells, model coefficients generated from random tracking accurately estimate simple spike firing in either circular tracking or center-out reach. These findings imply that the cerebellum controls movement kinematics, consistent with a forward internal model that predicts upcoming limb kinematics.

Feed forward control and estimates of the future state of the motor system are critical for fast and coordinated movements. One framework for generating these predictive signals is based on the central nervous system implementing internal models. Internal models provide for representations of the input-output properties of the motor apparatus or their inverses. It has been widely hypothesized that the cerebellum acquires and stores internal models of the motor apparatus. The results of psychophysical, functional imaging and transcranial magnetic stimulation studies in normal subjects support this hypothesis. Also, the deficits in patients with cerebellar dysfunction can be attributed to a failure of predictive feed forward control and/or to accurately estimate the consequences of motor commands. Furthermore, the computation performed by the cerebellar-like electrosensory lobes in several groups of fishes is to predict the sensory consequences of motor commands. However, only a few electrophysiological investigations have directly tested whether neurons in the cerebellar cortex have the requisite signals compatible with either an inverse or forward internal model. Our studies in the monkey performing manual pursuit tracking demonstrate that the simple spike discharge of Purkinje cells does not have the dynamics-related signals required to be the output of an inverse dynamics model. However, Purkinje cell firing has several of the characteristics of a forward internal model of the arm. A synthesis of the evidence suggests that the cerebellum is involved in integrating the current state of the motor system with internally generated motor commands to predict the future state. KeywordsPrimate; Cerebellum; Purkinje cell; Simple spike; Internal models ReviewInternal models are widely discussed as a mechanism by which the central nervous system (CNS) generates feed forward commands and/or makes predictions about the upcoming states. Forward internal models predict the state of the system, either the motor variables or the sensory output, as a consequence of the current state of the system and the motor commands. Inverse dynamics models, in response to the desired trajectory, generate the signals required to produce the joint torques/forces used to control a movement. Numerous psychophysical findings support the hypothesis that the CNS uses internal models. Prominent examples include the anticipatory changes in grip forces during predictable manipulations of object load [11,17] and our ability to adapt and generalize reaching movements in novel dynamic environments [38,42]. Furthermore, sensory feedback loops have delays that are too long and gains too low to control fast and coordinated movements.Correspondence to: Timothy J. Ebner. Many investigators postulate that the cerebellum acquires and stores internal models of the motor system [16,18,26,37,44]. Support for these hypotheses is largely based on deficits in patients with cerebellar dysfunction or on functional imaging studies. Consistent with the inverse d...