R. C. Miall

Is the Cerebellum a Smith Predictor

The motor system may use internal predictive models of the motor apparatus to achieve better control than would be possible by negative feedback. Several theories have proposed that the cerebellum may form these predictive representations. In this article, we review these theories and try to unify them by reference to an engineering control model known as a Smith Predictor. We suggest that the cerebellum forms two types of internal model. One model is a forward predictive model of the motor apparatus (e.g., limb and muscle), providing a rapid prediction of the sensory consequences of each movement. The second model is of the time delays in the control loop (due to receptor and effector delays, axonal conductances, and cognitive processing delays). This model delays a copy of the rapid prediction so that it can be compared in temporal register with actual sensory feedback from the movement. The result of this comparison is used both to correct for errors in performance and as a training signal to learn the first model. We discuss evidence that the cerebellum could form both of these models and suggest that the cerebellum may hold at least two separate Smith Predictors. One, in the lateral cerebellum, would predict the movement outcome in visual, egocentric, or peripersonal coordinates. Another, in the intermediate cerebellum, would predict the consequences in motor coordinates. Generalization of the Smith Predictor theory is discussed in light of cerebellar involvement in nonmotor control systems, including autonomic functions and cognition.

Brain activation patterns during measurement of sub- and supra-second intervals

The possibility that different neural systems are used to measure temporal durations at the sub-second and several second ranges has been supported by pharmacological manipulation, psychophysics, and neural network modelling. Here, we add to this literature by using fMRI to isolate differences between the brain networks which measure 0.6 and 3s in a temporal discrimination task with visual discrimination for control. We observe activity in bilateral insula and dorsolateral prefrontal cortex, and in right hemispheric pre-supplementary motor area, frontal pole, and inferior parietal cortex during measurement of both intervals, suggesting that these regions constitute a system used in temporal discrimination at both ranges. The frontal operculum, left cerebellar hemisphere and middle and superior temporal gyri, all show significantly greater activity during measurement of the shorter interval, supporting the hypotheses that the motor system is preferentially involved in the measurement of sub-second intervals, and that auditory imagery is preferentially used during measurement of the same. Only a few voxels, falling in the left posterior cingulate and inferior parietal lobe, are more active in the 3s condition. Overall, this study shows that although many brain regions are used for the measurement of both sub- and supra-second temporal durations, there are also differences in activation patterns, suggesting that distinct components are used for the two durations.

The cerebellum coordinates eye and hand tracking movements.

The cerebellum is thought to help coordinate movement. We tested this using functional magnetic resonance imaging (fMRI) of the human brain during visually guided tracking tasks requiring varying degrees of eye–hand coordination. The cerebellum was more active during independent rather than coordinated eye and hand tracking. However, in three further tasks, we also found parametric increases in cerebellar blood oxygenation signal (BOLD) as eye–hand coordination increased. Thus, the cerebellar BOLD signal has a non-monotonic relationship to tracking performance, with high activity during both coordinated and independent conditions. These data provide the most direct evidence from functional imaging that the cerebellum supports motor coordination. Its activity is consistent with roles in coordinating and learning to coordinate eye and hand movement.

Brain activity correlates differentially with increasing temporal complexity of rhythms during initialisation, synchronisation, and continuation phases of paced finger tapping.

Activity in parts of the human motor system has been shown to correlate with the complexity of performed motor sequences in terms of the number of limbs moved, number of movements, and number of trajectories. Here, we searched for activity correlating with temporal complexity, in terms of the number of different intervals produced in the sequence, using an overlearned tapping task. Our task was divided into three phases: movement selection and initiation (initiate), synchronisation of finger tapping with an external auditory cue (synchronise), and continued tapping in absence of the auditory pacer (continue). Comparisons between synchronisation and continuation showed a pattern in keeping with prior neuroimaging studies of paced finger tapping. Thus, activation of bilateral SMA and basal ganglia was greater in continuation tapping than in synchronisation tapping. Parametric analysis revealed activity correlating with temporal complexity during initiate in bilateral supplementary and pre-supplementary motor cortex (SMA and preSMA), rostral dorsal premotor cortex (PMC), basal ganglia, and dorsolateral prefrontal cortex (DLPFC), among other areas. During synchronise, correlated activity was observed in bilateral SMA, more caudal dorsal and ventral PMC, right DLPFC and right primary motor cortex. No correlated activity was observed during continue at P<0.01 (corrected, cluster level), though left angular gyrus was active at P<0.05. We suggest that the preSMA and rostral dorsal PMC activities during initiate may be associated with selection of timing parameters, while activation in centromedial prefrontal cortex during both initiate and synchronise may be associated with temporal error monitoring or correction. The absence of activity significantly correlated with temporal complexity during continue suggests that, once an overlearned timed movement sequence has been selected and initiated, there is no further adjustment of the timing control processes related to its continued production in absence of external cues.

Pedunculopontine nucleus stimulation improves akinesia in a Parkinsonian monkey

We have studied the effects of stimulating the pedunculopontine nuclei through a fully implanted macroelectrode with a s.c. implantable pulse generator whose parameters can be programmed telemetrically, in a macaque before and after inducing Parkinsonian akinesia with MPTP. Our results show that in the normal monkey high frequency stimulation of the pedunculopontine nuclei reduces motor activity while low frequency stimulation increases it significantly over baseline. After making the monkey Parkinsonian with MPTP, unilateral low frequency stimulation of the pedunculopontine nuclei led to significant increases in activity. These results suggest that pedunculopontine nuclei stimulation could be clinically effective in treating advanced Parkinsons disease and other akinetic disorders.

A right hemispheric prefrontal system for cognitive time measurement

Despite a growing body of neuroimaging data, little consensus has been reached regarding the neural correlates of temporal processing in humans. This paper presents a reanalysis of two previously published neuroimaging experiments, which used two different cognitive timing tasks and examined both sub- and supra-second intervals. By processing these data in an identical manner, this reanalysis allows valid comparison and contrasting across studies. Conjunction of these studies using inclusive masking reveals shared activity in right hemispheric dorsolateral and ventrolateral prefrontal cortex and anterior insula, supporting a general-purpose system for cognitive time measurement in the right hemispheric prefrontal cortex. Consideration of the patterns of activity in each dataset with respect to the others, and taking task characteristics into account, provides insight into the possible role of dorsolateral prefrontal cortex in working memory and of posterior parietal cortex and anterior cingulate in attentional processing during cognitive time measurement tasks.

Visuo-motor tracking during reversible inactivation of the cerebellum

SummaryTwo monkeys were trained to track a continuously moving target using a joystick. One then had a cooling probe implanted in nucleus interpositus of the cerebellum ipsilateral to his tracking arm. The other had a cannula implanted in the ipsilateral cortex of the lateral cerebellum through which local anaesthetic could be infused. Both monkeys showed similar tracking deficits during temporary inactivation of the cerebellum. The main effects seen were an increase in the peak velocity of their intermittent corrective tracking movements, and a decrease in the accuracy of these movements. Linear regression analyses were undertaken of the peak velocity and amplitude of each corrective movement against a number of possible control signals (target velocity, target position, error, error velocity etc.). The initially strong correlation of the amplitude of each movement made with target velocity was severely reduced during cerebellar inactivation, and movement amplitude became better predicted by the error between target and joystick positions. The peak velocity of movements became more strongly correlated with movement amplitude and less correlated with target velocity than in the intact animal. These results are consistent with the hypothesis that intermittent tracking is achieved by the production of ‘primitive’ movements, that are then adjusted to the correct amplitude and velocity required to catch up with the moving target. Our findings suggest that the cerebellum may normally be responsible for these adjustments, using visual and memorised cues about the target. The velocity of each movement may be reduced, and its amplitude adjusted, by combining measures of the current error with estimates of target speed and direction. We conclude that the cerebellum has an inhibitory role in tuning movements during visuo-motor tasks and that optimal tuning using feedforward measurements of target motion cannot be made without it.

Non-invasive Cerebellar Stimulation—a Consensus Paper

The field of neurostimulation of the cerebellum either with transcranial magnetic stimulation (TMS; single pulse or repetitive (rTMS)) or transcranial direct current stimulation (tDCS; anodal or cathodal) is gaining popularity in the scientific community, in particular because these stimulation techniques are non-invasive and provide novel information on cerebellar functions. There is a consensus amongst the panel of experts that both TMS and tDCS can effectively influence cerebellar functions, not only in the motor domain, with effects on visually guided tracking tasks, motor surround inhibition, motor adaptation and learning, but also for the cognitive and affective operations handled by the cerebro-cerebellar circuits. Verbal working memory, semantic associations and predictive language processing are amongst these operations. Both TMS and tDCS modulate the connectivity between the cerebellum and the primary motor cortex, tuning cerebellar excitability. Cerebellar TMS is an effective and valuable method to evaluate the cerebello-thalamo-cortical loop functions and for the study of the pathophysiology of ataxia. In most circumstances, DCS induces a polarity-dependent site-specific modulation of cerebellar activity. Paired associative stimulation of the cerebello-dentato-thalamo-M1 pathway can induce bidirectional long-term spike-timing-dependent plasticity-like changes of corticospinal excitability. However, the panel of experts considers that several important issues still remain unresolved and require further research. In particular, the role of TMS in promoting cerebellar plasticity is not established. Moreover, the exact positioning of electrode stimulation and the duration of the after effects of tDCS remain unclear. Future studies are required to better define how DCS over particular regions of the cerebellum affects individual cerebellar symptoms, given the topographical organization of cerebellar symptoms. The long-term neural consequences of non-invasive cerebellar modulation are also unclear. Although there is an agreement that the clinical applications in cerebellar disorders are likely numerous, it is emphasized that rigorous large-scale clinical trials are missing. Further studies should be encouraged to better clarify the role of using non-invasive neurostimulation techniques over the cerebellum in motor, cognitive and psychiatric rehabilitation strategies.

The precision of temporal judgement: Milliseconds, many minutes, and beyond

The principle that the standard deviation of estimates scales with the mean estimate, commonly known as the scalar property, is one of the most broadly accepted fundamentals of interval timing. This property is measured using the coefficient of variation (CV) calculated as the ratio between the standard deviation and the mean. In 1997, John Gibbon suggested that different time measurement mechanisms may have different levels of absolute precision, and would therefore be associated with different CVs. Here, we test this proposal by examining the CVs produced by human subjects timing a broad range of intervals (68 ms to 16.7 min). Our data reveal no evidence for multiple mechanisms, but instead show a continuous logarithmic decrease in CV as timed intervals increase. This finding joins other recent reports in demonstrating a systematic violation of the scalar property in timing data. Interestingly, the estimated CV of circadian judgements fits onto the regression of decreasing CV, suggesting a link between short interval and circadian timing mechanisms.

Involvement of the medial pallidum in focal myoclonic dystonia: A clinical and neurophysiological case study.

We successfully treated a patient with familial myoclonic dystonia (FMD), which primarily affected his neck muscles, with bilateral deep brain stimulation (DBS) to the medial pallidum, and investigated the role of the medial pallidum in FMD. A patient with FMD underwent bilateral implantation of DBS electrodes during which field potentials (FPs) in the medial pallidum and electromyograms (EMGs) from the affected neck muscles were recorded. The effects of high‐frequency DBS to the medial pallidum on the FMD were also assessed by recording EMGs during and immediately after implantation, as well as 6 days and 8 weeks postoperatively. During spontaneous myoclonic episodes, increased FPs oscillating at 4 and 8 Hz were recorded from the medial pallidum; these correlated strongly with phasic EMG activity at the same frequencies in the contralateral affected muscles. The EMG activity was suppressed by stimulating the contralateral medial pallidum at 100 Hz during the operation and continuous bilateral DBS from an implanted stimulator abolished myoclonic activity even more effectively postoperatively. The phasic pallidal activity correlated with and led the myoclonic muscle activity, and the myoclonus was suppressed by bilateral pallidal DBS, suggesting that the medial pallidum was involved in the generation of the myoclonic activity. High‐frequency DBS may suppress the myoclonus by desynchronising abnormal pallidal oscillations. This case study has significant clinical implications, because at present, there is no effective treatment for focal myoclonic dystonia.