Peter W. Dicke

Cerebellar-dependent motor learning is based on pruning a Purkinje cell population response

The improvement of motor behavior, based on experience, is a form of learning that is critically dependent on the cerebellum. A well studied example of cerebellar motor learning is short-term saccadic adaptation (STSA). In STSA, information on saccadic errors is used to improve future saccades. The information optimizing saccade metrics is conveyed by Purkinje cells simple spikes (PC-SS) because they are the critical input to the premotor circuits for saccades. We recorded PC-SS of monkeys undergoing STSA to reveal the code used for improving behavior. We found that the discharge of individual PC-SS was unable to account for the behavioral changes. The PC-SS population burst (PB), however, exhibited changes that closely paralleled the qualitatively different changes of saccade kinematics associated with gain-increase and gain-decrease STSA, respectively. Gain-increase STSA, characterized by an increase in saccade duration, replicates the relationship between saccade duration and the end of the PB valid for unadapted saccades. In contrast, gain-decrease STSA, which sports normal saccade duration but reduced saccadic velocity, is characterized by a PB that ends well before the adapted saccade. This suggests that the duration of normal as well as gain-increased saccades is determined by appropriately setting the end of PB end. However, the duration of gain-decreased saccades is apparently not modified by the cerebellum because the PB signals ends too early to determine saccade end. In summary, STSA, and most probably cerebellar-dependent learning in general, is based on optimizing the shape of a PC-SS population response.

Characteristics of Responses of Golgi Cells and Mossy Fibers to Eye Saccades and Saccadic Adaptation Recorded from the Posterior Vermis of the Cerebellum

The anatomical organization of the granular layer of the cerebellum suggests an important function for Golgi cells (GC) in the pathway conveying mossy fiber (MF) afferents to Purkinje cells. Based on such anatomic observations, early proposals have attributed a role in “gain control” for GCs, a function disputed by recent investigations, which assert that GCs instead contribute to oscillatory mechanisms. However, conclusive physiological evidence based on studies of cerebellum-dependent behavior supporting/dismissing the gain control proposition has been lacking as of yet. We addressed the possible function of this interneuron by recording the activity of a large number of both MFs and GCs during saccadic eye movements from the same cortical area of the monkey cerebellum, namely the oculomotor vermis (OMV). Our cellular identification conformed to previously established criteria, mainly to juxtacellular labeling studies correlating physiological parameters with cell morphology. Response patterns of both MFs and GCs were highly heterogeneous. MF discharges correlated linearly with eye saccade metrics and timing, showing directional preference and precise direction tuning. In contrast, GC discharges did not correlate strongly with the metrics or direction of movement. Their discharge properties were also unaffected by motor learning during saccadic adaptation. The OMV therefore receives a barrage of information about eye movements from different oculomotor areas over the MF pathway, which is not reflected in GCs. The unspecificity of GCs has important implications for the intricacies of neuronal processing in the granular layer, clearly discrediting their involvement in gain control and instead suggesting a more secluded role for these interneurons.

The role of the oculomotor vermis in the control of saccadic eye movements.

Abstract: The oculomotor vermis is a part of the posterior cerebellum, characterized by a low threshold (<10 μA) for evoked saccades. It comprises vermal lobuli VIc and VIIA. Many Purkinje cells in this area show eye position or saccade‐related responses or combinations of the two and usually lack responses to the presentation of visual targets, guiding the oculomotor behavior. The saccade‐related responses are directionally selective and show preferences for saccade amplitude or duration, which differ widely between cells. However, at the population level, these saccade‐related Purkinje cells give a very precise account of the timing of the saccadic eye movement and, specifically, of the time it ends. This population signal might therefore contribute to determining the end of the saccadic eye movement. Furthermore, by changing the duration of the population response, the amplitude of the saccade could be changed. In other words, saccadic adaptation could be a consequence of changing a representation of time in the cerebellum.

The Absence of Eye Muscle Fatigue Indicates That the Nervous System Compensates for Non-Motor Disturbances of Oculomotor Function

The physical properties of our bodies are subject to change (due to fatigue, heavy equipment, injury or aging) as we move around in the surrounding environment. The traditional definition of motor adaptation dictates that a mechanism in our brain needs to compensate for such alterations by appropriately modifying neural motor commands, if the vitally important accuracy of executed movements is to be preserved. In this article we describe how a repetitive eye movement task brings about changes in eye saccade kinematics that compromise accurate motor performance in the absence of a proper compensatory response. Surgical lesions in animals and human patient studies have previously demonstrated that an intact cerebellum is necessary for the compensation to arise and prevent the occurrence of hypometric movements. Here we identified the dynamic properties of the eye plant by recording from abducens motoneurons responsible for the required movement and measured the muscle response to microstimulation of the abducens nucleus in rhesus monkeys. The ensuing results demonstrate that the muscular periphery remains intact during the fatiguing eye movement task, while internal sources of noise (drowsiness, attentional modulation, neuronal fatigue etc.) must be responsible for a diminished oculomotor performance. This finding leads to the important realization that while supervising the accuracy of our movements, the nervous system takes additionally into account and adapts to any disruptive processes within the brain itself, clearly unrelated to the dynamical behavior of muscles or the environment. The existence of this supplementary mechanism forces a reassessment of traditional views of cerebellum-dependent motor adaptation.

The role of cortical area MST in a model of combined smooth eye-head pursuit

Abstract. The cortical medial superior temporal area (MST) is essential for the normal execution of smooth pursuit eye movements. Many pursuit-related neurons (visual-tracking neurons = VT neurons) in the lateral part of area MST (MSTl) are responsive to retinal image slip (r) as well as to eye (e) and head velocity (h) with similar preferred directions (isodirectionality). We show, by running a connectionist network with VT neuron-like elements, that an assembly of MSTl-VT neurons is able to reconstruct target motion in world-centered coordinates (t′). When t′ is fed into a subsequent model stage, converting t′ into gaze velocity (g′) with varying contributions of e and h, the overall model is able to account for many of the salient properties of visually guided pursuit including the consequences of MSTl lesions. However, the analysis of the MSTl network also clearly indicates that isodirectionality is not a prerequisite for its performance. The investigation of a second model suggests that isodirectionality indeed does not result from functional but from developmental constraints. This second model is a connectionist network with hidden units, which similar to MSTl-VT neurons receive input from modality specific units encoding retinal slip, eye and head velocity. After training this network to offer t′ as output, two subsets of hidden units emerged, one exhibiting isodirectionality, but not the other. Since only isodirectional hidden units contributed to the flow of information, the preponderance of isodirectional MSTl-VT neurons might be the result of developmental pruning, eliminating the second group.

Single-neuron evidence for a contribution of the dorsal pontine nuclei to both types of target-directed eye movements, saccades and smooth-pursuit

The primate dorsolateral pontine nucleus (DLPN) is a key link in a cerebro‐cerebellar pathway for smooth pursuit eye movements, a pathway assumed to be anatomically segregated from tegmental circuits subserving saccades. However, the existence of afferents from several cerebrocortical and subcortical centres for saccades suggests that the DLPN and neighbouring parts of the dorsal pontine nuclei (DPN) might contribute to saccades as well. In order to test this hypothesis, we recorded from the DPN of two monkeys trained to perform smooth pursuit eye movements as well as visually and memory‐guided saccades. Out of 281 neurons isolated from the DPN, 138 were responsive in oculomotor tasks. Forty‐five were exclusively activated in saccade paradigms, 68 exclusively by smooth pursuit and 25 neurons showed responses in both. Pursuit‐related responses reflected sensitivity to eye position, velocity or combinations of velocity and position with minor contributions of acceleration in many cases. When tested in the memory‐guided saccades paradigm, 65 out of 70 neurons activated in saccade paradigms showed significant saccade‐related bursts and 20 significant activity in the memory period. Our finding of saccade‐related activity in the DPN in conjunction with the existence of strong anatomical input from saccade‐related cerebrocortical areas suggests that the DPN serves as a precerebellar relay for both pursuit and saccade‐related information originating from cerebral cortex, in addition to the classical tecto‐tegmental circuitry for saccades.

Normal Spatial Attention But Impaired Saccades and Visual Motion Perception After Lesions of the Monkey Cerebellum

Lesions of the cerebellum produce deficits in movement and motor learning. Saccadic dysmetria, for example, is caused by lesions of the posterior cerebellar vermis. Monkeys and patients with such lesions are unable to modify the amplitude of saccades. Some have suggested that the effects on eye movements might reflect a more global cognitive deficit caused by the cerebellar lesion. We tested that idea by studying the effects of vermis lesions on attention as well as saccadic eye movements, visual motion perception, and luminance change detection. Lesions in posterior vermis of four monkeys caused the known deficits in saccadic control. Attention tested by examination of acuity threshold changes induced by prior cueing of the location of the targets remained normal after vermis lesions. Luminance change detection was also unaffected by the lesions. In one case, after a lesion restricted to lobulus VIII, the animal had impaired visual motion perception.

Cortical processing of head- and eye-gaze cues guiding joint social attention

Previous fMRI experiments showed an involvement of the STS in the processing of eye-gaze direction in joint attention. Since head-gaze direction can also be used for the assessment of another persons attentional focus, we compared the mechanisms underlying the processing of head- and eye-gaze direction using a combined psychophysical and fMRI approach. Subjects actively followed the head- or eye-gaze direction of a person in a photograph towards one of seven possible targets by moving their eyes. We showed that the right posterior superior temporal sulcus (STS) as well as the right fusiform gyrus (FSG) were involved in both processing of head- as well as eye-gaze direction. Another finding was a bilateral deactivation of a distinct area in the middle STS (mSTS) as well as the left anterior STS (aSTS), that was stronger when subjects followed eye-gaze direction than when they followed head-gaze direction. We assume that this deactivation is based on an active suppression of information arising from the distracting other directional cue, i.e. head-gaze direction in the eye-gaze direction task and eye-gaze direction in the head-gaze direction task. These results further support the hypothesis that the human equivalent of the gaze sensitive area in monkeys lies in more anterior parts of the STS than previously thought.

Specific vermal complex spike responses build up during the course of smooth-pursuit adaptation, paralleling the decrease of performance error

Contemporary theories of the cerebellum hold that the complex spike (CS) fired by cerebellar Purkinje cells (PCs) reports the error signal essential for motor adaptation, i.e., the CS serves as a teacher reducing the performance error. This hypothesis suggests a monotonic relationship between CS modulation and performance error: the modulation of CS responses should be maximal at adaptation onset and turn back to its pre-adaptation state when the error is nulled. An alternative viewpoint based on studies of saccades suggests that the modulation of the CS discharge builds up as performance error decreases, and maximum and stable CS modulation is found after adaptation has been completed (Catz et al. 2005). We wanted to know whether this pattern can be generalized to other forms of motor adaptation. We resorted to smooth-pursuit adaptation (SPA) as an example of cerebellar-dependent adaptation. SPA is induced by increasing or decreasing target velocity during pursuit initiation that leads to a gradual increase or decrease in eye velocity. We trained 2 rhesus monkeys and recorded CS from PC in vermal lobuli VI and VII during SPA. We find that SPA is accompanied by a pattern of CS firing, which at the onset of adaptation, i.e., when the error is large, is not modulated significantly. On the other hand, when initial eye velocity is stably increased or decreased by adaptation, the probability of CS occurrence during pursuit initiation decreases or increases, respectively. Overall, our results deviate from the predictions made by the classical error-coding concept.

Neuronal correlates of perceptual stability during eye movements

We are usually unaware of retinal image motion resulting from our own movement. For instance, during slow‐tracking eye movements the world around us remains perceptually stable despite the retinal image slip induced by the eye movement. It is commonly held that this example of perceptual invariance is achieved by subtracting an internal reference signal, reflecting the eye movement, from the retinal motion signal. If the two cancel each other, visual objects, which do not move, will also be perceived as non‐moving. If, however, the reference signal is too small or too large, a false eye movement‐induced motion of the external world, the Filehne illusion, will be perceived. We have exploited our ability to manipulate the size of the reference signal in an attempt to identify neurons in the visual cortex of monkeys, influenced by the percept of self‐induced visual motion or the reference signal rather than the retinal motion signal. We report here that such ‘percept‐related’ neurons can already be found in the primary visual cortex area, although few in numbers. They become more frequent in areas middle temporal and medial superior temporal in the superior temporal sulcus, and comprise almost 50% of all neurons in area visual posterior sylvian (VPS) in the posterior part of the lateral sulcus. In summary, our findings suggest that our ability to perceive a visual world, which is stable despite self‐motion, is based on a neuronal network, which culminates in the VPS located in the lateral sulcus below the classical dorsal stream of visual processing.