Biomedical subjects

Peter Thier

Publications and source records attributed to Peter Thier.

At least 19 recordsLinked to original sources

PubMed2006

Opposite dependencies on visual motion coherence in human area MT+ and early visual cortex.

In order to understand the relationship between brain activity and visual motion perception, knowledge of the cortical areas participating in signal processing alone is insufficient. Rather knowledge on how responses vary with the characteristics of visual motion is necessary. In this study, we measured whole brain activity using magnetoencephalography in humans discriminating the global motion direction of a random dot kinematogram whose strength was systematically varied by the percentage of coherently moving dot elements. Spectral analysis revealed 2 components correlating with motion coherence. A first component in the low-frequency domain ( approximately 3 Hz), linearly increasing with motion coherence, could be attributed to visual cortex including human area middle temporal (MT) +. A second component oscillating in the alpha frequency range and emerging after stimulus offset showed the inverse dependence on motion coherence and arose from early visual cortex. Based on these results, we first of all conclude that motion coherence is reflected in the population response of human extrastriate cortex. Second, we suggest that the occipital alpha activity represents a gating mechanism protecting visual motion integration in later cortical areas from disturbing upcoming signals.

Adult↗

PubMed2006

Internalizing agency of self-action: perception of one's own hand movements depends on an adaptable prediction about the sensory action outcome.

Extensive work on learning in reaching and pointing tasks has demonstrated high degrees of plasticity in our ability to optimize goal-directed motor behavior. However, studies focusing on the perceptual awareness of our own actions during motor adaptation are still rare. Here we present the first simultaneous investigation of sensorimotor adaptation on both levels, i.e., action and action perception. We hypothesized that self-action perception relies on internal predictions about the sensory action outcome that are updated in a way similar to that of motor control. Twenty human subjects performed out-and-back pointing movements that were fed back visually. Feedback was initially presented in spatiotemporal correspondence with respect to the actual finger position, but later rotated by a constant angle. When distorted feedback was applied repetitively, subjects' perceived pointing direction shifted in the direction of the trajectory rotation. A comparable perceptual reinterpretation was observed in control trials without visual feedback, indicating that subjects learned to predict the new visual outcome of their actions based on nonvisual, internal information. The perception of the world, however, remained unchanged. The changes in perception of one's own movements were accompanied by adaptive changes in motor performance of the same amount, i.e., a secondary motor compensation opposite to the direction of the imposed visual rotation. Our results show that the perception of one's own actions depends on adaptable internal predictions about the sensory action outcome, allowing us to attribute new sensory consequences of our actions to our own agency. Furthermore, they indicate that the updated sensory prediction can be used to optimize motor control.

Adult↗

PubMed2006

The oculomotor role of the pontine nuclei and the nucleus reticularis tegmenti pontis.

Cerebral cortex and the cerebellum interact closely in order to facilitate spatial orientation and the generation of motor behavior, including eye movements. This interaction is based on a massive projection system that allows the exchange of signals between the two cortices. This cerebro-cerebellar communication system includes several intercalated brain stem nuclei, whose eminent role in the organization of oculomotor behavior has only recently become apparent. This review focuses on the two major nuclei of this group taking a precerebellar position, the pontine nuclei and the nucleus reticularis tegmenti pontis, both intimately involved in the visual guidance of eye movements.

Animals↗

PubMed2006

Cerebrocerebellar circuits for the perceptual cancellation of eye-movement-induced retinal image motion.

Despite smooth pursuit eye movements, we are unaware of resultant retinal image motion. This example of perceptual invariance is achieved by comparing retinal image slip with an internal reference signal predicting the sensory consequences of the eye movement. This prediction can be manipulated experimentally, allowing one to vary the amount of self-induced image motion for which the reference signal compensates and, accordingly, the resulting percept of motion. Here we were able to map regions in CRUS I within the lateral cerebellar hemispheres that exhibited a significant correlation between functional magnetic resonance imaging signal amplitudes and the amount of motion predicted by the reference signal. The fact that these cerebellar regions were found to be functionally coupled with the left parieto-insular cortex and the supplementary eye fields points to these cortical areas as the sites of interaction between predicted and experienced sensory events, ultimately giving rise to the perception of a stable world despite self-induced retinal motion.

Brain Mapping↗

PubMed2005

Cerebellar complex spike firing is suitable to induce as well as to stabilize motor learning.

BACKGROUND: Cerebellar Purkinje cells (PC) generate two responses: the simple spike (SS), with high firing rates (>100 Hz), and the complex spike (CS), characterized by conspicuously low discharge rates (1-2 Hz). Contemporary theories of cerebellar learning suggest that the CS discharge pattern encodes an error signal that drives changes in SS activity, ultimately related to motor behavior. This then predicts that CS will discharge in relation to the error and at random once the error has been nulled by the new behavior. RESULTS: We tested this hypothesis with saccadic adaptation in macaque monkeys as a model of cerebellar-dependent motor learning. During saccadic adaptation, error information unconsciously changes the endpoint of a saccade prompted by a visual target that shifts its final position during the saccade. We recorded CS from PC of the posterior vermis before, during, and after saccadic adaptation. In clear contradiction to the "error signal" concept, we found that CS occurred at random before adaptation onset, i.e., when the error was maximal, and built up to a specific saccade-related discharge profile during the course of adaptation. This profile became most pronounced at the end of adaptation, i.e., when the error had been nulled. CONCLUSIONS: We suggest that CS firing may underlie the stabilization of a learned motor behavior, rather than serving as an electrophysiological correlate of an error.

Action Potentials↗

PubMed2005

Detection of speed changes during pursuit eye movements.

The human visual system is strikingly insensitive to speed changes attributed to the need to infer visual acceleration, observed during stationary fixation, indirectly by comparing velocities integrated over time. The objective of this study was to test if smooth pursuit eye movements improve the detection of speed changes. This was expected for two reasons: first, pursuit reduces the retinal image slip velocity, leading to smaller Weber fractions for velocity changes; secondly, pursuit provides acceleration-dependent retinal position cues unavailable during stationary fixation such as displacements of the target image away from the fovea due to unexpected changes in target velocity. In a first set of experiments thresholds for just noticeable speed changes were measured in ten healthy human subjects confronted with a horizontally moving target, changing its velocity unpredictably during its ramp-like movement. During stationary fixation, the Weber fraction averaged 0.13 for a starting velocity of the target being 15 degrees /s. Smooth pursuit of the same target significantly reduced the Weber fraction down to 0.08. In a second set of experiments, the discrimination of speed changes was tested in patients (n=10) with pursuit disturbances characterized by increased retinal image slip and unidirectional retinal image displacements. These patients showed a strong perceptual bias to report speed increments and an insensitivity to speed decrements. We argue that this asymmetry is a necessary consequence of a mechanism exploiting retinal position errors for the detection of speed change, confronted with directionally biased errors due to the pursuit impairment. In summary, the detection of speed changes is facilitated by pursuit eye movements but is highly susceptible to pursuit insufficiencies.

Acceleration↗

PubMed2005

The neural basis of smooth-pursuit eye movements.

Smooth-pursuit eye movements are used to stabilize the image of a moving object of interest on the fovea, thus guaranteeing its high-acuity scrutiny. Such movements are based on a phylogenetically recent cerebro-ponto-cerebellar pathway that has evolved in parallel with foveal vision. Recent work has shown that a network of several cerebrocortical areas directs attention to objects of interest moving in three dimensions and reconstructs the trajectory of the target in extrapersonal space, thereby integrating various sources of multimodal sensory and efference copy information, as well as cognitive influences such as prediction. This cortical network is the starting point of a set of parallel cerebrofugal projections that use different parts of the dorsal pontine nuclei and the neighboring rostral nucleus reticularis tegmenti pontis as intermediate stations to feed two areas of the cerebellum, the flocculus-paraflocculus and the posterior vermis, which make mainly complementary contributions to the control of smooth pursuit.

Animals↗

PubMed2005

Disorders of agency in schizophrenia correlate with an inability to compensate for the sensory consequences of actions.

Psychopathological symptoms in schizophrenia patients suggest that the concept of self might be disturbed in these individuals [1]. Delusions of influence make them feel that someone else is guiding their actions, and certain kinds of their hallucinations seem to be misinterpretations of their own inner voice as an external voice, the common denominator being that self-produced information is perceived as if coming from outside. If this interpretation were correct, we might expect that schizophrenia patients might also attribute the sensory consequences of their own eye movements to the environment rather than to themselves, challenging the percept of a stable world. Indeed, this seems to be the case because we found a clear correlation between the strength of delusions of influence and the ability of schizophrenia patients to cancel out such self-induced retinal information in motion perception. This correlation reflects direct experimental evidence supporting the view that delusions of influence in schizophrenia might be due to a specific deficit in the perceptual compensation of the sensory consequences of one's own actions [1, 2, 3, 4, 5 and 6].

Adult↗

PubMed2005

Disturbed overt but normal covert shifts of attention in adult cerebellar patients.

In an attempt to provide a common denominator for cognitive deficits observed in cerebellar patients, it has been suggested that they might be secondary to impaired control of attention, a 'dysmetria of attention', conceptually analogous to motor dysmetria. Albeit appealing and quite influential, the concept of attentional dysmetria as a consequence of cerebellar disease remains controversial. In an attempt to test this concept in a direct way, we compared the performance of patients with cerebellar disorders to that of normal controls on tasks requiring either overt or covert shifts of spatial attention. In the first experiment, visually guided saccades, i.e. overt shifts of spatial attention, were elicited. In the second experiment, covert shifts of attention were evoked by the need to discriminate the orientation of a Landolt C observed during controlled fixation and presented in the same locations as the saccade targets in the previous experiment. The allocation of attention was assessed by comparing acuity thresholds determined with and without spatial cueing. The patients exhibited dysmetric saccades as reflected by larger absolute position errors or a higher number of corrective saccades compared to controls. In contrast, the ability to shift attention covertly was unimpaired in the patients, as indicated by a robust improvement in visual acuity induced by spatial cueing which did not differ from the one observed in the controls and which was independent of the range of SOAs (stimulus onset asynchronies) tested. Finally, the individual amount of saccadic dysmetria did not correlate with the individual performance in the covert attentional paradigm. In summary, we conclude that the contributions of the cerebellum to attention are confined to overt manifestations based on goal-directed eye movements.

Adult↗

PubMed2005

Organization of tectopontine terminals within the pontine nuclei of the rat and their spatial relationship to terminals from the visual and somatosensory cortex.

We investigated the spatial relationship of axonal and dendritic structures in the rat pontine nuclei (PN), which transfer visual signals from the superior colliculus (SC) and visual cortex (A17) to the cerebellum. Double anterograde tracing (DiI and DiAsp) from different sites in the SC showed that the tectal retinotopy of visual signals is largely lost in the PN. Whereas axon terminals from lateral sites in the SC were confined to a single terminal field close to the cerebral peduncle, medial sites in the SC projected to an additional dorsolateral one. On the other hand, axon terminals originating from the two structures occupy close but, nevertheless, totally nonoverlapping terminal fields within the PN. Furthermore, a quantitative analysis of the dendritic trees of intracellularly filled identified pontine projection neurons showed that the dendritic fields were confined to either the SC or the A17 terminal fields and never extended into both. We also investigated the projections carrying cortical somatosensory inputs to the PN as these signals are known to converge with tectal ones in the cerebellum. However, terminals originating in the whisker representation of the primary somatosensory cortex and in the SC were located in segregated pontine compartments as well. Our results, therefore, point to a possible pontocerebellar mapping rule: Functionally related signals, commonly destined for common cerebellar target zones but residing in different afferent locations, may be kept segregated on the level of the PN and converge only later at specific sites in the granular layer of cerebellar cortex.

Animals↗

PubMed2004

Posterior parietal cortex neurons encode target motion in world-centered coordinates.

The motion areas of posterior parietal cortex extract information on visual motion for perception as well as for the guidance of movement. It is usually assumed that neurons in posterior parietal cortex represent visual motion relative to the retina. Current models describing action guided by moving objects work successfully based on this assumption. However, here we show that the pursuit-related responses of a distinct group of neurons in area MST of monkeys are at odds with this view. Rather than signaling object image motion on the retina, they represent object motion in world-centered coordinates. This representation may simplify the coordination of object-directed action and ego motion-invariant visual perception.

Action Potentials↗

PubMed2004

Neuromagnetic activity in medial parietooccipital cortex reflects the perception of visual motion during eye movements.

We usually perceive a stationary, stable world despite coherent visual motion induced by eye movements. This astonishing example of perceptual invariance results from a comparison of visual information with internal reference signals (nonretinal signals) predicting the visual consequences of an eye movement. The important consequence of this concept is that our subjective percept of visual motion reflects the outcome of this comparison rather than retinal image slip. To localize the cortical networks underlying this comparison, we compared magnetoencephalography (MEG) responses under two conditions of pursuit-induced retinal image motion, which were identical physically but--due to different calibrational states of the nonretinal signal prompted under our experimental conditions--gave rise to different percepts of visual motion. This approach allows us to demonstrate that our perception of self-induced visual motion resides in comparably "late" parts of the cortical hierarchy of motion processing sparing the early stages up to cortical area MT/V5 but including cortex in and around the medial aspect of the parietooccipital cortex as one of its core elements.

Attention↗

PubMed2004

Improvement of visual acuity by spatial cueing: a comparative study in human and non-human primates.

This study investigated the influence of spatial cueing (valid/invalid/no cue) on visual discrimination in human and non-human primates. We employed a spatial resolution task which required the accurate discrimination of the orientation of a Landolt "C" ring. The C appeared as single target in specific retinal locations while subjects maintained fixation of a central fixation point. The minimal discernable size of the "C" (=acuity threshold) was determined as a function of cue condition, retinal eccentricity (3 degrees -15 degrees ), and stimulus onset asynchrony (SOA) (200-1100 ms). For both species, we found consistent benefits from spatial cueing with differences in absolute thresholds ranging from 6% to 25%. These differences increased with retinal eccentricity and decreased with longer SOAs. Further experiments performed with humans only, showed that the effect of spatial cueing on visual discrimination is independent of spatial uncertainty, i.e. the number of possible target locations (2 versus 4), but fades with longer target presentation times. From our results we draw the following conclusions. (i) Since sensory noise and spatial uncertainty was small in our tasks, spatial shifts of attention involve signal enhancement in both, human and non-human primates. (ii) The similarity of the results obtained for humans and macaque monkeys indicates that the latter may serve as a suitable model system in studies trying to tackle the neural underpinnings of attentional control. (iii) In order to elicit robust effects on visual discrimination by spatial shifts of attention, a paradigm comprising short SOAs (approximately 200 ms) and target presentation times (approximately 150 ms), and retinal eccentricities larger than approximately 9 degrees seems most promising.

Adult↗

PubMed2004

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.

Action Potentials↗

PubMed2003

Neuron-specific contribution of the superior colliculus to overt and covert shifts of attention.

The analysis of a peripheral visual location can be improved in two ways: either by orienting one's gaze (usually by making a foveating saccade) or by 'covertly' shifting one's attention to the peripheral location without making an eye movement. The premotor theory of attention holds that saccades and spatial shifts of attention share a common functional module with a distinct neuronal basis. Using single-unit recording from the brains of trained rhesus monkeys, we investigated whether the superior colliculus, the major subcortical center for the control of saccades, is part of this shared network for attention and saccades. Here we show that a distinct type of neuron in the intermediate layer of the superior colliculus, the visuomotor neuron, which is known to be centrally involved in the preparation of saccades, is also active during covert shifts of attention.

Animals↗

PubMed2003

Visual tracking neurons in primate area MST are activated by smooth-pursuit eye movements of an "imaginary" target.

Because smooth-pursuit eye movements (SPEM) can be executed only in the presence of a moving target, it has been difficult to attribute the neuronal activity observed during the execution of these eye movements to either sensory processing or to motor preparation or execution. Previously, we showed that rhesus monkeys can be trained to perform SPEM directed toward an "imaginary" target defined by visual cues confined to the periphery of the visual field. The pursuit of an "imaginary" target provides the opportunity to elicit SPEM without stimulating visual receptive fields confined to the center of the visual field. Here, we report that a subset of neurons [85 "imaginary" visual tracking (iVT)-neurons] in area MST of 3 rhesus monkeys were identically activated during pursuit of a conventional, foveal dot target and the "imaginary" target. Because iVT-neurons did not respond to the presentation of a moving "imaginary" target during fixation of a stationary dot, we are able to exclude that responses to pursuit of the "imaginary" target were artifacts of stimulation of the visual field periphery. Neurons recorded from the representation of the central parts of the visual field in neighboring area MT, usually vigorously discharging during pursuit of foveal targets, in no case responded to pursuit of the "imaginary" target. This dissociation between MT and MST neurons supports the view that pursuit responses of MT neurons are the result of target image motion, whereas those of iVT-neurons in area MST reflect an eye movement-related signal that is nonretinal in origin. iVT-neurons fell into two groups, depending on the properties of the eye movement-related signal. Whereas most of them (71%) encoded eye velocity, a minority showed responses determined by eye position, irrespective of whether eye position was changed by smooth pursuit or by saccades. Only the former group exhibited responses that led the eye movement, which is a prerequisite for a causal role in the generation of SPEM.

Action Potentials↗

PubMed2003

Morphological classification of the rat lateral cerebellar nuclear neurons by principal component analysis.

The deep cerebellar nuclei (DCN) constitute the major structures by which the cerebellum forwards its output to the rest of the brain. Although the connectivity of the DCN has been well studied, little is known about the interface-the neurons' soma and dendrites-between the DCN's inputs and outputs. We therefore decided to analyze the neurons' somatic and dendritic morphology by applying a multivariate approach (principal component analysis; PCA), in order to define morphological groups possibly related to distinct positions in the nuclear microcircuitry. The PCA was based on intracellularly stained neurons from the rat's lateral DCN and on 19 parameters that described the neurons' morphology. The PCA yielded two principal components that accounted for 46% of the variance. The first component, correlated with soma size, separated the majority of neurons (type I) from a population of small neurons (type II). The second component showed negative correlation with larger cells with more numerous primary dendrites and a more multipolar appearance (type Ia) and positive correlation with smaller neurons with asymmetric dendritic fields and tufted dendrites (type Ib). The preponderance of small somata in our type Ib neurons suggests that these neurons probably correspond to the inferior olive projection neurons. In summary, our results are in agreement with previous classifications, which distinguished projection neurons (type I) from local neurons (type II); furthermore, our results point to a hitherto undescribed dendritic morphological difference in the projection neurons. The latter may be important for understanding the phylogenetic changes seen in the mammalian lateral cerebellar nucleus.

Animals↗

PubMed2002

Quantitative organization of neurotransmitters in the deep cerebellar nuclei of the Lurcher mutant.

The Lurcher mutant mouse is characterized by a primary selective loss of Purkinje cells, leading to the near total apoptotic death of these neurons. In contrast to the subsequent massive secondary degeneration of the granule cells and the inferior olivary neurons, only mild degeneration occurs in the deep cerebellar nuclei (DCN). However, it is not known to what extent the different populations of DCN neurons-glutamatergic principal projection neurons, gamma-aminobutyric acid (GABA)-ergic inferior olivary projection neurons, and glycinergic neurons-are affected in their neurotransmitter composition. To answer this question we studied the neurotransmitter contents (glutamate, GABA, and glycine) of DCN neurons and the size of synaptic boutons immunohistochemically on serial semithin sections in both Lurcher and wild-type mice. Applying the physical dissector counting method, our results confirmed the mild degeneration (a reduction by 20%) of large glutamatergic neurons and a more pronounced degeneration of GABAergic (by 42%) and glycinergic neurons (by 45%). On the other hand, an analysis of neurons colabeled for both GABA and glycine, revealed that this specific colabeling increased in the Lurcher mutant (by 40%). In addition, both the GABA-immunolabeled (IL) (by 56%) and the glycine-IL (by 45%) synaptic boutons showed an increase in diameter in the mutant. The density of these boutons showed a decrease of 30% each. In summary, the increase in the number of neurons colabeled for GABA and glycine, together with the increase in the size of the inhibitory synaptic boutons, could help in providing the minimum inhibition needed to maintain a residual "cerebellar" functionality in the Lurcher DCN.

Animals↗