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P Thier

Publications and source records attributed to P Thier.

At least 37 records · Page 2Linked to original sources

Electrical microstimulation distinguishes distinct saccade-related areas in the posterior parietal cortex.

Electrical microstimulation (0.1-ms bipolar pulses at 500 Hz, current strength usually between 100 and 200 microA) was used to delineate saccade-related areas in the posterior parietal cortex of monkeys. Stimulation-induced saccades were found to be restricted to the lateral intraparietal area (area LIP) in the intraparietal sulcus (IPS) and a region on the medial aspect of the parietal lobe (area MP, medial parietal area), close to the caudal end of the cingulate sulcus, whereas stimulation of area 7a did not evoke eye movements. Two different types of evoked saccades were observed. Modified vector saccades, whose amplitude was modified by the position of the eyes at stimulation onset were the hallmark of sites in area LIP and area MP. The same sites were characterized by a propensity of single units active in the memory and presaccadic response segments of the memory saccade paradigm. Goal-directed saccades driving the eyes toward a circumscribed region relative to the head were largely restricted to a small strip of cortex on the lateral bank and the floor of the IPS (the intercalated zone), separating the representation of upward and downward directed saccades in LIP. Unlike stimulation in LIP or MP, stimulation in the intercalated zone gave rise to head, pinnae, facial, and shoulder movements accompanying the evoked saccades. We propose that the amplitude modification of vector saccades characterizing LIP and MP may reflect a spatially distributed head-centered coding scheme for saccades. On the other hand, the goal-directed saccades found in the intercalated zone could indicate the use of a spatially much more localized representation of desired location in head-centered space.

Animals↗

An electrophysiological correlate of visual motion awareness in man.

It is usually held that perceptual spatial stability, despite smooth pursuit eye movements, is accomplished by comparing a signal reflecting retinal image slip with an internal reference signal, encoding the 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. In an attempt to localize the cortical networks underlying this comparison and therefore our subjective percept of visual motion, we exploited an imperfection inherent in it, which results in a movement illusion. If smooth pursuit is carried out across a stationary background, we perceive a tiny degree of illusionary background motion (Filehne illusion, or FI), rather than experiencing the ecologically optimal percept of stationarity. We have recently shown that this illusion can be modified substantially and predictably under laboratory conditions by visual motion unrelated to the eye movement. By making use of this finding, we were able to compare cortical potentials evoked by pursuit-induced retinal image slip under two conditions, which differed perceptually, while being identical physically. This approach allowed us to discern a pair of potentials, a parieto-occipital negativity (N300) followed by a frontal positivity (P300), whose amplitudes were solely determined by the subjective perception of visual motion irrespective of the physical attributes of the situation. This finding strongly suggests that subjective awareness of visual motion depends on neuronal activity in a parieto-occipito-frontal network, which excludes the early stages of visual processing.

Adult↗

False perception of motion in a patient who cannot compensate for eye movements.

We are usually unaware of the motion of an image across our retina that results from our own movement. For instance, during slow-tracking eye movements we do not mistake the shift of the image projected onto the retina for motion of the world around us, but instead perceive a stable world. Following early suggestions by von Helmholtz, it is commonly believed that this spatial stability is achieved by subtracting the retinal motion signal from an internal reference signal, such as a copy of the movement command (efference copy). Object motion is perceived only if the two differ. Although this concept is widely accepted, its anatomical underpinning remains unknown. Here we describe the case of a patient with bilateral extrastriate cortex lesions, suffering from false perception of motion due to an inability to take eye movements into account when faced with self-induced retinal image slip. This is indicated by the fact that during smooth-pursuit eye movements, he perceives motion of the stationary world at a velocity that corresponds to the velocity of his eye movement; that is, he perceives the raw retinal image slip uncorrected for his own eye movements. We suspect that this deficiency reflects damage of a distinct parieto-occipital region that disentangles self-induced and externally induced visual motion by comparing retinal signals with a reference signal encoding eye movements and possibly ego-motion in general.

Adult↗

[Cortical vertigo].

Dizziness of cortical origin is the subjective correlate of a disturbance of spatial orientation resulting from cerebrocortical dysfunction. Cortical dizziness in the form of vertigo is rare. If present, it most probably reflects a dysfunction of a vestibular representation in the insula. It may be accompanied by tinnitus, sensory disturbance and possibly also spontaneous nystagmus. The dysfunction of this region may result either from a focal seizure or from a lesion, for instance due to ischemia. Nondirectional, visual dizziness is most probably much more common than vertigo. This latter type of dizziness results from a functional disturbance of those parts of parietooccipital cortex, contributing to the discrimination of self-induced and externally-induced retinal image slip. It is not accompanied by additional symptoms and should immediately cease upon closure of the eyes or avoidance of ego motion.

Brain Mapping↗

Comparison of psychophysical and evoked potential methods in the detection of visual deficits in multiple sclerosis.

We compared the diagnostic sensitivity of traditional visual tests such as the Snellen-test and pattern reversal VEPs with psychophysical and electrophysiological tests involving motion processing and psychophysical tests of contrast processing in detecting visual deficits in a group of MS patients. A total of 30 patients with a definite diagnosis of MS and 22 age-matched controls selected from a pool of healthy volunteers participated in this study. Visual evoked potentials elicited by reversing checkerboards and moving random dot patterns (motion-onset VEPs) were recorded. The recognition of motion-defined forms (motion-defined letter test, MDL-test) and of contrast reduced optotypes was measured psychophysically. Of 30 patients, 29 showed deficits in at least one of the tests applied. The highest detection rate was obtained for a simple psychophysical test, the MDL-test, which revealed abnormalities in 80% of the patients. This is about 12% more than pattern VEPs could detect. Conversely, abnormalities in motion-onset VEPs were found in only 16% of the patients. Our results show that by adding a simple psychophysical test of form-from-motion analysis our capability to demonstrate an involvement of the visual system in MS patients may be promoted considerably.

Adult↗

Electrophysiological properties of rat pontine nuclei neurons In vitro. I. Membrane potentials and firing patterns.

We used a new slice preparation of rat brain stem to establish the basic membrane properties of neurons in the pontine nuclei (PN). Using standard intracellular recordings, we found that pontine cells displayed a resting membrane potential of -63 +/- 6 mV (mean +/- SD), an input resistance of 53 +/- 21 MOmega, a membrane time constant of 5.3 +/- 2.4 ms and were not spontaneously active. The current-voltage relationship of most of the PN neurons showed the characteristics of inward rectification in both depolarizing and hyperpolarizing directions. A prominent feature of the firing of pontine neurons was a marked firing rate adaptation, which eventually caused the cells to cease firing. Several types of membrane conductances possibly contribute to this feature. For one, a medium and a slow type of afterhyperpolarization (AHP) control the pattern of firing. The medium AHP was partly susceptible to blockade of calcium influx, whereas it was abolished completely by blockade of potassium channels with tetraethylammonium, indicating that it is based on at least two conductances: a calcium-dependent and a calcium-independent one. The slow AHP was carried by potassium ions and could be blocked effectively by preventing calcium influx into the cell. It was present after single spikes but was strongest after a high-frequency spike train. Calcium entry into the cell was mediated by high-threshold calcium channels that were detected by the generation of calcium spikes under blockade of potassium channels. Furthermore, the early phase of the firing rate adaptation was shown to be related to the time course of a slow, tetrodotoxin (TTX)-sensitive, persistent sodium potential, which was activated already in the subthreshold range of membrane potentials. This potential was time dependent and imposed as a depolarizing "hump" with a maximum occurring in most cases between 50 and 100 ms after stimulus onset. In the suprathreshold range, it generated plateau potentials following fast spikes, if potassium channels were blocked. After the complete adaptation of the firing rate, PN neurons were observed to display irregular fluctuations of the membrane potential, which sometimes reached firing threshold thereby eliciting an irregular low-frequency spike train. As these fluctuations could be blocked with TTX, they probably are based on the persistent sodium currents. The opposing drive in hyperpolarizing direction may be provided by strong outward currents that generated a marked outward rectification in the current-voltage relationship under TTX. In conclusion, PN neurons show complex membrane properties that are reminiscent in many ways to cerebrocortical "regular firing" neurons.

Animals↗

Electrophysiological properties of rat pontine nuclei neurons In vitro II. Postsynaptic potentials.

We investigated the postsynaptic responses of neurons of the rat pontine nuclei (PN) by performing intracellular recordings in parasagittal slices of the pontine brain stem. Postsynaptic potentials (PSPs) were evoked by brief (0.1 ms) negative current pulses (10-250 microA) applied to either the cerebral peduncle or the pontine tegmentum. First, excitatory postsynaptic potentials (EPSPs) could be evoked readily from peduncular stimulation sites. These EPSPs exhibited short latencies, a nonlinear increment in response to increased stimulation currents, and an unconventional dependency on the somatic membrane potential. Pharmacological blockade of the synaptic transmission using 6,7-dinitroquinoxaline-2, 3-dione and ,-2-amino-5-phosphonovaleric acid, selective antagonists of the alpha-amino-3-hydroxy-5-methyl-4-isoxazilepropionate- (AMPA) and the N-methyl--aspartate (NMDA)-type glutamate receptors, showed that these EPSPs were mediated exclusively by excitatory amino acids via both AMPA and NMDA receptors. Moreover, the pharmacological experiments indicated the existence of voltage-sensitive but NMDA receptor-independent amplification of EPSPs. Second, stimulations at peduncular and tegmental sites also elicited inhibitory postsynaptic potentials (IPSPs) in a substantial proportion of pontine neurons. The short latencies of all IPSPs argued against the participation of inhibitory interneurons. Their sensitivity to bicuculline and reversal potentials around -70 mV suggested that they were mediated by gamma-aminobutyric acid-A (GABAA) receptors. In addition to single PSPs, sequences consisting of two to four distinct EPSPs could be recorded after stimulation of the cerebral peduncle. Most remarkably, the onset latencies of the following EPSPs were multiples of the first one indicating the involvement of intercalated synapses. Finally, we used the classic paired-pulse paradigm to study whether the temporal structure of inputs influences the synaptic transmission onto pontine neurons. Pairs of electrical stimuli applied to the cerebral peduncle resulted in a marked enhancement of the amplitude of the second EPSP for interstimulus intervals of 10-100 ms. Delays >200 ms left the EPSP amplitude unaltered. These data provide evidence for a complex synaptic integration and an intrinsic connectivity within the PN too elaborate to support the previous notion that the PN are simply a relay station.

Animals↗

Comparison of projection neurons in the pontine nuclei and the nucleus reticularis tegmenti pontis of the rat.

Dendritic features of identified projection neurons in two precerebellar nuclei, the pontine nuclei (PN) and the nucleus reticularis tegmenti pontis (NRTP) were established by using a combination of retrograde tracing (injection of fluorogold or rhodamine labelled latex micro-spheres into the cerebellum) with subsequent intracellular filling (lucifer yellow) in fixed slices of pontine brainstem. A multivariate analysis revealed that parameters selected to characterize the dendritic tree such as size of dendritic field, number of branching points, and length of terminal dendrites did not deviate significantly between different regions of the PN and the NRTP. On the other hand, projection neurons in ventral regions of the PN were characterized by an irregular coverage of their distal dendrites by appendages while those in the dorsal PN and the NRTP were virtually devoid of them. The NRTP, dorsal, and medial PN tended to display larger somata and more primary dendrites than ventral regions of the PN. These differences, however, do not allow the differentiation of projection neurons within the PN from those in the NRTP. They rather reflect a dorso-ventral gradient ignoring the border between the nuclei. Accordingly, a cluster analysis did not differentiate distinct types of projection neurons within the total sample. In both nuclei, multiple linear regression analysis revealed that the size of dendritic fields was strongly correlated with the length of terminal dendrites while it did not depend on other parameters of the dendritic field. Thus, larger dendritic fields seem not to be accompanied by a higher complexity but rather may be used to extend the reach of a projection neuron within the arrangement of afferent terminals. We suggest that these similarities within dendritic properties in PN and NRTP projection neurons reflect similar processing of afferent information in both precerebellar nuclei.

Animals↗

Electrical microstimulation suggests two different forms of representation of head-centered space in the intraparietal sulcus of rhesus monkeys.

We examined the effects of eye position on saccades evoked by electrical stimulation of the intraparietal sulcus (IPS) of rhesus monkeys. Microstimulation evoked saccades from sites on the posterior bank, floor, and the medial bank of the IPS. The size and direction of the eye movements varied as a function of initial eye position before microstimulation. At many stimulation sites, eye position affected primarily the amplitude and not the direction of the evoked saccades. These "modified vector saccades" were characteristic of most stimulation-sensitive zones in the IPS, with the exception of a narrow strip located mainly on the floor of the sulcus. Stimulation in this "intercalated zone" evoked saccades that moved the eyes into a particular region in head-centered space, independent of the starting position of the eyes. This latter response is compatible with the stimulation site representing a goal zone in head-centered coordinates. On the other hand, the modified vector saccades observed outside the intercalated zone are indicative of a more distributed representation of head-centered space. A convergent projection from many modified vector sites onto each intercalated site may be a basis for a transition from a distributed to a more explicit representation of space in head-centered coordinates.

Animals↗

Different effects of visual deprivation on vasoactive intestinal polypeptide (VIP)-containing cells in the retinas of juvenile and adult rats.

Vasoactive intestinal polypeptide (VIP) is a 28 amino acid peptide that has been shown to be present in a distinct subset of retinal amacrine cells (VIP+ cells). Previous work has suggested that the expression of retinal VIP might depend on the lighting conditions prevailing. Reasoning that a careful analysis of the exact conditions of this interaction and its time course might offer clues to the functional role of retinal VIP, we performed a quantitative immunohistochemical analysis of the effects of visual deprivation on the retinal VIP+ system in adult and in visually inexperienced neonatal rats. In adult rats visual deprivation caused a marked suppression of VIP-like immunoreactivity (IR) in both somata and processes of VIP+ cells which increased linearly over time, reducing the number of VIP+ cells to about 30% of the control value after approximately 50 days of deprivation. The observed changes were specific for VIP and were independent of the form of deprivation used (monocular lid suture versus keeping rats in constant darkness). However, the effects of visual deprivation were dependent on the developmental state of the rats, since juvenile rats without previous visual experience exhibited a decrease in VIP+ cells and fibers which was much smaller and occurred significantly slower than in adult rats. The suppression of VIP-like IR was completely reversible in both juvenile and adult rats when previously deprived rats were returned to a normal visual environment.

Aging↗

Modification of the Filehne illusion by conditioning visual stimuli.

During smooth pursuit eye movements made across a stationary background an illusory motion of the background is perceived (Filehne illusion). The present study was undertaken in order to test if the Filehne illusion can be influenced by information unrelated to the retinal image slip prevailing and to the eye movement being executed. The Filehne illusion was measured in eight subjects by determining the amount of external background motion required to compensate for the illusory background motion induced by 12 deg/sec rightward smooth pursuit. Using a two-alternative forced-choice method, test trials, which yielded the estimate of the Filehne illusion, were randomly interleaved with conditioning trials, in which high retinal image slip was created by background stimuli moving at a constant horizontal velocity. There was a highly reproducible monotic relationship between the size and direction of the Filehne illusion and the velocity of the background stimulus in the conditioning trials with the following extremes: large Filehne illusions with illusory motion to the right occurred for conditioning stimuli moving to the left, i.e. opposite to the direction of eye movement in the test trials, while conversely, conditioning stimuli moving to the right yielded Filehne illusions close to zero. Additional controls suggest that passive motion aftereffects are unlikely to account for the modulation of the Filehne illusion by the conditioning stimulus. We hypothesize that this modification might reflect the dynamic character of the networks elaborating spatial constancy.

Adult↗

Inability of rhesus monkey area V1 to discriminate between self-induced and externally induced retinal image slip.

Retinal image slip can result from an eye movement across a stationary object or alternatively from motion of the object while the eyes are stationary. The ability to discriminate between these two kinds of retinal image slip is necessary for the perception of a stable visual world. In order to determine if this ability is already present in monkey visual area V1, we asked if single V1 units are able to differentiate between externally and self-induced retinal image slip. Externally induced retinal image slip was realized in the 'object motion' condition (OMC) by moving a behaviourally irrelevant visual stimulus ('object': a bar or a large random dot pattern) across the receptive field while the monkey fixated a small, stationary target. Conversely, self-induced retinal image slip of comparable size was evoked in the 'ego motion' condition (EMC) by asking the monkey to pursue the target, moving at the speed of the object in the OMC, while the object was kept stationary. We recorded 221 units from visual area V1, 51, (23%) of them directionally selective, and compared their responses to self-induced and externally induced retinal image slip. Many of them seemed to give some preference to externally induced retinal image slip. However, on closer examination it became clear that this seeming preference could be attributed to the fact that oculomotor performance was less precise in the EMC than in the OMC, causing a larger deviation from the optimal retinal image trajectory in the EMC. We show that the impact of eye position errors can be eliminated by the use of a position-invariant stimulus, such as large-field random dot patterns. We then show that the impact of both eye position errors and deviation of eye velocity from target velocity in the EMC can be eliminated by moving the stimulus in a given OMC trial according to an inverted replica of the eye movement trajectory in the preceding EMC trial, guaranteeing identical retinal stimulation in the OMC and the EMC. If identical retinal stimulation was ensured, none of the V1 units tested was able to differentiate between externally and self-induced retinal image slip. We conclude that V1 does not contribute to the perception of a world which is stable despite eye movements.

Animals↗

Brainstem afferents to the lateral mesencephalic tegmental region of the cat.

The lateral mesencephalic tegmental region (LTR) is a part of the midbrain reticular formation characterized by the presence of neurons exhibiting head movement-related discharge modulation. In addition, the LTR contains directionally selective visual units. Possible sources for these vestibular and visual signals were studied by retrograde axonal transport of horseradish peroxidase and three different fluorescent tracers (rhodamine, fast blue, and fluorogold) injected into various parts of the LTR. All injections into the LTR traced afferents from the vestibular nuclei and from the nucleus prepositus hypoglossi. Predominant projections were derived from the ipsilateral nucleus prepositus hypoglossi and the ipsilateral medial vestibular nucleus, whereas the observed inputs from the inferior, lateral, and superior vestibular nuclei were much weaker. Further inputs to the LTR originated in the deep and intermediate layers of the ipsilateral superior colliculus and the ipsilateral periaqueductal gray, the contralateral LTR, and the contralateral marginal nucleus of the brachium conjunctivum. Tracer deposits in medial parts of the tegmentum neighboring the LTR never produced the pattern of afferents observed after injections into the LTR. Our results suggest that afferents from the deeper layers of the superior colliculus are probably the source of visual signals in the LTR and that head movement-related responses are likely to be derived from the nucleus prepositus hypoglossi and the medial vestibular nucleus.

Afferent Pathways↗

The influence of structured visual backgrounds on smooth-pursuit initiation, steady-state pursuit and smooth-pursuit termination.

Smooth-pursuit eye movements were recorded in two rhesus monkeys in order to compare the influence of structured visual backgrounds on smooth-pursuit initiation, steady-state pursuit and pursuit termination. Different target trajectories were used in order to study smooth-pursuit initiation and termination. The influence of visual backgrounds on pursuit initiation was characterized by recording ocular responses elicited by step-ramp target displacements starting from straight ahead. Pursuit termination was characterized by analysing the transition from steady-state smooth-pursuit to fixation when a centripetally directed target ramp was terminated by a small target step in the direction of the ramp as soon as the target had come close to the straightahead position. The quantification of steady-state pursuit was based on ocular responses elicited by either paradigm. In accordance with previous work, we found that the onset of smooth-pursuit eye movements was delayed and initial eye acceleration reduced in the presence of a structured visual background. Likewise, mean eye velocity during steady-state pursuit was reduced by structured visual backgrounds. However, neither the latency nor the time course of smooth-pursuit termination was altered when the homogeneous background was replaced by a structured visual background. The lack of sensitivity of pursuit termination to the presence of visual structured backgrounds supports a previous contention that pursuit termination is mediated by a process which is different from the ones mediating smooth-pursuit initiation and steady-state pursuit. The absence of any noticeable effect of structured backgrounds on pursuit termination suggests that at least the fast component of the optokinetic reflex is suppressed during pursuit termination.

Algorithms↗

Modular organization of the pontine nuclei: dendritic fields of identified pontine projection neurons in the rat respect the borders of cortical afferent fields.

Cortical afferents transferring information destined for the cerebellum terminate in the pontine nuclei (PN) in a divergent and patchy fashion. We investigated whether the form of dendritic fields of pontine projection neurons which are postsynaptic to the cortical afferents are related to this patchy pattern. To this end we used a triple combination of (1) retrograde labeling (injection of Fluorogold into the brachium pontis), (2) anterograde labeling [injection of Dil into cortical areas A17 and Sml(forelimb)], and (3) subsequent intracellular fills of identified projection neurons (Lucifer yellow) in slightly fixed slices of pontine brainstem. In 64 projection neurons whose somata were located within 160 microns of the border defined by cortical afferent fields, most of the dendritic trees were found to respect the border. Strikingly, proximal dendrites which were oriented toward the border often bent in order to avoid the boundary. This observation was supported by a quantitative analysis. It revealed that overlap areas of dendritic fields with the neighboring compartment were significantly smaller than those of hypothetical, radially organized dendritic fields of the same size, indicating that the dendritic fields are indeed confined to single compartments. In a second series of experiments, double injections of the anterograde tracers Dil and DiAsp into adjacent sites within one cortical area (A17 or Sml) were made in order to test if the topology of the cortical map is preserved within individual pontine compartments. This, however, does not seem to be the case, since the terminal fields displayed a complex pattern of overlap and nonoverlap rather than a consistent shift of terminal fields expected in the case of preserved topology. The results of the present study are consistent with the view that pontine modules independently process information from different parts of individual cortical areas. We suggest that this characteristic property of the corticopontine projection system might be the morphological basis of the well established fact that somatotopically continuous sensory maps in the cortex are transformed into maps at the level of the cerebellar cortex, showing a fractured somatotopy.

Afferent Pathways↗

Patterns of projections from the pontine nuclei and the nucleus reticularis tegmenti pontis to the posterior vermis in the rhesus monkey: a study using retrograde tracers.

In an attempt to estimate the relative importance of the various afferent systems impinging on the oculomotor regions of the posterior cerebellar vermis of rhesus monkeys in quantitative terms, we made small injections of the retrograde tracers fast blue, fluorogold, and cholera toxin into different parts of a region of the posterior vermis, spanning lobuli VI through VIII. We found that the vast majority of cells retrogradely labeled by injections of lobulus VII and its vicinity lay in the pontine nuclei (PN), the nucleus reticularis tegmenti pontis (NRTP), and subnuclei a and b of the medial accessory olive. The remaining retrogradely labeled cells were distributed among a number of other brainstem nuclei or regions including the paramedian pontine reticular formation (PPRF). A quantitative analysis showed that the projection from the NRTP to the posterior vermis was focused on lobulus VII. While the projection from the PN as a whole demonstrated a preference for the more caudal parts of the posterior vermis, a closer look at the different regions of the PN revealed that cells located in the dorsal parts of the PN showed the same preference for lobulus VII as cells in the NRTP. The dorsal PN are a major gateway for cortical input to the cerebellum, related to visual processing and visually guided eye movements. Conversely, the NRTP, likewise involved in visually guided eye movements, is much more dependent on subcortical afferents. The observed convergence of input derived from the dorsal PN and the NRTP in oculomotor lobulus VII therefore suggests that a major function of this part of the vermis might be the integration of cortical and subcortical signals important for visually guided eye movements.

Afferent Pathways↗