Peter Thier

Parietal lobe contributions to orientation in 3D space

An overview of current thinking in parietal lobe functions. The text is divided into five sections dealing with the areas of functional anatomy and specific contributions of the parietal lobes to eye movements; reaching and grasping; attention and perception; and the representation of space. It includes recent findings that emphasize their general implications for an understanding of the role of parietal lobe processing. The book aims to unite neurophysiological and neuropsychological approaches. It reviews work based on monkeys and on the study of patients with parietal lobe lesions. The interrelationship of the two is discussed.

Gain Modulation: A Major Computational Principle of the Central Nervous System

A Brief History of Gain Fields The seminal problem is about locating objects in the world (Figure 1a). Imagine you are reading the newspaper. You look for your teacup and reach for it. After a sip, you leave the cup in the same place and continue Emilio Salinas*‡ and Peter Thier† *Computational Neurobiology Laboratory Howard Hughes Medical Institute The Salk Institute for Biological Studies 10010 North Torrey Pines Road reading. Now you reach for the cup again, but this time La Jolla, California 92037 you don’t shift your gaze, you use your peripheral vision †Department of Cognitive Neurology to locate the cup. In the two cases, the arm movements University of Tübingen toward the target are identical and its location in space Hoppe-Seyler-Strasse 3 is the same, yet the reaching movements are guided by 72076 Tübingen different images on the retina. Therefore, to reach the Germany cup, a coordinate transformation is required that takes into account the position of the eyes. Where and how are such transformations performed by the brain? A lot is known about how neurons in the brain represent For almost 100 years, work on patients and experithe physical world. In comparison, little is known about mental animals have implicated the posterior parietal how neurons compute, how they transform, combine, cortex (PPC) in spatial vision and in the visual guidance or compare those representations. Although the mechaof movement (for review, see Thier and Karnath, 1997). nisms underlying many single computations have been In the mid 70s, Vernon Mountcastle and colleagues reunraveled (Churchland and Sejnowski, 1992), researchcorded from the PPC of awake monkeys and found ers ultimately seek mechanisms that pervade multiple neurons that discharged immediately before a visually modalities, brain areas, and functions, and the problem guided saccade toward a peripheral target, provided is that these kinds of unifying computational principles that the direction of this saccade corresponded to the have rarely been identified. In the last two decades, preferred direction of the neuron (Lynch et al., 1977). however, gain modulation has emerged as such a neural These neurons seemed to encode a saccade command computational principle—maybe the most general one represented by a vector, in retinal coordinates, from the found so far. This motivated Richard Andersen from target image to the fovea. This vector is independent of Caltech and Larry Abbott from Brandeis University to the position of the eyes relative to the head, so the organize a meeting, sponsored by the Sloan Foundation, discharge of these neurons was expected to be insensithat brought together an international group of physiolotive to eye position. In the early 80s, Richard Andersen gists and theoreticians to a secluded resort in Monterey worked as a postdoc in Mountcastle’s laboratory. When Bay. Here the state of affairs in this subject, after 20 they tested this prediction from the simple retinal coding years of research, was scrutinized. scheme for saccades, they found exactly the opposite: Gain modulation is a change in the response amplineurons in parietal area 7a were highly sensitive to eye tude of a neuron that is independent of its selectivity or position (Andersen and Mountcastle, 1983). receptive field characteristics (although sometimes it is Andersen and collaborators later quantified the dedifficult to draw the line between selectivity proper and pendency of neuronal activity on gaze direction (Andermodulation, as was discussed during the meeting). It is sen et al., 1985; Andersen, 1989; Brotchie et al., 1995). a nonlinear way to combine or integrate information from In their experiments, eye position was first held fixed, different sensory, motor, and cognitive modalities. Much and the response of a parietal neuron was plotted as of the excitement about gain fields has been spurred a function of the position of a spot of light in retinal by theoretical considerations: these distributed, multicoordinates (Figure 1b). We call this position x. Typically, modal representations are ideally configured to facilitate the resulting curve had a single peak that could be fitted certain kinds of computations, most prominently, coorby a Gaussian function; we refer to it as f(x). Then the dinate transformations. Theoreticians have investigated measurements were repeated using a different fixation primarily how gain fields can be used to perform useful point and thus a different gaze direction, y. In this case, the neural responses followed curves with similar computations and how the cortical microcircuitry may shapes and preferred locations, but their amplitudes give rise to multiplicative interactions, which are the changed. Thus, the amplitude or gain of the receptive trademark of gain modulation. On the other hand, the fields of these parietal neurons depended on gaze. The experimental camp has focused on the role of gain fields term “gain field” was coined to describe this gazein sensory–motor integration and have used them to dependent gain modulation. The gain field refers to the obtain clues about the functions of different brain areas. function g(y), where the firing rates of these neurons are As a result, gain fields have been implicated in eye and well fitted by the expression reaching movements, spatial perception, attention, navigation, and object recognition. r 5 f(x)g(y). (1)

Saccadic Dysmetria and Adaptation after Lesions of the Cerebellar Cortex

We studied the effects of small lesions of the oculomotor vermis of the cerebellar cortex on the ability of monkeys to execute and adapt saccadic eye movements. For saccades in one horizontal direction, the lesions led to an initial gross hypometria and a permanent abolition of the capacity for rapid adaptation. Mean saccade amplitude recovered from the initial hypometria, although variability remained high. A series of hundreds of repetitive saccades in the same direction resulted in gradual decrement of amplitude. Saccades in other directions were less strongly affected by the lesions. We suggest the following. (1) The cerebellar cortex is constantly recalibrating the saccadic system, thus compensating for rapid biomechanical changes such as might be caused by muscle fatigue. (2) A mechanism capable of slow recovery from dysmetria is revealed despite the permanent absence of rapid adaptation.

Mirror Neurons Differentially Encode the Peripersonal and Extrapersonal Space of Monkeys

Actions performed by others may have different relevance for the observer, and thus lead to different behavioral responses, depending on the regions of space in which they are executed. We found that in rhesus monkeys, the premotor cortex neurons activated by both the execution and the observation of motor acts (mirror neurons) are differentially modulated by the location in space of the observed motor acts relative to the monkey, with about half of them preferring either the monkeys peripersonal or extrapersonal space. A portion of these spatially selective mirror neurons encode space according to a metric representation, whereas other neurons encode space in operational terms, changing their properties according to the possibility that the monkey will interact with the object. These results suggest that a set of mirror neurons encodes the observed motor acts not only for action understanding, but also to analyze such acts in terms of features that are relevant to generating appropriate behaviors.

A neuronal correlate of spatial stability during periods of self-induced visual motion

SummaryMotion of background visual images across the retina during slow tracking eye movements is usually not consciously perceived so long as the retinal image motion results entirely from the voluntary slow eye movement (otherwise the surround would appear to move during pursuit eye movements). To address the question of where in the brain such filtering might occur, the responses of cells in 3 visuo-cortical areas of macaque monkeys were compared when retinal image motion of background images was caused by object motion as opposed to a pursuit eye movement. While almost all cells in areas V4 and MT responded indiscriminately to retinal image motion arising from any source, most of those recorded in the dorsal zone of area MST (MSTd), as well as a smaller proportion in lateral MST (MST1), responded preferentially to externally-induced motion and only weakly or not at all to self-induced visual motion. Such cells preserve visuo-spatial stability during low-velocity voluntary eye movements and could contribute to the process of providing consistent spatial orientation regardless of whether the eyes are moving or stationary.

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 ones own actions [1, 2, 3, 4, 5 and 6].

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.

Reduced saccadic resilience and impaired saccadic adaptation due to cerebellar disease

The term short‐term saccadic adaptation (STSA) captures our ability to unconsciously move the endpoint of a saccade to the final position of a visual target that has jumped to a new location during the saccade. STSA depends on the integrity of the cerebellar vermis. We tested the hypothesis that STSA reflects the working of a cerebellar mechanism needed to avoid ‘fatigue’, a gradual drop in saccade amplitude during a long series of stereotypic saccades. To this end we compared the kinematics of saccades of 14 patients suffering from different forms of cerebellar disease with those of controls in two tests of STSA and a test of saccadic resilience. Controls showed an increase in saccade amplitude (SA) for outward adaptation, prompted by outward target shifts, due to an increase in saccade duration (SD) in the face of constant peak velocity (PV). The decrease in SA due to inward adaptation was, contrariwise, accompanied by a drop in PV and SD. Whereas patients with intact vermis did not differ from controls, those with vermal pathology lacked outward adaptation: SD remained constant, as did SA and PV. In contrast, vermal patients demonstrated a significant decrease in SA, paralleled by a decrease in PV but mostly unaltered SD in the inward adaptation experiment as well as in the resilience test. These findings support the notion that inward adaptation is at least partially based on uncompensated fatigue. On the other hand, outward adaptation reflects an active mechanism for the compensation of fatigue, residing in the cerebellum.

The cerebellum updates predictions about the visual consequences of one's behavior.

Each action has sensory consequences that need to be distinguished from sensations arising from the environment. This is accomplished by the comparing of internal predictions about these consequences with the actual afference, thereby isolating the afferent component that is self-produced. Because the sensory consequences of actions vary as a result of changes of the effectors efficacy, internal predictions need to be updated continuously and on a short time scale. Here, we tested the hypothesis that this updating of predictions about the sensory consequences of actions is mediated by the cerebellum, a notion that parallels the cerebellums role in motor learning. Patients with cerebellar lesions and their matched controls were equally able to detect experimental modifications of visual feedback about their pointing movements. When such feedback was constantly rotated, both groups instantly attributed the visual feedback to their own actions. However, in interleaved trials without actual feedback, patients did no longer account for this feedback rotation--neither perceptually nor with respect to motor performance. Both deficits can be explained by an impaired updating of internal predictions about the sensory consequences of actions caused by cerebellar pathology. Thus, the cerebellum guarantees both precise performance and veridical perceptual interpretation of actions.

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.