A generative learning model for saccade adaptation.

Plasticity in the oculomotor system ensures that saccadic eye movements reliably meet their visual goals-to bring regions of interest into foveal, high-acuity vision. Here, we present a comprehensive description of sensorimotor learning in saccades. We induced continuous adaptation of saccade amplitudes using a double-step paradigm, in which participants saccade to a peripheral target stimulus, which then undergoes a surreptitious, intra-saccadic shift (ISS) as the eyes are in flight. In our experiments, the ISS followed a systematic variation, increasing or decreasing from one saccade to the next as a sinusoidal function of the trial number. Over a large range of frequencies, we confirm that adaptation gain shows (1) a periodic response, reflecting the frequency of the ISS with a delay of a number of trials, and (2) a simultaneous drift towards lower saccade gains. We then show that state-space-based linear time-invariant systems (LTIS) represent suitable generative models for this evolution of saccade gain over time. This state-equation algorithm computes the prediction of an internal (or hidden state-) variable by learning from recent feedback errors, and it can be compared to experimentally observed adaptation gain. The algorithm also includes a forgetting rate that quantifies per-trial leaks in the adaptation gain, as well as a systematic, non-error-based bias. Finally, we study how the parameters of the generative models depend on features of the ISS. Driven by a sinusoidal disturbance, the state-equation admits an exact analytical solution that expresses the parameters of the phenomenological description as functions of those of the generative model. Together with statistical model selection criteria, we use these correspondences to characterize and refine the structure of compatible state-equation models. We discuss the relation of these findings to established results and suggest that they may guide further design of experimental research across domains of sensorimotor adaptation.

Cross-modal effects of value on perceptual acuity and stimulus encoding.

Cross-modal interactions are very common in perception. An important feature of many perceptual stimuli is their reward-predicting properties, the utilization of which is essential for adaptive behavior. What is unknown is whether reward associations in one sensory modality influence perception of stimuli in another modality. Here we show that auditory stimuli with high-reward associations increase the sensitivity of visual perception, even when sounds and reward associations are both irrelevant for the visual task. This increased sensitivity correlates with a change in stimulus representation in the visual cortex, indexed by increased multivariate decoding accuracy in simultaneously acquired functional MRI data. Univariate analysis showed that reward associations modulated responses in regions associated with multisensory processing in which the strength of modulation was a better predictor of the magnitude of the behavioral effect than the modulation in classical reward regions. Our findings demonstrate a value-driven cross-modal interaction that affects perception and stimulus encoding, with a resemblance to well-described modulatory effects of attention. We suggest that multisensory processing areas may mediate the transfer of value signals across senses.

The influence of motivational salience on saccade latencies.

Eye movements provide a direct link to study the allocation of overt attention to stimuli in the visual field. The initiation of saccades towards visual stimuli is known to be influenced by the bottom-up salience of stimuli as well as the motivational context of the task. Here, we asked whether the initiation of saccades is also influenced by the intrinsic motivational salience of a stimulus. Face stimuli were first associated with positive or negative motivational salience through instrumental learning. The same faces served as target stimuli in a subsequent saccade task, in which their motivational salience was no longer task-relevant. Participants performed either voluntary saccades, which required the selection of the saccade target out of two simultaneously presented stimuli (experiment 1), or reactive saccades, where only the target stimulus was presented (experiment 2). We found a specific effect of learned positive stimulus value on the latencies of voluntary saccades: For faces with high versus low positive motivational salience, saccadic latencies were significantly reduced. No such difference was observed for previously punished faces. In contrast, reactive saccades to both previously rewarded and punished faces were unaffected by learned stimulus value. Our findings show for the first time that saccadic preparation is susceptible to the acquired intrinsic motivational salience of visual stimuli. Based on the observation that only voluntary saccades but not reactive saccades were modulated, we conclude that the recruitment of neural processes for target identification is required to allow for an influence of motivational stimulus salience on saccadic preparation.

Theta-burst stimulation over human frontal cortex distorts perceptual stability across eye movements.

We perceive a stable outside world despite the constant changes of visual input induced by our eye movements. Internal monitoring of a corollary discharge associated with oculomotor commands may help to anticipate the perceptual consequences of impending eye movements. The primate frontal eye fields have repeatedly been presumed to participate in the maintenance of perceptual stability across eye movements. However, a direct link between integrity of frontal oculomotor areas and perceptual stability is missing so far. Here, we show that transcranial magnetic stimulation (TMS) over the right human frontal cortex impairs the integration of visual space across eye movements. We asked 9 healthy subjects to report the direction of transsaccadic stimulus displacements and applied TMS before the actual experiment in a novel offline stimulation protocol, continuous theta-burst stimulation (cTBS). A systematic perceptual distortion was observed after stimulation over the right frontal cortex that was best explained by an internal underestimation of executed eye movement amplitudes. cTBS apparently disturbed an internal prediction process for contraversive saccades, while the metrics of associated oculomotor actions remained unchanged. Our findings suggest an important role of the frontal cortex in the internal monitoring of oculomotor actions for the perceptual integration of space across eye movements.

Human thalamus contributes to perceptual stability across eye movements.

We continuously move our eyes when we inspect a visual scene. Although this leads to a rapid succession of discontinuous and fragmented retinal snapshots, we perceive the world as stable and coherent. Neural mechanisms underlying visual stability may depend on internal monitoring of planned or ongoing eye movements. In the macaque brain, a pathway for the transmission of such signals has been identified that is relayed by central thalamic nuclei. Here, we studied a possible role of this pathway for perceptual stability in a patient with a selective lesion affecting homologous regions of the human thalamus. Compared with controls, the patient exhibited a unilateral deficit in monitoring his eye movements. This deficit was manifest by a systematic inaccuracy both in successive eye movements and in judging the locations of visual stimuli. In addition, perceptual consequences of oculomotor targeting errors were erroneously attributed to external stimulus changes. These findings show that the human brain draws on transthalamic monitoring signals to bridge the perceptual discontinuities generated by our eye movements.

Lesions affecting the right hippocampal formation differentially impair short-term memory of spatial and nonspatial associations.

Converging evidence from behavioral and imaging studies suggests that within the human medial temporal lobe (MTL) the hippocampal formation may be particularly involved in recognition memory of associative information. However, it is unclear whether the hippocampal formation processes all types of associations or whether there is a specialization for processing of associations involving spatial information. Here, we investigated this issue in six patients with postsurgical lesions of the right MTL affecting the hippocampal formation and in ten healthy controls. Subjects performed a battery of delayed match-to-sample tasks with two delays (900/5,000 ms) and three set sizes. Subjects were requested to remember either single features (colors, locations, shapes, letters) or feature associations (color-location, color-shape, color-letter). In the single-feature conditions, performance of patients did not differ from controls. In the association conditions, a significant delay-dependent deficit in memory of color-location associations was found. This deficit was largely independent of set size. By contrast, performance in the color-shape and color-letter conditions was normal. These findings support the hypothesis that a region within the right MTL, presumably the hippocampal formation, does not equally support all kinds of visual memory but rather has a bias for processing of associations involving spatial information. Recruitment of this region during memory tasks appears to depend both on processing type (associative/nonassociative) and to-be-remembered material (spatial/nonspatial).

Reorganization of associative memory in humans with long-standing hippocampal damage.

Conflicting theories have been advanced to explain why hippocampal lesions affect distinct memory domains and spare others. Recent findings in monkeys suggest that lesion-induced plasticity may contribute to the seeming preservation of some of these domains. We tested this hypothesis by investigating visuo-spatial associative memory in two patient groups with similar surgical lesions to the right medial temporal lobe, but different preoperative disease courses (benign brain tumours, mean: 1.8 +/- 0.6 years, n = 5, age: 28.2 +/- 4.0 years; hippocampal sclerosis, mean: 16.8 +/- 1.9 years, n = 9, age: 38.9 +/- 4.1 years). Compared to controls (n = 14), tumour patients showed a significant delay-dependent deficit in memory of colour-location associations. No such deficit was observed in hippocampal sclerosis patients, which appeared to benefit from a compensatory mechanism that was inefficient in tumour patients. These results indicate that long-standing hippocampal damage can yield significant functional reorganization of the neural substrate underlying memory in the human brain. We suppose that this process accounts for some of the discrepancies between results from previous lesion studies of the human medial temporal lobe.

Perisaccadic compression correlates with saccadic peak velocity: differential association of eye movement dynamics with perceptual mislocalization patterns.

Objects flashed around the onset of a saccadic eye movement are grossly mislocalized. Perisaccadic mislocalization has been related to a spatiotemporal misalignment of an extraretinal eye position signal with the corresponding saccade. Two phenomena have been observed: a systematic shift of perceived positions in saccade direction and an additional compression toward the saccade target. At present, it is unclear whether these two components of mislocalization are mediated by distinct mechanisms and how extraretinal signals may contribute to either of them. Moreover, the pattern and strength of perisaccadic mislocalization varies considerably across studies and even between subjects tested under identical conditions. Here, we investigated whether interindividual differences in saccade parameters are related to differences in mislocalization. We found that the individual strength of perceptual compression selectively correlates with the peak velocity of corresponding saccades. Other saccade parameters did not correlate with compression. No correlation was found between the shift component of perisaccadic mislocalization and any saccade parameter. This dissociation suggests that shift and compression components are, at least partially, mediated by distinct mechanisms. Because neuronal activity in the superior colliculus and downstream oculomotor areas has been shown to correlate with saccadic peak velocity, our findings support the notion that a reafferent extraretinal signal associated with saccadic motor commands may contribute to perisaccadic compression of perceived positions.

The human hippocampal formation mediates short-term memory of colour-location associations.

The medial temporal lobe (MTL) has long been considered essential for declarative long-term memory, whereas the fronto-parietal cortex is generally seen as the anatomical substrate of short-term memory. This traditional dichotomy is questioned by recent studies suggesting a possible role of the MTL for short-term memory. In addition, there is no consensus on a possible specialization of MTL sub-regions for memory of associative information. Here, we investigated short-term memory for single features and feature associations in three humans with post-surgical lesions affecting the right hippocampal formation and in 10 healthy controls. We used three delayed-match-to-sample tasks with two delays (900/5000 ms) and three set sizes (2/4/6 items). Subjects were instructed to remember either colours, locations or colour-location associations. In colour-only and location-only conditions, performance of patients did not differ from controls. By contrast, a significant group difference was found in the association condition at 5000 ms delay. This difference was largely independent of set size, thus suggesting that it cannot be explained by the increased complexity of the association condition. These findings show that the hippocampal formation plays a significant role for short-term memory of simple visuo-spatial associations, and suggest a specialization of MTL sub-regions for associative memory.

Integration of retinal and extraretinal information across eye movements.

Visual perception is burdened with a highly discontinuous input stream arising from saccadic eye movements. For successful integration into a coherent representation, the visuomotor system needs to deal with these self-induced perceptual changes and distinguish them from external motion. Forward models are one way to solve this problem where the brain uses internal monitoring signals associated with oculomotor commands to predict the visual consequences of corresponding eye movements during active exploration. Visual scenes typically contain a rich structure of spatial relational information, providing additional cues that may help disambiguate self-induced from external changes of perceptual input. We reasoned that a weighted integration of these two inherently noisy sources of information should lead to better perceptual estimates. Volunteer subjects performed a simple perceptual decision on the apparent displacement of a visual target, jumping unpredictably in sync with a saccadic eye movement. In a critical test condition, the target was presented together with a flanker object, where perceptual decisions could take into account the spatial distance between target and flanker object. Here, precision was better compared to control conditions in which target displacements could only be estimated from either extraretinal or visual relational information alone. Our findings suggest that under natural conditions, integration of visual space across eye movements is based upon close to optimal integration of both retinal and extraretinal pieces of information.

Target size modulates saccadic eye movements in humans.

The authors investigated mechanisms involved in transformation of spatially extended targets into saccadic eye-movement vectors. Human subjects performed horizontal saccades to targets of varying diameter, which contained no conspicuous elements within the target shape. With increasing target size, express saccades and saccades with fast regular latencies decreased in frequency, whereas frequency of saccades with slow regular latencies increased. For all targets, saccade amplitude distributions showed a peak close to the geometric center of the targets. However, with large targets, increased scatter of saccade amplitudes and increased undershoot of the target center was observed. These effects may reflect distinct subprocesses involved in sensorimotor transformation to spatially extended targets, and may result from modulation of neuronal activity in the superior colliculus.

Saccades to spatially extended targets: the role of eccentricity.

Size and eccentricity of visual targets are known to modulate saccade parameters. Here we asked for a possible interaction between these target properties. We investigated latency and amplitude of saccades to targets of varying diameter presented at various eccentricities in the visual field. Effects of target size on saccadic eye movements highly depended on eccentricity of saccade targets. For large saccade targets, latencies increased and mean amplitudes decreased mainly at parafoveal eccentricities. By contrast, scatter of saccade amplitudes increased nearly linearly with target size and eccentricity. These effects are consistent with the known functional anatomy of the superior colliculus. Size- and eccentricity-related changes in saccade parameters may depend on distinct subpopulations of collicular neurons.

A role of the human thalamus in predicting the perceptual consequences of eye movements.

Internal monitoring of oculomotor commands may help to anticipate and keep track of changes in perceptual input imposed by our eye movements. Neurophysiological studies in non-human primates identified corollary discharge (CD) signals of oculomotor commands that are conveyed via thalamus to frontal cortices. We tested whether disruption of these monitoring pathways on the thalamic level impairs the perceptual matching of visual input before and after an eye movement in human subjects. Fourteen patients with focal thalamic stroke and 20 healthy control subjects performed a task requiring a perceptual judgment across eye movements. Subjects reported the apparent displacement of a target cue that jumped unpredictably in sync with a saccadic eye movement. In a critical condition of this task, six patients exhibited clearly asymmetric perceptual performance for rightward vs. leftward saccade direction. Furthermore, perceptual judgments in seven patients systematically depended on oculomotor targeting errors, with self-generated targeting errors erroneously attributed to external stimulus jumps. Voxel-based lesion-symptom mapping identified an area in right central thalamus as critical for the perceptual matching of visual space across eye movements. Our findings suggest that trans-thalamic CD transmission decisively contributes to a correct prediction of the perceptual consequences of oculomotor actions.

A dysexecutive syndrome of the medial thalamus.

Thalamic stroke is associated with neurological and cognitive sequelae. Resulting neuropsychological deficits vary with the vascular territory involved. Whereas sensory, motor and memory deficits following thalamic stroke are comparatively well characterized, the exact relationship between executive dysfunction and thalamic damage remains more ambiguous. To assess the pattern of executive-cognitive deficits following thalamic stroke and its possible association with distinct thalamic nuclei, 19 patients with focal thalamic lesions were examined with high-resolution structural imaging and neuropsychological testing. Twenty healthy individuals served as controls. Patient MRIs were co-registered to an atlas of the human thalamus. Lesion overlap and subtraction analyses were used for lesion-to-symptom mapping. In eight patients (42.1%), neuropsychological assessment demonstrated a disproportionate deficit in the Wisconsin Card Sorting Test (WCST), while other executive and memory functions were much less affected. Subtraction analysis revealed an area in the left medial thalamus, mainly consisting of the centromedian and parafascicular nuclei (CM-Pf complex) that was damaged in these patients and spared in patients with normal WCST performance. Thus, damage to the CM-Pf complex may yield a distinct dysexecutive syndrome in which deficient maintenance and shifting between cognitive sets predominates. We hypothesize that the CM-Pf complex may contribute to maintenance and shifting of cognitive sets by virtue of its dense connections with the striatum. The pattern of executive dysfunction following thalamic stroke may vary considerably with lesion location.

Subjective cognitive-affective status following thalamic stroke.

Previous patient studies suggest that thalamic stroke may yield persistent deficits in several cognitive domains. At present, the subjective dimension and everyday relevance of these impairments is unclear, since many patients with thalamic stroke only show minor changes on physical examination. Here, we have studied subjective consequences of focal thalamic lesions. A sample of 68 patients with a history of ischemic thalamic stroke was examined by using established clinical self-report questionnaires assessing memory, attention, executive functions, emotional status and health-related quality of life. In order to control for general factors related to cerebrovascular disease, self-reports were compared to an age-matched group of 34 patients with a history of transient ischemic attack. Thalamic lesions were co-registered to an atlas of the human thalamus. Lesion overlap and subtraction analyses were used for lesion-to-symptom mapping. When both patient groups were compared, no significant differences were found for either questionnaire. However, when subgroups were compared, patients with infarctions involving the posterior thalamus showed significant emotional disturbances and elevated anxiety levels compared to patients with more anterior lesions. Our findings thus point to the existence of a persistent affective impairment associated with chronic lesions of the posterior thalamus. This syndrome may result from damage to connections between medial pulvinar and extra-thalamic regions involved in affective processing. Our findings suggest that the posterior thalamus may contribute significantly to the regulation of mood.

Dynamics of saccade parameters in multiple sclerosis patients with fatigue.

Fatigue is one of the most frequent and disabling symptoms in multiple sclerosis (MS). Its pathophysiology remains poorly understood and objective measures to quantify fatigue are unavailable to date. To investigate whether analysis of ocular motor movements can provide diagnostic information in MS patients with fatigue, 37 MS patients (21 female, age 44 ± 9 years) and 20 age- and gender-matched healthy controls were prospectively recruited. Fatigue was assessed with the fatigue severity scale (FSS). Twenty-five MS patients were fatigued (defined as FSS ≥ 4) and 12 MS patients were not. Subjects performed a saccadic fatigue task that required execution of uniform saccades over a period of 10 min. Saccadic amplitude, latency and peak velocities during the task were analysed and selected parameters were tested in a receiver operating characteristic (ROC) analysis. Fatigued patients showed a significantly larger decrease of saccadic peak velocity and amplitude when compared to patients without fatigue and healthy controls. Furthermore, fatigued patients showed significantly longer latencies compared to non-fatigued patients and healthy controls. Peak velocity change over time and latencies correlated with FSS scores. The best parameter to discriminate between fatigued and non-fatigued patients was peak velocity change over time (ROC; area under the curve = 0.857). Assessment of peak velocity, amplitude and latency in a saccade fatigue task is a promising approach for quantifying fatigue in MS patients.

Impaired representation of geometric relationships in humans with damage to the hippocampal formation.

The pivotal role of the hippocampus for spatial memory is well-established. However, while neurophysiological and imaging studies suggest a specialization of the hippocampus for viewpoint-independent or allocentric memory, results from human lesion studies have been less conclusive. It is currently unclear whether disproportionate impairment in allocentric memory tasks reflects impairment of cognitive functions that are not sufficiently supported by regions outside the medial temporal lobe or whether the deficits observed in some studies are due to experimental factors. Here, we have investigated whether hippocampal contributions to spatial memory depend on the spatial references that are available in a certain behavioral context. Patients with medial temporal lobe lesions affecting systematically the right hippocampal formation performed a series of three oculomotor tasks that required memory of a spatial cue either in retinal coordinates or relative to a single environmental reference across a delay of 5000 ms. Stimulus displays varied the availability of spatial references and contained no complex visuo-spatial associations. Patients showed a selective impairment in a condition that critically depended on memory of the geometric relationship between spatial cue and environmental reference. We infer that regions of the medial temporal lobe, most likely the hippocampal formation, contribute to behavior in conditions that exceed the potential of viewpoint-dependent or egocentric representations. Apparently, this already applies to short-term memory of simple geometric relationships and does not necessarily depend on task difficulty or integration of landmarks into more complex representations. Deficient memory of basic geometric relationships may represent a core deficit that contributes to impaired performance in allocentric spatial memory tasks.