Abstract: 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.
Abstract: Recent behavioral studies in monkeys and humans have shown that holding an item in spatial working memory may lead to sustained and spatially selective prolongation of reaction times (RTs) to visual stimuli presented during the memory delay. In order to resolve the seeming contradiction between these findings and current theories on the interaction of working memory and attentional orienting, it has been hypothesized that memory-dependent modulation of orienting may be the net effect of superposed facilitatory and inhibitory mechanisms. Their relative strength during the memory delay may determine whether RTs to visual stimuli presented during the memory delay are shortened or prolonged. Here, we expand on this hypothesis by investigating the spatial distribution of memory-dependent inhibition with behavioral data from normal human subjects. The experiment consisted of a combination of an oculomotor spatial working memory task (memory-guided saccade task, 6-s delay) and a visual discrimination task (performed 1500, 2500, or 3500 ms after presentation of the memory cue). RTs to discrimination stimuli were analyzed as a function of memory-guided saccade amplitude. By fitting polynomial approximations to our data we show that the spatial distribution of memory-dependent inhibition of orienting significantly differs from a monotonic gradient across the visual field. Instead, we demonstrate the existence of a central inhibitory peak surrounded by a facilitatory annulus, forming a transient "inverted Mexican hat" profile, which mirror-images findings from recent studies on the spatial distribution of attention. These findings are consistent with the hypothesis of a highly flexible modulation of orienting in which both the signs and spatial distribution of memory-dependent bias signals are adapted to behavioral demands.
Abstract: 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.
Abstract: 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.
Abstract: Despite frequent saccadic gaze shifts we perceive the surrounding visual world as stable. It has been proposed that the brain uses extraretinal eye position signals to cancel out saccade-induced retinal image motion. Nevertheless, stimuli flashed briefly around the onset of a saccade are grossly mislocalized, resulting in a shift and, under certain conditions, an additional compression of visual space. Perisaccadic mislocalization has been related to a spatio-temporal misalignment of an extraretinal eye position signal with the corresponding saccade. Here, we investigated perceptual mislocalization of human observers both in saccade and fixation conditions. In the latter conditions, the retinal stimulation during saccadic eye movements was simulated by a fast saccade-like shift of the stimulus display. We show that the spatio-temporal pattern of both the shift and compression components of perceptual mislocalization can be surprisingly similar before real and simulated saccades. Our findings suggest that the full pattern of perisaccadic mislocalization can also occur in conditions which are unlikely to involve changes of an extraretinal eye position signal. Instead, we suggest that, under the conditions of our experiments, the arising difficulty to establish a stable percept of a briefly flashed stimulus within a given visual reference frame yields mislocalizations before fast retinal image motion. The availability of visual references appears to exert a major influence on the relative contributions of shift and compression components to mislocalization across the visual field.
Abstract: Saccade latencies are significantly reduced by extinguishing a foveal fixation stimulus before the appearance of a saccade target. It has been shown recently that this "fixation offset effect" (FOE) can be modulated by varying target probability. Cortico-collicular top-down effects have been assumed to mediate this strategic FOE modulation. Here, we have investigated strategic FOE modulation in 14 healthy human subjects performing gap and warning tasks. In the former task, the central fixation point was extinguished 200 ms before target onset. In the latter task, the central fixation point changed its colour 200 ms before target onset, but remained illuminated until the target appeared. Target probability was varied block-wise between 25 and 75%. In both tasks, mean latencies decreased with increasing target probability. However, in contrast with what can be expected from preceding studies, we found no differential modulation of mean latencies by target probability between tasks. Instead, we observed differential probability-dependent changes in latency distributions. In the gap task, discrete changes of saccade latencies were found, with a probability-dependent change in frequency of express and regular latencies. By contrast, in the warning task a shift of the entire latency distribution towards longer latencies with low target probability was found. We conclude that strategic modulation of saccade latencies by target probability may be mediated by two distinct neural mechanisms. Selection of either mechanism seems to depend critically on activation of the fixation system.
Abstract: 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.
Abstract: Voluntary behavior critically depends on attentional selection and short-term maintenance of perceptual information. Recent research suggests a tight coupling of both cognitive functions with visual processing being selectively enhanced by working memory representations. Here, we combined a memory-guided saccade paradigm (6-s delay) with a visual discrimination task, performed either 1,500, 2,500, or 3,500 ms after presentation of the memory cue. Contrary to what can be expected from previous studies, our results show that memory of spatial cues can transiently delay speeded discrimination of stimuli presented at remembered locations. This effect was not observed in a control experiment without memory requirements. Furthermore, delayed discrimination was dependent on the strength of actual memory representations as reflected by accuracy of memory-guided saccades. We propose an active inhibitory mechanism that counteracts facilitating effects of spatial working memory, promoting flexible orienting to novel information during maintenance of spatial memoranda for intended actions. Inhibitory delay-period activity in prefrontal cortex is a likely source for this mechanism which may be mediated by prefronto-tectal projections.
Abstract: 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.
Abstract: BACKGROUND: Experimental and clinical studies suggest that the dorsolateral prefrontal cortex (DLPFC) and the superior colliculus (SC) are crucial for the cancellation of reflexive eye movements toward distracting stimuli. However, the contribution of subcortical structures remains unknown. The basal ganglia provide serial tonic inhibitory connections between the DLPFC and the SC, and could therefore be involved in preventing the triggering of unnecessary saccades. The DLPFC could also exert its inhibitory effect on the SC through direct prefronto-tectal pathways that travel in the internal capsule (IC). Since thalamic dysfunction may be responsible for reduced DLPFC activation, it may be hypothesized that the thalamus could also participate in saccadic inhibition. METHODS: The authors recorded reflexive saccade triggering (prosaccade task) and inhibition (antisaccade task) in 29 patients with a single lesion affecting the striatum, the thalamus, or the IC, and compared these results to control subjects. RESULTS: A normal error rate in the antisaccade task was found in patients with 1) a basal ganglia lesion, 2) a thalamic lesion, or 3) a lesion restricted to the posterior half of the posterior limb of the IC. An increased error rate in the antisaccade task was found in patients with a lesion affecting the anterior limb, the genu, or the anterior half of the posterior limb of the IC. CONCLUSION: These results suggest that neither the basal ganglia nor the thalamus plays a major role in reflexive saccade suppression, but support the hypothesis of a direct DLPFC inhibitory control of saccade triggering on the SC.
Abstract: According to a classical view of visual object recognition, targets are detected "pre-attentively" if they carry unique features, whereas attention has to be deployed serially to object locations for feature binding if the targets can be distinguished from distracters only in terms of their feature conjunctions. Consistent with this view, recent reports suggest a contribution of the posterior parietal cortex (PPC; one major region controlling spatial attention) to conjunction search as opposed to feature search. However, PPC engagement in conjunction search might also reflect feature-based attention or the difficulty of target selection. The present fMRI study compared regions and amplitudes of cortical activity reflecting the attention mechanisms of a conjunction and a feature search of equal difficulty performed during maintenance of fixation. Attention-related activity was assessed by comparing each hard feature and conjunction search with an easy feature search. Hard feature and conjunction search activated overlapping regions in multiple PPC areas and in the frontal eye field (FEF). Most consistent PPC overlaps were located in the anterior and posterior intraparietal sulcus (IPS). The response amplitude of posterior IPS did not differ between both search tasks. However, the IPS junction with the transverse occipital sulcus and the FEF responded at a higher amplitude during conjunction search. Moreover, regions of the prefrontal cortex and the PPC were activated only during either hard feature or conjunction search. These findings suggest that equally difficult visual searches for features and conjunctions are controlled by overlapping frontoparietal networks, but also that both search types involve specific mechanisms.
Abstract: The significance of cannabinoid signaling for human cognition and motor control is still poorly understood. Here, we have investigated acute behavioral effects of oral delta-9-tetrahydrocannabinol (THC) with oculomotor paradigms in 12 healthy human subjects. Compared to baseline testing: (i) THC increased latencies of reflexive visually guided saccades, while their accuracy was not affected; (ii) latencies of memory-guided saccades were unaffected, but THC modulated accuracy of these eye movements by increasing average gain and gain variability; (iii) frequency of anticipated memory-guided saccades and antisaccade errors was increased; (iv) the saccade amplitude/peak velocity relationships were not affected. These results show that THC acts on selected aspects of saccade control, namely spatial attention shifts, fine tuning of volitional saccades, spatial working memory and inhibition of inappropriate saccades. The pattern of effects suggests modulation of neuronal activity in substantia nigra pars reticulata and/or dorsolateral prefrontal cortex and sparing of the eye fields and the final motor pathway for saccades. Behaviorally, our findings reflect the distribution of CB-1 cannabinoid receptors in the human neocortex, basal ganglia and brainstem and provide evidence for participation of the cannabinoidergic system in high level control of saccades and associated cognitive functions. Saccadic eye movements may provide an objective measure of motor and cognitive effects of cannabinoids.
Abstract: Neurophysiological studies in monkeys suggest selective representation of behaviourally relevant information in working memory. So far, no behavioural evidence for this has been reported for humans. Here, we investigated the role of behavioural relevance for access to human visuospatial working memory by using delayed oculomotor response tasks. Subjects were presented two successive visual cues in different and unpredictable locations while fixating on a central fixation point. After a delay, an unpredictable auditory signal (one beep or two beeps) sounded and the central fixation point was turned off, initiating the oculomotor response (i.e. memory-guided saccade) phase. Two groups of 10 subjects each were studied in two conditions: in the 'relevant' condition, subjects were instructed to memorize both visual cues and to move the eyes to the remembered position of the first cue (one beep) or the second cue (two beeps). The same stimuli were used in the 'irrelevant' condition, but subjects were instructed to memorize and move the eyes to the position of the first cue only, regardless of the second cue and the auditory signal. In the 'relevant' condition, we found a significant increase in errors of memory-guided saccades to the first cue, when the second cue was located between central fixation point and first cue. This spatially selective interference effect disappeared in the 'irrelevant' condition, despite identical stimuli. On a behavioural level, these results show for the first time the significance of behavioural relevance for access to human spatial working memory. These findings complement recent single-neuron studies in monkeys, showing that the neuronal substrates of working memory selectively represent behaviourally relevant perceptual information.
Abstract: Searching for a target object in a cluttered visual scene requires active visual attention if the target differs from distractors not by elementary visual features but rather by a feature conjunction. We used functional magnetic resonance imaging (fMRI) in human subjects to investigate the functional neuroanatomy of attentional mechanisms employed during conjunction search. In the experimental condition, subjects searched for a target defined by a conjunction of colour and orientation. In the baseline condition, subjects searched for a uniquely coloured target, regardless of its orientation. Eye movement recordings outside the scanner verified subjects' ability to maintain fixation during search. Reaction times indicated that the experimental condition was attentionally more demanding than the baseline condition. Differential activations between conditions were therefore ascribed to top-down modulation of neural activity. The frontal eye field, the ventral precentral sulcus and the following posterior parietal regions were consistently activated: (i) the postcentral sulcus; (ii) the posterior; and (iii) the anterior part of the intraparietal sulcus; and (iv) the junction of the intraparietal with the transverse occipital sulcus. Parietal regions were spatially distinct and displayed differential amplitudes of signal increase with a maximal amplitude in the posterior intraparietal sulcus. Less consistent activation was found in the lateral fusiform gyrus. These results suggest an involvement of the human frontal eye field in covert visual selection of potential targets during search. These results also provide evidence for a subdivision of posterior parietal cortex in multiple areas participating in covert visual selection, with a major contribution of the posterior intraparietal sulcus.
