Threat learning in space: how stimulus-outcome spatial compatibility modulates conditioned skin conductance response.

A central question in Pavlovian conditioning concerns the critical conditions that drive the acquisition and maintenance of the stimulus-outcome association. The spatial relationship between the conditioned (CS) and unconditioned (US) stimuli is considered to exert strong effects on learning. However, how spatial information modulates Pavlovian learning remains mostly unexplored in humans. Here, we test how the compatibility between the CS and the US location influences the acquisition, extinction, and recovery (following reinstatement) of Pavlovian conditioned threat. Participants (N = 20) completed a differential threat conditioning task in which visual CSs appeared on the same (compatible) or opposite (incompatible) hemispace as the US delivery (aversive shock to one hand), while their skin conductance response served as an index of learning. Results show that initial threat expectations were biased in favor of compatible CSs before conditioning. Nevertheless, this bias was revised during acquisition to reflect current stimulus-outcome contingencies. Computational modeling suggested that this effect occurred through a higher reliance on positive aversive prediction errors for incompatible CSs, thereby facilitating learning of their association with the US. Additionally, the conditioned response to incompatible CSs was associated with initially slower extinction and a greater recovery after threat reinstatement. These findings suggest that spatial information conveyed by stimuli and outcomes can be flexibly used to enact defensive responses to the current source of danger, highlighting the adaptive nature of Pavlovian learning.

Education protects against cognitive changes associated with multiple sclerosis.

PURPOSE: Although neuropsychological impairments are common in Multiple Sclerosis (MS), the manifestation of cognitive deficits may vary greatly across MS patients. Here, we explored the influence of cognitive reserve proxy indices (education and occupation) and perceived fatigue on cognitive performance. METHODS: Fifty relapsing-remitting MS patients were evaluated. Cognitive performance was measured using the Paced Auditory Serial Addition Test (PASAT), in which information processing speed can be manipulated by varying the presentation speed of stimuli. RESULTS: MS patients with low education performed worse than healthy controls at faster PASAT speeds. By contrast, no difference was observed between MS patients with high education and matched healthy controls, regardless of PASAT speed. Moreover, we found that neither occupational attainment nor perceived fatigue has an influence on MS patients' cognitive performance. CONCLUSION: These findings provide evidence that higher education could be protective against MS-associated cognitive deficits and that high speed PASAT versions are more suitable for identifying compensatory capacities compared to low speed PASAT versions.

Lexical processes and eye movements in neglect dyslexia.

Neglect dyslexia is a disturbance in the allocation of spatial attention over a letter string following unilateral brain damage. Patients with this condition may fail to read letters on the contralesional side of an orthographic string. In some of these cases, reading is better with words than with non-words. This word superiority effect has received a variety of explanations that differ, among other things, with regard to the spatial distribution of attention across the letter string during reading. The primary goal of the present study was to explore the interaction between attention and lexical processes by recording eye movements in a patient (F.C.) with severe left neglect dyslexia who was required to read isolated word and non-word stimuli of various length. F.C.'s ocular exploration of orthographic stimuli was highly sensitive to the lexical status of the letter string. We found that: (1) the location to which F.C. directed his initial saccade (obtained approximately 230 ms post-stimulus onset) differed between word and non-word stimuli; (2) the patient spent a greater amount of time fixating the contralesional side of word than non-word strings. Moreover, we also found that F.C. failed to identify the left letters of a string despite having fixated them, thus showing a clear dissociation between eye movement responses and conscious access to orthographic stimuli. Our data suggest the existence of multiple interactions between lexical, attentional and eye movement systems that occur from very initial stages of visual word recognition.

Seeing or not seeing where your hands are.

Previous findings have demonstrated the existence of a visual peripersonal space centered on the hand in humans and its modulatory effects on tactile perception. A strong modulatory effect of vision on touch perception was found when a visual stimulus was presented near the hand. In contrast, when the visual stimulus was presented far from the hand, only a weak modulatory effect was found. The aim of the present study was to verify whether such cross-modal links between touch and vision in the peripersonal space centered on the hand could be mediated by proprioceptive signals specifying the current hand positions or if they directly reflect an interaction between two sensory modalities, i.e., vision and touch. To this aim, cross-modal effects were studied in two different experiments: one in which patients could see their hands and one in which vision of their hands was prevented. The results showed strong modulatory effects of vision on touch perception when the visual stimulus was presented near the seen hand and only mild effects when the vision of the hand was prevented. These findings are explained by referring to the activity of bimodal neurons in premotor and parietal cortex of macaque, which have tactile receptive fields on the hand, and corresponding visual receptive fields in the space immediately adjacent to the tactile fields. One important feature of these bimodal neurons is that their responsiveness to visual stimuli delivered near the body part is reduced or even extinguished when the view of the body part is prevented. This implies that, at least for the hand, the vision of the hand is crucial for determining the spatial mapping between vision and touch that takes place in the peripersonal space. In contrast, the proprioceptive signals specifying the current hand position in space do not seem to be relevant in determining the cross-modal interaction between vision and touch.

Selective horizontal dysmetropsia following prestriate lesion.

We describe a patient (P.S.) who, following a right prestriate lesion, reported that objects in the left visual field appeared distorted and smaller than those on the right. Other aspects of visual processing were remarkably unaffected. We carried out a series of size comparison tests using simple or complex stimuli and requiring different types of behavioural responses. We found that P.S. significantly underestimated the size of stimuli presented in her left visual field. When comparison tasks involved stimuli placed along the vertical axis or in the right visual field, P.S. performed well. The vertical and horizontal components of size distortion were found to be differentially affected. We conclude that size processing may be dissociated from other aspects of visual processing, such as form or colour processing, and depends critically on part of the occipital, prestriate areas (Brodmann areas 18-19).

Neuropsychological evidence of an integrated visuotactile representation of peripersonal space in humans.

Current interpretations of extinction suggest that the disorder is due to an unbalanced competition between ipsilesional and contralesional representations of space. The question addressed in this study is whether the competition between left and right representations of space in one sensory modality (i.e., touch) can be reduced or exacerbated by the activation of an intact spatial representation in a different modality that is functionally linked to the damaged representation (i.e., vision). This hypothesis was tested in 10 right-hemisphere lesioned patients who suffered from reliable tactile extinction. We found that a visual stimulus presented near the patient"s ipsilesional hand (i.e., visual peripersonal space) inhibited the processing of a tactile stimulus delivered on the contralesional hand (cross-modal visuotactile extinction) to the same extent as did an ipsilesional tactile stimulation (unimodal tactile extinction). It was also found that a visual stimulus presented near the contralesional hand improved the detection of a tactile stimulus applied to the same hand. In striking contrast, less modulatory effects of vision on touch perception were observed when a visual stimulus was presented far from the space immediately around the patient"s hand (i.e., extrapersonal space). This study clearly demonstrates the existence of a visual peripersonal space centered on the hand in humans and its modulatory effects on tactile perception. These findings are explained by referring to the activity of bimodal neurons in premotor and parietal cortex of macaque, which have tactile receptive fields on the hand and corresponding visual receptive fields in the space immediately adjacent to the tactile fields.

Prosopagnosia and alexia without object agnosia.

Following a trauma causing bilateral posterior brain damage, a patient complained of dyslexia and prosopagnosia, but not object agnosia. On testing she showed intact recognition of object drawings, even when it was assessed with perceptually demanding tasks such as Ghent's overlapping figures and Street completion test. This pattern of deficit is inconsistent with Farah's (1990) prediction that the simultaneous occurrence of alexia and prosopagnosia is invariably associated with object agnosia. The patient's reading performance had the features typically found in letter-by-letter readers. On face tests, she showed a discrepancy between the impairment exhibited in familiarity recognition and famous face naming and the correct (though slow) performance in matching the names of famous persons with their photographs. This apparent contradiction was clarified by showing that the patient had maintained the ability to generate the mental images of famous faces in response to the presentation of their names. We assume that face recognition units were intact, but partially disconnected from the output of perceptual processing.

Visual extinction as a spatio-temporal disorder of selective attention.

Studies of normal behaviour have shown that the process of selection takes a finite time, one measure of which is the attentional dwell time, that is the period of interference produced by one attended stimulus on a subsequent one. Here we investigated the time for selection in FB, a neurological patient suffering from a visuospatial disorder of attention (unilateral extinction). FB was asked to identify two letters displayed in rapid succession either to the left (damaged), or to the right (intact) visual hemifield. By varying the interval between stimuli, we measured how long the first letter continued to interfere with accuracy on the second- that is the first letter's attentional demand over time. The results showed that the process of selection has an abnormal duration in the affected visual field, being at least twice as long as in the intact field. We suggest that the slowed visual processing for the contralesional object may contribute to the competitive bias against that object which is the hallmark of unilateral extinction.

A model that accounts for activity in primate frontal cortex during a delayed matching-to-sample task.

A fully recurrent neural network model was optimized to perform a spatial delayed matching-to-sample task (DMS). In DMS, a stimulus is presented at a sample location, and a match is reported when a subsequent stimulus appears at that location. Stimuli elsewhere are ignored. Computationally, a DMS system could consist of memory and comparison components. The model, although not constrained to do so, worked by using two corresponding classes of neurons in the hidden layer: storage and comparator units. Storage units form a dynamical system with one fixed point attractor for each sample location. Comparator units constitute a system receiving input from these storage units as well as from current input stimuli. Both unit types were tuned directionally. These two sources of information combine to create unique patterns of activity that determine whether a match has occurred. In networks with abundant hidden units, the storage and comparator functions were distributed so that individual units took part in both. We compared the model with single-neuron recordings from premotor (PM) and prefrontal (PF) cortex. As shown previously, many PM and PF neurons behaved like storage units. In addition, both regions contain neurons that behave like the comparator units of the model and appear to have dual functionality similar to that observed in the model units. No neuron in either area had properties identical to those of the match output neuron of the model. However, four PF neurons and one PM neuron resembled the output signal more closely than any of the hidden units of the model.

Spatial extinction on double asynchronous stimulation.

Despite the fact that visual extinction is widely considered a space-based disturbance of selective attention, there has been little theoretical consensus about the nature of its pathogenic mechanism. A specific disruption in the ability to disengage attention from ipsilesional stimuli, or a loss of weight with which contralesional objects compete for visual selection, have been hypothesized to account for the disorder. We tested the merits of these two explanations in a right-hemisphere-lesioned patient, FB, who failed to recognize a contralesional target only when it was shown concurrently to an ipsilesional target (i.e. visual extinction). His task was to report two target letters presented in rapid succession to the left and right of the fixation point. The order of stimulus presentation (Left-First vs Right-First), and the intertarget interval (stimulus onset asynchrony) were varied systematically. We showed that contralesional extinction may occur for successively presented targets, not just for stimuli displayed at the same time. Of most importance, FB was seriously and equally impaired in dealing with a contralesional stimulus when this either preceded the ipsilesional stimulus or followed it by an interval less than about 600 msec. The data appear to contradict the disengagement hypothesis, which predicted a substantial reduction of extinction when a stimulus was displayed first into the lesioned side of space. We suggest that a competitive model of visual selective attention fits the data quite well.

Time perception in a neglected space.

We have studied the distortion of perceived time in a patient with left neglect. This patient consistently over-estimated the duration of stimuli in the neglected space. Overestimation was observed both with an interval comparison (300/700 ms) and with a time production (1 s) paradigm. We suggest that encoding duration in the hundreds of milliseconds range is a process based on an internal clock mechanism. The functioning of that clock varies as a function of the processing load.

The premotor cortex and nonstandard sensorimotor mapping.

We often gaze at and attend to an object while preparing to reach toward and grasp it, and continue doing so when the plan is executed. Elaborate machinery, much of it in the brainstem and spinal cord, provides control systems for the spatially congruent guidance of the eyes, limbs, and body toward targets in visual space. We will use the term standard mapping for the sensorimotor transformations that underlie such behavior. Despite the common sense character of standard mapping, the targets of gaze, attention, and reaching can be dissociated from each other. We can attend to stimuli in locations that differ from the target of action. We can gaze in one direction while reaching in another. And we can guide spatial action with nonspatial stimuli, such as when, in conditional motor tasks, the color of an object instructs a movement elsewhere in space. All of these situations, and many others, call for a process that we term nonstandard mapping, wherein the central nervous system must reject the commonplace correspondences among visuospatial stimuli, gaze, attention, and reaching movements. We focus in this article on the possibility that premotor cortex underlies nonstandard mapping and, therefore, the behavioral flexibility that such a process allows.

Frontal lobe mechanisms subserving vision-for-action versus vision-for-perception.

In the typical course of daily events, we often gaze at an object, attend to its features and its place, reach toward it and grasp it, all with an awareness of what we are doing at the time. But behavior is not always thus. Gaze, attention, limb movement direction and awareness can be behaviorally dissociated from each other, and this review focuses on one such dissociation: that between the perception of an object and the use of that object's inherent spatial and nonspatial information for mediating visuomotor control. We review evidence that partially different neuronal systems underlie these two aspects of visual information processing. In neurophysiological studies of the primate frontal lobe, it has been possible to demonstrate that neural signals appearing to be visual responses reflect, at least in part, the motor significance of a stimulus. This finding has been confirmed, in separate studies, for both spatial and nonspatial visual information and supports the hypothesis that some frontal cortex activity reflects the selection and guidance of action rather than the properties of visual stimuli, per se. These findings are discussed in the context of neuropsychological studies indicating that accurate and appropriate movements are possible without perceptual awareness of the information guiding those movements.

Sparing of verbs and preserved, but ineffectual reading in a patient with impaired word production.

We report a patient who, following a left fronto-temporal lesion, showed a complete sparing of the semantic store and a deficit of word production characterized by two types of dissociations. First, oral and written output was severely disrupted in naming and partially impaired in repetition, writing to dictation and oral spelling, with the exception of verbs, which were normally produced in every modality and condition of stimulation. Second, reading was normal for all type of words as well as non-words. This pattern of deficits suggests two functional lesions, one affecting the connections between the semantic store and the phonological lexicon and the other damaging the sublexical route that converts sound to sound and sound to print. It also implies that words are independently organized in the phonological lexicon, based on their grammatical class and have discrete connections with the semantic store. However, CT scan evidence does not support the hypothesis that this functional dissociation finds its anatomical correlate in the specialization of the frontal premotor cortex for verbs and the antero-medial temporal cortex for nouns. In spite of his normal reading performance, both in terms of comprehension and of accuracy and speed in word production, the patient complained that he met with great difficulty in reading newspapers and books, to the point that he had to renounce to this previously favourite activity. It was found that it took him time and effort to grasp the meaning of complex sentences and passages and it was speculated that, contrary to single words and elementary sentences, comprehension of this type of material cannot be achieved by the mere access of orthographic stimuli to semantics, but requires the retrieval of word-forms. It would appear that a patient, whose lexical route is blocked, can only read passages, by first converting print to sound via the sublexical route and then re-entering the semantic store with oral input.

Coordinate frames for naming misoriented chimerics: a case study of visuo-spatial neglect.

A persistent line of inquiry for the students of visuo-spatial neglect has involved the perceptual frame of reference respect to which the neglected region of space is defined. On standard testing conditions viewer-centered and object-centered systems of coordinates are confounded. In order to disambiguate these two reference frames FB, a patient with severe left visual neglect consequent upon a right parieto-temporal haemorrhage, was asked to identify chimeric figures presented at different orientations. FB continued to recognize poorly the left side of chimeric figures even when the display was rotated 90 degrees clockwise or anticlockwise so that the 'left' of the chimeric fell on the patient's egocentric up or down, respectively. The result suggests that, at least under the present testing conditions, unilateral neglect is tied to the principal (top-bottom) axis of the object. Object-centered vs. (viewer-centered) representational accounts of this finding are discussed.