Subliminal modulation of voluntary action experience: A neuropsychological investigation.

Human voluntary actions are often associated with a distinctive subjective experience termed 'sense of agency'. This experience could be a reconstructive inference triggered by monitoring one's actions and their outcomes, or a read-out of brain processes related to action preparation, or some hybrid of these. Participants pressed a key with the right index finger at a time of their own choice, while viewing a rotating clock. Occasionally they received a mild shock on the same finger. They were instructed to press the key as quickly as possible if they felt a shock. On some trials, trains of subliminal shocks were also delivered, to investigate whether such subliminal cues could influence the initiation of voluntary actions, or the subjective experience of such actions. Participants' keypress were always followed by a tone 250 ms later. At the end of each trial they reported the time of the keypress using the rotating clock display. Shifts in the perceived time of the action towards the following tone, compared to a baseline condition containing only a keypress but no tone, were taken as implicit measures of sense of agency. The subliminal shock train enhanced this "action binding" effect in healthy participants, relative to trials without such shocks. This difference could not be attributed to retrospective inference, since the perceptual events were identical in both trial types. Further, we tested the same paradigm in a patient with anarchic hand syndrome (AHS). Subliminal shocks again enhanced our measure of sense of agency in the unaffected hand, but had a reversed effect on the 'anarchic' hand. These findings suggest an interaction between internal volitional signals and external cues afforded by the external environment. Damage to the neural pathways that mediate interactions between internal states and the outside world may explain some of the clinical signs of AHS.

Implicit associative priming in a patient with left visual neglect.

Recent studies have suggested that patients with visual neglect may process, even if without awareness, perceptual features of the neglected stimuli. The aim of the current study was to further investigate whether the ignored stimuli are processed at a deeper level. Findings from a patient with damage to the right hemisphere and with left visual neglect (no hemianopia) are reported. He showed an associative priming in the neglected space: response to a word in the right visual field was faster when the word was preceded by the brief presentation of an associated word in the neglected field. When obliged to orient attention to the left side of a computer screen, he was not able to detect the presence of, to read aloud, or to judge the lexical status and semantic content of left-sided stimuli. This patient was able to perform a covert post-perceptual processing of the neglected stimuli, but could not do so when explicitly requested.

Automatic and voluntary orienting of attention in patients with visual neglect: horizontal and vertical dimensions.

The present study was aimed at testing internally and externally-controlled mechanisms of covert orienting in patients with visuo-spatial neglect. Internally-controlled orienting was tested by presenting central informative cues. Externally-controlled orienting was tested by presenting peripheral non-informative cues. We also tested for the presence of vertical neglect in patients with horizontal neglect, and tried to assess whether altitudinal neglect is an attentional deficit. Finally we examined whether altitudinal neglect manifests itself only in the visual field contralateral to the lesion or, as has been shown for horizontal neglect, whether it is also present in the ipsilesional visual field. The results showed that patients with neglect have a deficit of externally-controlled covert orienting in the visual field opposite to that of the lesion. Further, the impairment appeared to be more pronounced in the lower than in the upper visual field and to be mainly evident in the visual field contralateral to the lesion. The deficit could, however, be partially compensated for by the use of internally-controlled covert orienting. These findings seems to support the dual-mechanisms hypothesis which maintains that automatic and voluntary orienting are subserved by separate mechanisms possibly located in different parts of the brain.

Passive limb movements improve visual neglect.

Recent studies have reported that left neglect can be ameliorated during active movements of a contralesional limb in the contralesional space. In contrast, a passive left hand movement does not seem to induce an amelioration of neglect, at least when it is associated to simultaneous active right movement (Robertson IH, North N, Neuropsychologia 31 (1993) 293-300). In the present study, we explored the possibility that a complex passive movement, such as abduction and adduction of the arm, is able to reduce neglect also when it is associated to simultaneous active right arm movements. To test this hypothesis neglect patients were required to perform an object cancellation test and a line bisection test by using the right hand, while the left arm was passively moved. Moreover, we verified the possibility that left arm stimulation activates the peripersonal more than the extrapersonal space, with the exception of the condition in which the far space can be reached by a tool that extends peripersonal space in the far space (Farnè A, Làdavas E, Neuroreport 11 (2000) 1645-1649). For this reason, patients were required to perform the tasks in near (70 cm) and in far (140 cm) space by means of a light pen (pointing task) and of a stick (reaching task). When the left arm was passively moved the results showed a significant reduction of neglect with respect to the baseline condition, and the improvement equally affected the near and the far space. A different effect for the near and far space was observed in relation to the task (pointing vs. reaching). In the pointing task, neglect was more severe in the far than in near space; however, this difference disappeared when the patients had to reach objects by means of a stick. In conclusion, the present study shows that the entity of improvement of visual neglect due to a left passive movement is related to the entity of proprioceptive signals specifying left hand position.

Lexical and semantic processing in the absence of word reading: evidence from neglect dyslexia.

Nine patients with left-sided neglect and nine matched control patients performed three tasks on horizontal (either normal or mirror-reversed) letter strings. The tasks were: reading aloud, making a lexical decision (word vs non-word), and making a semantic decision (living vs non-living item). Relative to controls, neglect patients performed very poorly in the reading task, whereas they performed nearly normally in the lexical and semantic tasks. This was considered to be a dissociation between direct tasks, rather than a dissociation between explicit and implicit knowledge. The explanation offered for the dissociation is in terms of both a dual-route model for reading aloud and a degraded representation of the letter string.

Deficit of auditory space perception in patients with visuospatial neglect.

There have been many studies of visuospatial neglect, but fewer studies of neglect in relation with other sensory modalities. In the present study we investigate the performance of six right brain damaged (RBD) patients with left visual neglect and six RBD patients without neglect in an auditory spatial task. Previous work on sound localisation in neglect patients adopted measure of sound localisation based on directional motor responses (e.g., pointing to sounds) or judgement of sound position with respect to the body midline (auditory midline task). However, these measures might be influenced by non-auditory biases related with motor and egocentric components. Here we adopted a perceptual measure of sound localisation, consisting in a verbal judgement of the relative position (same or different) of two sequentially presented sounds. This task was performed in a visual and in a blindfolded condition. The results revealed that sound localisation performance of visuospatial neglect patients was severely impaired with respect to that of RBD controls, especially when sounds originated in contralesional hemispace. In such condition, neglect patients were always unable to discriminate the relative position of the two sounds. No difference in performance emerged as a function of the visual condition in either group. These results demonstrate a perceptual deficit of sound localisation in patients with visuospatial neglect, suggesting that the spatial deficits of these patients can arise multimodally for the same portion of external space.

In search of biased egocentric reference frames in neglect.

The present study was aimed at assessing, by means of visual as well as proprioceptive-kinaesthetic straight-ahead tasks, the possible causal role of the ipsilesional deviation of the egocentric reference frame in determining neglect syndrome. The hypothesis, originally proposed by Ventre et al. [3], that an alteration of the representation of body-centred space can be a cause of asymmetrical spatial behaviour in humans has been recently revived by Karnath and co-workers [24]. The results of the present study seem to challenge the view that a systematic ipsilesional displacement of the egocentric reference is the crucial mechanism responsible for unilateral visual neglect. Under visual conditions, in which patients were required to stop a moving spot as it crossed their perceived midline, the ipsilesional deviation of the egocentric reference frame was dependent upon the direction of visual scanning. Right to left visual scanning direction produced a rightward displacement of the egocentric reference. In contrast, left to right visual scanning direction allowed neglect patients to correctly locate their perceived egocentre with an accuracy which did not differ from controls. The notion that the effect of a deviation of the egocentric reference frame is actually dependent on a bias in the visual scanning orienting response was also confirmed in the proprioceptive straight-ahead pointing tasks, in which the patients were blindfolded and therefore no visual information was available. In these conditions, in which patients were required to judge the subjective midline by using head, trunk and shoulder co-ordinate systems, the displacement of the subjective egocentric midline was not present.

Unilateral attention deficits and hemispheric asymmetries in the control of visual attention.

The present study sought to determine the roles of the two hemispheres in arousal and the selective components of attention. Ten patients with left and right parietal lesions and ten with left and right temporal lesions participated in the experiment. The hypothesis that posterior parietal lesions, whether left or right, cause two selective attentional deficits, namely, a reduced reactivity to stimuli in the visual field contralateral to the lesion, and a reduced reactivity to any stimulus which occupies a relative contralateral spatial position, was tested by asking the patient to tilt their head either to the left or to the right by 90 degrees and to respond to two stimuli displayed above and on either side of fixation mark. The arousal component of attention was studied by analysing the overall RT to visual stimuli independent of their spatial positions. The results showed that (1) patients with either left or right parietal damage are impaired in shifting attention from the ipsilateral to the contralateral visual field, and, within each visual field, in a direction contraversive to the lesion and (2) these two attentional deficits are more severe after right than after left parietal damage. Furthermore, the results show that the difficulty in maintaining a high level of alertness is a specific deficit of patients with right hemispheric lesion and not of patients with an extinction syndrome, insofar as there is no significant difference in overall RT between patients with parietal and temporal lesions.

Ventriloquism in patients with unilateral visual neglect.

Can visual stimuli that go undetected, because they are presented in the extinguished region of neglect patients' visual field, nevertheless shift in their direction the apparent location of simultaneous sounds (the well-known 'ventriloquist effect')? This issue was examined using a situation in which each trial involved the simultaneous presentation of a tone over loudspeakers, together with a bright square area on either the left, the right or both sides of fixation. Participants were required to report the presence of squares, and indicate by hand pointing the apparent location of the tone. Five patients with left hemineglect consistently failed to detect the left square, either presented alone or together with another square on the right. Nevertheless, on bimodal trials with a single undetected square to the left, their sound localization was significantly shifted in the direction of that undetected square. By contrast, in bimodal trials with either a single square on the right or a square on each side, their sound localization showed only small and non-significant shifts. This particular result might be due to a combination of low discrimination of lateral sound deviations with variable individual strategies triggered by conscious detection of the right square. The important finding is the crossmodal bias produced by the undetected left visual distractors. It provides a new example of implicit processing of inputs affected by unilateral visual neglect, and on the other hand is consistent with earlier demonstrations of the automaticity of crossmodal bias.

Preserved semantic access in neglect dyslexia.

The aim of this study was to investigate the preservation of semantic access in patients with severe neglect dyslexia for words and non-words. Patients were given the following tasks: (1) reading aloud letter strings (first basic reading task), (2) making semantic decisions (categorial and inferential judgements), (3) making semantic decisions and reading the letter strings immediately afterwards (semantic-reading tasks), (4) reading letter strings again (final basic reading tasks) and (5) auditory control tasks. Of 23 patients with visual neglect, four showed neglect dyslexia for both words and non-words. Of these four patients, three showed a performance in the semantic tasks that was as good as in the auditory condition. Moreover, the reading of the patients improved dramatically in the semantic-reading tasks but this was not maintained in the final basic reading task. Non-words showed only a minor improvement. Findings are discussed in terms of an interaction between the attentional system and the different reading routes, and provide evidence that semantic routes are less affected by neglect.

Right hemisphere interference during negative affect: a reaction time study.

Two experiments are described in which simple reaction times (RTs) to lateralized visual stimuli were measured in normal subjects during negative affect and during recollection of everyday life scenes. In both experiments the mental activity produced a remarkable increase of RTs with respect to a control situation without interfering activity. During production of the negative affect there was a selective lengthening of RTs mediated by the right hemisphere. The role of the right hemisphere in producing emotions is discussed.

The role of right side objects in left side neglect: a dissociation between perceptual and directional motor neglect.

Based on a test introduced by Tegnér and Levander, Brain 114, 1943-1951, 1991, right brain-damaged patients were assigned to a group with unilateral perceptual neglect and a group with directional motor neglect. Brain scans showed that all directional motor neglect patients had frontal lesions, whereas in perceptual neglect patients the frontal lobes were always spared. All patients were asked to execute two tasks, which were also administered to a control group. One task consisted in pointing to tokens symmetrically distributed on a display. The other task consisted in picking up the same tokens. The tasks were first executed with the aid of vision and then in a blindfolded condition. In the case of patients with perceptual neglect, performance on the left side was better in the pick-up task than in the pointing task and improved in the blindfolded condition. Neither patients with directional motor neglect nor control patients showed these effects. The results were explained in terms of the hyperattentional hypothesis of perceptual neglect, according to which, in this form of neglect, attention is captured by the objects that lie on the right side of space.

Dynamic size-change of hand peripersonal space following tool use.

Humans and monkeys share similar sensory integrated processing of tactile and peri-hand visual inputs for coding peripersonal space surrounding the hand. In monkeys, tool use is known to induce a transient elongation of hand-centred peripersonal space along the tool axis. Here we report evidence that, also in humans, the use of a tool can increase the spatial extent of the representation of peri-hand visual space to incorporate the tool. We investigated this phenomenon in patients with tactile extinction, by using a cross-modal paradigm well suited to reveal visual-tactile integration near patients' hand. In the present study cross-modal extinction was assessed far from patients' ipsilesional hand, at the distal edge of a hand-held rake. We found that cross-modal extinction was more severe after patients used the rake to retrieve distant objects with respect to a condition in which the rake was not used. This evidence of an expansion of peri-hand space lasted only a few minutes after tool use. By contrast, peri-hand space expansion was not observed when motor actions towards distant objects did not involve the tool. These findings show that visual peri-hand space has important dynamic properties in humans; it can be expanded and contracted depending upon tool use.

Neuropsychological evidence of the functional integration of visual, auditory and proprioceptive spatial maps.

We infer the functional integration of the visual, auditory and proprioceptive spatial maps from the behaviour of a patient (G.A.) with left visual neglect, i.e. a derangement of visual space representation. G.A. was required to point manually to left, centre or right acoustic stimuli, under visual control or blindfolded, with the responding hand (left or right) located either on the left, centre or right space. G.A.'s manual pointing responses to left auditory stimuli were strongly influenced by the visual spatial information and by the proprioceptive spatial information related to the position of the responding effector. In the visual control condition, when the patient performed the task with the left effector located on the left, pointing responses to left auditory stimuli were shifted towards the right intact visual space. In contrast, when the visual spatial information was rendered less salient, i.e. in the blindfolded condition, and the effector was again located on the left, manual pointing responses were confined to the previously ignored left space. These findings are consistent with the view that the acoustic representation is modulated by the impaired visual representation and by the proprioceptive spatial map related to the position of the responding effector.

The development of facedness.

Thirty-two children of both sexes, ranging in age from 6 to 13 years, were photographed while posing or imitating happiness, sadness or surprise. Full-face photographs which were considered by independent judges to express the intended emotions were submitted to a split-face recombination procedure that created two composites from each face, one from the left side and the other from the right. Independent observers found the left composites to be more expressive than the right in the older group (age 12-13), but not in the younger groups, who evinced no left-right asymmetries. This finding applied similarly to the three emotions, and did not depend on an age-related change in the capacity for emotional expression. Further, left-right asymmetries in facial expression, where present, did not correlate with difference in size between the two halves of the face, and were found for both the upper and lower parts of the face. It is concluded that the advantage of the left hemiface for emotional expression, which is typical of adults, is the result of growth and development. While this facial asymmetry is likely to depend on an hemispheric asymmetry favoring the right side of the brain for the volitional control of the facial musculature, the neural mechanisms of the phenomenon of facedness are still largely obscure.

The deployment of visual attention in the intact field of hemineglect patients.

Patients with left hemispatial neglect after right hemisphere lesions and control patients with right hemisphere lesions were presented in the ipsilesional (i.e., intact) visual field with stimuli that could occupy left-right relative positions. The patients were required to discriminate between target stimuli and distractors by emitting go/no-go responses. Reaction times (RTs) and measures of sensitivity (d') and response bias (beta) were obtained. The within-subjects comparisons showed that neglect patients were faster in the right than the left relative position, whereas control patients were faster in the left than the right relative position. The between-subjects comparisons showed that neglect patients were faster than control patients in the right relative position but slower in the left relative position. These effects were due to changes in processing efficiency, as attested by the fact that the differences in response speed were accompanied by congruent differences in sensitivity, whereas no differences in response bias were found. The results were interpreted by assuming that neglect patients focus attention on the right relative position and, therefore, have a small attentional focus concentrated on that position. By contrast, control patients, like normal subjects, would distribute attention between the two possible stimulus positions and, therefore, allocate attention to a larger portion of the visual field.

Must egocentric and environmental frames of reference be aligned to produce spatial S-R compatibility effects?

Four experiments were conducted to determine the effects of misaligning egocentric and environmental frames of reference on spatial S-R compatibility effects. In Experiments 1 and 3, subjects looked at two lights that were aligned horizontally, one each on either side of the body midline. They held their head upright or tilted 90 degrees to the left or right. In the upright condition the hands were uncrossed and rested opposite the lights (frames of reference aligned), whereas in the head tilt condition the hands were either crossed or uncrossed but positioned perpendicular to the lights (frames of reference not aligned). Manual choice reaction times to the lights produced spatial S-R compatibility effects that were as large when the frames of reference were aligned as when they were not. In Experiments 2 and 4, which also used upright and tilted conditions, we found generally similar results when the lights were displayed vertically and the hands disposed horizontally. The results indicate that under conditions of head rotation and with stimulus and response arrays perpendicular to each other, spatial S-R compatibility effects still occur. By taking into account both frames of reference, the subject classifies the stimuli as left or right whether they are horizontally or vertically disposed and maps them onto the responding hand, thereby producing the observed compatibility effects.

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.

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.

Low-frequency rTMS promotes use-dependent motor plasticity in chronic stroke: a randomized trial.

OBJECTIVE: To investigate the long-term behavioral and neurophysiologic effects of combined time-locked repetitive transcranial magnetic stimulation (rTMS) and physical therapy (PT) intervention in chronic stroke patients with mild motor disabilities. METHODS: Thirty patients were enrolled in a double-blind, randomized, single-center clinical trial. Patients received 10 daily sessions of 1 Hz rTMS over the intact motor cortex. In different groups, stimulation was either real (rTMS(R)) or sham (rTMS(S)) and was administered either immediately before or after PT. Outcome measures included dexterity, force, interhemispheric inhibition, and corticospinal excitability and were assessed for 3 months after the end of treatment. RESULTS: Treatment induced cumulative rebalance of excitability in the 2 hemispheres and a reduction of interhemispheric inhibition in the rTMS(R) groups. Use-dependent improvements were detected in all groups. Improvements in trained abilities were small and transitory in rTMS(S) patients. Greater behavioral and neurophysiologic outcomes were found after rTMS(R), with the group receiving rTMS(R) before PT (rTMS(R)-PT) showing robust and stable improvements and the other group (PT-rTMS(R)) showing a slight improvement decline over time. CONCLUSION: Our findings indicate that priming PT with inhibitory rTMS is optimal to boost use-dependent plasticity and rebalance motor excitability and suggest that time-locked rTMS is a valid and promising approach for chronic stroke patients with mild motor impairment. CLASSIFICATION OF EVIDENCE: This interventional study provides Class I evidence that time-locked rTMS before or after physical therapy improves measures of dexterity and force in the affected limb in patients with chronic deficits more than 6 months poststroke.