In analgesic clinical trials, adverse events are reported for the painkiller under evaluation and compared with adverse events in the placebo group. Interestingly, patients who receive the placebo often report a high frequency of adverse events, but little is understood about the nature of these negative effects. In the present study, we compared the rates of adverse events reported in the placebo arms of clinical trials for three classes of anti-migraine drugs: NSAIDs, triptans and anticonvulsants. We identified 73 clinical trials in 69 studies describing adverse events in placebo groups: 8 were clinical trials with NSAIDs, 56 were trials with triptans, and 9 were trials with anticonvulsants. Studies were selected of all Medline/PubMed or CENTRAL referenced trials published until 2007. Adverse event profiles of the three classes were compared using a systematic review approach. We found that the rate of adverse events in the placebo arms of trials with anti-migraine drugs was high. In addition, and most interestingly, the adverse events in the placebo arms corresponded to those of the anti-migraine medication against which the placebo was compared. For example, anorexia and memory difficulties, which are typical adverse events of anticonvulsants, were present only in the placebo arm of these trials. These results suggest that the adverse events in placebo arms of clinical trials of anti-migraine medications depend on the adverse events of the active medication against which the placebo is compared. These findings are in accordance with the expectation theory of placebo and nocebo effects.

Following destruction or deafferentation of primary visual cortex (area V1, striate cortex), clinical blindness ensues, but residual visual functions may, nevertheless, persist without perceptual consciousness (a condition termed blindsight). The study of patients with such lesions thus offers a unique opportunity to investigate what visual capacities are mediated by the extrastriate pathways that bypass V1. Here we provide evidence for a crucial role of the collicular-extrastriate pathway in nonconscious visuomotor integration by showing that, in the absence of V1, the superior colliculus (SC) is essential to translate visual signals that cannot be consciously perceived into motor outputs. We found that a gray stimulus presented in the blind field of a patient with unilateral V1 loss, although not consciously seen, can influence his behavioral and pupillary responses to consciously perceived stimuli in the intact field (implicit bilateral summation). Notably, this effect was accompanied by selective activations in the SC and in occipito-temporal extrastriate areas. However, when instead of gray stimuli we presented purple stimuli, which predominantly draw on S-cones and are thus invisible to the SC, any evidence of implicit visuomotor integration disappeared and activations in the SC dropped significantly. The present findings show that the SC acts as an interface between sensory and motor processing in the human brain, thereby providing a contribution to visually guided behavior that may remain functionally and anatomically segregated from the geniculo-striate pathway and entirely outside conscious visual experience.

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The present study used the redundant target paradigm on healthy subjects to investigate functional hemispheric asymmetries and interhemispheric cooperation in the perception of emotions from faces. In Experiment 1 participants responded to checkerboards presented either unilaterally to the left (LVF) or right visual half field (RVF), or simultaneously to both hemifields (BVF), while performing a pointing task for the control of eye movements. As previously reported (Miniussi et al. in J Cogn Neurosci 10:216-230, 1998), redundant stimulation led to shorter latencies for stimulus detection (bilateral gain or redundant target effect, RTE) that exceeded the limit for a probabilistic interpretation, thereby validating the pointing procedure and supporting interhemispheric cooperation. In Experiment 2 the same pointing procedure was used in a go/no-go task requiring subjects to respond when seeing a target emotional expression (happy or fearful, counterbalanced between blocks). Faster reaction times to unilateral LVF than RVF emotions, regardless of valence, indicate that the perception of positive and negative emotional faces is lateralized toward the right hemisphere. Simultaneous presentation of two congruent emotional faces, either happy or fearful, produced an RTE that cannot be explained by probability summation and suggests interhemispheric cooperation and neural summation. No such effect was present with BVF incongruent facial expressions. In Experiment 3 we studied whether the RTE for emotional faces depends on the physical identity between BVF stimuli, and we set a second BVF congruent condition in which there was only emotional but not physical or gender identity between stimuli (i.e. two different faces expressing the same emotion). The RTE and interhemispheric cooperation were present also in this second BVF congruent condition. This shows that emotional congruency is the sufficient condition for the RTE to take place in the intact brain and that the cerebral hemispheres can interact in spite of physical differences between stimuli.

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One patient with left neglect (FM) and four right brain-damaged controls were tested on a line bisection task with pictures of neutral and emotional faces as unilateral cues. We thus manipulated the attentional salience of the cues (higher for emotional and lower for neutral faces) while keeping constant their physical dimensions. Our findings showed that left emotional faces were more effective than left neutral faces in reducing bisection errors only in FM. These data indicate that in the neglected hemispace cues bias attention rather than simply altering the perceptual point of balance of the line in the horizontal plane.

The study of visuospatial representations and visuospatial memory can profit from the analysis of the performance of specific groups. in particular, the surprising skills and limitations of blind people may be an important source of information. For example, converging evidence indicates that, even though blind individuals are able to develop both egocentric and allocentric space representations, the latter tend to be much more restricted than those in blindfolded sighted individuals. however, no study has explored yet whether this conclusion also holds when people receive practice with the spatial environment and are supported by auditory stimuli. The present research examined these issues with the use of an experimental apparatus based on the morris Water maze (morris et al., 1982). in this setup, blind people and blindfolded controls were given the opportunity to develop knowledge of the environment with the support of simultaneous auditory cues. The results show that even in this favourable case blind people spontaneously maintain to rely on an egocentric spatial representation.

T he present study investigated the relationship between anosognosia for cognitive, functional and psychopathological disorders in Alzheimer's disease (AD) and vascular dementia (VD). Ten patients with probable Alzheimer's disease and 10 patients with probable vascular dementia were matched for age, education, illness duration and dementia severity. Cognitive, functional and psychopathological characteristics of the patients were assessed by means of different self-rating scales. The same questionnaires were submitted to patients' caregivers, blind to the patients' answers. Anosognosia was defined as the positively signed difference between patients' and caregivers' ratings. Three anosognosia indices for each domain investigated were obtained. We found lack of insight to be a common and consistent feature of AD and VD. However, unawareness for cognitive and functional domains was more severe in AD than in VD. Furthermore, in AD patients anosognosia for cognitive, functional and psychopathological domains dissociated from one another, as shown by lack of significant correlations between the three indices. Conversely, in VD patients these three anosognosic domains were closely related, indicating a generalised unawareness. These findings suggest that heterogeneity of anosognosic deficits may help differentiate AD from VD.