Alessandro Piedimonte

‘Moving’ a paralysed hand: bimanual coupling effect in patients with anosognosia for hemiplegia

Selective neurological impairments can shed light on different aspects of motor cognition. Brain-damaged patients with anosognosia for hemiplegia deny their motor deficit and believe they can still move the paralysed limb. Here we study, for the first time, if the anomalous subjective experience that their affected hand can still move, may have objective consequences that constrain movement execution with the opposite, intact hand. Using a bimanual motor task, in which anosognosic patients were asked to simultaneously trace out lines with their unaffected hand and circles with their paralysed hand, we found that the trajectories of the intact hand were influenced by the requested movement of the paralysed hand, with the intact hand tending to assume an oval trajectory (bimanual coupling effect). This effect was comparable to that of a group of healthy subjects who actually moved both hands. By contrast, brain-damaged patients with motor neglect or actual hemiplegia but no anosognosia did not show this bimanual constraint. We suggest that anosognosic patients may have intact motor intentionality and planning for the plegic hand. Rather than being merely an inexplicable confabulation, anosognosia for the plegic hand can produce objective constraints on what the intact hand does.

Embodiment of an alien hand interferes with intact-hand movements

Summary Can we fully incorporate into our body schema the body parts of others, altering our sense of ownership [1]? And, to what extent, given the tight link between body and motor representations, does an altered sense of body-ownership affect motor awareness [2] and the sense of agency [3,4]? The new study we report here demonstrates that a body part of one individual can become so deeply embedded in anothers sensory-motor circuits as to have objective effects on the latters motor execution. Indeed, we found, in right-brain-damaged hemiplegic patients who identified another persons hand as belonging to themselves, significant interference effects of the alien hand movements on the actual movements of their own intact hand.

Increasing uncertainty in CNS clinical trials: the role of placebo, nocebo, and Hawthorne effects

As modern research continues to unravel the details of the placebo phenomenon in CNS disorders, uncertainty about therapeutic outcomes in trials of treatments for several neurological conditions is growing. Advances in understanding the mechanisms of different placebo effects have emphasised the substantial challenges inherent in interpreting the results of CNS clinical trials. In the past few years, new mechanisms and concepts have emerged in the study of placebo, nocebo, and Hawthorne effects in CNS clinical trials. For example, the mere step of recruitment in a trial or social interaction among trial participants can change the baseline conditions and therefore affect the interpretation of therapeutic outcomes. Moreover, different genotypes have been shown to respond differently to placebos-eg, in studies of social anxiety, depression, and pain. Increasing recognition of these factors in the general population raises the question of whether attempts should be made to reduce placebo responses in CNS clinical trials. Both clinical trial design and medical practice could benefit from further investigation of these effects across a range of neuropsychiatric disorders.

Role of explicit verbal information in conditioned analgesia.

The exact role of expectation in conditioned analgesia is still elusive as it is not clear whether conditioning is an automatic process or rather it is cognitively mediated. This study is aimed at understanding the role of explicit verbal information in conditioned analgesia.

An educational and physical program to reduce headache, neck/shoulder pain in a working community: a cluster-randomized controlled trial.

Background Noninvasive physical management is often prescribed for headache and neck pain. Systematic reviews, however, indicate that the evidence of its efficacy is limited. Our aim was to evaluate the effectiveness of a workplace educational and physical program in reducing headache and neck/shoulder pain. Methodology/Principal Findings Cluster-randomized controlled trial. All municipal workers of the City of Turin, Italy, were invited to participate. Those who agreed were randomly assigned, according to their departments, to the intervention group (IG) or to the control group and were given diaries for the daily recording of pain episodes for 1 month (baseline). Subsequently, only the IG (119 departments, 923 workers) began the physical and educational program, whereas the control group (117 departments, 990 workers) did not receive any intervention. All participants were again given diaries for the daily recording of pain episodes after 6 months of intervention. The primary outcome was the change in the frequency of headache (expressed as the proportion of subjects with a ≥50% reduction of frequency; responder rate); among the secondary outcomes there were the absolute reduction of the number of days per month with headache and neck/shoulder pain. Differences between the two groups were evaluated using mixed-effect regression models. The IG showed a higher responder rate [risk ratio, 95% confidence interval (CI)] for headache (1.58; 1.28 to 1.92) and for neck/shoulder pain (1.53; 1.27 to 1.82), and a larger reduction of the days per month (95% CI) with headache (−1.72; −2.40 to −1.04) and with neck/shoulder pain (−2.51; −3.56 to −1.47). Conclusions The program effectively reduced headache and neck/shoulder pain in a large working community and appears to be easily transferable to primary-care settings. Further trials are needed to investigate the program effectiveness in a clinical setting, for highly selected patients suffering from specific headache types. Trial Registration ClinicalTrials.gov NCT00551980

Placebo and Nocebo Effects: A Complex Interplay Between Psychological Factors and Neurochemical Networks

Placebo and nocebo effects have recently emerged as an interesting model to understand some of the intricate underpinnings of the mind–body interaction. A variety of psychological mechanisms, such as expectation, conditioning, anxiety modulation, and reward, have been identified, and a number of neurochemical networks have been characterized across different conditions, such as pain and motor disorders. What has emerged from the recent insights into the neurobiology of placebo and nocebo effects is that the psychosocial context around the patient and the therapy, which represents the ritual of the therapeutic act, may change the biochemistry and the neuronal circuitry of the patient’s brain. Furthermore, the mechanisms activated by placebos and nocebos have been found to be the same as those activated by drugs, which suggests a cognitive/affective interference with drug action. Overall, these findings highlight the important role of therapeutic rituals in the overall therapeutic outcome, including hypnosis, which may have profound implications both in routine medical practice and in the clinical trials setting.

Executed and Imagined Bimanual Movements: A Study across Different Ages.

Movements with both hands are essential to our everyday life, and it has been shown that performing asymmetric bimanual movements produces an interference effect between hands. There have been many studies--using varying methods--investigating the development of bimanual movements that show that this skill continues to evolve during childhood and adolescence. In the current study we used a spatial bimanual task to delineate the development of bimanual movements not only during different stages of childhood but also during late stages of adulthood. Furthermore, we used the same task as a window to observe the involvement of motor imagery through the same age groups. For this study we recruited participants from 4 different age groups and asked them to perform congruent and noncongruent bimanual movements in a Real condition, where participants moved both hands, and in an Imagery condition, where they had to imagine 1 hands movements while actually using the other hand. Our results showed that, with actual movement execution, the interference between motor programs of the 2 hands is higher in children (6-10 years old) than in younger adults (20-30 years old), while it tends to increase again in the elderly adults (60-80 years old). Interestingly, in the Imagery condition, the interference was present only among 10-year-old and 20- to 30-year-old participants, suggesting that motor imagery, not yet developed in young children and compromised by age in the elderly subjects, did not modulate motor performance in these last 2 groups.

Anosognosia for hemianaesthesia: A voxel-based lesion-symptom mapping study

Brain-damaged patients affected by hemianaesthesia (i.e., the loss of tactile sensibility on the contralesional side of the body) may deny their deficits (i.e., anosognosia for tactile deficits) even reporting tactile experience when stimuli are delivered on the impaired side. So far, descriptive analysis on small samples of patients reported that the insular cortex, the internal/external capsule, the basal ganglia and the periventricular white matter would subserve anosognosia for hemianaesthesia. Here, we aimed at examining in depth the anatomo-functional nature of anosognosia for hemianaesthesia by means of a voxelwise statistical analysis. We compared two groups of left hemiplegic patients due to right brain damages differing only for the presence/absence of anosognosia for left hemianaesthesia. Our findings showed a lesional cluster confined mainly to the anterior part of the putamen. According to the current anatomical evidence on the neural basis of sensory expectancies, we suggested that anosognosia for hemianaesthesia might be explained as a failure to detect the mismatch between expected and actual tactile stimulation.

Abnormal Sense of Agency in Patients with Schizophrenia: Evidence from Bimanual Coupling Paradigm

A fruitful approach to the understanding the human awareness of action is the study of those pathologies in which some aspects of it are altered. Previous evidences showed that patients with schizophrenia tend to attribute someone else’ actions to their own, as internally, rather than externally, generated. Here, we asked whether schizophrenics have an “excessive” sense of agency, while observing others’ movements. We took advantage from the circles-lines task, known to show bimanual interferences. Twenty schizophrenics and 20 age-matched healthy controls were administered: (a) the bimanual version of the task: drawing lines with one hand and circles with the other; and (b) a modified version: drawing lines while observing the examiner drawing circles. In the bimanual version, patients and controls showed a comparable interference effect. In the observation version, schizophrenics, compared to controls, showed a significantly greater interference effect of the examiners’ hand drawing circles on the own hand drawing lines. This effect was significantly correlated to the strength of the positive symptoms (hallucinations and delusions) and to the alteration of the sense of agency, reported during the task. These findings suggest that an altered sense of agency, as shown by schizophrenics, can induce objective consequences on the motor system.

Placebo‐induced decrease in fatigue: evidence for a central action on the preparatory phase of movement

Placebos have been found to affect a number of pathological processes and physiological functions through expectations of clinical improvement. Recently, the study of the placebo effect has moved from the clinical to the physical performance setting, wherein placebos can boost performance by increasing muscle work and by decreasing perceived exertion. However, nothing is known about the neurobiological underpinnings of this phenomenon. Here we show for the first time that a placebo, which subjects believed to be endurance‐increasing caffeine, reduces fatigue by acting at the central level on the preparatory phase of movement. In fact, we recorded the readiness potential, which is the expression of the preparatory phase of movement at the level of the supplementary motor area, during repeated flexions of the index finger in a control group that did not receive any treatment and in a placebo group that received placebo caffeine. In the control group, as the number of flexions increased, both fatigue and readiness potential amplitude increased. By contrast, in the placebo group, as the number of flexions increased we found a decrease in perceived exertion along with no increase in readiness potential amplitude. This placebo‐induced modulation of the readiness potential suggests that placebos reduce fatigue by acting centrally during the anticipatory phase of movement, thus emphasizing the important role of the central nervous system in the generation of fatigue.