Disrupting the supplementary motor area makes physical effort appear less effortful.

The perception of physical effort is relatively unaffected by the suppression of sensory afferences, indicating that this function relies mostly on the processing of the central motor command. Neural signals in the supplementary motor area (SMA) correlate with the intensity of effort, suggesting that the motor signal involved in effort perception could originate from this area, but experimental evidence supporting this view is still lacking. Here, we tested this hypothesis by disrupting neural activity in SMA, in primary motor cortex (M1), or in a control site by means of continuous theta-burst transcranial magnetic stimulation, while measuring effort perception during grip forces of different intensities. After each grip force exertion, participants had the opportunity to either accept or refuse to replicate the same effort for varying amounts of reward. In addition to the subjective rating of perceived exertion, effort perception was estimated on the basis of the acceptance rate, the effort replication accuracy, the influence of the effort exerted in trial t on trial t+1, and pupil dilation. We found that disruption of SMA activity, but not of M1, led to a consistent decrease in effort perception, whatever the measure used to assess it. Accordingly, we modeled effort perception in a structural equation model and found that only SMA disruption led to a significant alteration of effort perception. These findings indicate that effort perception relies on the processing of a signal originating from motor-related neural circuits upstream of M1 and that SMA is a key node of this network.

Pupil size variations correlate with physical effort perception.

It has long been established that the pupil diameter increases during mental activities in proportion to the difficulty of the task at hand. However, it is still unclear whether this relationship between the pupil size and effort applies also to physical effort. In order to address this issue, we asked healthy volunteers to perform a power grip task, at varied intensity, while evaluating their effort both implicitly and explicitly, and while concurrently monitoring their pupil size. Each trial started with a contraction of imposed intensity, under the control of a continuous visual feedback. Upon completion of the contraction, participants had to choose whether to replicate, without feedback, the first contraction for a variable monetary reward, or whether to skip this step and go directly to the next trial. The rate of acceptance of effort replication and the amount of force exerted during the replication were used as implicit measures of the perception of the effort exerted during the first contraction. In addition, the participants were asked to rate on an analog scale, their explicit perception of the effort for each intensity condition. We found that pupil diameter increased during physical effort and that the magnitude of this response reflected not only the actual intensity of the contraction but also the subjects' perception of the effort. This finding indicates that the pupil size signals the level of effort invested in a task, irrespective of whether it is physical or mental. It also helps refining the potential brain circuits involved since the results of the current study imply a convergence of mental and physical effort information at some level along this pathway.

Immunogenicity and safety of yellow fever vaccine among 115 HIV-infected patients after a preventive immunisation campaign in Mali.

The immune response to yellow fever (YF) vaccine and its safety among HIV-infected individuals living in YF endemic areas is not well understood. Following a national YF preventive immunisation campaign in Mali in April 2008, we assessed the immunogenicity and safety of 17D yellow fever vaccine (17DV) among HIV-infected patients in two HIV treatment centres in Bamako, Mali, by testing for neutralising antibodies and identifying serious adverse events following immunisation (AEFI). A YF neutralisation titre (NT) of 1:≥20 was considered to be adequate and protective. A serious AEFI included hospitalisation, any life-threatening condition, or death, occurring within 30 days following 17DV administration. Of 115 HIV-infected patients who reported having received 17DV, 110 (96%) were on combination antiretroviral therapy and 83 patients were tested for neutralising antibodies. Around the time of vaccination, median CD4 cell count was 389 cells/mm(3) (IQR 227-511cells/mm(3)); HIV-RNA was undetectable in 24 of 46 patients tested. Seventy-six (92%) of 83 participants had adequate immune titres 9 months after the immunisation campaign. Previous vaccination or flavivirus exposure could contribute to this finding. No serious AEFI was found in the 115 participants. In this small series, YF vaccine appeared to be immunogenic with a favourable safety profile in HIV-infected patients on antiretroviral therapy. Higher CD4 cell counts and suppressed HIV-RNA were associated with the presence of an adequate immune titre and higher NTs.