Modulation of inhibitory corticospinal circuits induced by a nocebo procedure in motor performance.

As recently demonstrated, a placebo procedure in motor performance increases force production and changes the excitability of the corticospinal system, by enhancing the amplitude of the motor evoked potentials (MEP) and reducing the duration of the cortical silent period (CSP). However, it is not clear whether these neurophysiological changes are related to the behavioural outcome (increased force) or to a general effect of expectation. To clarify this, we investigated the nocebo effect, in which the induced expectation decreases force production. Two groups of healthy volunteers (experimental and control) performed a motor task by pressing a piston with the right index finger. To induce a nocebo effect in the experimental group, low frequency transcutaneous electrical nerve stimulation (TENS) was applied over the index finger with instructions of its detrimental effects on force. To condition the subjects, the visual feedback on their force level was surreptitiously reduced after TENS. Results showed that the experimental group reduced the force, felt weaker and expected a worse performance than the control group, who was not suggested about TENS. By applying transcranial magnetic stimulation over the primary motor cortex, we found that while MEP amplitude remained stable throughout the procedure in both groups, the CSP duration was shorter in the experimental group after the nocebo procedure. The CSP reduction resembled previous findings on the placebo effect, suggesting that expectation of change in performance diminishes the inhibitory activation of the primary motor cortex, independently of the behavioural outcome

Electrophysiological properties of thalamic, subthalamic and nigral neurons during the anti-parkinsonian placebo response

Placebo administration to Parkinson patients is known to induce dopamine release in the striatum and to affect the activity of subthalamic nucleus (STN) neurons. By using intraoperative single-neuron recording techniques in awake patients, here we extend our previous study on STN recording, and characterize part of the neuronal circuit which is affected by placebos. In those patients who showed a clinical placebo response, there was a decrease in firing rate in STN neurons that was associated with a decrease in the substantia nigra pars reticulata (SNr) and an increase in the ventral anterior (VA) and anterior ventral lateral (VLa) thalamus. These data show that placebo decreases STN and SNr activity whereas it increases VA/VLa activity. By contrast, placebo non-responders showed either a lack of changes in this circuit or partial changes in the STN only. Thus, changes in activity in the whole basal ganglia–VA/VLa circuit appear to be important in order to observe a clinical placebo improvement, although the involvement of other circuits, such as the direct pathway bypassing the STN, cannot be ruled out. The circuit we describe in the present study is likely to be a part of a more complex circuitry, including the striatum and the internal globus pallidus (GPi), that is modified by placebo administration. These findings indicate that a placebo treatment, which is basically characterized by verbal suggestions of benefit, can reverse the malfunction of a complex neuronal circuit, although these placebo-associated neuronal changes are short-lasting and occur only in some patients but not in others

A multiscale analytical approach for bone remodeling simulations : linking scales from collagen to trabeculae

Bone is a dynamic and hierarchical porous material whose spatial and temporal mechanical properties can vary considerably due to differences in its microstructure and due to remodeling. Hence, a multiscale analytical approach, which combines bone structural information at multiple scales to the remodeling cellular activities, could form an efficient, accurate and beneficial framework for the prognosis of changes in bone properties due to, e.g., bone diseases. In this study, an analytical formulation of bone remodeling integrated with multiscale micromechanical models is proposed to investigate the effects of structural changes at the nanometer level (collagen scale) on those at higher levels (tissue scale). Specific goals of this study are to derive a mechanical stimulus sensed by the osteocytes using a multiscale framework, to test the accuracy of the multiscale model for the prediction of bone density, and to demonstrate its multiscale capabilities by predicting changes in bone density due to changes occurring at the molecular level. At each different level, the bone composition was modeled as a two-phase material which made it possible to: 1) find a closed-form solution for the energy-based mechanical stimulus sensed by the osteocytes and 2) describe the anisotropic elastic properties at higher levels as a function of the stiffness of the elementary components (collagen, hydroxyapatite and water) at lower levels. The accuracy of the proposed multiscale model of bone remodeling was tested first by comparing the analytical bone volume fraction predictions to those obtained from the corresponding µFE-based computational model. Differences between analytical and numerical predictions were less than 1% while the computational time was drastically reduced, namely by a factor of 1 million. In a further analysis, the effects of changes in collagen and hydroxyapatite volume fractions on the bone remodeling process were simulated, and it was found that such changes considerably affect the bone density at the millimeter scale. In fact, smaller tissue density induces remodeling activities leading to finally higher overall bone density. The multiscale analytical model proposed in this study potentially provides an accurate and efficient tool for simulating patient-specific bone remodeling, which might be of importance in particular for the hip and spine, where an accurate assessment of bone micro-architecture is not possible