Interactions between cognitive and sensorimotor functions in the motor cortex: evidence from the preparatory motor sets anticipating a perturbation

The many signs of cognitive processes in the activation pattern of the primary motor cortex or in corticospinal (CS) excitability gave rise to the idea that the motor cortex is a crucial node in the processing of cognitive information related to sensorimotor functions. Moreover, it became clear that the preparatory motor sets offer a privileged window to investigate the interaction between cognitive and sensorimotor function in the motor cortex. In the present review, we examine how the study of the preparatory motor sets anticipating a mechanical movement perturbation contributes to enlightening this question. Following the initial observation made by Hammond that some components of the stretch reflex can be modulated by a prior intention either to resist or to relax in response to a subsequent perturbation, first evidence of the phenomenon was obtained in behaving monkeys. Moreover, this study related this peripheral fact to the observed anticipatory activity of motor cortex neurons after a prior instruction telling the animal how to respond to the subsequent perturbation, which triggered the instructed movement. Indeed, this anticipatory activity was found to be different according to the instruction. In the 1980s, this work inspired a lot of studies in human beings that brought support to the idea of a cognitive tuning of the long latency stretch response (LLSR). Specifically, the MI component of the response was shown to be modulated by a prior intent to resist versus to let go when faced with the perturbation. Recently, new approaches have been developed to obtain evidence of a cognitive tuning of CS excitability, thanks to transcranial magnetic stimulation (TMS). TMS has been used both as a reliable tool for quantifying the CS excitability via the motor evoked potentials (MEPs), and to centrally perturb the organization of movement. Such central perturbations offer the unique opportunity to activate the descending motor tracts while shunting, for a short time period, the ascending tracts assisting the movement. Thus, CS excitability was measured before the movement was perturbed. These studies demonstrated the readiness of the CS tract to be involved in anticipatory compensatory responses to central movement perturbations induced by TMS in relation to the subject's cognitive attitudes. The question of the cerebral regions upstream of the motor cortex that could be responsible for this modulation in CS excitability remains largely open.     

Cognitive tuning of corticospinal excitability during human gait: adaptation to the phase

The aim of this study was to investigate how the cognitive tuning of corticospinal (CS) excitability adapts to the type of evoked-movement (Flexion vs. Extension) during human gait. Transcranial magnetic stimulation (TMS) was used both as a central perturbation evoking a movement and as a tool for quantifying the CS excitability of the muscles under study (RF/BF). In the first condition (Dst), the TMS occurred at mid-stance, inducing hip extension, whereas in the second condition (Dsw), the TMS occurred at the beginning of the swing phase, inducing hip flexion. In both conditions, the subjects were asked to cognitively prepare to either not intervene (NINT) or to compensate (COMP) for the evoked-movements. The results showed that, regardless of the type of evoked-movement, preparing to compensate resulted in a selective increase in the CS excitability to those muscles that would be involved in counteracting the possible central perturbation, i.e. the hip extensor muscle (BF) to compensate for an evoked flexion during the swing phase or the hip flexor muscle (RF) to compensate for an evoked extension during the stance phase. This latter result offers the first evidence of a modulation in CS excitability to the proximal muscles during the stance phase. In conclusion, the cognitive tuning of CS excitability was found to adapt to the gait phases. Moreover, the same selective preparation strategy was observed whether the central perturbation occurred during the stance or the swing phase of the step cycle.     

Growth hormone stimulates the selective trafficking of thymic CD4+CD8- emigrants to peripheral lymphoid organs

Growth hormone (GH) has been shown to stimulate T cell development. However, its mechanisms of action on the peripheral T cell pool remain unknown. To address this question, intrathymic injection of GH in combination with fluorescein isothiocyanate (FITC) was used to assess the effects of GH on T cell trafficking from the thymus to the periphery. GH promoted a significant increase in the percentage and differential distribution of thymic CD4+CD8-FITC+ cells in secondary lymphoid organs. A significantly higher percentage of CD4+CD8-FITC+ cells was observed in the lymph nodes, while a relative decrease of these cells was found in the spleen. Moreover, we verified that GH treatment resulted in increased numbers of CD62L+CD4+CD8-FITC+ T cells in the lymph nodes, while the same treatment resulted in a decline in the percentage of VLA-6+CD4+CD8-FITC+ T cells in the spleen. Together, these findings suggest that GH is a potent immunoregulatory molecule which selectively stimulates the preferential homing of CD4+CD8- thymic emigrants to the subcutaneous lymph nodes possibly via the differential expression of CD62L and VLA-6.     

Musical and auditory hallucinations: A spectrum

Musical hallucinosis is a rare and poorly understood clinical phenomenon. While an association appears to exist between this phenomenon and organic brain pathology, aging and sensory impairment the precise association remains unclear. The authors present two cases of musical hallucinosis, both in elderly patients with mild-moderate cognitive impairment and mild-moderate hearing loss, who subsequently developed auditory hallucinations and in one case command hallucinations. The literature in reference to musical hallucinosis will be reviewed and a theory relating to the development of musical hallucinations will be proposed.     

Stage-based lifestyle interventions in primary care: are they effective?

BACKGROUND: To systematically review the literature concerning the effect of stages-of-change-based interventions in primary care on smoking, physical activity, and dietary behavior. METHODS: An extensive search (until July 2002) was performed using the following inclusion criteria: (1) (randomized) controlled trial (RCT/CT), (2) intervention initiated in primary care, (3) and intervention aimed at changing smoking, physical activity, or dietary behavior, and stages-of-change-based outcomes, and (4) behavioral outcomes. Methodologic quality was assessed, and conclusions on the effectiveness at short-, medium-, and long-term follow-up were based on a rating system of five levels of evidence. Odds ratios were calculated when methodologically appropriate. RESULTS: A total of 29 trials were selected for inclusion. Thirteen studies included a physical activity intervention, 14 aimed at smoking cessation, and five included a dietary intervention. Overall methodologic quality was good. No evidence was found for an effect on stages of change and actual levels of physical activity. Based on the strength of the evidence, limited to no evidence was found for an effect on stages of change for smoking and smoking quit rates. Odds ratios for quitting smoking showed a positive trend. Strong evidence was found for an effect on fat intake at short- and long-term follow-up. Limited evidence was found for an effect on stages of change for fat intake at short-term follow-up. CONCLUSIONS: The scientific evidence for the effect of stages-of-change-based lifestyle interventions in primary care is limited. Limiting aspects in the stages-of-change concept with respect to complex behaviors as physical activity and dietary behavior are discussed.     

Rapid detection of the deltaF508 mutation in single cells using DHPLC: implications for preimplantation genetic diagnosis

Purpose: Practice of preimplantation genetic diagnosis (PGD) requires efficient amplification and analysis techniques. We have tested Denaturing High Performance Liquid Chromatography (DHPLC) to screen the F508 mutation in heterozygous single cells in order to assess its usefulness for PGD of cystic fibrosis. Methods: One hundred and two single lymphocytes—including N/N and N/F508—were studied. F508 locus was amplified by nested PCR followed by the analysis of PCR products by DHPLC in non-denaturing conditions. Results: On the basis of PCR-amplified product analysis, total efficiency of amplification was 98.78% (101/102), and allele dropout (ADO) rate was 3.7% (3/81). For each sample, results were obtained in less than 4 min with high resolution. Conclusions: DHPLC is a rapid and efficient technique to detect the F508 mutation in single cells and is therefore appropriate for clinical application of preimplantation genetic diagnosis of cystic fibrosis.     

The efficacy of medical and surgical treatment of endometriosis-associated infertility and pelvic pain

This article is a review of the efficacy of medical and surgical treatment of endometriosis-associated infertility and pelvic pain. Endometriosis is the cause of pelvic pain (dysmenorrhea, dyspareunia) and infertility in more than 35% of women of reproductive age. Complete resolution of endometriosis is not yet possible but therapy has essentially three main objectives: (1) to reduce pain; (2) to increase the possibility of pregnancy; (3) to delay recurrence for as long as possible. It could be concluded that a consensus will probably never be reached on minimal and mild endometriosis. Nevertheless, because the Canadian study reported a large number of cases, we strongly support the view that visible endometriosis must be removed at the time of surgery. In cases of moderate and severe endometriosis-associated infertility, the combined approach (operative laparoscopy with GnRH-a) must be considered as 'first-line' treatment. The mean pregnancy rate of 50% reported in the literature following surgery provides scientific proof that operative treatment should be undertaken first to give our patients the best chance of conceiving naturally.     

Mechanisms of membrane potential sensing with second-harmonic generation microscopy

We characterize the transmembrane voltage response of a novel second-harmonic generation (SHG) marker using a screening protocol with giant unilamellar vesicles. Two mechanisms are found to contribute to the voltage response: (1) an electro-optic-induced alteration of the molecular hyperpolarizability and (2) an electric-field-induced alteration of the degree of molecular alignment. We quantify the relative weights and of these contributions and provide an upper limit to their response time, which is found to be submillisecond. The identification of two voltage response mechanisms leads to new strategies for the molecular design of membrane potential markers.     

Blood-tissue barriers in the male reproductive tract of the dog: a morphological study using lanthanum nitrate as an electron-opaque tracer

Blood-tissue barriers preventing an uncontrolled exchange of larger molecules between adjacent but metabolically separate compartments have been demonstrated in various organs. One prominent example is the blood-testis barrier which has been investigated in a number of species. A key function of this barrier is to shield developing germ cells from the immune system in order to avoid autoimmune reactions. This requirement also applies to the male excurrent duct system. Yet, very few investigations have addressed the morphology of the blood-epididymal barrier. The goal of the present study, therefore, was to revisit the blood-testis barrier in the dog and to identify the structures constituting the blood-epididymal barrier in this species. Lanthanum nitrate was used as a tracer for electron microscopy. In the testis, lanthanum had free access to the intercellular space of the seminiferous epithelium up to the Sertoli cell junctions. Similarly, epithelial tight junctions were found to represent the permeability barrier in the epididymis. The present study highlights species differences with respect to the blood-testis barrier and extends the knowledge of the blood-epididymal barrier by providing morphofunctional data in this domestic species.