Neuroscience
-
Gene therapy for rare monogenetic neurological disorders is reaching clinics and offering hope to families affected by these diseases. There is also potential for gene therapy to offer new and effective treatments for common, non-genetic disorders. Treatments for Parkinson's Disease are in clinical trials, and treatments for refractory epilepsies are due to enter first-in-human clinical trials in 2022. ⋯ Several lines of research are aimed at developing gene therapy approaches that allow for the treatment to be turned on and off, including: using proteins activated by exogenous ligands, and promoters turned on by activators. We review these approaches and propose an overall de-risking strategy for gene therapy for common neurological and psychiatric diseases. This approach is based on using a temporary mRNA-based treatment to initially assess efficacy and safety of the planned manipulation, and only following with permanent, virally-delivered treatment if the approach appears safe and effective.
-
This study examined how semantic transparency modulated the processing of spoken Chinese compound words with event-related potential (ERP) recording. A reverse-block passive oddball paradigm was adopted to elicit mismatch negativity (MMN), which responds to holistic and combinatorial processing in opposite directions. Specifically, linguistic inputs that are processed as holistic lexical representations will elicit stronger MMNs (lexical enhancement) than those that do not have such representations. ⋯ Opaque words did not differ from pseudocompounds, which was interpreted as parallel employment of the holistic and combinatorial processing routes. Overall, the results are consistent with the idea that native Chinese speakers routinely attempt to process Chinese compound words by retrieving and combining morphemes. However, because the meanings of opaque words are irrelevant to their constituent morphemes, Chinese speakers must construct and retrieve their holistic representations to ensure accurate processing.
-
Early-life stress (ELS) has long-term consequences, including an increased risk for drug abuse and psychiatric disorders later in life, which is higher in women than in men. The consequences of ELS include heightened sensitivity to stressful events. Here, we hypothesized that ELS changes the stress sensitivity of dopaminergic (DAergic) neurons in the ventral tegmental area (VTA) and orexin (OXA) neurons in the lateral hypothalamus (LH), that are crucial for the control of motivated behaviors. ⋯ Furthermore, an increase in spine head diameter of VTA neurons and a concurrent decrease in dendritic spine density in dorsal VTA were observed. We also showed that MS changed the stress sensitivity of OXA neurons selectively in the dorsomedial hypothalamus (DMH), which is implicated in arousal and the stress response. These findings show the long-lasting consequences of ELS and indicate the selective, regional sensitivity of structures involved in the control of arousal, motivational behaviors and the stress response to ELS.
-
Physiological movement develops on the basis of sensorimotor integration through synchronisation between the copy of signals sent to the effector muscles and the incoming flow of sensory information. Our aim is to study corticomuscular coherence (CMC), the most widely used measure of synchronization between brain and muscle electrical activities, in dependence on the level of visual feedback and the executing body side. We analysed CMC in 18 healthy volunteers while performing a weak isometric handgrip of an air bulb with either the right or the left hand, in either the presence or absence of visual feedback on the exerted pressure. ⋯ The lack of dependence of CMC on the controlled hand involved in the movement can be considered in agreement with small hemispheric asymmetries of hand representations in primary sensorimotor cortices. Modulation of visual information changed corticomuscular synchronizations and cortical involvement, reflecting the crucial role of gaze in human behaviour. Given the fundamental role of sensory integration in motor execution, the availability of a simple index sensitive to modulations of perceptual afferents may prove useful in determining the use or the monitoring of the effects of sensory enrichments in personalized rehabilitation.
-
Fear of falling increases conscious control of balance and postural threat warrants accurate anticipatory motor commands for keeping a safe body posture. This study examines the anticipatory (APAs) and compensatory (CPAs) postural adjustments generated in response to an external perturbation while individuals are positioned at two different altitudes (2 cm and 80 cm) from the floor level. The main result indicates that due to the perceived emotional threat, different agonist and antagonist muscles synergies (R and C-Indexes) are manifested, particularly during the anticipatory phase. ⋯ Interestingly, the APAs strategies were modified under different postural threats by controlling the agonist-antagonist muscles at different joints of lower extremity. For CPAs the reciprocal activation was less applied compared to muscles co-activation to unsure larger margin for compensatory adjustments as needed and re-establish the postural stability. The results indicate that when facing to a postural threat, the CNS modulates the anticipatory and compensatory phases of postural adjustments to minimize the risk of falling.